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  1. Taenia crassiceps Infection Attenuates Multiple Low-Dose Streptozotocin-Induced Diabetes

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    Arlett Espinoza-Jiménez

    2010-01-01

    Full Text Available Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronic T. crassiceps infection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS. Healthy or previously T. crassiceps-infected mice received MLDS and type 1 diabetes (T1D symptoms were evaluated for 6 weeks following the induction of MLDS. T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage of T. crassiceps-infected mice (40% developed T1D compared to the uninfected group (100%. Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-α. Therefore, infection with T. crassiceps causes an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

  2. Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats

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    Kirsch, Michael; Petrat, Frank

    2017-01-01

    Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats. PMID:28817064

  3. Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

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    Minglong Shao

    Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

  4. Low-dose attenuation correction in diagnosis of non-alcoholic fatty liver disease.

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    Ahmed, Amjad M; Ebid, Mohamed E; Ajlan, Amr M; Al-Mallah, Mouaz H

    2017-10-01

    Non-enhanced computed tomography (CT) is a valuable modality in the diagnosis of non-alcoholic fatty liver disease (NAFLD). However, it is not clear if low-dose CT attenuation correction (CTAC) scans have the same accuracy to diagnose NAFLD. Our aim is to evaluate the diagnostic accuracy of low-dose CTAC in the diagnosis of NAFLD using non-enhanced CT as a gold standard. A total of 864 patients who underwent a clinically indicated hybrid nuclear imaging scanning between May 2011 and April 2014 were included in the study. Diagnosis of fatty liver was established if an absolute liver attenuation was attenuation correction were 9.9 and 12.9% (using liver attenuation attenuation or ratio-to-spleen criteria), correspondingly. Low-dose CTAC had sensitivity (81.3%), specificity (94.0%), positive predictive value (60.2%), and negative predictive value (97.8%) using both diagnostic criteria. Using either of the diagnostic criteria resulted in sensitivity (76.8%), specificity (83.5%), PPV (66.3%), and NPV (89.5%). Low-dose CT could be used as a tool to rule out the presence of fatty liver if neither liver attenuation of less than 40 HU nor liver-to-spleen below 1.1 is present.

  5. Low Dose of Apelin-36 Attenuates ER Stress-Associated Apoptosis in Rats with Ischemic Stroke

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    Jian Qiu

    2017-10-01

    Full Text Available Cerebral ischemia/reperfusion (I/R injury-induced cellular apoptosis contributes to neuronal death in ischemic stroke, while endoplasmic reticulum stress (ERS and subsequently triggered unfolded protein response (UPR are the major mechanisms of cerebral I/R injury-induced apoptosis. A number of studies indicated that apelin-13 protects neurons from I/R injury-induced apoptosis. Apelin-36, the longest isoform of apelin, has stronger affinity to apelin receptor than apelin-13 does. However, the role of apelin-36 in ischemic stroke is less studied. In addition, preventive administration of apelin was applied in most studies, which could not precisely reflect its therapeutic potential in ischemic stroke. Here, we first reported that low dose of apelin-36, other than apelin-13, administrated after ischemic stroke significantly reduced infarct volume in rats. Moreover, apelin-36 attenuated cerebral I/R injury-induced apoptosis and caspase-3 activation. Furthermore, apelin-36 suppressed I/R injury-induced CHOP and GRP78 elevation, indicating that apelin-36 inhibited ERS/UPR activation. Our study first demonstrated that post-stroke administration of low-dose apelin-36 could attenuate cerebral I/R injury-induced infarct and apoptosis, which is associated with the inhibition of cerebral I/R injury-induced ERS/UPR activation. Our data support the therapeutic potential of apelin-36 in ischemic stroke although further investigation is needed.

  6. Evaluation of a combination of low-dose ketamine and low-dose midazolam in terminal dyspnea-attenuation of "double-effect"

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    Abhijit Kanti Dam

    2008-01-01

    Full Text Available Aim: Of all symptoms in palliative medicine those concerning respiration are most excruciating and difficult to treat. Reticence about the use of morphine for palliation of dyspnea is common, especially in nonmalignant diseases, as there is a fear of causing respiratory depression, particularly where Chronic Obstructive Pulmonary Disease (COPD exists. This factor is also compounded by the lack of availability of morphine in parts of developing countries. Ketamine has excellent anesthetic and analgesic effects in addition to being easily available. It produces bronchodilatation and does not produce respiratory or cardiovascular depression. The author seeks to evaluate the role of low-dose (0.2 mg/kg ketamine and midazolam (0.02 mg/kg in the attenuation of terminal dyspnea. Methods: Sixteen patients with terminal dyspnea, admitted to the Critical Care Unit (CCU with cancer and other noncancer diagnoses were recruited. The subjective component of dyspnea was assessed using the Graphic Rating Scale (GRS, which has values from 0 - 10, 10 being maximum dyspnea. Each patient received a low-dose of ketamine and midazolam for relief of dyspnea. All the patients received low-flow (2 L/min. oxygen therapy via nasal cannula. Immediately after admission, all the patients were reassured and nursed in a decubitus position of their choice. The GRS was recorded at the point of admission, 10 minutes after starting oxygen therapy, and ten minutes after administration of low-dose ketamine and midazolam. Hemodynamic parameters were also recorded at these three points. Result: All the patients who enrolled in our study had significant dyspnea at admission, as was evident from the GRS scores of 8.250 (SD 0.91, respiratory rate of 28.56 (SD 5.0, mean arterial blood pressure (MABP of 102.7 (SD 14.63, pulse rate of 115.62 (SD 23.3, and SpO2 of 92.43 (SD 2.38. All the patients benefited from the combination of ketamine and midazolam, as evidenced by the statistically

  7. Ultra-low Dose CT for Attenuation Correction of 82Rb Cardiac PET

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    Sørensen, Maria Balshøj; Bouchelouche, Kirsten; Tolbod, Lars Poulsen

    Aim: Myocardial perfusion imaging (MPI) using cardiac PET with tracers like 82Rb and 15O-water is substantially lower in radiation dose than classic MIBI-based SPECT. However, for cardiac PET, the dose contribution of CT for attenuation correction (CTAC) is typically 20-30% of the total dose....... To reduce the total radiation dose of cardiac PET further, we set out to examine if the use of ultra-low dose CTAC (UL-CTAC) would affect the accuracy of the quantitative parameters related to MPI. Furthermore, we examined whether the low quality of the UL-CTAC would affect the technologist’s ability...... to perform manual adjustment for misalignment between PET and CTAC. The CT reconstruction algorithm Q.AC was used to improve quality and consistency of the CTAC. Method: 23 consecutive clinical patients (BMI: 26.9 [range: 15.4-38.8]) referred for 82Rb PET rest and stress imaging were included in the study...

  8. Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

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    Nicoletti, F; Di Marco, R; Conget, I

    2000-01-01

    We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every...

  9. Retrospective study comparing low-dose versus standard dose of bortezomib in patients with multiple myeloma

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    Marcela Espinoza Zelada

    2015-03-01

    Full Text Available INTRODUCTION Bortezomib is a selective inhibitor of the proteosoma that is used in multiple myeloma. In combination with other antineoplastic drugs, it has a well-documented impact in progression-free survival rates and overall survival rates with standard doses (1.3-1.5 mg/m2. However, up to 88% of patients on standard doses have unwanted side effects (neutropenia, neuropathy or anemia. Standard dose (1.3 mg/m2 is used in almost all patients and low dose (0.7-0.8 mg/m2 is reserved for patients with kidney disease and neuropathy. OBJECTIVE We aim to describe clinical, cytological, and cytometric outcomes, as well as overall survival and side effects of low dose versus standard dose of bortezomib in our institution. METHODS Retrospective, descriptive study based on data recovered from clinical charts of 48 multiple myeloma patients treated in our hospital between 2011 and 2013. We included data on age, gender, type of multiple myeloma, serum albumin, serum creatinine, beta 2 microglobulin, calcemia, imaging studies, disease stage, pre-and post-therapy bone marrow studies, adverse events and rate of progression. We also recorded events like date of death or of the last medical appointment. RESULTS Forty-eight multiple myeloma patients were treated with bortezomib-cyclophosphamide-dexamethasone. Twenty-one patients received low dose and 27 patients were treated with the standard dose. No statistical differences between the two groups were found for clinical response (p=0.6, cytological response (p=0.28, flow cytometric response (p= 0.3, rate of adverse effects and overall survival rates. CONCLUSION This retrospective analysis suggests that lower doses of bortezomib have similar effects in disease control measured by flow cytometry and cytology compared to standard doses in multiple myeloma patients.

  10. Low doses of celecoxib attenuate gut barrier failure during experimental peritonitis.

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    Short, Scott S; Wang, Jin; Castle, Shannon L; Fernandez, G Esteban; Smiley, Nancy; Zobel, Michael; Pontarelli, Elizabeth M; Papillon, Stephanie C; Grishin, Anatoly V; Ford, Henri R

    2013-12-01

    The intestinal barrier becomes compromised during systemic inflammation, leading to the entry of luminal bacteria into the host and gut origin sepsis. Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of cyclooxygenase-2 (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut barrier failure during experimental peritonitis in mice. I.p. injection of LPS or cecal ligation and puncture (CLP) increased the levels of COX-2 and its product prostaglandin E2 (PGE2) in the ileal mucosa, caused pathologic sloughing of the intestinal epithelium, increased passage of FITC-dextran and bacterial translocation across the barrier, and increased internalization of the tight junction (TJ)-associated proteins junction-associated molecule-A and zonula occludens-1. Luminal instillation of PGE2 in an isolated ileal loop increased transepithelial passage of FITC-dextran. Low doses (0.5-1 mg/kg), but not a higher dose (5 mg/kg) of the specific COX-2 inhibitor Celecoxib partially ameliorated the inflammatory gut barrier failure. These results demonstrate that high levels of COX-2-derived PGE2 seen in the mucosa during peritonitis contribute to gut barrier failure, presumably by compromising TJs. Low doses of specific COX-2 inhibitors may blunt this effect while preserving the homeostatic function of COX-2-derived prostanoids. Low doses of COX-2 inhibitors may find use as an adjunct barrier-protecting therapy in critically ill patients.

  11. Low-dose DHA-induced astrocyte proliferation can be attenuated by insufficient expression of BLBP in vitro.

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    Li, Haoming; Yang, Qingqing; Han, Xiao; Tan, Xuefeng; Qin, Jianbing; Jin, Guohua

    2017-09-14

    Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid (PUFA) that is involved in a wide range of cellular processes in human cells. Brain lipid binding protein (BLBP) exhibits a high affinity for n-3 PUFAs, especially DHA, but the precise functional contributions of DHA and BLBP in astrocytes are not clear. We analyzed cell viability and the ratio of Ki67 positive cells after manipulating DHA and/or BLBP levels in cultured astrocytes, and found that low-dose DHA stimulated proliferation of astrocytes, whereas this proliferative effect could be attenuated by downregulation of BLBP. Moreover, we found that astrocyte proliferation was directly regulated by BLBP independently of DHA. Taken together, low-dose DHA-induced astrocyte proliferation was disturbed by insufficient BLBP; and besides acting as a fatty acid transporter, BLBP was also involved in the proliferation of astrocytes directly. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis

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    Cook, S.D.; Zito, G.; Dowling, P.C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Neurology Service, Department of Veterans Affairs Medical Center, NJ (United States); Devereux, C. [Univrsity of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark, and Radiation Oncology, Clara Maass Medical Center, Belleville, NU (United States); Troiano, R.; Jotkowitz, A.; Rohowsky-Kochan, C. [University of Medicine and Dentistry of New Jersey, Department of Neurosciences, Newark (United States); Sheffet, A. [University of Medicine and Dentistry of New Jersey, Department of Preventive Medicine and Community Health, Newark (United States)

    1995-01-01

    Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. Methods - In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. Results - Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. Conclusion - These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated. (au) (14 refs.).

  13. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

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    Boutry, Nathalie [University Hospital of Jeanne de Flandre and University of Lille 2, Departments of Pediatric and Musculoskeletal Imaging, Lille (France); University Hospital of Jeanne de Flandre and University of Lille 2, Department of Pediatric Imaging, Lille (France); Hopital Jeanne de Flandre, Service de Radiopediatrie, Lille (France); Dutouquet, Bastien; Cotten, Anne [University Hospital of Roger Salengro and University of Lille 2, Department of Musculoskeletal Imaging, Lille (France); Leleu, Xavier [University Hospital of Claude Huriez and University of Lille 2, Clinical Hematology Department, Lille (France); Vieillard, Marie-Helene [University Hospital of Roger Salengro and University of Lille 2, Rheumatology Department, Lille (France); Duhamel, Alain [University of Lille 2, Department of Medical Statistics, Lille (France)

    2013-08-15

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  14. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

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    Sotirchos, Elias S.; Bhargava, Pavan; Eckstein, Christopher; Van Haren, Keith; Baynes, Moira; Ntranos, Achilles; Gocke, Anne; Steinman, Lawrence; Mowry, Ellen M.

    2016-01-01

    Objective: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS). Methods: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months. Results: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0–44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0–13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17+CD4+ T cells (p = 0.016), CD161+CD4+ T cells (p = 0.03), and effector memory CD4+ T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4+ T cells (p = 0.018) and naive CD4+ T cells (p = 0.04). These effects were not observed in the low-dose group. Conclusions: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4+ T cells and decreased proportion of effector memory CD4+ T cells with concomitant increase in central memory CD4+ T cells and naive CD4+ T cells. Classification of evidence: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects. PMID:26718578

  15. Radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line.

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    Djan, Igor; Solajic, Slavica; Djan, Mihajla; Vucinic, Natasa; Popovic, Dunja; Ilic, Miroslav; Lučić, Silvija; Bogdanovic, Gordana

    2014-01-01

    Aim of the study was to compare radiobiological effects of multiple vs. single low-dose pre-irradiation on the HT29 cell line. This regime is designed to be as similar as possible to fractionated tumour radiotherapy treatment, and to provide data on radiobiological effects on human tumour cells. The cell line used in the study was HT29 (human colorectal adenocarcinoma, American Type Culture Collection HTB-38™). Also, for comparison, the MRC5 cell line (human foetal lung fibroblasts, American Type Culture Collection CCL 171) was used. Four-day treatment in a 4 × 2 Gy regime was performed. Cell viability was evaluated by tetrazolium colorimetric MTT assay. Multiple low-dose pre-irradiation induced a stronger radioadaptive response compared to single low-dose application in the HT29 cell line. Multiple pre-irradiation with 0.03 Gy and 0.05 Gy caused radioadaptive effects, while in both single and multiple low-dose pre-irradiation regimes 0.07 Gy led to radiosensitivity. Radiobiological effects induced in the HT29 cell line by low-dose pre-irradiation were evidently weak during the treatment time, because a single low-dose applied only on the first day gave no radioadaptive effects. In the MRC5 cell line different effects were registered, since radioadaptive response has not been observed after multiple or single pre-irradiation. The obtained data are interesting, especially for the possible application of low-dose pre-irradiation in radiotherapy.

  16. Achieving consistent multiple daily low-dose Bacillus anthracis spore inhalation exposures in the rabbit model

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    Roy E Barnewall

    2012-06-01

    Full Text Available Repeated low-level exposures to Bacillus anthracis could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as Bacillus anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU of B. anthracis spores and included a pilot feasibility characterization study, acute exposure study, and a multiple fifteen day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 x 102, 1 x 103, 1 x 104, and 1 x 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 x 102, 1 x 103, and 1 x 104 CFU. In all studies, targeted inhaled doses remained fairly consistent from rabbit to rabbit and day to day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and multiple exposure days.

  17. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

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    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  18. Immunological studies in multiple low-dose streptozotocin-induced diabetes in mice

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    Malik, A.I.

    1988-01-01

    Multiple low doses of streptozotocin (MSZ) treatment successfully induced diabetes in male TO, MF1 and HO lean mice. In contrast however, BALB/c mice failed to develop persistent hyperglycemia. Single streptozotocin (SSZ) treatment also produced diabetes in TO mice. SSZ treatment however, produced severe weight loss and atrophy of the lymphoid organs. MSZ treatment on the other hand, was not cytotoxic towards lymphoid organs and, while there was no loss of body weight, growth rates were reduced in MSZ treated mice. Following sheep red blood cell (SRBC) immunization of MSZ-treated mice, hemagglutination titers, and numbers of antigen reactive cells and plaque forming cells were all significantly lower than control values. In-vitro proliferation of spleen cells in response to phytohemagglutinin (PHA) andconcanavalin and concanavalin A (ConA) was found to be significantly depressed in MSZ treated mice. However, T-lymphocyte responses were intact when the mice were not overtly hyperglycemic. In contrast, however, T cell independent responses to lipopolysaccharide (LPS) were generally intact throughout the study period. Cell mediated immunity, as assessed by measurements of delayed (Type 4) hypersensitivity, was also depressed in MSZ treated mice. Both natural killer cell activity and antibody dependent cell mediated cytotoxicity were found to be significantly increased in MSZ treated mice. Histological examination of the pancreas showed the presence of insulitis, in MSZ treated mice, and cytotoxic effector cells against obese mice islet cells (as assessed by {sup 51}Cr release) and HIT-T15 cells (as assessed by insulin secretion) were found to be significantly increased. Furthermore, these effector cells were also found to show increased proliferation in the presence of homogenates prepared from HIT-T15 cells.

  19. Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis.

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    Bookstaver, P Brandon; Norris, Leann; Rudisill, Celeste; DeWitt, Tammy; Aziz, Shahid; Fant, James

    2008-11-15

    A case of toxicity encountered with low-dose methotrexate therapy is discussed. A 59-year-old African American woman receiving long-term therapy for psoriasis came to the hospital with painful ulcers, difficulty swallowing, cutaneous lesions, and acute renal failure. Her medical history included type 2 diabetes mellitus, hypertension, coronary artery disease, morbid obesity, and psoriasis. On admission, the patient looked ill and had a low-grade fever; maculopapular skin lesions; and bullae and vesicles in her mouth and on her hands, legs, groin, and buttocks. With the exception of carvedilol, all home medications, including methotrexate, were discontinued. A complete medication history revealed that the patient had been taking methotrexate 2.5 mg daily, instead of 2.5 mg three times weekly as prescribed. This error translated into an estimated cumulative dose of 360 mg, nearly twice the prescribed amount. There were no clinically significant drug-drug interactions noted among her prescribed medications; however, the patient did report increased ibuprofen use secondary to the painful ulcerations in the previous few months. Leucovorin 15 mg i.v. every six hours was initiated along with additional supportive care. Skin and mucosal lesions, as well as her pain, had dramatically improved on day 5 of hospitalization. The patient was discharged after a six-day hospitalization and was provided with leucovorin 15 mg orally ever day for seven additional days until rheumatology follow-up. The patient was instructed to avoid any future methotrexate therapy. A patient who erroneously took oral methotrexate daily rather than thrice weekly for psoriasis developed multiple manifestations of methotrexate toxicity.

  20. Comparison of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation

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    Singh Sarvesh

    2010-01-01

    Full Text Available Objective: The present study compared the efficacy of esmolol and labetalol, in low doses, for attenuation of sympathomimetic response to laryngoscopy and intubation. Design: Prospective, randomized, placebo controlled, double-blinded study. Setting: Operation room. Patients and Methods: 75 ASA physical status I and II adult patients, aged 18-45 years undergoing elective surgical procedures, requiring general anesthesia and orotracheal intubation. Interventions: Patients were allocated to any of the three groups (25 each-Group C (control10 ml 0.9% saline i.v. Group E (esmolol 0.5 mg/kg diluted with 0.9% saline to 10 ml i.v. Group L (labetalol 0.25 mg/kg diluted with 0.9% saline to 10 ml i.v. In the control group 10 ml of 0.9% saline was given both at 2 and 5 min prior to intubation. In the esmolol group 0.5 mg/kg of esmolol (diluted with 0.9% saline to 10 ml was given 2 min prior and 10 ml of 0.9% saline 5 min prior to intubation. In the labetalol group 10 ml of 0.9% saline was administered 2 min prior and 0.25 mg/kg of labetalol (diluted with 0.9% saline to 10 ml 5 min prior to intubation. All the patients were subjected to the same standard anesthetic technique. Measurements: Heart rate (HR, systolic blood pressure (SBP and diastolic blood pressure (DBP were recorded prior to induction, at time of intubation and 1, 3, 5, and 10 min after intubation. Mean arterial pressure (MAP and rate pressure product (RPP were calculated. Abnormal ECG changes were also recorded. Results: Compared to placebo and esmolol (0.5 mg/kg, labetalol (0.25 mg/kg significantly attenuated the rise in heart rate, systolic blood pressure, and RPP during laryngoscopy and intubation. However, the difference was not statistically significant among the values for DBP and MAP. Conclusion: In lower doses, labetalol (0.25 mg/kg is a better agent than esmolol (0.5 mg/kg in attenuating the sympathomimetic response to laryngoscopy and intubation.

  1. High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.

    Science.gov (United States)

    Acevedo, Luz M; López, Ignacio; Peralta-Ramírez, Alan; Pineda, Carmen; Chamizo, Verónica E; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2016-05-01

    Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats. Copyright © 2016 the American Physiological Society.

  2. Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone.

    Science.gov (United States)

    Ludwig, Michael D; Zagon, Ian S; McLaughlin, Patricia J

    2017-09-01

    Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met 5 ]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation. Preclinical studies have reported that enkephalin levels are deficient in animal models of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that serum enkephalin levels are diminished in humans with multiple sclerosis and experimental autoimmune encephalomyelitis mice, and that change in serum opioid growth factor levels may serve as a reasonable candidate biomarker for the onset of experimental autoimmune encephalomyelitis and response to therapy. To address this, we designed a two-part study to measure endogenous opioids in multiple sclerosis patients, and to investigate the temporal pattern of decline in serum enkephalin concentrations in mice with chronic progressive experimental autoimmune encephalomyelitis and treated with low-dose naltrexone. For comparison, we investigated whether low-dose naltrexone exposure in normal mice also resulted in altered enkephalin levels. In both animal models, we monitored tactile and heat sensitivity, as well as differential white blood cell counts as indicators of inflammation. Serum [Met 5 ]-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels. In experimental

  3. Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients

    NARCIS (Netherlands)

    Waal, de Esther G. M.; de Munck, Linda; Hoogendoorn, Mels; Woolthuis, Gerhard; van der Velden, Annette; Tromp, Yvonne; Vellenga, Edo; Hovenga, Sjoerd

    2015-01-01

    Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of

  4. Induction of anti-glioma NK cell response following multiple low-dose intracerebral CpG therapy

    Science.gov (United States)

    Alizadeh, Darya; Zhang, Leying; Brown, Christine E.; Farrukh, Omar; Jensen, Michael C.; Badie, Behnam

    2010-01-01

    Purpose Stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG-ODN) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. These studies, however, have used high doses of CpG-ODN which can induce toxicity in a clinical setting. The goal of this study was to evaluate the anti-tumor efficacy of multiple low-dose intratumoral CpG- ODN in a glioma model. Experimental Design Mice bearing four-day old intracranial GL261 gliomas received a single or multiple (two or four) intratumoral injections of CpG-ODN (3 μg) every 4 days. Tumor growth was measured by bioluminescent imaging, brain histology, and animal survival. Flow cytometry and cytotoxicity assays were used to assess anti-glioma immune response. Results Two and four intracranial injections of low-dose CpG-ODN, but not a single injection, eradicated gliomas in 70% of mice. Moreover, surviving animals exhibited durable tumor free remission (> 3 months), and were protected from intracranial rechallenge with GL21 gliomas, demonstrating the capacity for long-term anti-tumor immunity. Although most inflammatory cells appeared to increase, activated NK cells (i.e. NK+CD107a+) were more frequent than CD8+CD107a+ in the brains of rechallenged CpG-ODN-treated animals and demonstrated a stronger in vitro cytotoxicity against GL261 target cells. Leukocyte depletion studies confirmed that NK cells played an important role in the initial CpG-ODN anti-tumor response, but both CD8 and NK cells were equally important in long-term immunity against gliomas. Conclusions These findings suggest that multiple low-dose intratumoral injections of CpG-ODN can eradicate intracranial gliomas possibly through mechanisms involving NK mediated effector function. PMID:20570924

  5. Induction of anti-glioma natural killer cell response following multiple low-dose intracerebral CpG therapy.

    Science.gov (United States)

    Alizadeh, Darya; Zhang, Leying; Brown, Christine E; Farrukh, Omar; Jensen, Michael C; Badie, Behnam

    2010-07-01

    Stimulation of toll-like receptor-9 by CpG oligodeoxynucleotides (CpG-ODN) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. These studies, however, have used high doses of CpG-ODN, which can induce toxicity in a clinical setting. The goal of this study was to evaluate the antitumor efficacy of multiple low-dose intratumoral CpG-ODN in a glioma model. Mice bearing 4-day-old intracranial GL261 gliomas received a single or multiple (two or four) intratumoral injections of CpG-ODN (3 microg) every 4 days. Tumor growth was measured by bioluminescent imaging, brain histology, and animal survival. Flow cytometry and cytotoxicity assays were used to assess anti-glioma immune response. Two and four intracranial injections of low-dose CpG-ODN, but not a single injection, eradicated gliomas in 70% of mice. Moreover, surviving animals exhibited durable tumor-free remission (> 3 months) and were protected from intracranial rechallenge with GL261 gliomas, showing the capacity for long-term antitumor immunity. Although most inflammatory cells seemed to increase, activated natural killer (NK) cells (i.e., NK(+)CD107a(+)) were more frequent than CD8(+)CD107a(+) in the brains of rechallenged CpG-ODN-treated animals and showed a stronger in vitro cytotoxicity against GL261 target cells. Leukocyte depletion studies confirmed that NK cells played an important role in the initial CpG-ODN antitumor response, but both CD8 and NK cells were equally important in long-term immunity against gliomas. These findings suggest that multiple low-dose intratumoral injections of CpG-ODN can eradicate intracranial gliomas possibly through mechanisms involving NK-mediated effector function.

  6. Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide.

    Science.gov (United States)

    Papaccio, G; Pisanti, F A; Latronico, M V; Ammendola, E; Galdieri, M

    2000-02-01

    Streptozotocin (STZ) is a widely used diabetogenic agent that damages pancreatic islet beta cells by activating immune mechanisms, when given in multiple low doses, and by alkylating DNA, when given at a single high dose. Actually, STZ contains a nitroso moiety. Incubation of rat islets with this compound has been found to generate nitrite; moreover, photoinduced NO production from STZ has been demonstrated. These reports have suggested that direct NO generation may be a mechanism for STZ toxicity in diabetogenesis. Several other studies have denied such a mechanism of action. This study has shown that (1) the multiple low-dose (MLDS) treatment does not stimulate NO production at the islet level; in fact, nitrite + nitrate levels and aconitase activity (also in the presence of an NO-synthase inhibitor, namely NAME) remain unmodified; RT-PCR analysis demonstrates that this treatment does not stimulate iNOS activity; (2) the high-dose (HDS) treatment does not stimulate NO production; in fact nitrite + nitrate levels remain unmodified and iNOS mRNA levels are not altered, although aconitase activity is significantly decreased. Moreover, we have confirmed that the MLDS treatment is able to decrease SOD activity by day 11 and that STZ, given in a single high dose, transiently increases superoxide dismutase (SOD) values (24 h from the administration), then dramatically lowers SOD levels. On the basis of our results, we conclude that STZ, "in vivo" is unable to generate NO, both as a MLDS or HDS treatment, thus excluding that NO exerts a role in streptozotocin-dependent diabetes mellitus. Copyright 2000 Wiley-Liss, Inc.

  7. Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination.

    Directory of Open Access Journals (Sweden)

    Dedeke Rockx-Brouwer

    Full Text Available Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia.

  8. Emphysema quantification on low-dose CT using percentage of low-attenuation volume and size distribution of low-attenuation lung regions: Effects of adaptive iterative dose reduction using 3D processing

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Mizuho, E-mail: nmizuho@med.kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Matsumoto, Sumiaki, E-mail: sumatsu@med.kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Seki, Shinichiro, E-mail: sshin@med.kobe-u.ac.jp [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Koyama, Hisanobu, E-mail: hkoyama@med.kobe-u.ac.jp [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Fujisawa, Yasuko, E-mail: yasuko1.fujisawa@toshiba.co.jp [Toshiba Medical Systems Corporation, 1385 Shimoishigami, Otawara, Tochigi 324-8550 (Japan); Sugihara, Naoki, E-mail: naoki.sugihara@toshiba.co.jp [Toshiba Medical Systems Corporation, 1385 Shimoishigami, Otawara, Tochigi 324-8550 (Japan); and others

    2014-12-15

    Highlights: • Emphysema quantification (LAV% and D) was affected by image noise on low-dose CT. • For LAV% and D, AIDR 3D improved agreement of quantification on low-dose CT. • AIDR 3D has the potential to quantify emphysema accurately on low-dose CT. - Abstract: Purpose: To evaluate the effects of adaptive iterative dose reduction using 3D processing (AIDR 3D) for quantification of two measures of emphysema: percentage of low-attenuation volume (LAV%) and size distribution of low-attenuation lung regions. Method and materials: : Fifty-two patients who underwent standard-dose (SDCT) and low-dose CT (LDCT) were included. SDCT without AIDR 3D, LDCT without AIDR 3D, and LDCT with AIDR 3D were used for emphysema quantification. First, LAV% was computed at 10 thresholds from −990 to −900 HU. Next, at the same thresholds, linear regression on a log–log plot was used to compute the power law exponent (D) for the cumulative frequency-size distribution of low-attenuation lung regions. Bland–Altman analysis was used to assess whether AIDR 3D improved agreement between LDCT and SDCT for emphysema quantification of LAV% and D. Results: The mean relative differences in LAV% between LDCT without AIDR 3D and SDCT were 3.73%–88.18% and between LDCT with AIDR 3D and SDCT were −6.61% to 0.406%. The mean relative differences in D between LDCT without AIDR 3D and SDCT were 8.22%–19.11% and between LDCT with AIDR 3D and SDCT were 1.82%–4.79%. AIDR 3D improved agreement between LDCT and SDCT at thresholds from −930 to −990 HU for LAV% and at all thresholds for D. Conclusion: AIDR 3D improved the consistency between LDCT and SDCT for emphysema quantification of LAV% and D.

  9. Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis.

    Science.gov (United States)

    Hiremath, G S; Cettomai, D; Baynes, M; Ratchford, J N; Newsome, S; Harrison, D; Kerr, D; Greenberg, B M; Calabresi, P A

    2009-06-01

    Vitamin D is important for bone health and immune regulation, and has been shown to be low in multiple sclerosis (MS). We sought to determine the effect of over the counter low dose cholecalciferol (LDC) and high dose ergocalciferol (HDE) on the vitamin D levels in MS patients. We retrospectively evaluated serum 25-hydroxy-vitamin D [25(OH)D] levels of 199 patients (CIS, n = 32; RRMS, n = 115; PPMS, n = 10; SPMS, n = 16; Transverse Myelitis (TM), n = 9; other neurological diseases, n = 16) attending our clinic between 2004 and 2008. We examined the change in 25(OH)D levels in 40 MS patients who took either LDC ( or =100 nmol/L) were only achieved in less than 40% of patients. We conclude that large numbers of patients with MS and TM in our cohort are deficient in vitamin D. HDE significantly elevated 25(OH)D levels in MS patients and was more effective at increasing 25(OH)D levels than LDC. Prospective studies are required to determine appropriate dosing regimen to achieve optimal levels in the majority of MS patients and to ascertain the safety, immunological response, and ultimately the clinical efficacy of vitamin D replacement therapy.

  10. Multiple attenuation using eigenvalue decomposition | Aigbedion ...

    African Journals Online (AJOL)

    Multiple reflections constitute one of the most troublesome forms of coherent noise in seismic exploration, especially in marine surveys. There are many approaches to attenuating or suppressing multiples, but none can remove all multiple reflections under all conditions. We have eveloped two new methods to attenuate ...

  11. In vitro mesenchymal-epithelial transition in NIH3T3 fibroblasts results in onset of low-dose radiation hypersensitivity coupled with attenuated connexin-43 response.

    Science.gov (United States)

    Mathur, Ankit; Kumar, Ashish; Babu, Bincy; Chandna, Sudhir

    2017-12-04

    Mesenchymal-to-epithelial transition (MET) is associated with altered cell adhesion patterns. Independent studies showed that cellular adhesion regulates low-dose hyper-radiosensitivity (HRS), a phenomenon reported widely in tumour cells. Therefore, present study aimed to investigate whether MET and associated cellular adhesion alterations affect cellular radiosensitivity. We established multiple stages of MET by in vitro transformation of NIH3T3 mouse embryonic fibroblasts. Nutritional deprivation followed by repetitive treatment cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate with frequent isolation of foci established three progressive strains (NIH3T3.1, NIH3T3x3, NIH3T3x8x3) depicting MET, and one strain (NIH3T3x12) with partial reversion. Alterations in morphology, cell adhesion properties, expression/intracellular localization of cell adhesion proteins, microRNA expression and cellular radiosensitivity were studied in these stably transformed cell strains. All four transformants had increased proliferation rate, saturation density, bipolarity, E-cadherin expression; coupled with reduced cell size/spreading, pseudopodia/migration, and fibroblast marker protein and vimentin. The most aggressive trans-differentiated (phenotypically epithelial) cell strain, NIH3T3x8x3 acquired ~30% higher growth potential associated with more than two-fold reduction in cell size and migration. These phenotypic changes accompanied ~40% reduction in endogenous or radiation-induced connexin-43 expression/mitochondrial translocation. Incidentally, all three progressive strains displayed prominent HRS (αs/αr: 7.95-37.29) whereas parental (NIH3T3) and reverting (NIH3T3x12) strains lacked HRS and had distinct radiation-induced Cx43 translocation into mitochondria. Our study shows that trans-differentiating fibroblasts progressively acquiring epithelial features during MET process, display low-dose hyper-radiosensitivity associated with altered Cx43 behaviour. This

  12. Real-time respiratory triggered SPECT myocardial perfusion imaging using CZT technology: impact of respiratory phase matching between SPECT and low-dose CT for attenuation correction.

    Science.gov (United States)

    Clerc, Olivier F; Fuchs, Tobias A; Possner, Mathias; Vontobel, Jan; Mikulicic, Fran; Stehli, Julia; Liga, Riccardo; Benz, Dominik C; Gräni, Christoph; Pazhenkottil, Aju P; Gaemperli, Oliver; Buechel, Ronny R; Kaufmann, Philipp A

    2017-01-01

    To assess the impact of respiratory phase matching between single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) and low-dose computed tomography (CT) for attenuation correction (AC). Forty patients underwent 1-day 99mTc-tetrofosmin pharmacological stress/rest SPECT-MPI using a cadmium-zinc-telluride gamma camera. Low-dose CT for AC was performed at deep-inspiration breath-hold. SPECT-MPI was acquired once with free-breathing (FB) and repeated at deep-inspiration breath-hold (BH) to match the respiratory phase of AC. From these acquisitions we reconstructed four data sets: free-breathing SPECT-MPI without AC (non-corrected; FB-NC), breath-hold SPECT-MPI without AC (non-corrected; BH-NC), free-breathing SPECT-MPI with AC (FB-AC), and breath-hold SPECT-MPI with AC (BH-AC), the latter representing respiratory-phase-matched AC SPECT-MPI. We compared semi-quantitative segmental tracer uptake, visual diagnosis, inter-observer agreement, and image quality. Compared with FB-NC, deep-inspiration BH-NC increases inferior and lateral uptake, but decreases septal uptake. Addition of AC to FB increases inferior and septal uptake, but decreases anterolateral uptake. Combining breath-hold MPI with breath-hold CT AC (BH-AC) increases inferior, inferolateral, and septal uptake, but reduces apical uptake, without affecting anterolateral uptake, with significant differences to all other protocols. Frequency of normal scans increases across protocols: 10% with FB-NC, 21% with BH-NC, 38% with FB-AC, and 51% with BH-AC. Image quality and inter-observer agreement were highest for BH-AC among all protocols. Compared with non-corrected breath-hold SPECT-MPI and with free-breathing AC SPECT-MPI, respiratory-phase-matched AC SPECT-MPI significantly affects segmental semi-quantitative uptake, increases the frequency of normal scans, yields the best inter-observer agreement, and significantly improves image quality. These findings suggest a potential role of

  13. SU-E-I-86: Ultra-Low Dose Computed Tomography Attenuation Correction for Pediatric PET CT Using Adaptive Statistical Iterative Reconstruction (ASiR™)

    Energy Technology Data Exchange (ETDEWEB)

    Brady, S; Shulkin, B [St. Jude Children’s Research Hospital, Memphis, TN (United States)

    2015-06-15

    Purpose: To develop ultra-low dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultra-low doses (10–35 mAs). CT quantitation: noise, low-contrast resolution, and CT numbers for eleven tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% CTDIvol (0.39/3.64; mGy) radiation dose from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET images were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUVbw) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation organ dose, as derived from patient exam size specific dose estimate (SSDE), was converted to effective dose using the standard ICRP report 103 method. Effective dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative patient population dose reduction and noise control. Results: CT numbers were constant to within 10% from the non-dose reduced CTAC image down to 90% dose reduction. No change in SUVbw, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols reconstructed with ASiR and down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62%–86% (3.2/8.3−0.9/6.2; mSv). Noise magnitude in dose-reduced patient images increased but was not statistically different from pre dose-reduced patient images. Conclusion: Using ASiR allowed for aggressive reduction in CTAC dose with no change in PET reconstructed images while maintaining sufficient image quality for co

  14. A Comparative Study of Intravenous Esmolol, Labetalol and Lignocaine in Low Doses for Attenuation of Sympathomimetic Responses to Laryngoscopy and Endotracheal Intubation.

    Science.gov (United States)

    Ratnani, Ekta; Sanjeev, Om Prakash; Singh, Abhishek; Tripathi, Manoj; Chourasia, Hemant Kumar

    2017-01-01

    Direct layngoscopy and endotracheal intubation is a noxious stimuli and induces sympathomimetic responses. Although well tolerated in healthy subjects, it may impose life threatening arrhythmias, left ventricular failure or rupture of cerebral aneurysm in susceptible patients. Esmolol, Labetalol and Lignocaine attenuate these responses but are associated with side effects of bradycardia, hypotension etc. In lower doses, chances of these side effects are comparatively low. So we designed this prospective clinical trial to assess the efficacy of intravenous esmolol, labetalol and lignocaine in low doses for attenuation of sympathomimetic responses to endotracheal intubation. Seventy-five consenting patients of ASA physical status I or II of age range 20 to 60 years, scheduled for different general surgical procedures were randomly assigned to one of the three groups; group ES, group LB and group LG. Participants of group ES, group LB and group LG was given esmolol HCL 0.5 mg/Kg, labetalol HCL 0.25 mg/kg and lignocaine HCL 1 mg/Kg body weight respectively. Outcome variables were HR, SBP, DBP, MAP and RPP. These variables were recorded just after intubation and thereafter at 1,3,5, 7 and 10 minutes of intubation. There was no statistically significant difference regarding the demographic characteristics of the groups. Heart rate and systolic blood pressure was lower throughout the study period in labetalol group. But the values of study parameters were always higher than the baseline in esmolol and lignocaine group. Values of mean arterial pressure was slightly higher in labetalol group but it was much higher in two other groups throughout the study period. Diastolic blood pressure was higher in all the groups. Values of rate pressure product was higher during intubation and at 1minute after intubation in labetalol group but thereafter it was always lower than baseline values. Labetalol 0.25 mg Kg(-1) is an effective and safe drug to be used for attenuation of

  15. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

    DEFF Research Database (Denmark)

    Alkharusi, Amira; Mirecki-Garrido, Mercedes; Ma, Zuheng

    2016-01-01

    be overcome by ligands, which bind to GH or PRL receptors. Conclusion: Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy...... prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity. Methodology: The elevated sensitivity of SOCS2-/- mice to GH and possibly to PRL was the rationale to analyze the effects of multiple low dose streptozotocin (MLDSTZ)-induced diabetes...

  16. Oxygen free-radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose streptozocin-induced insulitis.

    Science.gov (United States)

    Mendola, J; Wright, J R; Lacy, P E

    1989-03-01

    We examined the effects of desferrioxamine (DFX), a potent inhibitor of the formation of oxygen-derived hydroxyl radicals, and nicotinamide (NIC), a poly(ADP-ribose) synthetase inhibitor and a weak free-radical scavenger, on two models of immune destruction of murine islets [i.e., allograft rejection and multiple low-dose streptozocin (STZ)-induced insulitis]. Freshly isolated or low-temperature-cultured BALB/cJ islets were transplanted beneath the kidney capsules of C57BL/6J recipients. The recipients were treated with NIC alone (500 mg.kg-1.day-1), DFX alone (4.2 mg/day x 14 days), or NIC + DFX. Only recipients treated with NIC + DFX, receiving cultured islets, showed a mean graft survival time significantly longer than control mice receiving freshly isolated or cultured islets. Control CD-1 mice treated with multiple low doses of STZ developed insulitis and diabetes. Treatment with NIC alone, DFX alone, or NIC + DFX decreased the severity of hyperglycemia relative to the controls. Treatment with DFX alone was more effective than NIC alone or NIC + DFX. Only the group treated with DFX alone had a lower incidence of diabetes (mean plasma glucose level greater than 200 mg/dl) than the controls after 4 wk. Histologically, islets from control mice showed severe insulitis, islet destruction, and absence of stainable insulin, whereas islets from DFX-treated mice showed only mild peri-insulitis and a relative preservation of beta-cell granulation. Our study showed that NIC and DFX partially protect islets from immune destruction in allograft rejection and in low-dose STZ-induced insulitis. Apparently, hydroxyl radicals play important roles in both of these models.

  17. Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model

    Science.gov (United States)

    Castillo, Gerardo M.; Nishimoto-Ashfield, Akiko; Banerjee, Aryamitra A.; Landolfi, Jennifer A.; Lyubimov, Alexander V.; Bolotin, Elijah M.

    2013-01-01

    Purpose Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/− PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice. Method HBEGF, PGC-HBEGF, Omeprazole, Omeprazole+PGC-HBEGF, Omeprazole+PGC-gastrin+PGC-HBEGF and epidermal growth factor (EGF)+gastrin were tested in multiple low dose streptozotocin diabetic mice. Results Omeprazole+PGC-HBEGF normalized FBG and is better than EGF+gastrin at improving islet function and decreasing insulitis. Groups treated with Omeprazole, Omeprazole+PGC-HBEGF, or EGF+gastrin have significantly improved islet function versus saline control. All animals that received PGC-HBEGF had significantly reduced islet insulitis versus saline control. Non-FBG was lower for Omeprazole+PGC-gastrin+PGC-HBEGF but Omeprazole+PGC-HBEGF alone showed better FBG and glucose tolerance. Conclusions Omeprazole+PGC-HBEGF provides a sustained exposure to both EGFRA and gastrin, improves islet function, and decreases insulitis in multiple low dose streptozotocin diabetic mice. Although HBEGF or EGF elevates non-FBG, it facilitates a reduction of insulitis and, in the presence of Omeprazole, provides normalization of FBG at the end of treatment. The study demonstrates Omeprazole and PGC-HBEGF is a viable treatment for diabetes. PMID:23793991

  18. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma.

    Science.gov (United States)

    Dimopoulos, Meletios A; Palumbo, Antonio; Corradini, Paolo; Cavo, Michele; Delforge, Michel; Di Raimondo, Francesco; Weisel, Katja C; Oriol, Albert; Hansson, Markus; Vacca, Angelo; Blanchard, María Jesús; Goldschmidt, Hartmut; Doyen, Chantal; Kaiser, Martin; Petrini, Mario; Anttila, Pekka; Cafro, Anna Maria; Raymakers, Reinier; San-Miguel, Jesus; de Arriba, Felipe; Knop, Stefan; Röllig, Christoph; Ocio, Enrique M; Morgan, Gareth; Miller, Neil; Simcock, Mathew; Peluso, Teresa; Herring, Jennifer; Sternas, Lars; Zaki, Mohamed H; Moreau, Philippe

    2016-07-28

    Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789. © 2016 by The American Society of Hematology.

  19. Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: Preliminary Findings of a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2012-01-01

    Full Text Available The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS. A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly (P<0.001. In the 25 patients treated with placebo, the mean (SD Expanded Disability Status Scale (EDSS increased from 1.70 (1.21 at baseline to 1.94 (1.41 at the end of study period (P<0.01. Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

  20. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).

    Science.gov (United States)

    Hájek, R; Masszi, T; Petrucci, M T; Palumbo, A; Rosiñol, L; Nagler, A; Yong, K L; Oriol, A; Minarik, J; Pour, L; Dimopoulos, M A; Maisnar, V; Rossi, D; Kasparu, H; Van Droogenbroeck, J; Yehuda, D B; Hardan, I; Jenner, M; Calbecka, M; Dávid, M; de la Rubia, J; Drach, J; Gasztonyi, Z; Górnik, S; Leleu, X; Munder, M; Offidani, M; Zojer, N; Rajangam, K; Chang, Y-L; San-Miguel, J F; Ludwig, H

    2017-01-01

    This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

  1. Evaluation of low-dose thalidomide as induction and maintenance therapy in patients with multiple myeloma not eligible for stem cell transplantation.

    Science.gov (United States)

    Aznab, Mozaffar; Rezaei, Mansour; Navabi, Jafar; Moieni, Ali

    2017-04-01

    The role of thalidomide in induction and long-term maintenance therapy in patients with multiple myeloma not eligible for stem cell transplantation remains unclear. The aim of the present study was to evaluate the effect of low-dose thalidomide as induction therapy and as maintenance therapy for 24 months in patients with a complete remission after the induction chemotherapy and to monitor the survival and relapse rates. Between October 2005 and September 2013, 50 patients with multiple myeloma received six courses of Cyclophosphamide-Vincristine Adriamycin and Dexamethazone (c-VAD) and pamidronate, and thalidomide 100 mg daily during induction, then thalidomide 100 mg daily for 24 months as maintenance. The effects of thalidomide were assessed objectively and subjectively. Whenever necessary, electromyography and nerve capacity volume were performed monthly for 6 months, then once every 3 months until the end of treatment. Primary response was 96% (CR or very good PR in 48/50 patients). Fifteen out of the remaining 48 patients relapsed during the follow-up period. Nine out of the 15 patients who relapsed showed very good partial response to treatment and four patients showed partial response. Survival rate was 81% in these patients. The primary outcome measures showed a mean and median progression-free survival of 33 and 27 months, respectively, and a mean and median overall survival of 43 and 39 months, respectively. Low-dose thalidomide during induction therapy combined with conventional chemotherapy and a 2-year maintenance may be effective in preventing the relapse and improving the overall survival. © 2015 Wiley Publishing Asia Pty Ltd.

  2. Vaccination of Volunteers with Low-Dose, Live-Attenuated, Dengue Viruses Leads to Serotype-specific Immunologic and Virologic Profiles

    Science.gov (United States)

    Lindow, Janet C.; Durbin, Anna P.; Whitehead, Stephen S.; Pierce, Kristen K.; Carmolli, Marya P.; Kirkpatrick, Beth D.

    2013-01-01

    There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1 – DENV-4). Two doses (10 PFU and 1000 PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4Δ30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1Δ30, DEN2/4Δ30, and DEN3Δ30/31) were very infectious, each with a Human Infectious Dose 50% ≤ 10 PFU. Further, infectivity rates ranged from 90 −100% regardless of dose, excepting DEN2/4Δ30 which dropped from 100% at the 1000 PFU dose to 60% at the 10 PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1Δ30 (92 ± 19 vs. 214 ± 97, p = 0.08); however, significant differences were observed between the 10 PFU and 1000 PFU doses for DEN2/4Δ30, 19 ± 9 vs. 102 ± 25 (p = 0.001), and DEN3Δ30/31, 119 ± 135 vs. 50 ± 50 (p=0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1Δ30 was higher at the 1000 PFU dose (0.5 ± 0 vs. 1.1 ± 0.1, p = 0.007). These data demonstrate that atarget dose of 1000 PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes. PMID:23735680

  3. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  4. A low-dose, 6-week bovine colostrum supplementation maintains performance and attenuates inflammatory indices following a Loughborough Intermittent Shuttle Test in soccer players.

    Science.gov (United States)

    Kotsis, Yiannis; Mikellidi, Anastasia; Aresti, Cleopatra; Persia, Eleni; Sotiropoulos, Aristomenis; Panagiotakos, Demosthenes B; Antonopoulou, Smaragdi; Nomikos, Tzortzis

    2017-03-11

    The aim of the study was to investigate the effect of a 6-week, low-dose bovine colostrum (BC) supplementation on exercise-induced muscle damage (EIMD) and performance decline in soccer players following the Loughborough Intermittent Shuttle Test (LIST) during a competitive season period. In a double-blind, randomized, placebo-controlled design, two groups of soccer players were allocated to a 3.2 g/day of whey protein (WP, N = 8) or BC (N = 10) and performed a pre- and a post-supplementation LIST. Maximum isometric voluntary contraction, squat jump (SQJ), countermovement jump, muscle soreness, blood cell counts, creatine kinase (CK), C-reactive protein (CRP) and interleukin-6 (IL-6) were monitored for 2, 24, 48, 72 h post-LIST. LIST induced transient increases in leukocytes, granulocytes, CK, muscle soreness, CRP, IL-6 and declines in lymphocytes and performance indices. Supplementation resulted in a faster recovery of SQJ, CK and CRP compared to pre-supplementation kinetics (trial × time: p = 0.001, 0.056, 0.014, respectively) and lower incremental area under the curve (iAUC) for IL-6, only in the BC group [pre-: 31.1 (6.78-46.9), post-: 14.0 (-0.16 to 23.5) pg h/ml, p = 0.034]. Direct comparison of the two groups after supplementation demonstrated higher iAUC of SQJ [WP: -195.2 (-229.0 to (-52.5)), BC: -15.8 (-93.2 to 16.8) cm h, p = 0.034], a trend for lower iAUC of CK in the BC group [WP: 18,785 (4651-41,357), BC: 8842 (4807-14,802) U h/L, p = 0.081] and a significant intervention × time interaction for CRP (p = 0.038) in favor of BC. Post-exercise EIMD may be reduced and performance better maintained by a low dose of BC administration following LIST in soccer players.

  5. Evaluation of dosimetry and image of very low-dose computed tomography attenuation correction for pediatric positron emission tomography/computed tomography: phantom study

    Science.gov (United States)

    Bahn, Y. K.; Park, H. H.; Lee, C. H.; Kim, H. S.; Lyu, K. Y.; Dong, K. R.; Chung, W. K.; Cho, J. H.

    2014-04-01

    In this study, phantom was used to evaluate attenuation correction computed tomography (CT) dose and image in case of pediatric positron emission tomography (PET)/CT scan. Three PET/CT scanners were used along with acryl phantom in the size for infant and ion-chamber dosimeter. The CT image acquisition conditions were changed from 10 to 20, 40, 80, 100 and 160 mA and from 80 to 100, 120 and 140 kVp, which aimed at evaluating penetrate dose and computed tomography dose indexvolume (CTDIvol) value. And NEMA PET Phantom™ was used to obtain PET image under the same CT conditions in order to evaluate each attenuation-corrected PET image based on standard uptake value (SUV) value and signal-to-noise ratio (SNR). In general, the penetrate dose was reduced by around 92% under the minimum CT conditions (80 kVp and 10 mA) with the decrease in CTDIvol value by around 88%, compared with the pediatric abdomen CT conditions (100 kVp and 100 mA). The PET image with its attenuation corrected according to each CT condition showed no change in SUV value and no influence on the SNR. In conclusion, if the minimum dose CT that is properly applied to body of pediatric patient is corrected for attenuation to ensure that the effective dose is reduced by around 90% or more compared with that for adult patient, this will be useful to reduce radiation exposure level.

  6. Accumulation and persistence of nicotine derived DNA and hemoglobin adducts in mice after multiple administration of {sup 14}C-nicotine at low dose level

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hongfang; Li, Hongli; Zhu, Jiadan; Wang, Haifang; Liu, Yuanfang [Peking Univ., Beijing (China). Dept. of Chemical Biology, College of Chemistry and Molecular Engineering; Liu, Kexin; Peng, Shixiang [Peking Univ., Beijing (China). Inst. of Heavy Ion Physics, School of Physics

    2004-07-01

    The hypothetic role of nicotine in causing smoking related diseases has not been well established. Based on our early finding of the genotoxicity of nicotine, a sub-chronic study on the accumulation and persistence of nicotine derived DNA and hemoglobin (Hb) adducts in mice following multiple low dose exposures was carried out by accelerator mass spectrometry (AMS). AMS is a sophisticated ultrasensitive nuclear method, which facilitates the detection of adduction of DNA and other bio-macromolecules with xenobiotics at human relevant environmental dose levels. Briefly, in this study [N-{sup 14}CH{sub 3}]-nicotine (s.a. 16.2 {mu}Ci/{mu}mol) was administered to mice by gavage once daily at 3.0 {mu}g/kg b.w., which is equivalent to an estimated nicotine dose inhaled by a 70 kg person smoking 5 cigarettes, for 14 consecutive days. Lung DNA, liver DNA and Hb were isolated from tissues and blood samples which were collected at 1, 3, 5, 7, 10, 14, 15, 17, 21 and 25 days time point, respectively. (orig.)

  7. Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Zacchino, M.; Minetti, V.; Dore, R.; Calliada, F. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Institute of Radiology, Pavia (Italy); Bonaffini, P.A.; Nasatti, A.; Sironi, S. [University of Milano Bicocca, San Gerardo Hospital, Department of Diagnostic Radiology, Monza (Italy); Corso, A. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Division of Hematology, Pavia (Italy); Tinelli, C. [University of Pavia, Fondazione IRCCS Policlinico San Matteo, Service of Biometry and Statistics, Pavia (Italy)

    2015-11-15

    We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. (orig.)

  8. Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin.

    Science.gov (United States)

    Kobayashi, Takao; Song, Qing-Hua; Hong, Tie; Kitamura, Hajime; Cyong, Jong-Chol

    2002-06-01

    We have reported that an aqueous extract from the flowers of Inula britannica L. subsp. japonica Kitam. (IB) prevented immunologically induced experimental hepatitis in mice and suggested that the antihepatitic effect of IB is due to inhibition of IFN-gamma production. We then investigated the effects of IB on diabetes in mice induced by multiple low doses of streptozotocin (MLDSTZ), which is a mouse model for IFN-gamma-dependent autoimmune diabetes. C57BL/KsJ mice (male, 7 weeks) were provided with IB extract (500 mg/ kg/ day) in drinking water ad libitum, starting 7 days before the first STZ injection. Autoimmune diabetes was induced by MLDSTZ (40 mg/kg/day for 5 daily doses, i.p.). The IB treatment significantly suppressed the increase of blood glucose levels. Histological analysis of the pancreas showed that the degree of insulitis and destruction of beta-cells were reduced by IB treatment. The IFN-gamma production from stimulated splenic T lymphocytes was inhibited by the IB treatment. Moreover, the proportion of IFN-gamma-producing cells in the CD4(+) population, which was increased by MLDSTZ, was significantly decreased by the IB treatment. These results suggest that IB has a preventative effect on autoimmune diabetes by regulating cytokine production. Copyright 2002 John Wiley & Sons, Ltd.

  9. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM)

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito, Davide, E-mail: davide.atena@tiscalinet.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Besostri, Valeria, E-mail: valeriabesostri@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Bonaffini, Pietro Andrea, E-mail: pa.bonaffini@gmail.com [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Rossini, Fausto, E-mail: valeriabesostri@hotmail.it [Department of Hematology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Di Lelio, Alessandro, E-mail: valebeso@libero.it [Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy); Sironi, Sandro, E-mail: sandrosironi@libero.it [School of Medicine, University of Milano-Bicocca, Via Pergolesi 33, 20900 Monza (MB) (Italy); Department of Diagnostic Radiology, H. San Gerardo, Via Pergolesi 33, 20900 Monza (MB) (Italy)

    2013-12-01

    Purpose: To assess the role of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of patients with suspicion of multiple myeloma (MM). Materials and methods: A total of 138 patients (76 male and 62 female; mean age 63.5 years, range 50–81 years), with early MM, underwent WBLDCT protocol study, performed on 16-slice scanner (Brilliance, Philips Medical System, Eindhoven, The Netherlands): tube voltage 120 kV; tube current time product 40 mAs. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done by using multiplanar reformatted images. The overall dose delivered to each patient was 4.2 mSv. Every patient gave personal informed consent, as required by our institution guidelines. Results: The diagnosis was established either by histopathology or imaging follow-up (size increase of over a period time). In all 138 patients, image resolution was diagnostic, enabling correct classification of multiple myeloma patients. WBLDCT showed a total of 328 pathologic bone findings in 81/138 patients. CT scanning resulted in complete evaluation of the bone lesions in these areas of the skeleton: skull (42), humerus (15), femur (20), ribs (7), scapulae (13), pelvis (35), clavicle (13), sternum (10), cervical (39), dorsal (65), lombar (48) and sacral rachis (21). In 40/81 bone involvement detected by CT was the only CRAB criterion present. Furthermore, WBLDCT demonstrated pleuro-pulmonary lesions in 20 patients (11 infective, 9 as MM localizations) and 1 renal neoplasia. Conclusion: WBLDCT, detecting bone marrow localizations and demonstrating extra-osseous findings, with a fast scanning time and high resolution images, is a reliable imaging-based tool for a proper management of MM patients.

  10. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.

    Science.gov (United States)

    Richardson, Paul G; Siegel, David S; Vij, Ravi; Hofmeister, Craig C; Baz, Rachid; Jagannath, Sundar; Chen, Christine; Lonial, Sagar; Jakubowiak, Andrzej; Bahlis, Nizar; Song, Kevin; Belch, Andrew; Raje, Noopur; Shustik, Chaim; Lentzsch, Suzanne; Lacy, Martha; Mikhael, Joseph; Matous, Jeffrey; Vesole, David; Chen, Min; Zaki, Mohamed H; Jacques, Christian; Yu, Zhinuan; Anderson, Kenneth C

    2014-03-20

    This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM+LoDEX (n = 113) or POM (n = 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio = 0.68, P = .003), overall response rates (ORRs) were 33% and 18% (P = .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM+LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM+LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833.

  11. Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography.

    Science.gov (United States)

    Horger, Marius; Claussen, Claus D; Bross-Bach, Ulrike; Vonthein, Reinhard; Trabold, Tobias; Heuschmid, Martin; Pfannenberg, Christina

    2005-05-01

    The goal of this study was to establish the feasibility of a low-dose whole-body multidetector row-CT (MDCT) protocol in the diagnosis of multiple myeloma (MM), as an alternative to conventional X-ray imaging, which is currently still state-of-the-art in these patients, with emphasis on the comparison of image resolution on axial and multiplanar reformatted (MPR) scans and reduction of radiation dose. 100 patients with known MM, or monoclonal gammopathy of unknown significance (MGUS) underwent unenhanced whole-body MDCT on a 16-slice scanner in a randomised fashion, using a 16 x 1.5 mm collimation and four different energy parameters (40, 50, 60 and 70 mAs). Three different reconstruction algorithms were used in every patient (B40f, B50f and B60f kernel). CT scans were reviewed independently by two radiologists, with regard to correct classification into one of the three known MM stages, and recognition of fracture risk. Thereafter, axial and MPR images were evaluated in consensus by both readers, with respect to image resolution. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done only on MPR images. The distribution of image resolution categories (very good, good, sufficient, insufficient for diagnosis) was evaluated depending on following parameters: current time product, patient's weight, bone density and reconstruction algorithm. The effective radiation dose was determined with the aid of an anthropomorphic Alderson Rando-Phantom, using a tube current time product of 40 mAs, and then extrapolating it on all current time products applied in this study on a commercially available software program WinDose (Institute of Medical Physics, Erlangen, Germany). In all 100 patients, image resolution was diagnostic, regardless of scanning parameters, enabling correct classification of multiple myeloma patients. Image quality of MPR images was either

  12. Is Lipotoxicity presents in the early stages of an experimental model of autoimmune diabetes? Further studies in the multiple low dose of streptozotocin model.

    Science.gov (United States)

    Karabatas, Liliana; Oliva, Maria Eugenia; Dascal, Eduardo; Hein, Gustavo J; Pastorale, Claudia; Chicco, Adriana; Lombardo, Yolanda B; Basabe, Juan C

    2010-01-01

    An increased availability of plasma free fatty acids (FFA) seems to play a role in the early stages of experimental type 1 diabetes mellitus induced in C57BL/6J mice by multiple low doses of streptozotoxin (mld-STZ). We analyzed the temporal changes of: (1) plasma and skeletal muscle lipids and their relationship with glucose metabolism; (2) triglyceride (Tg) concentration in isolated islets; (3) intraperitoneal glucose tolerance test; and (4) insulin secretion patterns when the three mutually interactive glucose signaling pathways were activated. Animals were killed by cervical dislocation at days 4, 6, 7, 8, 9 and 12 post first injection of mld-STZ. Compared with control mice, we observed: (1) at day 6, a significant increase of plasma FFA and both muscle and islet Tg content and a significant decrease of muscle pyruvate dehydrogenase activity. These parameters further deteriorated with time. (2) plasma Tg, glucose and insulin levels and glucose tolerance test were significantly different only after day 8. (3) an increase in both phases of the glucose plus palmitate-stimulated insulin secretion was observed at day 4. This effect progressively decreased since day 7 up to day 9. Moreover, an inhibitory action of cerulenin over glucose plus palmitate-stimulated insulin secretion was observed between days 6 and 9. Taken together these results suggest that early alteration in carbohydrate and lipid metabolism could represent a "metabolic window" which would develop between days 6 and 8. Afterwards, subsequent immunological alterations, apoptosis and necrosis induced the destruction of β cells and would mask the results mentioned above.

  13. Lenalidomide and low-dose dexamethasone (Rd) versus bortezomib, melphalan, prednisone (VMP) in elderly newly diagnosed multiple myeloma patients: A comparison of two prospective trials.

    Science.gov (United States)

    Gentile, Massimo; Magarotto, Valeria; Offidani, Massimo; Musto, Pellegrino; Bringhen, Sara; Teresa Petrucci, Maria; Gay, Francesca; Larocca, Alessandra; Uccello, Giuseppina; Petrungaro, Annamaria; Vigna, Ernesto; Greco, Rosa; Grazia Recchia, Anna; Tripepi, Giovanni; Ria, Roberto; Di Raimondo, Francesco; Palumbo, Antonio; Morabito, Fortunato

    2017-03-01

    There are currently no direct head-to-head clinical trials evaluating bortezomib-melphalan-prednisone (VMP) versus lenalidomide and low-dose dexamethasone (Rd). VMP (257 cases) and Rd (222 cases) arms of two randomized phase III trials were employed to assess the treatment influence on outcome in untreated elderly MM patients. Progression free survival (PFS) and overall survival (OS) were the primary and secondary end-points, respectively, and were investigated according to treatments administered over a 60-months follow-up period. While VMP significantly reduced the disease progression rate between enrolment and 12 months of follow-up, no difference between the two schedules was found between 12 and 32 months. After 32 months, Rd-treated patients had a lower incidence of disease progression. A statistically significant higher OS rate was seen in the VMP arm, which was maintained after data adjustment for potential confounders. Both approaches showed acceptable toxicity profiles. The profound tumor reduction by VMP over Rd justifies the initial higher PFS rate in favor of the bortezomib schedule, while the Rd regimen overcomes this evident initial drawback in reducing the tumor burden by long-term drug administration, gaining a subsequent improved disease control. VMP is associated with a significant reduced risk of death. This study may help physicians make a more informed therapy choice. © 2016 Wiley Periodicals, Inc.

  14. Multiple effects of a commercial Roundup® formulation on the soil filamentous fungus Aspergillus nidulans at low doses: evidence of an unexpected impact on energetic metabolism.

    Science.gov (United States)

    Nicolas, Valérie; Oestreicher, Nathalie; Vélot, Christian

    2016-07-01

    Soil microorganisms are highly exposed to glyphosate-based herbicides (GBH), especially to Roundup® which is widely used worldwide. However, studies on the effects of GBH formulations on specific non-rhizosphere soil microbial species are scarce. We evaluated the toxicity of a commercial formulation of Roundup® (R450), containing 450 g/L of glyphosate (GLY), on the soil filamentous fungus Aspergillus nidulans, an experimental model microorganism. The median lethal dose (LD50) on solid media was between 90 and 112 mg/L GLY (among adjuvants, which are also included in the Roundup® formulation), which corresponds to a dilution percentage about 100 times lower than that used in agriculture. The LOAEL and NOAEL (lowest- and no-observed-adverse-effect levels) associated to morphology and growth were 33.75 and 31.5 mg/L GLY among adjuvants, respectively. The formulation R450 proved to be much more active than technical GLY. At the LD50 and lower concentrations, R450 impaired growth, cellular polarity, endocytosis, and mitochondria (average number, total volume and metabolism). In contrast with the depletion of mitochondrial activities reported in animal studies, R450 caused a stimulation of mitochondrial enzyme activities, thus revealing a different mode of action of Roundup® on energetic metabolism. These mitochondrial disruptions were also evident at a low dose corresponding to the NOAEL for macroscopic parameters, indicating that these mitochondrial biomarkers are more sensitive than those for growth and morphological ones. Altogether, our data indicate that GBH toxic effects on soil filamentous fungi, and thus potential impairment of soil ecosystems, may occur at doses far below recommended agricultural application rate.

  15. LOW DOSE INTRAVAGINAL MISOPROSTOL VERSUS ...

    African Journals Online (AJOL)

    hi-tech

    2003-02-02

    Feb 2, 2003 ... for oxytocin augmentation was less in the misoprostol group (RR 0.76, 95% CI 0.64 to 0.91). No significant differences existed in rates for uterine hyperstimulation,. Caesarean section, maternal and neonatal morbidity. Conclusion: Intravaginal misoprostol in a low dose was compared to intracervical balloon.

  16. Multiple attenuation to reflection seismic data using Radon filter and Wave Equation Multiple Rejection (WEMR) method

    Energy Technology Data Exchange (ETDEWEB)

    Erlangga, Mokhammad Puput [Geophysical Engineering, Institut Teknologi Bandung, Ganesha Street no.10 Basic Science B Buliding fl.2-3 Bandung, 40132, West Java Indonesia puput.erlangga@gmail.com (Indonesia)

    2015-04-16

    Separation between signal and noise, incoherent or coherent, is important in seismic data processing. Although we have processed the seismic data, the coherent noise is still mixing with the primary signal. Multiple reflections are a kind of coherent noise. In this research, we processed seismic data to attenuate multiple reflections in the both synthetic and real seismic data of Mentawai. There are several methods to attenuate multiple reflection, one of them is Radon filter method that discriminates between primary reflection and multiple reflection in the τ-p domain based on move out difference between primary reflection and multiple reflection. However, in case where the move out difference is too small, the Radon filter method is not enough to attenuate the multiple reflections. The Radon filter also produces the artifacts on the gathers data. Except the Radon filter method, we also use the Wave Equation Multiple Elimination (WEMR) method to attenuate the long period multiple reflection. The WEMR method can attenuate the long period multiple reflection based on wave equation inversion. Refer to the inversion of wave equation and the magnitude of the seismic wave amplitude that observed on the free surface, we get the water bottom reflectivity which is used to eliminate the multiple reflections. The WEMR method does not depend on the move out difference to attenuate the long period multiple reflection. Therefore, the WEMR method can be applied to the seismic data which has small move out difference as the Mentawai seismic data. The small move out difference on the Mentawai seismic data is caused by the restrictiveness of far offset, which is only 705 meter. We compared the real free multiple stacking data after processing with Radon filter and WEMR process. The conclusion is the WEMR method can more attenuate the long period multiple reflection than the Radon filter method on the real (Mentawai) seismic data.

  17. A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

    Science.gov (United States)

    Nath, Sayantan; Ghosh, Sankar Kumar; Choudhury, Yashmin

    A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg-1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg-1 bw daily) and metformin (50mgkg-1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Pomalidomide and Low-Dose Dexamethasone Improves Health-Related Quality of Life and Prolongs Time to Worsening in Relapsed/Refractory Patients With Multiple Myeloma Enrolled in the MM-003 Randomized Phase III Trial.

    Science.gov (United States)

    Weisel, Katja; Dimopoulos, Meletios; Song, Kevin W; Moreau, Philippe; Palumbo, Antonio; Belch, Andrew; Schey, Stephen; Sonneveld, Pieter; Sternas, Lars; Yu, Xin; Amatya, Ramesh; Gibson, Craig J; Zaki, Mohamed; Jacques, Christian; San Miguel, Jesus

    2015-09-01

    Health-related quality of life (HRQoL) is an important element for consideration in treatment decisions in patients with relapsed/refractory multiple myeloma (RRMM). The pivotal MM-003 (A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone vs. High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study [NIMBUS]) randomized, open-label, multicenter, phase III trial demonstrated improved progression-free survival (PFS) and prolonged overall survival (OS) with pomalidomide (POM) plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in patients with RRMM in whom lenalidomide (LEN) and bortezomib (BORT) had failed. MM-003 also investigated HRQoL as a predefined secondary end point. Recruited patients (n = 455) were refractory to their last treatment and had failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Eight clinically relevant and validated HRQoL domains from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-MY20, and EQ-5D questionnaires were selected for analysis. Time to symptom worsening based on minimally important differences (MIDs) was calculated. Clinically meaningful improvements in HRQoL as determined by MIDs, regression analyses, and best response analyses were observed more frequently in patients receiving POM + LoDEX than in those receiving HiDEX. POM + LoDEX significantly extended median time to clinically meaningful worsening in HRQoL versus HiDEX in 4 HRQoL domains and demonstrated a trend in an additional 3 domains. Patients in the HiDEX arm experienced earlier HRQoL deterioration compared with those in the POM + LoDEX arm in each domain analyzed. POM + LoDEX offer good clinical outcomes that lead to improved and prolonged HRQoL compared with HiDEX in patients with RRMM and end

  19. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants

    Science.gov (United States)

    Willis, Daniel N.; Liu, Boyi; Ha, Michael A.; Jordt, Sven-Eric; Morris, John B.

    2011-01-01

    Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities.— Willis, D. N., Liu, B., Ha, M. A., Jordt, S.-E., Morris, J. B. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. PMID:21903934

  20. Low dose intravaginal misoprostol versus intracervical balloon ...

    African Journals Online (AJOL)

    Background:The efficacy and safety of low dose misoprostol as a ripening agent compared to the widely used balloon catheter in developing countries is undetermined. Objective:To compare the safety and efficacy of a low dose intravaginal misoprostol and intracervical Foley's catheter for cervical ripening. Design:A ...

  1. Intermediate-dose versus low-dose cyclophosphamide and granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in patients with multiple myeloma treated with novel induction therapies.

    Science.gov (United States)

    Hamadani, Mehdi; Kochuparambil, S Thomas; Osman, Salman; Cumpston, Aaron; Leadmon, Sonia; Bunner, Pamela; Watkins, Kathy; Morrison, Devi; Speir, Ethan; Deremer, David; Kota, Vamsi; Jillella, Anand; Craig, Michael; Awan, Farrukh

    2012-07-01

    Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide (ID-CY) and granulocyte colony-stimulating factor (G-CSF) has been shown to be more efficacious, albeit more toxic, than low-dose cyclophosphamide (LD-CY) mobilization regimens in patients with multiple myeloma treated with conventional therapies. However, the relative importance of cyclophosphamide dose intensity in peripheral blood progenitor cell mobilization after novel induction regimens is not known. Here we report mobilization outcomes of 123 patients who underwent transplantation within 1 year of starting induction chemotherapy with novel agents. We compared consecutive patients undergoing mobilization with ID-CY/G-CSF (3-4 g/m(2)) at one institution (n = 55) with patients receiving LD-CY/G-CSF (1.5 g/m(2)) at a different transplantation center (n = 68). At baseline, the 2 groups were well balanced, except for more frequent previous lenalidomide use in the ID-CY group (P = .04). Compared with LD-CY, ID-CY use was associated with higher median peak PB CD34(+) cell count (35/μL versus 160/μL; P < .001), CD34(+) cell yield on day 1 of collection (2.6 × 10(6)/kg versus 11.7 × 10(6)/kg, P ≤ .001), and total CD34(+) cell yield (7.5 × 10(6)/kg versus 16.6 × 10(6)/kg; P ≤ .001). Six patients in the LD-CY group had mobilization failure, compared with no patients in the ID-CY group. A significantly higher proportion of patients in the LD-CY group (P < .001) were unable to collect ≥5 × 10(6)/kg and ≥10 × 10(6)/kg CD34(+) cells. Neutrophil and platelet engraftment were significantly faster in the ID-CY group, likely because of higher infused CD34(+) cell doses. In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY-containing mobilization strategies in patients with multiple myeloma undergoing stem cell

  2. African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge.

    Science.gov (United States)

    O'Donnell, Vivian; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Carlson, Jolene; Sanford, Brenton; Alfano, Marialexia; Kramer, Edward; Lu, Zhiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R; Borca, Manuel V

    2015-08-01

    African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs. Disease control strategies have been hampered by the unavailability of vaccines against ASFV. Since its introduction in the Republic of Georgia, a highly virulent virus, ASFV Georgia 2007 (ASFV-G), has caused an epizootic that spread rapidly into Eastern European countries. Currently no vaccines are available or under development to control ASFV-G. In the past, genetically modified ASFVs harboring deletions of virulence-associated genes have proven attenuated in swine, inducing protective immunity against challenge with homologous parental viruses. Deletion of the gene 9GL (open reading frame [ORF] B119L) in highly virulent ASFV Malawi-Lil-20/1 produced an attenuated phenotype even when administered to pigs at 10(6) 50% hemadsorption doses (HAD50). Here we report the construction of a genetically modified ASFV-G strain (ASFV-G-Δ9GLv) harboring a deletion of the 9GL (B119L) gene. Like Malawi-Lil-20/1-Δ9GL, ASFV-G-Δ9GL showed limited replication in primary swine macrophages. However, intramuscular inoculation of swine with 10(4) HAD50 of ASFV-G-Δ9GL produced a virulent phenotype that, unlike Malawi-Lil-20/1-Δ9GL, induced a lethal disease in swine like parental ASFV-G. Interestingly, lower doses (10(2) to 10(3) HAD50) of ASFV-G-Δ9GL did not induce a virulent phenotype in swine and when challenged protected pigs against disease. A dose of 10(2) HAD50 of ASFV-G-Δ9GLv conferred partial protection when pigs were challenged at either 21 or 28 days postinfection (dpi). An ASFV-G-Δ9GL HAD50 of 10(3) conferred partial and complete protection at 21 and 28 dpi, respectively. The information provided here adds to our recent report on the first attempts toward experimental vaccines against ASFV-G. The main problem for controlling ASF is the lack of vaccines. Studies on ASFV virulence lead to the production of genetically modified attenuated viruses that induce protection

  3. Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: Cone/ring artifact correction and multiple GPU implementation

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Hao, E-mail: steve.jiang@utsouthwestern.edu, E-mail: xun.jia@utsouthwestern.edu; Shi, Feng; Jiang, Steve B.; Jia, Xun, E-mail: steve.jiang@utsouthwestern.edu, E-mail: xun.jia@utsouthwestern.edu [Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 (United States); Wang, Xiaoyu; Cervino, Laura [Center for Advanced Radiotherapy Technologies and Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California 92037 (United States); Bai, Ti [Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 and Institute of Image Processing and Pattern Recognition, Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Folkerts, Michael [Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 and Department of Physics, University of California San Diego, La Jolla, California 92037 (United States)

    2014-11-01

    , an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. Conclusions: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation.

  4. Converting low dose radiation to redox signaling

    OpenAIRE

    Pristov, Jelena Bogdanović; Spasić, Mihajlo; Spasojević, Ivan

    2013-01-01

    In contrast to the damaging effects of high doses, low dose radiation (UV, gamma) has been reported to provoke constructive changes in plants. However, the mechanisms by which plants recognize and respond to low dose radiation are not understood. We have shown recently that polygalacturonic acid, cell wall polysaccharide, converts the highly reactive product of radiation - hydroxyl radical into superoxide which may be further dismutated to hydrogen peroxide. Superoxide has been proposed to ac...

  5. Low-Dose Pretreatment for Radiation Therapy

    OpenAIRE

    Blankenbecler, Richard

    2010-01-01

    In radiotherapy, a large radiation dose must be applied to both cancer and neighboring healthy cells. Recent experiments have shown that a low dose of ionizing radiation turns on certain protective mechanisms that allow a cell to better survive a subsequent high dose of radiation. This adaptive response can have important and positive consequences for radiotherapy. This paper describes a simple change in treatment procedures to make use of these beneficial effects. A low dose applied only to ...

  6. Ultrasound attenuation estimation using backscattered echoes from multiple sources

    OpenAIRE

    Bigelow, Timothy A.

    2008-01-01

    The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Δf=mfo+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation,...

  7. Radiation Leukemogenesis at Low Dose Rates

    Energy Technology Data Exchange (ETDEWEB)

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  8. Update on low-dose corticosteroids.

    Science.gov (United States)

    Briegel, Josef; Bein, Thomas; Möhnle, Patrick

    2017-04-01

    Low-dose hydrocortisone is recommended in patients with septic shock unresponsive to fluid and vasopressor therapy. Recent research added new data for patients with septic shock and other target groups such as patients with severe sepsis, acute respiratory distress syndrome (ARDS), community-acquired pneumonia, and burns. The objective of this review is to summarize and comment recent findings on low-dose corticosteroids (LDC) in critically ill patients. In the last 2 years, a series of clinical trials and retrospective analyses investigated LDC therapy in critically ill patients with severe systemic inflammation of various origins. Improvement in morbidity has been demonstrated in ARDS and community-acquired pneumonia. Retrospective propensity-score analyses also suggest that LDC administered in severe septic shock or in septic shock due to community-acquired pneumonia or intestinal perforation may improve survival. Low-dose hydrocortisone or a corresponding low-dose corticosteroid therapy may improve morbidity in specific target groups of critically ill patients. Beneficial effects on mortality remain to be demonstrated in large-scale randomized controlled trials.

  9. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  10. Low dose intravaginal misoprostol versus intracervical balloon ...

    African Journals Online (AJOL)

    Need for oxytocin augmentation was less in the misoprostol group (RR 0.76, 95% CI 0.64 to 0.91). No significant differences existed in rates for uterine hyperstimulation, Caesarean section, maternal and neonatal morbidity. Conclusion:Intravaginal misoprostol in a low dose was compared to intracervical balloon catheter for ...

  11. Simple pulmonary eosinophilia detected at low-dose CT for lung cancer screening

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Kyung Nyeo; Bae, Kyung Soo; Kim, Ho Cheol [Gyeongsang National University Hospital, Jinju (Korea, Republic of)] (and others)

    2006-05-15

    The aim of this study was to evaluate the frequency, radiologic findings and clinical significance of the simple pulmonary eosinophilia (SPE) that was diagnosed among the asymptomatic patients who underwent low-dose CT scans for the early detection of lung cancer. From June 2003 to May 2005, 1,239 asymptomatic patients (1,275 examinations) who visited the health promotion center in our hospital and who underwent low-dose CT were enrolled in this study. SPE was defined as the presence of > 500 eosinophils per microliter of peripheral blood and the presence of abnormal parenchymal lesions such as nodules, airspace consolidation or areas of ground-glass attenuation (GGA) on CT, and there was spontaneous resolution or migration of the lesions on the follow-up examination. We analyzed the CT findings of SPE and we investigated the relationship between the occurrence of SPE and the season, smoking and the presence of parasite infestation. 36 patients were finally diagnosed as having SPE; this was 24% of the 153 patients who were diagnosed with parasite infestation and 2.8% of the total low-dose CT scans. These 36 patients consisted of 31 men and 5 women with a mean age 45.7 years. There was no significant relationship between SPE and the presence of parasite infestation, smoking or gender. Among the patients with peripheral blood eosinophilia, the eosinophil count was significantly higher in the patients with SPE than that in the patients without pulmonary infiltration ({rho} < 0.05). SPE more frequently occurred in winter and spring than in summer and autumn ({rho} < 0.05). The CT findings were single or multiple nodules in 18 patients, nodules and focal GGA in 9 patients and GGA only in 9 patients. Most of the nodules were less than 10 mm (88%, 49/56) in diameter and they showed an ill-defined margin (82%, n = 46); 30% of the nodules (n = 17) showed a halo around them. Simple pulmonary eosinophilia can be suggested as the cause if single or multiple ill-defined nodules

  12. Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN).

    Science.gov (United States)

    Chopra, Pradeep; Cooper, Mark S

    2013-06-01

    Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome, which involves glial activation and central sensitization in the central nervous system. Here, we describe positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone (a glial attenuator), in combination with other CRPS therapies. Prominent CRPS symptoms remitted in these two patients, including dystonic spasms and fixed dystonia (respectively), following treatment with low-dose naltrexone (LDN). LDN, which is known to antagonize the Toll-like Receptor 4 pathway and attenuate activated microglia, was utilized in these patients after conventional CRPS pharmacotherapy failed to suppress their recalcitrant CRPS symptoms.

  13. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  14. Adaption By Low Dose Radiation Exposure

    OpenAIRE

    Mitchel, Ron E.J.

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to ?as low as reasonably achievable? (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. L...

  15. Deep learning for low-dose CT

    Science.gov (United States)

    Chen, Hu; Zhang, Yi; Zhou, Jiliu; Wang, Ge

    2017-09-01

    Given the potential risk of X-ray radiation to the patient, low-dose CT has attracted a considerable interest in the medical imaging field. Currently, the main stream low-dose CT methods include vendor-specific sinogram domain filtration and iterative reconstruction algorithms, but they need to access raw data whose formats are not transparent to most users. Due to the difficulty of modeling the statistical characteristics in the image domain, the existing methods for directly processing reconstructed images cannot eliminate image noise very well while keeping structural details. Inspired by the idea of deep learning, here we combine the autoencoder, deconvolution network, and shortcut connections into the residual encoder-decoder convolutional neural network (RED-CNN) for low-dose CT imaging. After patch-based training, the proposed RED-CNN achieves a competitive performance relative to the-state-of-art methods. Especially, our method has been favorably evaluated in terms of noise suppression and structural preservation.

  16. Low-dose aspirin and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Jørgensen, Trine M M; Høgh, Annette

    2016-01-01

    OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk...

  17. Effect of low-dose ketamine on post-operative serum IL-6 production ...

    African Journals Online (AJOL)

    Serum IL-6 and IL-1β levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine sup- pressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1β assayed. Conclusion: Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced ...

  18. Low-dose aspirin and rupture ofabdominal aortic aneurysm: A nationwide, population-based study

    DEFF Research Database (Denmark)

    Wemmelund, H.; Jørgensen, T.; Høgh, A.

    OBJECTIVE: The use of low-dose aspirin (acetylsalicylic acid [ASA]) has been suggested to attenuate growth of abdominal aortic aneurysms (AAAs), yet solid clinical evidence of this hypothesis is still missing. This study aimed to investigate whether preadmission ASA use influenced the risk...

  19. Normal tissue complications from low-dose proton therapy.

    Science.gov (United States)

    Mahajan, Anita

    2012-11-01

    Proton therapy is an attractive method to attenuate toxicities of radiotherapy because of the decrease of integral radiation dose to normal tissues, which should lead to fewer late side effects. This potential benefit is of particular interest in the pediatric population, since children are more vulnerable to the risks of radiation. In addition, overall survival rates for pediatric malignancies continue to improve, which will lead to more long-term survivors who will be at risk from the late effects of radiation therapy that was used for treatment. In this review, the potential benefits afforded by proton therapy in the low-dose area for radiosensitive organs will be evaluated. Because robust clinical information is not available for low-dose proton therapy, information from the experience of photon therapy in radiosensitive structures will be reviewed. In general, because the low-dose bath is reduced or on occasion eliminated with the use of proton therapy, a reduction of early and late toxicities related to low-dose radiotherapy such as vomiting, mucositis, cardiovascular complications, pulmonary injury, and developmental effects in children is expected. Other authors review the current evidence and potential benefits supporting the use of proton therapy for the reduction in neuro-cognitive sequelae and secondary malignancies. Currently, a relative biological effectiveness of 1.1 is used in clinical situations to calculate the equivalent biologic dose for proton therapy relative to photon therapy. The unit of dose is commonly referred to as gray equivalent (GyEq). The interaction of a proton at a cellular level is postulated to lead to a higher frequency of double-strand breaks, so in theory there is a higher probability of cell kill and a lower probability of mutagenesis. At this time, however, once the physical properties of the interaction of proton with matter are accounted for, there is no definite data that 1 GyEq has any different biologic outcome than 1

  20. Consistency of attenuation across multiple fittings of custom and non-custom earplugs.

    Science.gov (United States)

    Tufts, Jennifer B; Jahn, Kelly N; Byram, John P

    2013-06-01

    Hearing protection devices (HPDs) play a significant role in protecting workers from occupational noise-induced hearing loss. Individual HPD fit-testing estimates the amount of protection, or attenuation, that an individual achieves from a given HPD as it is worn. Results from a single fit-test may not be representative of real-world HPD performance over time, however, due to inconsistency in how the individual fits the HPD from time to time. In this study, the effects of HPD type and user training on the consistency of attenuation achieved across multiple fittings were evaluated in a within-subjects design. Attenuation measurements using a real-ear attenuation at threshold procedure were obtained on 30 participants wearing custom-molded and non-custom earplugs. The subjects were initially naive to proper earplug insertion techniques and later received one-on-one training for the second half of the attenuation measurements. Consistency, or reliability, of fit was assessed using (i) the standard deviation of the 'distance to ear mean attenuation', a measure of fitting uncertainty, and (ii) the standard deviation of the attenuation values across multiple fit-tests for each subject. The custom earplug provided statistically significantly better consistency of attenuation than the non-custom earplug at 500, 1000, and 2000 Hz. Training effects were statistically significant at 250, 500, and 1000 Hz and at the Personal Attenuation Rating. No interactions were statistically significant. These results indicate that, in general, subjects obtained more consistent attenuation with the custom earplugs than with the non-custom earplugs and that consistency improved with training for both earplug types.

  1. [Complications of low-dose amiodarone].

    Science.gov (United States)

    Feigl, D; Gilad, R; Katz, E

    1991-11-15

    Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated.

  2. Antidiabetic effects of dietary administration of Aloe arborescens Miller components on multiple low-dose streptozotocin-induced diabetes in mice: investigation on hypoglycemic action and systemic absorption dynamics of aloe components.

    Science.gov (United States)

    Beppu, Hidehiko; Shimpo, Kan; Chihara, Takeshi; Kaneko, Takaaki; Tamai, Ikuko; Yamaji, Sachiyo; Ozaki, Sayaka; Kuzuya, Hiroshi; Sonoda, Shigeru

    2006-02-20

    We carried out three experimental trials to determine antidiabetic effects of Aloe arborescens Miller components. Firstly, ICR mice which received frequent injections of streptozotocin (Sz) in small doses (low-dose Sz-induced diabetes mice) were fed ad libitum with basal diets supplemented with components of Aloe arborescens Miller var. natalensis Berger (Kidachi aloe) and Aloe vera Linne from 31 days before to 73 days after the Sz injections. Variation in blood glucose levels, incidence rates of insulitis and blood insulin levels were examined during the trial. As a result, groups receiving diets supplemented at the rate of 2% with whole leaf of Kidachi aloe and 10 KDa fraction powder (a fraction with less than 10 KDa molecular weight derived from Kidachi aloe leaf skin juice by ultra filtration) significantly suppressed the elevation of blood sugar as compared to a control group receiving basal diet. In contrast, there was no significant effect with Aloe vera leaf pulp powder. Insulitis emerged at the rate of 87% in the basal diet group. On the contrary, the whole aloe leaf and 10 KDa fraction groups significantly decreased the incidence of insulitis and incidence rates of whole aloe leaf and 10 KDa fraction powder were 51 and 38%, respectively. While insulin levels in the basal diet group averaged at 0.05 ng, more than four times the insulin level was observed in the 10 KDa group relative to the basal diet group. Secondary, the inhibitory effects of test materials on intestinal glucose absorption were observed using the jejunum of rats. A strong inhibitory action on intestinal glucose absorption was observed in the 10 KDa fraction powder group. Thirdly, phenol compounds derived from aloe in the blood serum and organs were quantitatively measured by a HPLC following forced administration of aloe components to rats to determine absorption kinetics of aloe components inside the body. The primary component of aloe phenol compounds is the same component of the 10 KDa

  3. Determination of the Absorption Coefficient and Cloudiness Multiplicity Attenuation During the Gamma-Radiation Passage

    Science.gov (United States)

    Orlova, K. N.; Borovikov, I. F.; Gaidamak, M. A.

    2016-08-01

    The paper presents background value equivalent dose of gamma-radiation investigation in different weather: clear cloudy and overcast. The change of the dose rate of gamma radiation, depending on the weather and the ability cloudiness to shield gamma rays is shown. A new method for eliminating the consequences of accidents at nuclear power plants or plants using radioactive elements is proposed. A calculation method of cloudiness coefficient absorption and cloudiness gamma-radiation multiplicity attenuation is developed. The gamma- radiation multiplicity attenuation and the absorption coefficient of gamma radiation were calculated.

  4. Vibration Attenuation of Plate Using Multiple Vibration Absorbers

    Directory of Open Access Journals (Sweden)

    Zaman Izzuddin

    2014-07-01

    Full Text Available Vibrations are undesired phenomenon and it can cause harm, distress and unsettling influence to the systems or structures, for example, aircraft, automobile, machinery and building. One of the approach to limit this vibration by introducing passive vibration absorber attached to the structure. In this paper, the adequacy of utilizing passive vibration absorbers are investigated. The vibration absorber system is designed to minimize the vibration of a thin plate fixed along edges. The plate’s vibration characteristics, such as, natural frequency and mode shape are determined using three techniques: theoretical equations, finite element (FE analysis and experiment. The results demonstrate that the first four natural frequencies of fixed-fixed ends plate are 48, 121, 193 and 242 Hz, and these results are corroborated well with theoretical, FE simulation and experiment. The experiment work is further carried out with attached single and multiple vibration absorbers onto plate by tuning the absorber’s frequency to match with the excitation frequency. The outcomes depict that multiple vibration absorbers are more viable in lessening the global structural vibration.

  5. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  6. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  7. Practical Implementation of Multiple Attenuation Methods on 2D Deepwater Seismic Data : Seram Sea Case Study

    Directory of Open Access Journals (Sweden)

    Tumpal Bernhard Nainggolan

    2017-08-01

    Full Text Available Some deepwater multiple attenuation processing methods have been developed in the past with partial success. The success of surface multiple attenuation relies on good water bottom reflections for most deepwater marine situations. It brings the bigger ability to build an accurate water bottom multiple prediction model. Major challenges on 2D deepwater seismic data processing especially such a geologically complex structure of Seram Sea, West Papua – Indonesia are to attenuate surface related multiple and to preserve the primary data. Many multiple attenuation methods have been developed to remove surface multiple on these seismic data including most common least-squares, prediction-error filtering and more advanced Radon transform. Predictive Deconvolution and Surface Related Multiple Elimination (SRME method appears to be a proper solution, especially in complex structure where the above methods fail to distinguish interval velocity difference between primaries and multiples. It does not require any subsurface info as long as source signature and surface reflectivity are provided. SRME method consists of 3 major steps: SRME regularization, multiple modeling and least-square adaptive subtraction. Near offset regularization is needed to fill the gaps on near offset due to unrecorded near traces during the acquisition process. Then, isolating primaries from multiples using forward modeling. Inversion method by subtraction of input data with multiple models to a more attenuated multiple seismic section. Results on real 2D deepwater seismic data show that SRME method as the proper solution should be considered as one of the practical implementation steps in geologically complex structure and to give more accurate seismic imaging for the interpretation. Keywords : multiple attenuation, 2D deepwater seismic, Radon transform, Surface Related Multiple Elimination (SRME.   Banyak metode atenuasi pengulangan ganda dikembangkan pada pengolahan data

  8. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  9. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  10. Low-dose effects of hormones and endocrine disruptors.

    Science.gov (United States)

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately. © 2014 Elsevier Inc. All rights reserved.

  11. Linking multiple relaxation, power-law attenuation, and fractional wave equations.

    Science.gov (United States)

    Näsholm, Sven Peter; Holm, Sverre

    2011-11-01

    The acoustic wave attenuation is described by an experimentally established frequency power law in a variety of complex media, e.g., biological tissue, polymers, rocks, and rubber. Recent papers present a variety of acoustical fractional derivative wave equations that have the ability to model power-law attenuation. On the other hand, a multiple relaxation model is widely recognized as a physically based description of the acoustic loss mechanisms as developed by Nachman et al. [J. Acoust. Soc. Am. 88, 1584-1595 (1990)]. Through assumption of a continuum of relaxation mechanisms, each with an effective compressibility described by a distribution related to the Mittag-Leffler function, this paper shows that the wave equation corresponding to the multiple relaxation approach is identical to a given fractional derivative wave equation. This work therefore provides a physically based motivation for use of fractional wave equations in acoustic modeling.

  12. Low-dose radiotherapy for primary cutaneous anaplastic large-cell lymphoma while on low-dose methotrexate.

    Science.gov (United States)

    Cornejo, Christine M; Novoa, Roberto A; Krisch, Robert E; Kim, Ellen J

    2016-10-01

    Primary cutaneous anaplastic large-cell lymphoma (pcALCL) is part of a spectrum of CD30+ primary cutaneous lymphoproliferative disorders (pcLPDs) that also includes lymphomatoid papulosis (LyP). Localized radiotherapy at doses of 34 to 44 Gy is first-line treatment of pcALCL, but the use of low-dose radiotherapy for pcALCL has not been reported. We present the case of a patient with a history of pcALCL/LyP who was treated with low-dose radiotherapy while on oral low-dose methotrexate (MTX) once weekly. This report suggests that low-dose radiotherapy can be an effective palliative treatment of pcALCL. Low-dose radiotherapy may offer certain advantages over traditional radiotherapy, such as a more economical and efficient treatment for patients, potentially fewer short-term and long-term side effects, and the potential for concomitant use with low-dose MTX.

  13. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  14. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies

    Directory of Open Access Journals (Sweden)

    Noriyuki Yanagida

    2016-04-01

    With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

  15. Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study.

    Science.gov (United States)

    Mc Menamin, Úna C; Cardwell, Chris R; Hughes, Carmel M; Murray, Liam J

    2017-04-01

    Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality. Post-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use. In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Does low dose oral ketamine have oxytocic effect? | Okorie ...

    African Journals Online (AJOL)

    Objectives: To evaluate if low dose oral Ketamine has oxytotic effect on term pregnant uterus. Methodology: This is a cross sectional double blind placebo control prospective study. A total of 745 parturients were studied, 261 had low dose oral Ketamine in active phase of labour (group A), 227 had Oxytocin augmentation ...

  17. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  18. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  19. [Indications for low-dose CT in the emergency setting].

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  20. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Directory of Open Access Journals (Sweden)

    Nedeljkovic Milan

    2003-06-01

    Full Text Available Abstract Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

  1. Low-dose CT denoising with convolutional neural network

    CERN Document Server

    Chen, Hu; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2016-01-01

    To reduce the potential radiation risk, low-dose CT has attracted much attention. However, simply lowering the radiation dose will lead to significant deterioration of the image quality. In this paper, we propose a noise reduction method for low-dose CT via deep neural network without accessing original projection data. A deep convolutional neural network is trained to transform low-dose CT images towards normal-dose CT images, patch by patch. Visual and quantitative evaluation demonstrates a competing performance of the proposed method.

  2. Low-Dose CT via Deep Neural Network

    CERN Document Server

    Chen, Hu; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2016-01-01

    In order to reduce the potential radiation risk, low-dose CT has attracted more and more attention. However, simply lowering the radiation dose will significantly degrade the imaging quality. In this paper, we propose a noise reduction method for low-dose CT via deep learning without accessing the original projection data. An architecture of deep convolutional neural network was considered to map the low-dose CT images into its corresponding normal-dose CT images patch by patch. Qualitative and quantitative evaluations demonstrate a state-the-art performance of the proposed method.

  3. Low-dose propranolol and exercise capacity in postural tachycardia syndrome

    Science.gov (United States)

    Arnold, Amy C.; Okamoto, Luis E.; Diedrich, André; Paranjape, Sachin Y.; Raj, Satish R.; Biaggioni, Italo

    2013-01-01

    Objective: To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS). Methods: We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO2max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort. Results: Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO2max in patients with POTS (24.5 ± 0.7 placebo vs 27.6 ± 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO2max in POTS was associated with attenuated peak heart rate responses (142 ± 8 propranolol vs 165 ± 4 bpm placebo; p = 0.005) and improved stroke volume (81 ± 4 propranolol vs 67 ± 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO2max, despite similar lowering of heart rate. Conclusions: These findings suggest that nonselective β-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity. Classification of evidence: This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication. PMID:23616163

  4. Acute Low-Dose Hydralazine-Induced Lupus Pneumonitis

    Directory of Open Access Journals (Sweden)

    Sarah K. Holman

    2017-01-01

    Full Text Available A 35-year-old female was started on hydralazine 10 mg orally three times a day for treatment of postpartum hypertension. Three months later, after multiple unsuccessful courses of prednisone and antibiotics for presumed pneumonia and asthma exacerbations, her respiratory symptoms progressed in severity and she developed resting hypoxia. Previous diagnostic work-up included spirometry with a restrictive pattern, chest CT showing bilateral basilar consolidation, negative BAL, and nonspecific findings on lung biopsy of mild inflammatory cells. Review of systems was positive for arthralgia, lymphadenopathy, paresthesia, and fatigue that began four weeks after starting hydralazine. A clinical diagnosis of hydralazine-induced lupus (HIL with pneumonitis was made. Antihistone antibodies were positive supporting a diagnosis of HIL. Management included cessation of hydralazine and a prolonged steroid taper. Within days, patient began improving symptomatically. Six weeks later, CT chest showed complete resolution of infiltrates. Genetic testing revealed she was heterozygous for N-acetyltransferase 2 (intermediate acetylator. Drug-induced lupus should be considered in patients with lupus-like symptoms taking medications with a known association. While the majority of HIL cases occur with high doses and prolonged treatment, cases of low-dose HIL have been reported in patients who are slow acetylators.

  5. Morphine sparing effect of low dose ketamine during patient ...

    African Journals Online (AJOL)

    PCIA) of low dose morphine plus ketamine with morphine. Design: Double blind case control study. Setting: Academic hospital. Patients: Thirty-six patients scheduled for elective abdominal hysterectomy were randomly divided into two groups to ...

  6. Low-dose rituximab as an adjuvant therapy in pemphigus

    Directory of Open Access Journals (Sweden)

    Jaya Gupta

    2017-01-01

    Conclusion: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

  7. Bronchiolitis obliterans organizing pneumonia during low-dose amiodarone therapy

    NARCIS (Netherlands)

    Jessurun, GAJ; Hoogenberg, K; Crijns, HJGM

    Two cases of amiodarone-induced pulmonary toxicity during a relatively short period of low-dose amiodarone treatment are reported. The toxicity risk of amiodarone is determined by cumulative factors in individual patients.

  8. Scientific Risk Estimation on Health Effects of Low Dose and Low Dose-Rate Radiation - An Overview

    Directory of Open Access Journals (Sweden)

    Tetsuya Ono

    2009-06-01

    Full Text Available Estimation of the scientific risks of high dose radiation has been successfully quantified by many studies using several different approaches. However, the risk for low and low dose-rate radiation is obscure because of a lack of evidence. This risk is currently estimated by extrapolating the radiation response at high doses into low dose ranges for practical purposes. Recent challenges to examine directly the biological responses to low dose radiation using newly developed technologies are unveiling interesting alterations at the molecular level. The interpretation of these data, however, needs careful consideration because they may not be related to any change in biological functions.

  9. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek (and others)

    2007-07-15

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources.

  10. Partial Sleep Deprivation Attenuates the Positive Affective System: Effects Across Multiple Measurement Modalities.

    Science.gov (United States)

    Finan, Patrick H; Quartana, Phillip J; Remeniuk, Bethany; Garland, Eric L; Rhudy, Jamie L; Hand, Matthew; Irwin, Michael R; Smith, Michael T

    2017-01-01

    Ample behavioral and neurobiological evidence links sleep and affective functioning. Recent self-report evidence suggests that the affective problems associated with sleep loss may be stronger for positive versus negative affective state and that those effects may be mediated by changes in electroencepholographically measured slow wave sleep (SWS). In the present study, we extend those preliminary findings using multiple measures of affective functioning. In a within-subject randomized crossover experiment, we tested the effects of one night of sleep continuity disruption via forced awakenings (FA) compared to one night of uninterrupted sleep (US) on three measures of positive and negative affective functioning: self-reported affective state, affective pain modulation, and affect-biased attention. The study was set in an inpatient clinical research suite. Healthy, good sleeping adults (N = 45) were included. Results indicated that a single night of sleep continuity disruption attenuated positive affective state via FA-induced reductions in SWS. Additionally, sleep continuity disruption attenuated the inhibition of pain by positive affect as well as attention bias to positive affective stimuli. Negative affective state, negative affective pain facilitation, nor negative attention bias were altered by sleep continuity disruption. The present findings, observed across multiple measures of affective function, suggest that sleep continuity disruption has a stronger influence on the positive affective system relative to the negative affective affective system.

  11. ATTENUATION OF DIFFRACTED MULTIPLES WITH AN APEX-SHIFTED TANGENT-SQUARED RADON TRANSFORM IN IMAGE SPACE

    Directory of Open Access Journals (Sweden)

    Alvarez Gabriel

    2006-12-01

    Full Text Available In this paper, we propose a method to attenuate diffracted multiples with an apex-shifted tangent-squared Radon transform in angle domain common image gathers (ADCIG . Usually, where diffracted multiples are a problem, the wave field propagation is complex and the moveout of primaries and multiples in data space is irregular. The method handles the complexity of the wave field propagation by wave-equation migration provided that migration velocities are reasonably accurate. As a result, the moveout of the multiples is well behaved in the ADCIGs. For 2D data, the apex-shifted tangent-squared Radon transform maps the 2D space image into a 3D space-cube model whose dimensions are depth, curvature and apex-shift distance.
    Well-corrected primaries map to or near the zero curvature plane and specularly-reflected multiples map to or near the zero apex-shift plane. Diffracted multiples map elsewhere in the cube according to their curvature and apex-shift distance. Thus, specularly reflected as well as diffracted multiples can be attenuated simultaneously. This approach is illustrated with a segment of a 2D seismic line over a large salt body in the Gulf of Mexico. It is shown that ignoring the apex shift compromises the attenuation of the diffracted multiples, whereas the approach proposed attenuates both the specularly-reflected and the diffracted multiples without compromising the primaries.

  12. Low Dose Suppression of Neoplastic Transformation in Vitro

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  13. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  14. The effects of Fhit on tumorigenesis after multi-exposure to low-dose radiation

    Science.gov (United States)

    Yu, Xiaoyan; Lu, Lin; Wen, Siyuan; Wang, Ya

    2009-01-01

    Low-dose (≤ 0.1 Gy) radiation could reduce high-dose induced damage including tumorigenesis. However, it remains unclear whether multi-exposure to low-dose radiation at a high dose rate has any risk for increasing tumorigenesis, and whether Fhit plays any role in the process. The purpose of this study is to investigate the effects of multi-exposure to low-dose radiation at a high dose rate on tumorigenesis, and the role of Fhit in it. We irradiated Fhit+/+ and Fhit-/- mice with 1 Gy/1 or 0.1 Gy × 10 exposures at a dose rate of 1 Gy/min, sacrificed the mice at 1.5 years after radiation and observed multi-organ tumorigenesis. The results showed that although the spontaneous tumorigenesis in these mice was relatively high, 1 Gy/1-exposure dramatically increased the tumorigenesis including lung and liver tumor. Fhit-/- mice showed more tumorigenesis than Fhit+/+ mice after 1 Gy/1-exposure. However, 0.1 Gy × 10 exposures did not increase tumorigenesis, and there was no statistical difference in tumorigenesis between Fhit+/+ mice and Fhit-/- mice following 0.1 Gy × 10 exposures. Our results suggest that 0.1 Gy, even after multiple exposures, does not increase tumorigenesis, and Fhit could prevent high-dose radiation-induced tumors but has no effect in a low-dose environment. PMID:20057978

  15. Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

    Science.gov (United States)

    Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

    2012-03-01

    In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

  16. Benzodiazepine dependence and its treatment with low dose flumazenil.

    Science.gov (United States)

    Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth

    2014-02-01

    Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  17. SPECTCT cerebral perfusion scintigraphy; is the low-dose CT component of diagnostic value?

    Energy Technology Data Exchange (ETDEWEB)

    Sulkin, T.V.C. [Department of Clinical Imaging, Royal Cornwall Hospital, Truro, Cornwall (United Kingdom)], E-mail: tom.sulkin@rcht.cornwall.nhs.uk; Cousens, C. [Department of Clinical Imaging, Royal Cornwall Hospital, Truro, Cornwall (United Kingdom)

    2008-03-15

    Aim: To assess the potential diagnostic value of the low-dose computed tomography (CT) component of dual-examination single photon emission CT and CT (SPECTCT) cerebral perfusion studies. Method and materials: Two hundred and forty consecutive 99 mTc hexamethylpropylene amine oxime (HMPAO) SPECTCT studies were considered for inclusion. The images were acquired on a hybrid dual-head gamma camera/low-dose CT system. The CT component had a fixed tube current of 2.5 mA. The CT section thickness was 5 mm and total acquisition time approximately 7.5 min. Studies in which no CT images were acquired, or those excessively degraded by movement artefact were excluded. The CT images of each of the remaining studies were retrospectively reviewed and categorized as normal or abnormal. Details of the abnormalities were recorded. Results: Fifteen of the 240 studies were excluded as no CT images were obtained. A further 14 were excluded as they were considered excessively degraded by movement artefact. A single abnormality was demonstrated on 48 (23%), and two abnormalities on four (2%) of the remaining 211 studies. The most common abnormal findings were low attenuation in the deep cortical white matter (n = 22), infarcts (n = 12), cerebral atrophy (n = 7), dilated ventricles (n = 5), basal ganglia calcification (n = 4), and post-surgical change (n = 3). Other findings included a chronic subdural haematoma, a meningioma, and a posterior fossa cyst. Previous cerebral imaging was available for comparison in 31% of cases. There was 85% concordance between previous imaging and the low-dose CT images. Conclusion: Twenty-five percent of the low-dose CT images in this study demonstrated abnormalities. Therefore the CT component of cerebral perfusion SPECTCT investigations should be routinely reported in their own right.

  18. High-resolution low-dose scanning transmission electron microscopy.

    Science.gov (United States)

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  19. Statistical distributions of ultra-low dose CT sinograms and their fundamental limits

    Science.gov (United States)

    Lee, Tzu-Cheng; Zhang, Ruoqiao; Alessio, Adam M.; Fu, Lin; De Man, Bruno; Kinahan, Paul E.

    2017-03-01

    Low dose CT imaging is typically constrained to be diagnostic. However, there are applications for even lowerdose CT imaging, including image registration across multi-frame CT images and attenuation correction for PET/CT imaging. We define this as the ultra-low-dose (ULD) CT regime where the exposure level is a factor of 10 lower than current low-dose CT technique levels. In the ULD regime it is possible to use statistically-principled image reconstruction methods that make full use of the raw data information. Since most statistical based iterative reconstruction methods are based on the assumption of that post-log noise distribution is close to Poisson or Gaussian, our goal is to understand the statistical distribution of ULD CT data with different non-positivity correction methods, and to understand when iterative reconstruction methods may be effective in producing images that are useful for image registration or attenuation correction in PET/CT imaging. We first used phantom measurement and calibrated simulation to reveal how the noise distribution deviate from normal assumption under the ULD CT flux environment. In summary, our results indicate that there are three general regimes: (1) Diagnostic CT, where post-log data are well modeled by normal distribution. (2) Lowdose CT, where normal distribution remains a reasonable approximation and statistically-principled (post-log) methods that assume a normal distribution have an advantage. (3) An ULD regime that is photon-starved and the quadratic approximation is no longer effective. For instance, a total integral density of 4.8 (ideal pi for 24 cm of water) for 120kVp, 0.5mAs of radiation source is the maximum pi value where a definitive maximum likelihood value could be found. This leads to fundamental limits in the estimation of ULD CT data when using a standard data processing stream

  20. The postoperative analgesic effects of low-dose gabapentin in ...

    African Journals Online (AJOL)

    Objective. Clinical studies have suggested that gabapentin may produce analgesia in postoperative patients. The aim of this study was to investigate the analgesic effects of low-dose gabapentin administered during the first 24 hours after abdominal hysterectomy. Methods. A prospective, double-blind, randomised study ...

  1. Beneficial effects of low dose Musa paradisiaca on the semen ...

    African Journals Online (AJOL)

    Background: This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. Materials and Methods: The animals used for the study were grouped into three: the control group, given 2 ml of double distilled water, a low dose group given ...

  2. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... stay of the patients. Therefore, reducing the side effects associated with intrathecal anesthesia is quite helpful to support better postoperative management. Combined low dose local anesthetics and opioids versus single use of LA for transurethral urological surgery: A meta‑analysis. Y Ding, M Li, L Chen1, ...

  3. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  4. Use of combined paracetamol and low dose ketamine in pain ...

    African Journals Online (AJOL)

    Objective: To determine the effectiveness of Paracetamol and low dose Ketamine in controlling burn pain during dressings. Setting: The burns ward of Moi Teaching and Referral Hospital, a 750 bed capacity tertiary centre in Western Kenya. Subjects: Consenting patients were recruited to the study on admission. Babies and ...

  5. Low-dose aspirin and risk of intracranial bleeds

    DEFF Research Database (Denmark)

    Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse

    2017-01-01

    OBJECTIVE: To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom. METHODS: A cohort of new users of low-dose aspirin (75-300 mg; n = 199,079) aged 40-84 years and a 1:1 matched...... cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95......% confidence intervals (CIs) were calculated for current low-dose aspirin use (0-7 days before the index date [ICB date for cases, random date for controls]); reference group was never used. RESULTS: There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH...

  6. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    Introduction: The combination of reduced dose of local anesthetics (LA) and highly lipid‑soluble synthetic opioids for patients undergoing transurethral surgery could reduce block duration and side‑effects. However, it remains unclear what are the most appropriate levels of low dose and the extent to which the side‑effects ...

  7. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

    Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

  8. Chemi-luminescent technique using low dose effect characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmenko, A.I.; Porokhnyak, L.A. [A.V. palladin Institute of Biochemistry, Ukrainian National Academy of Sciences, Kiev (Ukraine)

    1997-03-01

    Some Ukrainian and Belarusian territories are polluted by radioactive elements as Chernobyl AES accident consequence in 1986. Radioactive substances enter to animals and human organism with the food and lead to internal irradiation. The purpose of this work is he changes characteristic for an organism under internal irradiation low dose estimated by means of chemi-luminescent (Chl) techniques. (authors)

  9. Low-dose spinal anaesthesia provides effective labour analgesia ...

    African Journals Online (AJOL)

    Low-dose spinal anaesthesia provides effective labour analgesia and does not limit ambulation. T Anabaha*, A Olufolabia,b,d, J Boydc and R Georgec,d. aSchool of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana. bDuke University Medical Centre, Durham, NC, USA. cIWK Health Centre ...

  10. Topics on study of low dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takeshi [Toho Univ., School of Medicine, Tokyo (Japan); Ohyama, Harumi

    1999-09-01

    It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

  11. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  12. Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy-era with plerixafor and G-CSF has superior efficacy but significantly higher costs compared to mobilization with low-dose cyclophosphamide and G-CSF.

    Science.gov (United States)

    Chaudhary, Lubna; Awan, Farrukh; Cumpston, Aaron; Leadmon, Sonia; Watkins, Kathy; Tse, William; Craig, Michael; Hamadani, Mehdi

    2013-10-01

    Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens. Copyright © 2013 Wiley Periodicals, Inc.

  13. Multiple Lines Of Evidence Supporting Natural Attenuation: Lines Of Inquiry Supporting Monitored Natural Attenuation And Enhanced Attenuatin Of Chlorinated Solvents

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, Karen; Widemeirer, T. H.; Barden, M.J.; Dickson, W. Z.; Major, David

    2004-12-31

    The Department of Energy (DOE) is sponsoring an initiative to facilitate efficient, effective and responsible use of Monitored Natural Attenuation (MNA) and Enhanced Attenuation (EA) for chlorinated solvents. This Office of Environmental Management (EM) ''Alternative Project,'' focuses on providing scientific and policy support for MNA/EA. A broadly representative working group of scientists supports the project along with partnerships with regulatory organizations such as the Interstate Technology Regulatory Council (ITRC) and the United States Environmental Protection Agency (USEPA). The initial product of the technical working group was a summary report that articulated the conceptual approach and central scientific tenants of the project, and that identified a prioritized listing of technical targets for field research. This report documented the process in which: (1) scientific ground rules were developed, (2) lines of inquiry were identified and then critically evaluated, (3) promising applied research topics were highlighted in the various lines of inquiry, and (4) these were discussed and prioritized. The summary report will serve as a resource to guide management and decision making throughout the period of the subject MNA/EA Alternative Project. To support and more fully document the information presented in the summary report, the DOE is publishing a series of supplemental documents that present the full texts from the technical analyses within the various lines of inquiry (see listing). The following report--documenting our evaluation of the state of the science for the lines of evidence for supporting decision-making for MNA--is one of those supplemental documents.

  14. Uncomfortable issues in radiation protection posed by low-dose radiobiology.

    Science.gov (United States)

    Mothersill, Carmel; Seymour, Colin

    2013-08-01

    This paper aims to stimulate discussion about the relevance for radiation protection of recent findings in low-dose radiobiology. Issues are raised which suggest that low-dose effects are much more complex than has been previously assumed. These include genomic instability, bystander effects, multiple stressor exposures and chronic exposures. To date, these have been accepted as being relevant issues, but there is no clear way to integrate knowledge about these effects into the existing radiation protection framework. A further issue which might actually lead to some fruitful approaches for human radiation protection is the need to develop a new framework for protecting non-human biota. The brainstorming that is being applied to develop effective and practical ways to protect ecosystems widens the debate from the narrow focus of human protection which is currently about protecting humans from radiation-induced cancers.

  15. Detection and size measurements of pulmonary nodules in ultra-low-dose CT with iterative reconstruction compared to low dose

    NARCIS (Netherlands)

    Sui, Xin; Meinel, Felix G.; Song, Wei; Xu, Xiaoli; Wang, Zixing; Wang, Yuyan; Jin, Zhengyu; Chen, Jiuhong; Vliegenthart, Rozemarijn; Schoepf, U. Joseph

    Background: In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated. Methods: Eighty-four individuals referred for lung cancer screening (mean age: 54.5 +/- 10.8 years) underwent

  16. Animal Studies of Residual Hematopoietic and Immune System Injury from Low Dose/Low Dose Rate Radiation and Heavy Metals.

    Science.gov (United States)

    1998-09-01

    fission products were released, workers involved in reactor or weapons construction, and perhaps astronauts/cosmonauts exposed to space irradiation. It is...dose rates [5,6]. long-term animal experiments. Such data could be extrap - The long-term consequences of low dose irradiation may olated to human

  17. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

  18. Attenuation of virus production at high multiplicities of infection in Aureococcus anophagefferens

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Christopher M.; Bidle, Kay D., E-mail: bidle@marine.rutgers.edu

    2014-10-15

    Infection dynamics (saturation kinetics, infection efficiency, adsorption and burst size) for the Aureococcus anophagefferens-Brown Tide virus (AaV) system were investigated using susceptible and resistant strains. Adsorption assays revealed that virus affinity to the cell surface is a key determinant of infectivity. Saturation of infection occurred at a multiplicity of infection (MOI) of 8 viruses per host and resulted in ∼90–95% of infected cells, with burst sizes ranging from 164 to 191. Insight from the AaV genome implicates recycling of host nucleotides rather than de novo synthesis as a constraint on viral replication. Viral yields and mean burst sizes were significantly diminished with increasing MOI. This phenomenon, which was reminiscent of phage-induced ‘lysis from without’, appeared to be caused by viral contact and was unrelated to bacteria, signaling/toxic compounds, or defective interfering viruses. We posit that high-MOI effects attenuate viral proliferation in natural systems providing a negative feedback on virus-induced bloom collapse.

  19. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better

  20. Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2013-01-01

    Full Text Available Cystoid macular edema (CME is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME in a middle-age woman taking low dose of niacin (18 mg of nicotinic acid. Optical coherence tomography (OCT showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy.

  1. Low dose ionizing radiation induced acoustic neuroma: A putative link?

    Directory of Open Access Journals (Sweden)

    Sachin A Borkar

    2012-01-01

    Full Text Available Although exposure to high dose ionizing radiation (following therapeutic radiotherapy has been incriminated in the pathogenesis of many brain tumors, exposure to chronic low dose ionizing radiation has not yet been shown to be associated with tumorigenesis. The authors report a case of a 50-year-old atomic reactor scientist who received a cumulative dose of 78.9 mSv over a 10-year period and was detected to have an acoustic neuroma another 15 years later. Although there is no proof that exposure to ionizing radiation was the cause for the development of the acoustic neuroma, this case highlights the need for extended follow-up periods following exposure to low dose ionizing radiation.

  2. In Vivo Mutagenic Effect of Very Low Dose Radiation

    Science.gov (United States)

    Sykes, Pamela J.; Day, Tanya K.; Swinburne, Sarah J.; Lane, Joanne M.; Morley, Alexander A.; Hooker, Antony M.; Bhat, Madhava

    2006-01-01

    Almost all of our knowledge about the mutational effect of radiation has come from high dose studies which are generally not relevant to public exposure. The pKZ1 mouse recombination mutagenesis assay enables study of the mutational effect of very low doses of low LET radiation (μGy to cGy range) in a whole animal model. The mutational end-point studied is chromosomal inversion which is a common mutation in cancer. We have observed 1) a non-linear dose response of induced inversions in pKZ1 mice exposed to a wide dose range of low LET radiation, 2) the ability of low priming doses to cause an adaptive response to subsequent higher test doses and 3) the effect of genetic susceptibility where animals that are heterozygous for the Ataxia Telangiectasia gene (Atm) exhibit different responses to low dose radiation compared to their normal litter-mates. PMID:18648587

  3. Effect of low-dose radiation on ocular circulation

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1999-05-01

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  4. Low dose aspirin and pregnancy: how important is aspirin resistance?

    OpenAIRE

    Navaratnam, K; Alfirevic, A; Alfirevic, Z

    2016-01-01

    Antiplatelet agents are pivotal for prevention of coronary artery disease and cerebrovascular disease worldwide. Individual patient data meta?analysis indicates that low?dose aspirin causes a 10% risk reduction in pre?eclampsia for women at high individual risk. However, in the last 15 years it has emerged that a significant proportion of aspirin?treated individuals exhibit suboptimal platelet response, determined biochemically and clinically, termed ?aspirin non?responsiveness?, ?aspirin res...

  5. Corticosteroids in acute severe asthma: effectiveness of low doses.

    OpenAIRE

    Bowler, S D; Mitchell, C. A.; Armstrong, J. G.

    1992-01-01

    BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intra...

  6. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

    2001-07-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  7. Transportable, Low-Dose Active Fast-Neutron Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mihalczo, John T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wright, Michael C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McConchie, Seth M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Archer, Daniel E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Palles, Blake A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-08-01

    This document contains a description of the method of transportable, low-dose active fast-neutron imaging as developed by ORNL. The discussion begins with the technique and instrumentation and continues with the image reconstruction and analysis. The analysis discussion includes an example of how a gap smaller than the neutron production spot size and detector size can be detected and characterized depending upon the measurement time.

  8. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

    Directory of Open Access Journals (Sweden)

    Jin Ok Kim

    2015-03-01

    Full Text Available Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC, but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE, radiofrequency thermal ablation (RFTA, and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone. The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

  9. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient.

    Science.gov (United States)

    Kim, Jin Ok; Jun, Dae Won; Tae, Hye Jin; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul; Hahm, Joon Soo

    2015-03-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

  10. Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion

    Directory of Open Access Journals (Sweden)

    Yaqi eYou

    2014-06-01

    Full Text Available Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance. Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome of food animals, which is subsequently transferred to animal waste. This waste contains complex constituents that are challenging to treat, including antimicrobial resistance determinants and low-dose antimicrobials. Unconfined storage or land deposition of a large volume of animal waste causes its wide contact with the environment and drives the expansion of the environmental resistome through mobilome facilitated horizontal genet transfer. The expanded environmental resistome, which encompasses both natural constituents and anthropogenic inputs, can persist under multiple stressors from agriculture and may re-enter humans, thus posing a public health risk to humans. For these reasons, this review focuses on agricultural antimicrobial use as a laboratory for understanding low-dose antimicrobials as drivers of resistome expansion, briefly summarizes current knowledge on this topic, highlights the importance of research specifically on environmental microbial ecosystems considering antimicrobial resistance as environmental pollution, and calls attention to the needs for longitudinal studies at the systems level.

  11. Adaption By Low Dose Radiation Exposure: A Look at Scope and Limitations for Radioprotection.

    Science.gov (United States)

    Mitchel, Ron E J

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to "as low as reasonably achievable" (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations.

  12. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Joel

    2014-04-18

    activity) were examined after exposure of synchronized G1 cells to 137Cs c rays. DNA-PKcs mutant cells defective in phosphorylation at multiple sites withinthe T2609 cluster or within the PI3K domain displayed extreme radiosensitivity. Cells defective at the S2056 cluster or T2609 single site alone were only mildly radiosensitive, but cells defective at even one site in both the S2056 and T2609 clusters were maximally radiosensitive. Thus a synergism between the capacity for phosphorylation at the S2056 and T2609 clusterswas found to be critical for induction of radiosensitivity.

  13. Molecular targets for radioprotection by low dose radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hang Rhan; Lee, Yoon Jin; Cho, Chul Koo; Lee, Su Jae; Bae, Sang woo; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    Adaptive response is a reduced effect from a higher challenging dose of a stressor after a smaller inducing dose had been applied a few hrs earlier. Radiation induced fibrosarcoma (RIF) cells did not show such an adaptive response, i.e. a reduced effect from a higher challenging dose (2 Gy) of a radiation after a priming dose (1 cGy) had been applied 4 or 7 hrs earlier, but its thermoresistant clone (TR) did. Since inducible HSP70 and HSP25 expressions were different between these two cell lines, the role of inducible HSP70 and HSP25 in adaptive response was examined. When inducible hsp70 or hsp25 genes were transfected to RIF cells, radioresistance in clonogenic survival and reduction of apoptosis was detected. The adaptive response was also acquired in these two cell lines, and inducible hsp70 transfectant showed more pronounced adaptive response than hsp25 transfectant. From these results, inducible HSP70 and HSP25 are at least partly responsible for the induction of adaptive response in these cells. Moreover, when inducible HSP70 or HSP25 genes were transfected to RIF cells, coregulation of each gene was detected and heat shock factor (HSF) was found to be responsible for these phenomena. In continuation of our earlier study on the involvement of heat shock protein (HSP) 25 and HSP70 in the induction of adaptive response, we have now examined the involvement of these proteins in the induction of the adaptive response, using an animal model system. C57BL6 mice were irradiated with 5 cGy of gamma radiation 3 times for a week (total of 15cGy) and a high challenge dose (6Gy) was given on the day following the last low dose irradiation. Survival rate of the low dose pre-irradiated mice was increased to 30%. Moreover, high dose-mediated induction of apoptosis was also reduced by low dose pre-irradiation. To elucidate any link existing between HSP and induction of the adaptive response, reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis was performed

  14. Consequences of low dose ionizing radiation exposure on the hippocampal microenvironment.

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    Full Text Available The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy, few studies have been conducted at much lower doses (≤ 2 Gy, where the response of the CNS (like many other tissues may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.

  15. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Directory of Open Access Journals (Sweden)

    Yixin He

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI, a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  16. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

    Science.gov (United States)

    Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

    2016-04-01

    A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  17. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis.

    Science.gov (United States)

    Roberge, S; Nicolaides, K H; Demers, S; Villa, P; Bujold, E

    2013-05-01

    To compare early vs late administration of low-dose aspirin on the risk of perinatal death and adverse perinatal outcome. Databases were searched for keywords related to aspirin and pregnancy. Only randomized controlled trials that evaluated the prophylactic use of low-dose aspirin (50-150 mg/day) during pregnancy were included. The primary outcome combined fetal and neonatal death. Pooled relative risks (RR) with their 95% CIs were compared according to gestational age at initiation of low-dose aspirin (≤ 16 vs > 16 weeks of gestation). Out of 8377 citations, 42 studies (27 222 women) were included. Inclusion criteria were risk factors for pre-eclampsia, including: nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or endocrine disease, prior gestational hypertension or fetal growth restriction, and/or abnormal uterine artery Doppler. When compared with controls, low-dose aspirin started at ≤ 16 weeks' gestation compared with low-dose aspirin started at >16 weeks' gestation was associated with a greater reduction of perinatal death (RR = 0.41 (95% CI, 0.19-0.92) vs 0.93 (95% CI, 0.73-1.19), P = 0.02), pre-eclampsia (RR = 0.47 (95% CI, 0.36-0.62) vs 0.78 (95% CI, 0.61-0.99), P perinatal death and other adverse perinatal outcomes than when initiated at >16 weeks. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

  18. Uncommon toxicity of low-dose methotrexate: case report

    Directory of Open Access Journals (Sweden)

    Zohreh Yousefi

    2015-10-01

    Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m², intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose

  19. Low-dose lung cancer screening with photon-counting CT: a feasibility study

    Science.gov (United States)

    Symons, Rolf; Cork, Tyler E.; Sahbaee, Pooyan; Fuld, Matthew K.; Kappler, Steffen; Folio, Les R.; Bluemke, David A.; Pourmorteza, Amir

    2017-01-01

    To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema. The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P  cancer screening while maintaining diagnostic quality.

  20. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  1. Low dose aspirin therapy and renal function in elderly patients

    Directory of Open Access Journals (Sweden)

    Akinwusi PO

    2013-01-01

    Full Text Available Patience Olayinka Akinwusi,1,2 Rotimi Oluyombo,2 Paul Sunday Ogunro,3 Adetunji Oladeni Adeniji,4 Oluyomi Olusola Okunola,5 Olugbenga Edward Ayodele21Department of Medicine, Osun State University, Osogbo, Osun State, Nigeria; 2Department of Medicine, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3Department of Chemical Pathology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 4Department of Obstetrics and Gynecology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 5Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, NigeriaPurpose: To determine whether low dose aspirin has any deleterious effects on renal function in elderly patients.Methods: We conducted a prospective pilot study of 30 Nigerians older than 60 years with various chronic ailments necessitating the use of low dose aspirin. Patients gave their consent, and institutional ethical clearance was obtained. Each patient's baseline samples at enrolment (before commencing aspirin use served as a control, and subsequent weekly samples were compared. The weekly mean of each parameter was calculated, and the differences of means from baseline were determined, and values were compared for statistical differences with the Statistical Package for the Social Sciences, version 16.Results: We found that a majority of patients (86.67% had basal renal functions at chronic kidney disease stages 1 and 2. When compared with the corresponding baseline parameters, the mean weekly serum and urinary electrolytes, urea, creatinine, and uric acid parameters did not change, and the P-value did not show any statistical significance. However, there was positive statistical significance for the creatinine clearance (P = 0.025. Also, unlike in previous studies, anemia and hypoalbuminemia did not affect the renal function parameters.Conclusion: This study did not show any deleterious effects with short-term, low dose (75 mg daily aspirin use on kidney functions in

  2. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Zhi-Min [Harvard School of Public Health

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  3. [Gastrointestinal bleeding following ingestion of low-dose ibuprofen].

    Science.gov (United States)

    Vaquero Sosa, E; Bodas Pinedo, A; Maluenda Carrillo, C

    2013-01-01

    Ibuprofen is a non-steroidal anti-inflammatory drug frequently used in children for fever and pain. It is usually considered to be safe and of low risk at low doses and short-term use. The aim of our study was to review the cases of gastrointestinal bleeding and assessment of gastrointestinal bleeding after recommended doses of ibuprofen. We describe 9 previously healthy patients with upper gastrointestinal bleeding after receiving weight-related doses of ibuprofen for fever. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier España. All rights reserved.

  4. Mild Hypothermia in a Child with Low-Dose Risperidone.

    Science.gov (United States)

    Grau, Katharina; Plener, Paul L; Gahr, Maximilian; Denzer, Christian; Freudenmann, Roland W

    2017-07-01

    Risperidone is a widely used, second-generation antipsychotic approved for treating schizophrenia as well as for treating aggression in children and adolescents with mental retardation. The substance has a well-established risk profile including alterations of body temperature. Apart from hyperthermia with and without full-blown malignant neuroleptic syndrome, low body temperatures (hypothermia) have also been reported anecdotally, usually appearing in the context of comedication. Here, we report a case of hypothermia associated with a low-dose risperidone monotherapy in a child.

  5. Exposure to low dose ionising radiation: Molecular and clinical consequences.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

    This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

  6. Effect of low dose oral contraceptives on exercise performance.

    OpenAIRE

    Bryner, R W; Toffle, R C; Ullrich, I H; Yeater, R A

    1996-01-01

    OBJECTIVE--to examine the effect of cycle phase or a low dose oral contraceptive on exercise performance in young women. METHODS--As controls, 15 men were tested twice by a maximal treadmill test (Vo2 max) and by an endurance run 14 d apart to determine performance variability from causes other than hormonal fluctuations. Ten women ages 18-30 were then tested for Vo2 max and endurance in the same way in both the follicular and the luteal phase (random order, ovulation assessed by sonography)....

  7. Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

    Science.gov (United States)

    Xing, Xiao; Zhang, Chi; Shao, Minglong; Tong, Qingyue; Zhang, Guirong; Li, Cai; Cheng, Jie; Jin, Shunzi; Ma, Jisheng; Wang, Guanjun; Li, Xiaokun; Cai, Lu

    2012-01-01

    Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above. PMID:23227273

  8. Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Xiao Xing

    2012-01-01

    Full Text Available Repetitive exposure of diabetic mice to low-dose radiation (LDR at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

  9. Repeated head CT in the neurosurgical intensive care unit: feasibility of sinogram-affirmed iterative reconstruction-based ultra-low-dose CT for surveillance.

    Science.gov (United States)

    Corcuera-Solano, I; Doshi, A H; Noor, A; Tanenbaum, L N

    2014-07-01

    Patients in the neurosurgical intensive care unit undergo multiple head CT scans, resulting in high cumulative radiation exposures. Our aim was to assess the acceptability of a dedicated, special-purpose sinogram-affirmed iterative reconstruction-based ultra-low-dose CT protocol for neurosurgical intensive care unit surveillance head CT examinations, comparing image quality with studies performed with our standard-of-care sinogram-affirmed iterative reconstruction low-dose CT and legacy filtered back-projection standard-dose CT protocols. A retrospective analysis was performed of 54 head CT examinations: ultra-low-dose CT (n = 22), low-dose CT (n = 12), and standard-dose CT (n = 20) in 22 patients in the neurosurgical intensive care unit. Standard-dose CT was reconstructed by using filtered back-projection on a Somatom Sensation 64 scanner. Ultra-low-dose CT and ultra-low-dose CT examinations were performed on a Siemens AS+128 scanner with commercially available sinogram-affirmed iterative reconstruction. Qualitative and quantitative parameters, including image quality and dose, were evaluated. Sinogram-affirmed iterative reconstruction ultra-low-dose CT represented a 68% lower dose index volume compared with filtered back-projection standard-dose CT techniques in the same patients while maintaining similar quality and SNR levels. Sinogram-affirmed iterative reconstruction low-dose CT offered higher image quality than filtered back-projection standard-dose CT (P CT, ultra-low-dose CT had significantly lower SNR (P = .001) but demonstrated clinically satisfactory measures of image quality. In this cohort of patients in the neurosurgical intensive care unit, dedicated ultra-low-dose CT for surveillance head CT imaging led to a significant dose reduction while maintaining adequate image quality. © 2014 by American Journal of Neuroradiology.

  10. Low doses of neutrons induce changes in gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Chang-Liu, C.M. (Argonne National Lab., IL (United States)); Panozzo, J.; Libertin, C.R. (Loyola Univ., Maywood, IL (United States))

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following [gamma]-ray exposure in fibroblasts. Our past work had shown differences in the expression of [beta]-protein kinase C and c-fos genes, both being induced following [gamma]-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not [gamma]-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to [gamma] rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  11. Low doses of neutrons induce changes in gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Chang-Liu, C.M. [Argonne National Lab., IL (United States); Panozzo, J.; Libertin, C.R. [Loyola Univ., Maywood, IL (United States)

    1993-06-01

    Studies were designed to identify genes induced following low-dose neutron but not following {gamma}-ray exposure in fibroblasts. Our past work had shown differences in the expression of {beta}-protein kinase C and c-fos genes, both being induced following {gamma}-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not {gamma}-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to {gamma} rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  12. Low Dose Intermittent Isotretinoin Therapy in Moderate Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    Belçın İzol

    2012-03-01

    Full Text Available Objective: In this study, we aimed to investigate the efficiency and side effects of intermittent low dose isotretinoin therapy in moderate acne. Materials and Methods: Patients followed up at our acne outpatient clinic between September 2007 and April 2009 were evaluated. Those treated with 20 mg/day isotretinoin three times a week were included in the study. Relevant data were recorded from patient files. We recorded the age and weight of the cases, duration of acne, previous treatments, acne grading based on global acne scoring system, side effects and pretreatment and posttreatment Dermatology Life Quality Index scores. Hemogram, liver function tests, lipid profiles at baseline and monthly follow-ups were noted. Results: Global acne scoring of complete response rate in 94.3% of 35 patients was achieved after one year of therapy. The partial response rate was 5.7%. The earliest clinical response was observed after four weeks. The Dermatology Life Quality Index was 7.8 at baseline and 1.8 at the end of the treatment. Cheilitis was the only side effect observed. We observed mild degree relapses in 5 cases in the evaluation 17 months after the end of the treatment.Conclusion: Our results show that low dose intermittent isotretinoin therapy is an effective and tolerable treatment in moderate acne.

  13. Low-dose aripiprazole for refractory burning mouth syndrome

    Directory of Open Access Journals (Sweden)

    Umezaki Y

    2016-05-01

    Full Text Available Yojiro Umezaki,1 Miho Takenoshita,2 Akira Toyofuku2 1Psychosomatic Dentistry Clinic, Dental Hospital, 2Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Abstract: We report a case of refractory burning mouth syndrome (BMS ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. Keywords: burning mouth syndrome, low-dose aripiprazole, chronic pain

  14. Low-dose theophylline reduces symptoms of acute mountain sickness.

    Science.gov (United States)

    Küpper, Thomas E A H; Strohl, Kingman P; Hoefer, Markus; Gieseler, Ulf; Netzer, Cordula M; Netzer, Nikolaus C

    2008-01-01

    Headache, nausea, and sleeplessness at altitude [acute mountain sickness (AMS)] are major health problems for several million mountain recreationists who ascend to high altitudes each year. We aimed to test the efficacy of low-dose, slow-release theophylline for the prevention of AMS in a placebo-controlled, double-blind, randomized trial. Twenty healthy male volunteers (mean age 34.7 y) were randomized (random allocation) to receive either 300 mg theophylline daily or placebo 5 days prior, during ascent, and during a stay at 4,559 m altitude. AMS symptoms were collected using the Lake Louise Score on each day during ascent and at high altitude. A 12-channel sleep recorder recorded sleep and breathing parameters during the first night at 4,559 m. Theophylline serum levels were drawn prior to the sleep study. Seventeen completed the entire study. Theophylline (n = 9) compared to placebo (n = 8) significantly reduced AMS symptoms at 4,559 m (Lake Louise Score: 1.5 +/- 0.5 vs placebo 2.3 +/- 2.37; p adverse drug effects were reported. Low-dose, slow-release theophylline reduces symptoms of AMS in association with alleviation of events of periodic breathing and oxygen desaturations.

  15. Locoregional IL-2 low dose applications for gastrointestinal tumors

    Science.gov (United States)

    Krastev, Zachary; Koltchakov, V; Tomova, R; Deredjian, S; Alexiev, A; Popov, D; Tomov, B; Koten, Jan-Willem; Jacobs, John; Otter, Willem Den

    2005-01-01

    AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages III and IV of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses. RESULTS: No major problems applying locoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose locoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging. PMID:16222748

  16. Transfer of Low Dose Aspirin Into Human Milk.

    Science.gov (United States)

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

    2017-05-01

    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  17. Non linear processes modulated by low doses of radiation exposure

    Science.gov (United States)

    Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

    The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

  18. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris

    Science.gov (United States)

    Stark, Karolina; Scott, David E.; Tsyusko, Olga; Coughlin, Daniel P.; Hinton, Thomas G.

    2015-01-01

    Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae. PMID:25927361

  19. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris.

    Directory of Open Access Journals (Sweden)

    Karolina Stark

    Full Text Available Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later, to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

  20. Multiple vaccinations with UV- attenuated cercariae in pig enhance protective immunity against Schistosoma japonicum infection as compared to single vaccination.

    Science.gov (United States)

    Lin, Dandan; Tian, Fang; Wu, Haiwei; Gao, Yanan; Wu, Jingjiao; Zhang, Donghui; Ji, Minjun; McManus, Donald P; Driguez, Patrick; Wu, Guanling

    2011-06-10

    Schistosomiasis japonica is a major public health problem in the endemic areas of China, the Philippines, and Indonesia. To date, a vaccine has not been developed against this disease but immunization with UV-attenuated cercariae can induce a high level of protective immunity in Landrace/Yorkshire/Duroc crossbred pigs. To compare the efficacy of a single vaccination and multiple vaccinations with UV-attenuated Schistosoma japonicum cercariae, two groups of pigs received either one or three exposures to 10,000 cercariae attenuated with 400 μw UV. Pigs with a single immunization had a 59.33% reduction in adult worm burden, a 89.87% reduction in hepatic eggs and a 86.27% reduction in fecal eggs at eight weeks post-challenge (P vaccinated groups were higher than in the infection-control group. Triple vaccinations resulted in higher levels of antibodies, especially IgG2, compared with a single vaccination and IFN-γ levels increased with repeated immunization with UV-irradiated cercariae. The high levels of protection against S. japonicum infection can be achieved with a UV-attenuated vaccine in pigs, and that three vaccinations were possibly more effective than a single vaccination. Moreover, triple vaccinations evoked a more vigorous IFN-γ response and a stronger antibody-mediated response, especially an increase in the levels of IgG2 antibodies.

  1. Seismic‐wave attenuation determined from tectonic tremor in multiple subduction zones

    Science.gov (United States)

    Yabe, Suguru; Baltay, Annemarie S.; Ide, Satoshi; Beroza, Gregory C.

    2014-01-01

    Tectonic tremor provides a new source of observations that can be used to constrain the seismic attenuation parameter for ground‐motion prediction and hazard mapping. Traditionally, recorded earthquakes of magnitude ∼3–8 are used to develop ground‐motion prediction equations; however, typical earthquake records may be sparse in areas of high hazard. In this study, we constrain the distance decay of seismic waves using measurements of the amplitude decay of tectonic tremor, which is plentiful in some regions. Tectonic tremor occurs in the frequency band of interest for ground‐motion prediction (i.e., ∼2–8  Hz) and is located on the subducting plate interface, at the lower boundary of where future large earthquakes are expected. We empirically fit the distance decay of peak ground velocity from tremor to determine the attenuation parameter in four subduction zones: Nankai, Japan; Cascadia, United States–Canada; Jalisco, Mexico; and southern Chile. With the large amount of data available from tremor, we show that in the upper plate, the lower crust is less attenuating than the upper crust. We apply the same analysis to intraslab events in Nankai and show the possibility that waves traveling from deeper intraslab events experience more attenuation than those from the shallower tremor due to ray paths that pass through the subducting and highly attenuating oceanic crust. This suggests that high pore‐fluid pressure is present in the tremor source region. These differences imply that the attenuation parameter determined from intraslab earthquakes may underestimate ground motion for future large earthquakes on the plate interface.

  2. Ultra-low-dose computed tomographic angiography with model-based iterative reconstruction compared with standard-dose imaging after endovascular aneurysm repair: a prospective pilot study.

    Science.gov (United States)

    Naidu, Sailen G; Kriegshauser, J Scott; Paden, Robert G; He, Miao; Wu, Qing; Hara, Amy K

    2014-12-01

    An ultra-low-dose radiation protocol reconstructed with model-based iterative reconstruction was compared with our standard-dose protocol. This prospective study evaluated 20 men undergoing surveillance-enhanced computed tomography after endovascular aneurysm repair. All patients underwent standard-dose and ultra-low-dose venous phase imaging; images were compared after reconstruction with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction. Objective measures of aortic contrast attenuation and image noise were averaged. Images were subjectively assessed (1 = worst, 5 = best) for diagnostic confidence, image noise, and vessel sharpness. Aneurysm sac diameter and endoleak detection were compared. Quantitative image noise was 26% less with ultra-low-dose model-based iterative reconstruction than with standard-dose adaptive statistical iterative reconstruction and 58% less than with ultra-low-dose adaptive statistical iterative reconstruction. Average subjective noise scores were not different between ultra-low-dose model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction (3.8 vs. 4.0, P = .25). Subjective scores for diagnostic confidence were better with standard-dose adaptive statistical iterative reconstruction than with ultra-low-dose model-based iterative reconstruction (4.4 vs. 4.0, P = .002). Vessel sharpness was decreased with ultra-low-dose model-based iterative reconstruction compared with standard-dose adaptive statistical iterative reconstruction (3.3 vs. 4.1, P model-based iterative reconstruction and standard-dose adaptive statistical iterative reconstruction aneurysm sac diameters were not significantly different (4.9 vs. 4.9 cm); concordance for the presence of endoleak was 100% (P standard-dose technique, an ultra-low-dose model-based iterative reconstruction protocol provides comparable image quality and diagnostic assessment at a 73

  3. Optical fiber sensor for low dose gamma irradiation monitoring

    Science.gov (United States)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  4. Incidence of toxic optic neuropathy with low-dose ethambutol.

    Science.gov (United States)

    Yang, H K; Park, M J; Lee, J-H; Lee, C-T; Park, J S; Hwang, J-M

    2016-02-01

    To investigate the incidence of ethambutol (EMB) induced optic neuropathy prescribed at a relatively low dose of ≤ 15 mg/kg/day for the treatment of tuberculosis (TB) or Mycobacterium avium complex (MAC) lung disease. Patients diagnosed with TB or MAC lung disease received multidrug regimens including EMB at a single institution from August 2003 to July 2009. Visual monitoring was performed at baseline and at regular follow-up. The incidence of EMB-induced visual disturbances was evaluated. Of the 415 patients included in the study, three (0.7%) developed toxic optic neuropathy over the 6-year period. Of the 289 patients prescribed a dose of ≤ 15 mg/kg/day EMB, only one (0.3%) developed toxic optic neuropathy. The incidence of EMB-induced optic neuropathy among Koreans is estimated to be 0.7%, and can be reduced with lower doses of EMB.

  5. Low dose techniques and cryo-electron microscopy.

    Science.gov (United States)

    Fujiyoshi, Yoshinori

    2013-01-01

    Our understanding of subcellular structures has been greatly increased owing to electron microscopy, even though radiation damage of biological samples by the electron beam demanded staining techniques. Technological and instrumental advances of electron microscopy have, however, established various highly sophisticated techniques to study biological systems in their native states without staining and thus facilitated comprehension of rather intact structures of biological components. Among these techniques, electron crystallography is a well-established one to analyze membrane protein structures within lipid bilayers, without staining at close-to-physiological conditions. Structures of membrane proteins could be analyzed at resolutions better than 3Å by electron crystallography due to techniques of low dose and cryo-electron microscopy (cryo-EM). Here, recent cryo-EM technological and instrumental advances crucial to optimal data collection in electron crystallography are summarized as well as examples of structures of membrane proteins analyzed with the help of this method.

  6. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tracy Frech

    2011-01-01

    Full Text Available Pruritus is a common symptom in systemic sclerosis (SSc, an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT. Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN for pruritus, pain, and quality of life (QOL in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0 questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc.

  7. Ultra Low Dose CT Pulmonary Angiography with Iterative Reconstruction.

    Science.gov (United States)

    Sauter, Andreas; Koehler, Thomas; Fingerle, Alexander A; Brendel, Bernhard; Richter, Vivien; Rasper, Michael; Rummeny, Ernst J; Noël, Peter B; Münzel, Daniela

    2016-01-01

    Evaluation of a new iterative reconstruction algorithm (IMR) for detection/rule-out of pulmonary embolism (PE) in ultra-low dose computed tomography pulmonary angiography (CTPA). Lower dose CT data sets were simulated based on CTPA examinations of 16 patients with pulmonary embolism (PE) with dose levels (DL) of 50%, 25%, 12.5%, 6.3% or 3.1% of the original tube current setting. Original CT data sets and simulated low-dose data sets were reconstructed with three reconstruction algorithms: the standard reconstruction algorithm "filtered back projection" (FBP), the first generation iterative reconstruction algorithm iDose and the next generation iterative reconstruction algorithm "Iterative Model Reconstruction" (IMR). In total, 288 CTPA data sets (16 patients, 6 tube current levels, 3 different algorithms) were evaluated by two blinded radiologists regarding image quality, diagnostic confidence, detectability of PE and contrast-to-noise ratio (CNR). iDose and IMR showed better detectability of PE than FBP. With IMR, sensitivity for detection of PE was 100% down to a dose level of 12.5%. iDose and IMR showed superiority to FBP regarding all characteristics of subjective (diagnostic confidence in detection of PE, image quality, image noise, artefacts) and objective image quality. The minimum DL providing acceptable diagnostic performance was 12.5% (= 0.45 mSv) for IMR, 25% (= 0.89 mSv) for iDose and 100% (= 3.57 mSv) for FBP. CNR was significantly (p < 0.001) improved by IMR compared to FBP and iDose at all dose levels. By using IMR for detection of PE, dose reduction for CTPA of up to 75% is possible while maintaining full diagnostic confidence. This would result in a mean effective dose of approximately 0.9 mSv for CTPA.

  8. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    Science.gov (United States)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  9. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  10. Low dose radiation enhances the Locomotor activity of D. melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ki Moon; Lee, Buyng Sub; Nam Seon Young; Kim, Ji Young; Yang, Kwang Hee; Choi, Tae In; Kim, Cha Soon [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Gyeongju (Korea, Republic of)

    2013-04-15

    Mild stresses at low level including radiation can induce the beneficial effects in many vertebrate and invertebrate species. However, a large amount of studies in radiation biology have focused on the detrimental effects of high dose radiation (HDR) such as the increased incidence of cancers and developmental diseases. Low dose radiation (LDR) induces biologically favorable effects in diverse fields, for example, cancer development, genomic instability, immune response, and longevity. Our previous data indicated that LDR promotes cells proliferation of which degree is not much but significant, and microarray data explained that LDR irradiated fruit flies showing the augmented immunity significantly changed the program for gene expression of many genes in Gene Ontology (GO) categories related to metabolic process. Metabolic process in development one of major contributors in organism growth, interbreeding, motility, and aging. Therefore, it is valuable to examine whether LDR change the physiological parameters related to metabolism, and how LDR regulates the metabolism in D. melanogaster. In this study, to investigate that LDR influences change of the metabolism, a representative parameter, locomotor activity. In addition, the activation of several cellular signal molecules was determined to investigate the specific molecular mechanism of LDR effects on the metabolism. We explored whether ionizing radiation affects the motility activity. We performed the RING assays to evaluate the locomotor activity, a representative parameter presenting motility of fruit flies. HDR dramatically decreased the motor activity of irradiated flies. Surprisingly, the irradiated flies at low dose radiation in both acute and chronic showed the significantly increased locomotor activity, compared to non-irradiated flies. Irradiation would induce change of the several signal pathways for flies to respond to it. The activation of some proteins involved in the cells proliferation and stress

  11. Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.

    Science.gov (United States)

    Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

    2017-12-01

    Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential 'rapamycin metabolic signature.' These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.

  12. Low Doses of Celecoxib Attenuate Gut Barrier Failure During Experimental Peritonitis

    OpenAIRE

    Short, Scott S.; Wang, Jin; Castle, Shannon L.; Fernandez, G. Esteban; Smiley, Nancy; Zobel, Michael; Pontarelli, Elizabeth M.; Papillon, Stephanie C.; Grishin, Anatoly V.; Ford, Henri R

    2013-01-01

    The intestinal barrier becomes compromised during systemic inflammation, leading to entry of luminal bacteria into the host and gut origin sepsis. Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study we examined the role of cyclooxygenase-2 (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut barrier failure during experimental peritonitis in mice. I.p. injection of LPS or cecal ligation and puncture (CLP...

  13. Treatment with Fenofibrate plus a low dose of Benznidazole attenuates cardiac dysfunction in experimental Chagas disease

    Directory of Open Access Journals (Sweden)

    Ágata C. Cevey

    2017-12-01

    Full Text Available Trypanosoma cruzi induces serious cardiac alterations during the chronic infection. Intense inflammatory response observed from the beginning of infection, is critical for the control of parasite proliferation and evolution of Chagas disease. Peroxisome proliferator-activated receptors (PPAR-α, are known to modulate inflammation.In this study we investigated whether a PPAR-α agonist, Fenofibrate, improves cardiac function and inflammatory parameters in a murine model of T. cruzi infection. BALB/c mice were sequentially infected with two T. cruzi strains of different genetic background. Benznidazole, commonly used as trypanocidal drug, cleared parasites but did not preclude cardiac pathology, resembling what is found in human chronic chagasic cardiomyopathy. Fenofibrate treatment restored to normal values the ejection and shortening fractions, left ventricular end-diastolic, left ventricular end-systolic diameter, and isovolumic relaxation time. Moreover, it reduced cardiac inflammation and fibrosis, decreased the expression of pro-inflammatory (IL-6, TNF-α and NOS2 and heart remodeling mediators (MMP-9 and CTGF, and reduced serum creatine kinase activity. The fact that Fenofibrate partially inhibited NOS2 expression and NO release in the presence of a PPAR-α non-competitive inhibitor, suggested it also acted through PPAR-α-independent pathways. Since IκBα cytosolic degradation was inhibited by Fenofibrate, it can be concluded that the NFκB pathway has a role in its effects. Thus, we demonstrate that Fenofibrate acts through PPAR-α-dependent and -independent pathways.Our study shows that combined treatment with Fenofibrate plus Benznidazole is able both to reverse the cardiac dysfunction associated with the ongoing inflammatory response and fibrosis and to attain parasite clearance in an experimental model of Chagas disease. Keywords: Trypanosoma cruzi, Heart dysfunction, PPAR-α, Fenofibrate treatment, Inflammatory mediators

  14. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  15. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

    Science.gov (United States)

    Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

    2015-06-01

    Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

  16. Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

    Science.gov (United States)

    Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

    2015-07-08

    The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in

  17. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    Energy Technology Data Exchange (ETDEWEB)

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellular mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

  18. Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use.

    Science.gov (United States)

    Iijima, Katsunori; Shimosegawa, Tooru

    2015-01-01

    Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified.

  19. Low doses effects and gamma radiations low dose rates; Les effets des faibles doses et des faibles debits de doses de rayons gamma

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D. [Institut Curie, CNRS UMR 2027, 75 - Paris (France)

    1999-07-01

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  20. Low dose naltrexone for induction of remission in Crohn's disease.

    Science.gov (United States)

    Segal, Dan; Macdonald, John K; Chande, Nilesh

    2014-02-21

    Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Register was performed from inception to February 2013 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also reviewed. Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.2). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response

  1. Lymphatic fistulas: obliteration by low-dose radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, R.; Stranzl, H.; Prettenhofer, U.; Poschauko, J. [Dept. of Radiation Oncology, Medical Univ. of Graz (Austria); Sminia, P. [Dept. of Radiation Oncology, Section Radiobiology, VU Univ. Medical Center, Amsterdam (Netherlands); McBride, W.H. [Roy E. Coats Research Labs., Dept. of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Fruhwirth, J. [Dept. of Vascular Surgery, Dept. of Surgery, Medical Univ. of Graz (Austria)

    2005-10-01

    Background: lymphatic drainage from the surgical wound is an uncommon but challenging complication of surgical intervention. Protracted lymphorrhea contributes to morbidity, favors infections and results in a prolonged hospital stay. Treatment options include surgical ligation and, more conservatively, leg elevation, continuous local pressure, subatmospheric pressure dressings, and low-dose radiotherapy. This study examines the efficacy of low-dose radiotherapy. Patients and methods: 17 patients (19 fistulas) with lymphorrhea following vena saphena harvesting (n = 7), femoropopliteal bypass (n = 3), varicose vein surgery (n = 2), hip arthroplasty (n = 3; five fistulas), shunt surgery (n = 1), and piercing (n = 1) were referred for external radiotherapy. Depending on the depth of the fistula, orthovoltage (n = 12), electrons (4-11 MeV; n = 2) or photons (8 MV; n = 3) were used. Fractions between 0.3 Gy and 2 Gy were applied; the individual total dose depended on the success of the radiotherapy, i.e., the obliteration of the lymph fistula, and varied from 1 to 12 Gy. Results: In 13 out of 17 patients complete obliteration of the fistula was achieved. Interestingly, this was achieved in nine of the ten patients irradiated with total doses of {<=} 3 Gy and with fraction sizes ranging from 0.3 to 0.5 Gy. In one patient with hip arthroplasty, only two out of three fistulas disappeared after 12 Gy and in a further three cases no distinct benefit was observed after 2.4 Gy, 8 Gy, and 10.5 Gy, respectively. No treatment-related side effects occurred. Conclusion: radiotherapy represents an efficacious and economical treatment option in cases of persistent lymphorrhea and is able to reduce the risk of secondary infection, to decrease the duration of hospitalization, and to reduce overall costs for the individual patient. Daily scoring of treatment efficacy is recommended, because radiotherapy can be terminated as soon as lymphorrhea has stopped. Very low total doses with 0

  2. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    Science.gov (United States)

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  3. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    Science.gov (United States)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  4. Low dose radiation damage effects in silicon strip detectors

    Science.gov (United States)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  5. Low dose 320-row CT for left atrium and pulmonary veins imaging--the feasibility study.

    Science.gov (United States)

    Yang, Lin; Xu, Lei; Yan, Zixu; Yu, Wei; Fan, Zhanming; Lv, Biao; Zhang, Zhaoqi

    2012-07-01

    To evaluate the feasibility of low dose target-CTA volume scan for left atrium and pulmonary veins imaging using 320-row CT. Forty-two patients (females 12, males 30; mean age 55.2 years; mean body mass index (BMI) 25.7 kg/m(2)) with persistent or intermittent atrial fibrillation before catheter ablation were enrolled in this study. Scan protocol was target-CTA volume scan under prospective ECG-gating. The target of the exposure was only set at 40% of the R-R interval (which was at the left atrium maximal volume). The exposure time was minimal setting (350 ms). Tube voltage 100 kV (BMI ≤ 25 kg/m(2)) or 120 kV (BMI>25 kg/m(2)), tube current 350-420 mA, and field of view of 180 mm × 180 mm-200 mm × 200 mm were used. The scanning range was from the level of the tracheal bifurcation to the diaphragm, and enabled to cover the left atrium and central pulmonary veins (120-140 mm). All of patients were divided into two groups according kV setting (100 kV and 120 kV). The image quality (good, moderate and poor) was evaluated by two reviewers. The CT-attenuation, image noise and contrast to noise ratio (CNR) of left atrium and every pulmonary vein branch were evaluated, respectively. The effective dose (ED) was calculated using a conversion coefficient for the chest 0.017. Of 42 patients, the image quality was good in 26 cases (62%) and moderate in 16 cases (38%). There was no statistical difference in the CT-attenuation and CNR of left atrium and central pulmonary veins between the two groups (P>0.05). The mean ED was 1.90 ± 0.19 mSv (range 1.57-2.25 mSv) in 100 kV group, and 3.83 ± 0.31 mSv (range 3.39-4.54 mSv) in 120 kV group. The low dose target-CTA volume scan is feasible in pulmonary veins and left atrium imaging using 320-row CT. Slim patients can be scanned at 100 kV setting without loss of image quality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: low doses induce hypolocomotion.

    Science.gov (United States)

    Singh, Rana A K; Kosten, Therese A; Kinsey, Berma M; Shen, Xiaoyun; Lopez, Angel Y; Kosten, Thomas R; Orson, Frank M

    2012-12-01

    The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3-10mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses. Published by Elsevier Inc.

  7. Low-dose CT reconstruction using spatially encoded nonlocal penalty.

    Science.gov (United States)

    Kim, Kyungsang; El Fakhri, Georges; Li, Quanzheng

    2017-10-01

    Computed tomography (CT) is one of the most used imaging modalities for imaging both symptomatic and asymptomatic patients. However, because of the high demand for lower radiation dose during CT scans, the reconstructed image can suffer from noise and artifacts due to the trade-off between the image quality and the radiation dose. The purpose of this paper is to improve the image quality of quarter dose images and to select the best hyperparameters using the regular dose image as ground truth. We first generated the axially stacked two-dimensional sinograms from the multislice raw projections with flying focal spots using a single slice rebinning method, which is an axially approximate method to provide simple implementation and efficient memory usage. To improve the image quality, a cost function containing the Poisson log-likelihood and spatially encoded nonlocal penalty is proposed. Specifically, an ordered subsets separable quadratic surrogates (OS-SQS) method for the log-likelihood is exploited and the patch-based similarity constraint with a spatially variant factor is developed to reduce the noise significantly while preserving features. Furthermore, we applied the Nesterov's momentum method for acceleration and the diminishing number of subsets strategy for noise consistency. Fast nonlocal weight calculation is also utilized to reduce the computational cost. Datasets given by the Low Dose CT Grand Challenge were used for the validation, exploiting the training datasets with the regular and quarter dose data. The most important step in this paper was to fine-tune the hyperparameters to provide the best image for diagnosis. Using the regular dose filtered back-projection (FBP) image as ground truth, we could carefully select the hyperparameters by conducting a bias and standard deviation study, and we obtained the best images in a fixed number of iterations. We demonstrated that the proposed method with well selected hyperparameters improved the image quality

  8. Low dose Mifepristone (100 mg for medical termination of pregnancy

    Directory of Open Access Journals (Sweden)

    Shikha Seth

    2011-02-01

    Full Text Available Background: Abortion is the most common entity in the practice of obstetrics and gynaecology. Different methods and modes have been opted for until now to find an effective regimen with the least complications. We have tried the minimal dose (100 mg of Mifepristone (PO instead of the presently recommended 200 mg for medical abortion in early first trimester cases. Objectives: The objective of the study was to determine the efficacy of low dose (100 mg Mifepristone for medical termination of early pregnancy with oral Misoprostol 800 μg, 24 hours later.Design: A prospective analytical study was conducted on a population of 82 early-pregnant patients who have requested medical abortions.Method: Pregnant women of less than 56 days gestation age from their last menstrual period, requesting medical abortion were selected over a period of 14 months from January 2007 to March 2008. They were given 100 mg Mifepristone orally on Day-1, followed by 800 μg Misoprostol orally 24 hours later on Day-2, keeping the patient in the ward for at least 6 hours. Abortion interval, success rate, post-abortion bleeding and side-effects were noted. Success was defined as complete uterine evacuation without the need for surgical intervention.Results: The total success rate of this minimal dose Mifepristone regimen was 96.25%. Pain and nausea were the predominant side-effects noted. In total 72 (90% women had completely aborted within 5 hours of taking Misoprostol. Three (3.75% women only required suction aspiration, hence termed as failed medical abortion. The abortion interval increased with the gestation age. All three failures were of the more-than-42-day gestational age group. The overall mean abortion interval was 4.68 ± 5.32 hours.Conclusion: Mifepristone 100 mg, followed 24 hours later by Misoprostol 800 μg orally, is a safe and effective regimen for medical abortion.

  9. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Science.gov (United States)

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L -1 . In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO 3 ) 2 up to 20 mg L -1 . The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L -1 significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L -1 and presence of micronuclei (MN) were detected for 20 mg L -1 . Also, cell cycle impairment was observed for doses as low as 0.05 mg L -1 and 0.5 mg L -1 (mostly G 2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Low dose CT perfusion in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Amanda; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I. [Sunnybrook Health Sciences Centre, Toronto, ON (Canada); So, Aaron; Lee, Ting-Yim [Robarts Research Institute, London, Ontario (Canada)

    2014-12-15

    The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54 % male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements. (orig.)

  11. Evidence for estrogeno-mimetic effects of a mixture of low-dose pollutants in a model of ovariectomized mice.

    Science.gov (United States)

    Julien, Benoit; Pinteur, Claudie; Vega, Nathalie; Labaronne, Emmanuel; Vidal, Hubert; Naville, Danielle; Le Magueresse-Battistoni, Brigitte

    2018-01-01

    We recently hypothesized that a mixture of low-dosed dioxin, polychlorobiphenyl, phthalate and bisphenol may induce estrogeno-mimetic activities in a model of lifelong-exposed female mice. Herein, we evaluated the impact of this mixture in estrogen deficiency conditions. Based on the protective effects of estrogens against metabolic disorders, we reasoned that exposure to pollutants should attenuate the deleterious metabolic effects induced by ovariectomy. In line with the hypothesis, exposure to pollutants was found to reduce the impact of ovariectomy on glucose intolerance and insulin resistance, to enhance the expression levels of the hepatic estrogen receptor α and to attenuate the ovariectomy-induced enhancement of the chemokine MCP-1/CCL2 considered as an indicator of estrogen signalling. Because of the very low doses of pollutants used in mixture, these findings may have strong implications in terms of understanding the potential role of environmental contaminants in the development of metabolic diseases, specifically in females during menopausal transition. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Low-Dose Formaldehyde Delays DNA Damage Recognition and DNA Excision Repair in Human Cells

    Science.gov (United States)

    Luch, Andreas; Frey, Flurina C. Clement; Meier, Regula; Fei, Jia; Naegeli, Hanspeter

    2014-01-01

    Objective Formaldehyde is still widely employed as a universal crosslinking agent, preservative and disinfectant, despite its proven carcinogenicity in occupationally exposed workers. Therefore, it is of paramount importance to understand the possible impact of low-dose formaldehyde exposures in the general population. Due to the concomitant occurrence of multiple indoor and outdoor toxicants, we tested how formaldehyde, at micromolar concentrations, interferes with general DNA damage recognition and excision processes that remove some of the most frequently inflicted DNA lesions. Methodology/Principal Findings The overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA-binding) and XPC (xeroderma pigmentosum group C) was analyzed by assessing real-time protein dynamics in the nucleus of cultured human cells exposed to non-cytotoxic (formaldehyde concentrations. The DNA lesion-specific recruitment of these damage sensors was tested by monitoring their accumulation at local irradiation spots. DNA repair activity was determined in host-cell reactivation assays and, more directly, by measuring the excision of DNA lesions from chromosomes. Taken together, these assays demonstrated that formaldehyde obstructs the rapid nuclear trafficking of DNA damage sensors and, consequently, slows down their relocation to DNA damage sites thus delaying the excision repair of target lesions. A concentration-dependent effect relationship established a threshold concentration of as low as 25 micromolar for the inhibition of DNA excision repair. Conclusions/Significance A main implication of the retarded repair activity is that low-dose formaldehyde may exert an adjuvant role in carcinogenesis by impeding the excision of multiple mutagenic base lesions. In view of this generally disruptive effect on DNA repair, we propose that formaldehyde exposures in the general population should be further decreased to help reducing cancer risks. PMID:24722772

  13. Estimating the Total Ultrasound Attenuation Along the Propagation Path by Applying Multiple Filters to Backscattered Echoes From a Single Spherically Focused Source

    OpenAIRE

    Bigelow, Timothy A.

    2010-01-01

    Quantifying the correlation length of the tissue microstructure has shown potential for differentiating between benign and malignant tumors. To implement these advances in the clinic, the total frequency-dependent attenuation along the propagation path must be determined on a patient specific basis. Previously, an algorithm was developed to estimate this attenuation using echoes from multiple sources. In this study, the developed algorithm was extended to echoes from a single source by filter...

  14. Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat.

    Science.gov (United States)

    Polomano, Rosemary C; Buckenmaier, Chester C; Kwon, Kyung H; Hanlon, Alexandra L; Rupprecht, Christine; Goldberg, Cynthia; Gallagher, Rollin M

    2013-07-01

    Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. Walter Reed Army Medical Center, Washington, DC. Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. A 3-day IV infusion of ketamine at doses ≤ 120 μg/kg/h. Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. A significant reduction in PPI (P injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP. Wiley Periodicals, Inc.

  15. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Science.gov (United States)

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Effect of iterative reconstruction on image quality of low-dose chest computed tomography.

    Science.gov (United States)

    Pavarani, Antonio; Martini, Chiara; Gafa', Veronica; Bini, Paola; Silva, Mario; Ghetti, Caterina; Sverzellati, Nicola

    2016-09-13

    To assess quality and radiologists' preference of low-dose computed tomography (LDCT) reconstructed with filtered back projection (FBP) or Iterative Reconstruction. Thin-section LDCTs (1-mm thick contiguous images; 120 kVp; 30 mAs) of 38 consecutive unselected patients, evaluated for various clinical indications, were reconstructed by four different reconstruction algorithms: FBP and Sinogram-AFfirmed Iterative Reconstruction (SAFIRE) with three different strengths, from 2 to 4 (i.e. S2, S3, S4). The image noise was recorded. Two thoracic radiologists visually compared both anatomic structures (interlobular septa, lung fissures, centrilobular artery, bronchial wall, and small vessels) and lung abnormalities (intralobular reticular opacities, nodules, emphysema, cystic lung disease, decreased-attenuation areas related to constrictive obliterans bronchiolitis, patchy ground-glass opacity, consolidation, and bronchiectasis) using a qualitative four-point scale grading system of the image quality. A lower amount of noise was recorded for LDCTs reformatted with any SAFIRE algorithm, as compared to FBP (P Iterative reconstructions showed lower image noise but did not provide any real improvement for the radiologists' evaluation of thin-section LDCT of the lung.

  17. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro.

    Science.gov (United States)

    Scherzad, Agmal; Hackenberg, Stephan; Froelich, Katrin; Rak, Kristen; Hagen, Rudolf; Taeger, Johannes; Bregenzer, Maximillian; Kleinsasser, Norbert

    2016-03-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems.

  18. Second International MELODI Workshop on Low Dose Risk Research - Slides of the presentations

    Energy Technology Data Exchange (ETDEWEB)

    Repussard, J.; Weiss, W.; Quintana Trias, O.; Rosario Perez, M. del; Andersen, M.; Rudiger Trott, K.; Ottolenghi, A.; Smyth, V.; Graw, J.; Little, M.P.; Yonai, S.; Barcellos-Hoff, M.H.; Bouffler, S.; Chevillard, S.; Jeggo, P.; Sabatier, L.; Baatout, S.; Niwa, O.; Oesch, F.; Atkinson, M.; Averbeck, D.; Lloyd, D.; O' Neill, P.

    2011-07-01

    The MELODI (Multidisciplinary European Low Dose Initiative) mission is to impulse low dose risk research in Europe through a strategic research agenda (SRA) and road-map of priorities. The last presentation is dedicated to the SRA and its preference research programs. The other presentations deal principally with the low-dose exposure in medical uses of ionizing radiations, radiosensitivity, radiation-induced cataracts, or epidemiology and radiobiology of cardiovascular disease. This document is composed of the slides of the presentations

  19. Low-dose CT perfusion with projection view sharing.

    Science.gov (United States)

    Martin, Thomas; Hoffman, John; Alger, Jeff R; McNitt-Gray, Michael; Wang, Danny Jj

    2018-01-01

    CT Perfusion (CTP) is a widely used clinical imaging modality. However, CTP typically involves the use of substantial radiation dose (CTDIvol ≥~200 mGy). The purpose of this study is to present a low-dose CTP technique using a projection view-sharing reconstruction algorithm originally developed for dynamic MRI - "K-space Weighted Image Contrast" (KWIC). The KWIC reconstruction is based on an angle-bisection scheme. In KWIC, a Fourier transform was performed along each projection to form a "k-space"-like CT data space, based on the central-slice theorem. As a projection view-sharing technique, KWIC preserves the spatiotemporal resolution of undersampled CTP data by progressively increasing the number of projection views shared for more distant regions of "k-space". KWIC reconstruction was evaluated on a digital FORBILD head phantom with numerically simulated time-varying objects. The numerically simulated scans were undersampled using the angle-bisection scheme to achieve 50%, 25%, and 12.5% of the original dose (288, 144, and 72 projections, respectively). The area-under-the-curve (AUC), time-to-peak (TTP), and full width half maximum (FWHM) were measured in KWIC recons and compared to fully sampled filtered back projection (FBP) reconstructions. KWIC reconstruction and dose reduction was also implemented for three clinical CTP cases (45 s, 1156 projections per turn, 1 s/turn, CTDIvol 217 mGy). Quantitative perfusion metrics were computed and compared between KWIC reconstructed CTP data and those of standard FBP reconstruction. The AUC, TTP, and FWHM in the numerical simzulations were unaffected by the undersampling/dose reduction (down to 12.5% dose) with KWIC reconstruction compared to the fully sampled FBP reconstruction. The normalized root-mean-square-error (NRMSE) of the AUC in the FORBILD head phantom is 0.04, 0.05, and 0.07 for 50%, 25%, and 12.5% KWIC, respectively, as compared to FBP reconstruction. The cerebral blood flow (CBF) and cerebral blood

  20. Romifidine and low doses of tiletamine-zolazepam in dogs.

    Science.gov (United States)

    Gómez-Villamandos, Rafael J; Martínez, Carmen; Navarrete, Rocío; Morgaz, Juan; Domínguez, Juan M; López, Ignacio; Muñoz, Pilar; Fernández, Andrés; Granados, María M

    2013-11-01

    To evaluate clinical effects of romifidine and low doses of tiletamine-zolazepam (TZ) in dogs. Randomized "blinded" cross-over study. Six healthy beagle dogs (two males, four females). In separate preliminary experiments dogs received intravenous (IV) tiletamine-zolazepam (TZ) at 1 and 2 mg kg(-1). For the main trial, dogs received romifidine (R) followed 5 minutes later by IV at six dose regimens: R40TZ1, R60TZ1, R80TZ1 (Romifidine at 40, 60, 80 μg kg(-1) and TZ at 1 mg kg(-1)), R40TZ2, R60TZ2 and R80TZ2 (Romifidine at 40, 60, 80 μg kg(-1) and TZ at 2 mg kg(-1)). Dogs underwent endotracheal intubation, but breathed room air. Cardiorespiratory variables were measured and arterial blood analyzed. Quality of sedation, duration of anaesthesia and time to recovery (TR) were recorded. Data were analysed by anova or Friedman test as relevant. Endotracheal intubation was possible with all romifidine/TZ combinations but not with TZ alone. Mean times (minutes) from TZ injection to return of pedal reflex were 1-3 minutes for TZ alone, and 9-17 minutes for romifidine combinations. In the main trial (romifidine combinations) mean time (minutes) to standing increased with increasing dosage (R40TZ1 13; R80TZ2 32). Five minutes after TZ administration, when compared with baseline arterial blood pressures and arterial carbon dioxide had increased, and respiratory rate, pH and arterial oxygen tensions decreased, these changes becoming statistically significant with the higher dose rates. One dog in R60TZ2 and three dogs in R80TZ2 became hypoxaemic. Romifidine improves the quality and lengthens the duration of anaesthesia induced by TZ. The combination provides a suitable protocol for induction of or short-term anaesthesia in healthy dogs. However, the higher doses cause cardiovascular stimulation and respiratory depression, and precautions should be taken accordingly. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  1. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Deborah Ferguson

    Full Text Available Vaccination of Mauritian cynomolgus macaques with the attenuated nef-truncated C8 variant of SIVmac251/32H (SIVmacC8 induces early, potent protection against pathogenic, heterologous challenge before the maturation of cognate immunity. To identify processes that contribute to early protection in this model the pathogenesis, anatomical distribution and viral vaccine kinetics were determined in relation to localised innate responses triggered by vaccination. The early biodistribution of SIVmacC8 was defined by rapid, widespread dissemination amongst multiple lymphoid tissues, detectable after 3 days. Cell-associated viral RNA dynamics identified mesenteric lymph nodes (MLN and spleen, as well as the gut mucosae, as early major contributors of systemic virus burden. Rapid, localised infection was populated by discrete foci of persisting virus-infected cells. Localised productive infection triggered a broad innate response, with type-1 interferon sensitive IRF-7, STAT-1, TRIM5α and ApoBEC3G genes all upregulated during the acute phase but induction did not prevent viral persistence. Profound changes in vaccine-induced cell-surface markers of immune activation were detected on macrophages, B-cells and dendritic cells (DC-SIGN, S-100, CD40, CD11c, CD123 and CD86. Notably, high DC-SIGN and S100 staining for follicular and interdigitating DCs respectively, in MLN and spleen were detected by 3 days, persisting 20 weeks post-vaccination. Although not formally evaluated, the early biodistribution of SIVmacC8 simultaneously targets multiple lymphoid tissues to induce strong innate immune responses coincident at the same sites critical for early protection from wild-type viruses. HIV vaccines which stimulate appropriate innate, as well as adaptive responses, akin to those generated by live attenuated SIV vaccines, may prove the most efficacious.

  2. Dosimetric effect by the low-dose threshold levels in gamma analysis on VMAT QA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ji Hye; Kim, Min Joo; Park, So Hyun; Lee, Seu Ran; Lee, Min Young; Suh, Tae Suk [Dept. of Biomedical Engineering and Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Dong Soo [Dept. of Radiation Oncology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea, Republic of)

    2015-10-15

    Based on a survey by Nelms and Simon, more than 70% of institutions use a low-dose threshold between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the low-dose threshold on the gamma index. Therefore, we performed a gamma analysis with low-dose thresholds of 0%, 5%, 10%, and 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm, and 1%/1 mm. Applying low-dose threshold in the global normalization does not have critical effect to judge patient-specific QA results.

  3. Estimating the total ultrasound attenuation along the propagation path by applying multiple filters to backscattered echoes from a single spherically focused source.

    Science.gov (United States)

    Bigelow, Timothy

    2010-04-01

    Quantifying the correlation length of the tissue microstructure has shown potential for differentiating between benign and malignant tumors. To implement these advances in the clinic, the total frequency-dependent attenuation along the propagation path must be determined on a patient specific basis. Previously, an algorithm was developed to estimate this attenuation using echoes from multiple sources. In this study, the developed algorithm was extended to echoes from a single source by filtering the echoed signal into multiple frequency bands. This step was needed because it would be challenging to scan exactly the same tissue region using multiple sources in the clinic. Computer simulations and phantom experiments were conducted to verify the attenuation could be determined by filtering the echoes from a single source. The simulations utilized a spherically focused single-element source (5 cm focal length, f/4, 14 MHz center frequency, 50% bandwidth) exposing a homogeneous tissue region (Gaussian scattering structures with effective radii of 5 to 55 mum at a density of 250/mm(3), attenuation of 0.1 to 0.9 dB/cm.MHz). The phantom experiments utilized a spherically focused single-element source (5.08 cm focal length, f/4, 7.5 MHz center frequency) exposing a 0.5 dB/cm.MHz homogeneous glass bead phantom. The computer simulations and phantom experiment confirmed that the total attenuation along the propagation path can be determined by appropriately applying multiple filters to the backscattered echoes from a single source.

  4. Mitigating the Effects of Fog Attenuation in FSO Communication Link Using Multiple Transceivers and EDFA

    Science.gov (United States)

    Singh, Mehtab

    2017-05-01

    Free Space Optics (FSO) technique is an advanced form of the wireless communication system capable of transmitting data at higher transmission rates with higher channel bandwidth and over longer link distances. One of the major challenges faced by FSO technology is the distortion of received signal due to atmospheric effects which degrade the performance of the communication link by increasing the bit error rate (BER). By implementing Erbium Doped Fiber Amplifier (EDFA) in the FSO link, the degradation of the information signal due to atmospheric effects can be minimized. Also, by deploying spatial diversity technique in the FSO link, where multiple copies of the information signal are transmitted to increase the redundancy of the system, the system performance can be enhanced. In this paper, the performance of an FSO communication link has been analyzed under fog weather condition using a different number of Tx/Rx pairs and EDFA amplifier using OPTISYSTEM simulation software. Performance has been analyzed on the basis of Q Factor, SNR, BER, and total power of the received signal. Results show a significant improvement in the system performance by deploying multiple transceiver techniques.

  5. Comparison of biophysical factors influencing on emphysema quantification with low-dose CT

    Science.gov (United States)

    Heo, Chang Yong; Kim, Jong Hyo

    2014-03-01

    Emphysema Index(EI) measurements in MDCT is known to be influenced by various biophysical factors such as total lung volume, and body size. We investigated the association of the four biophysical factors with emphysema index in low-dose MDCT. In particular, we attempted to identify a potentially stronger biophysical factor than total lung volume. A total of 400 low-dose MDCT volumes taken at 120kVp, 40mAs, 1mm thickness, and B30f reconstruction kernel were used. The lungs, airways, and pulmonary vessels were automatically segmented, and two Emphysema Indices, relative area below -950HU(RA950) and 15th percentile(Perc15), were extracted from the segmented lungs. The biophysical factors such as total lung volume(TLV), mode of lung attenuation(ModLA), effective body diameter(EBD), and the water equivalent body diameter(WBD) were estimated from the segmented lung and body area. The association of biophysical factors with emphysema indices were evaluated by correlation coefficients. The mean emphysema indices were 8.3±5.5(%) in RA950, and -930±18(HU) in Perc15. The estimates of biophysical factors were 4.7±1.0(L) in TLV, -901±21(HU) in ModLA, 26.9±2.2(cm) in EBD, and 25.9±2.6(cm) in WBD. The correlation coefficients of biophysical factors with RA950 were 0.73 in TLV, 0.94 in ModLA, 0.31 in EBD, and 0.18 WBD, the ones with Perc15 were 0.74 in TLV, 0.98 in ModLA, 0.29 in EBD, and 0.15 WBD. Study results revealed that two biophysical factors, TLV and ModLA, mostly affects the emphysema indices. In particular, the ModLA exhibited strongest correlation of 0.98 with Perc15, which indicating the ModLA is the most significant confounding biophysical factor in emphysema indices measurement.

  6. Enteric coating can lead to reduced antiplatelet effect of low-dose acetylsalicylic acid

    DEFF Research Database (Denmark)

    Fentz Haastrup, Peter; Grønlykke, Thor; Jarbøl, Dorte Ejg

    2015-01-01

    Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric coated ASA has been developed in order to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically be....... Therefore, low dose enteric coated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis....

  7. Low doses of glyphosate change the response of soybean to later glyphosate exposures

    Science.gov (United States)

    The stimulatory effect of low doses of toxic substances is known as hormesis. Many herbicides that cause severe injury to plants at recommended rates, promote growth or have other stimulatory effects at very low doses. The objective of this study was to evaluate glyphosate-induced hormesis in soyb...

  8. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  9. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  10. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  11. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

    Science.gov (United States)

    Goodson, William H.; Lowe, Leroy; Carpenter, David O.; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K.; Collins, Andrew R.; Ward, Andrew; Salzberg, Anna C.; Colacci, Anna Maria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J.; Zhou, Binhua P.; Blanco-Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clement; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L.; Van Schooten, Frederik J.; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme P.; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, A.Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph A.; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen-Solal, Karine A.; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D’Abronzo, Leandro S.; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J.; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; Gonzalez Guzman, Michael J.; Karamouzis, Michalis V.; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P.K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky-Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Leung, Po Sing; Nangia-Makker, Pratima; Cheng, Qiang (Shawn); Robey, R.Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K.; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Hamid, Roslida A.; Langie, Sabine A.S.; Eltom, Sakina E.; Brooks, Samira A.; Ryeom, Sandra; Wise, Sandra S.; Bay, Sarah N.; Harris, Shelley A.; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C.; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W.Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-01-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. PMID:26106142

  12. Effectiveness of low-dose midazolam plus ketamine in the ...

    African Journals Online (AJOL)

    2012-11-01

    Nov 1, 2012 ... 2013;19(3). South Afr J Anaesth Analg. Introduction. Regional anaesthesia may impair thermoregulatory control.1 .... influences thermoregulation, a history of multiple-drug allergies, patients with an initial body ..... such as a cold ambient operation theatre temperature.21 The decrease in core temperature in ...

  13. Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Elisa K. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Fung, Sharon [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Pintile, Melania [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2011-12-01

    Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

  14. Low-dose high-pitch CT angiography of the supraaortic arteries using sinogram-affirmed iterative reconstruction.

    Directory of Open Access Journals (Sweden)

    Dietrich Beitzke

    Full Text Available OBJECTIVE: To prospectively evaluate image quality and radiation dose using a low-dose computed tomography angiography protocol and iterative image reconstruction for high-pitch dual-source CT-angiography (DSCTA of the supraaortic arteries. MATERIAL AND METHODS: DSCTA was performed in 42 patients, using either 120 kVp tube voltage, 120 mAS tube current, 2.4 pitch and filtered back projection, or 100 kVp tube voltage, 100 mAs tube current, 3.2 pitch, and sinogram affirmed iterative reconstruction. Measurements of vessel attenuation, of the contrast-to-noise ratio (CNR and the signal-to-noise ratio (SNR were performed to objectively evaluate image quality. Two readers evaluated subjective image quality and image noise, using a four-point scale. Effective dose was used to compare the differences in radiation dose. RESULTS: Low-dose protocol application showed significantly higher vessel opacification (p = 0.013, and non-significantly higher CNR and SNR values. There was no difference in the subjective image quality and image noise reading between the protocols. Effective dose was significantly lower using the low-dose protocol (1.29 ± 0.21 mSv vs. 2.92 ± 0.72 mSv; p < 0.001. CONCLUSION: The combined use of reduced tube voltage, reduced tube current, and iterative reconstruction reduces radiation dose by 55.4% in high-pitch DSCTA of the supraaortic arteries without impairment of image quality.

  15. Korean Society of Thoracic Radiology Guideline for Lung Cancer Screening with Low-Dose CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Ju [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Jin Hwan [Dept. of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Kim, Yoon Kyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of); Park, Chang Min [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Jeong, Yeon Joo [Dept. of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan (Korea, Republic of)

    2012-09-15

    The National Lung Screening Trial (NLST), a nation-wide randomized controlled trial involving more than 50,000 current and former heavy smokers ages 55 to 74, compared the effects of two screening procedures (low-dose helical CT and standard chest radiography) on lung cancer mortality and found 20 percent fewer lung cancer deaths among trial participants screened with low-dose CT. Korean Society of Thoracic Radiology (KSTR) planned to establish an effective guideline for lung cancer screening with low-dose CT to improve health of Korean people and to reduce harms from misuse of lung cancer screening with low-dose CT. KSTR guideline for lung cancer screening with low-dose CT established based on objective medical evidences obtained by NLST.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. A Challenge to Scientific Risk Estimation on Health Effects of Low Dose Radiation - An Overview

    Directory of Open Access Journals (Sweden)

    Tetsuya Ono

    2007-03-01

    Full Text Available Although experimental as well as epidemiological studies have revealed the health effects of ionizing radiation, most of our knowledge is for high doses of radiation, while little is known for low doses. For practical purposes, we estimate the risk of low dose radiation by extrapolating the effects at high doses to low doses in a linear relationship. However, several lines of evidence have accumulated in recent years that suggest this linear extrapolation is not necessarily correct and needs further scientific evaluation. Today, many scientists in the field are striving to understand the biological responses to low dose radiation. This work will provide new and perhaps convincing data which are necessary for risk estimation of low dose radiation. Here, I overview the background of the issue.

  18. Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

    Energy Technology Data Exchange (ETDEWEB)

    David G. Hoel, PhD

    2012-04-19

    The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival function and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact

  19. CMV infection attenuates the disease course in a murine model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Istvan Pirko

    Full Text Available Recent evidence in multiple sclerosis (MS suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV infection affects the course of the Theiler's murine encephalitis virus (TMEV induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1 monthly monitoring of disability via rotarod for 8 months; (2 in vivo MRI for brain atrophy studies and (3 FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024. In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19. A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026, while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003. There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17 while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies.

  20. Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

    Science.gov (United States)

    Szucs-Farkas, Zsolt; Megyeri, Boglarka; Christe, Andreas; Vock, Peter; Heverhagen, Johannes T; Schindera, Sebastian T

    2014-08-01

    To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. • 80 kVp CTPA is safe in patients weighing Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

  1. Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights

    Energy Technology Data Exchange (ETDEWEB)

    Szucs-Farkas, Zsolt [University Hospital Bern, University Institute of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Berne (Switzerland); Hospital Centre of Biel, Institute of Radiology, Biel/Bienne (Switzerland); Megyeri, Boglarka [University of Debrecen, Health and Medical Science Centre, Department of Anaesthesiology and Intensive Care, Debrecen (Hungary); Christe, Andreas; Vock, Peter; Heverhagen, Johannes T. [University Hospital Bern, University Institute of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Berne (Switzerland); Schindera, Sebastian T. [University Hospital Bern, University Institute of Diagnostic, Interventional and Paediatric Radiology, Inselspital, Berne (Switzerland); University Hospital Basel, Department of Radiology, Basel (Switzerland)

    2014-08-15

    To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. (orig.)

  2. Decreased postoperative C-reactive protein production in dogs with pyometra through the use of low-dose ketamine.

    Science.gov (United States)

    Liao, Pei-Yu; Chang, Shi-Chieh; Chen, Kuan-Sheng; Wang, Hsien-Chi

    2014-01-01

    To determine the effects of subanesthetic ketamine in dogs with pyometra on C-reactive protein (CRP) concentrations following surgery. Prospective, nonconcealed, alternating allocation controlled trial. Veterinary teaching hospital. Sixteen dogs diagnosed with pyometra. The tentative diagnosis of canine pyometra was based on compatible history, physical examination findings, ultrasonographic findings, and hematological evaluation. Two different anesthesia and analgesic protocols with and without low-dose ketamine were used during and following ovariohysterectomy in 16 female dogs (n = 8 per group) that were diagnosed with naturally occurring pyometra. Dogs were sequentially allocated to treatment groups in an alternating fashion without concealment. Serum was collected before, 24, and 48 hours after surgery for CRP measurement. Perioperative physical parameters in the 2 groups of dogs were similar. The serum concentrations of CRP in both groups were essentially the same before surgery, but significantly increased in the control group and decreased in ketamine group at 48 hours after surgery. Low-dose ketamine attenuated the postoperative concentration of serum CRP in dogs with pyometra compared with dogs that did not receive ketamine in the perioperative period. Further studies are warranted to determine the clinical implications of these findings. © Veterinary Emergency and Critical Care Society 2014.

  3. Analysis of low-dose radiation shield effectiveness of multi-gate polymeric sheets

    Science.gov (United States)

    Kim, S. C.; Lee, H. K.; Cho, J. H.

    2014-07-01

    Computed tomography (CT) uses a high dose of radiation to create images of the body. As patients are exposed to radiation during a CT scan, the use of shielding materials becomes essential in CT scanning. This study was focused on the radiation shielding materials used for patients during a CT scan. In this study, sheets were manufactured to shield the eyes and the thyroid, the most sensitive parts of the body, against radiation exposure during a CT scan. These sheets are manufactured using silicone polymers, barium sulfate (BaSO4) and tungsten, with the aim of making these sheets equally or more effective in radiation shielding and more cost-effective than lead sheets. The use of barium sulfate drew more attention than tungsten due to its higher cost-effectiveness. The barium sulfate sheets were coated to form a multigate structure by applying the maximum charge rate during the agitator and subsequent mixing processes and creating multilayered structures on the surface. To measure radiation shielding effectiveness, the radiation dose was measured around both eyes and the thyroid gland using sheets in three different thicknesses (1, 2 and 3 mm). Among the 1 and 2 mm sheets, the Pb sheets exhibited greater effectiveness in radiation shielding around both eyes, but the W sheets were more effective in radiation shielding around the thyroid gland. In the 3 mm sheets, the Pb sheet also attenuated a higher amount of radiation around both eyes while the W sheet was more effective around the thyroid gland. In conclusion, the sheets made from barium sulfate and tungsten proved highly effective in shielding against low-dose radiation in CT scans without causing ill-health effects, unlike lead.

  4. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Directory of Open Access Journals (Sweden)

    Hae Mi Joo

    Full Text Available Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6 and LAD2 cells, mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6 and LAD2 cells that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i. The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13, and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  5. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    Science.gov (United States)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  6. Low-Dose Bevacizumab Is Effective in Radiation-Induced Necrosis

    Directory of Open Access Journals (Sweden)

    Matheus Alessandretti

    2013-12-01

    Full Text Available Background: Radiation-induced necrosis is a complication of brain irradiation. Treatment options are limited. Methods: The response to treatment with low-dose bevacizumab in 2 patients with radiation-induced necrosis was reported. Results: Both patients with metastatic melanoma, aged 48 and 51 years, had significant symptomatic and radiological improvement with low-dose bevacizumab treatment. Doses as low as 5 mg/kg every 6 weeks and 7.5 mg/kg i.v. every 4 weeks were used and were highly effective. Conclusions: Low-dose bevacizumab is a solid option in the management of edema associated with radiation necrosis.

  7. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Dennis, Mike; Russell, Nigel; Hills, Robert K

    2015-01-01

    -tolerated in older patients with relapsed/refractory disease. In vitro data suggested synergy with cytarabine (Ara-C). To evaluate vosaroxin, we performed 2 randomized comparisons within the "Pick a Winner" program. A total of 104 patients were randomized to vosaroxin vs low-dose Ara-C (LDAC) and 104 to vosaroxin...

  8. Cine CT for Attenuation Correction in Cardiac PET/CT

    Science.gov (United States)

    Alessio, Adam M.; Kohlmyer, Steve; Branch, Kelley; Chen, Grace; Caldwell, James; Kinahan, Paul

    2008-01-01

    In dual-modality PET/CT systems, the CT scan provides the attenuation map for PET attenuation correction. The current clinical practice of obtaining a single helical CT scan provides only a snapshot of the respiratory cycle, whereas PET occurs over multiple respiratory cycles. Misalignment of the attenuation map and emission image because of respiratory motion causes errors in the attenuation correction factors and artifacts in the attenuation-corrected PET image. To rectify this problem, we evaluated the use of cine CT, which acquires multiple low-dose CT images during a respiratory cycle. We evaluated the average and the intensity-maximum image of cine CT for cardiac PET attenuation correction. Methods Cine CT data and cardiac PET data were acquired from a cardiac phantom and from multiple patient studies. The conventional helical CT, cine CT, and PET data of an axially translating phantom were evaluated with and without respiratory motion. For the patient studies, we acquired 2 cine CT studies for each PET acquisition in a rest–stress 13N-ammonia protocol. Three readers visually evaluated the alignment of 74 attenuation image sets versus the corresponding emission image and determined whether the alignment provided acceptable or unacceptable attenuation-corrected PET images. Results In the phantom study, the attenuation correction from helical CT caused a major artifactual defect in the lateral wall on the PET image. The attenuation correction from the average and from the intensity-maximum cine CT images reduced the defect by 20% and 60%, respectively. In the patient studies, 77% of the cases using the average of the cine CT images had acceptable alignment and 88% of the cases using the intensity maximum of the cine CT images had acceptable alignment. Conclusion Cine CT offers an alternative to helical CT for compensating for respiratory motion in the attenuation correction of cardiac PET studies. Phantom studies suggest that the average and the intensity

  9. Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Eleni Stamoula

    2015-11-01

    Full Text Available Background/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma were treated with various concentrations of the non-essential amino acid glutamate for 0.5-24 hours. The effect of glutamate on cell morphology was monitored with electron microscopy and haematoxylin-eosin staining. Cell survival was calculated with the MTT assay. Expression analysis of chaperones associated with the observed phenotype was performed using either Western Blotting at the protein level or qRT-PCR at the mRNA level. Results: Administration of glutamate in PC12 cells in doses as low as 10 μM causes an up-regulation of GRP78, GRP94 and HSC70 protein levels, while their mRNA levels show the opposite kinetics. At the same time, GAPDH and GRP75 show reduced protein levels, irrespective of their transcriptional rate. On a cellular level, low concentrations of glutamate induce an autophagy-mediated pro-survival phenotype, which is further supported by induction of the autophagic marker LC3. Conclusion: The findings in the present study underline a discrete effect of glutamate on neuronal cell fate depending on its concentration. It was also shown that a low dose of glutamate orchestrates a unique expression signature of various chaperones and induces cell autophagy, which acts in a neuroprotective fashion.

  10. Low-dose 4D myocardial perfusion with x-ray micro-CT

    Science.gov (United States)

    Clark, D. P.; Badea, C. T.

    2017-03-01

    X-ray CT is widely used, both clinically and pre-clinically, for fast, high-resolution, anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, temporally-resolved CT data can detail cardiac motion and blood flow dynamics for one-stop cardiovascular CT imaging procedures. In previous work, we demonstrated efficient, low-dose projection acquisition and reconstruction strategies for cardiac micro-CT imaging and for multiple-injection micro-CT perfusion imaging. Here, we extend this previous work with regularization based on rank-sparse kernel regression and on filtration with the Karhunen-Loeve transform. Using a dual source, prospectively gated sampling strategy which produces an approximately uniform distribution of projections, we apply this revised algorithm to the assessment of both myocardial perfusion and cardiac functional metrics from the same set of projection data. We test the algorithm in simulations using a modified version of the MOBY mouse phantom which contains realistic perfusion and cardiac dynamics. The proposed algorithm reduces the reconstruction error by 81% relative to unregularized, algebraic reconstruction. The results confirm our ability to simultaneously solve for cardiac temporal motion and perfusion dynamics. In future work, we will apply the algorithm and sampling protocol to small animal cardiac studies.

  11. Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

    Science.gov (United States)

    Durbin, Anna P.; Kirkpatrick, Beth D.; Pierce, Kristen K.; Schmidt, Alexander C.; Whitehead, Stephen S.

    2011-01-01

    The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LATV dengue vaccine. PMID:21781997

  12. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity.

    Science.gov (United States)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A; Cadusseau, Josette; Gherardi, Romain K

    2017-01-15

    Aluminium (Al) oxyhydroxide (Alhydrogel(®)), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180days after injection of various doses of Alhydrogel(®) (200, 400 and 800μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel(®) was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200μg Al/kg but not at 400 and 800μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6 months in these animals. We conclude that Alhydrogel(®) injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose

  13. The Effect of Low-Dose Oxytocin Infusion on Cerebral Hemodynamics in Pregnant Women

    NARCIS (Netherlands)

    van Veen, Teelkien R.; Belfort, Michael A.; Zeeman, Gerda G.

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive,

  14. Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars

    2015-01-01

    is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. METHODS AND MATERIALS: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over ...: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong...... the beneficial effects of low-dose TSEBT....

  15. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    Science.gov (United States)

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?AbstractHigh doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  16. Effects of age and low doses of alcohol on compensatory tracking during angular acceleration.

    Science.gov (United States)

    1995-01-01

    Heightened interest in existing FAA regulations regarding alcohol and flying, with emphasis on the potential effects of low blood alcohol levels on performance, indicated a need for research to help define effects of low doses of alcohol on performan...

  17. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    Science.gov (United States)

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  18. Low-dose helical computed tomography (CT) in the perioperative workup of adolescent idiopathic scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Abul-Kasim, Kasim; Overgaard, Angelica; Maly, Pavel [Malmoe University Hospital, Department of Radiology, Section of Neuroradiology, University of Lund, Malmoe (Sweden); Ohlin, Acke [Malmoe University Hospital, Department of Orthopaedic Surgery, University of Lund, Malmoe (Sweden); Gunnarsson, Mikael [Malmoe University Hospital, Department of Radiation Physics, University of Lund, Malmoe (Sweden); Sundgren, Pia C. [University of Michigan Health Systems, Department of Radiology, Division of Neuroradiology, Ann Arbor (United States)

    2009-03-15

    The study aims were to estimate the radiation dose in patients examined with low dose spine CT and to compare it with that received by patients undergoing standard CT for trauma of the same region, as well as to evaluate the impact of dose reduction on image quality. Radiation doses in 113 consecutive low dose spine CTs were compared with those in 127 CTs for trauma. The inter- and intraobserver agreement in measurements of pedicular width, and vertebral rotation, measurements of signal-to-noise ratio and assessment of hardware status were the indicators in the evaluation of image quality. The effective dose of the low dose spine CT (0.37 mSv) was 20 times lower than that of a standard CT for trauma (13.09 mSv). This dose reduction conveyed no impact on image quality. This low dose spine CT protocol allows detailed evaluation that is necessary for preoperative planning and postoperative evaluation. (orig.)

  19. Curcumin uptake enhancement using low dose light illumination during incubation in Candida albicans

    Science.gov (United States)

    Romano, Renan A.; Pratavieira, Sebastião.; da Silva, Ana P.; Kurachi, Cristina; Bagnato, Vanderlei S.; Guimarães, Francisco E. G.

    2017-07-01

    A new PDI protocol is presented in this study. C. albicans cells pre-illuminated with a low dose light demonstrated an increase of curcumin uptake when compared to dark incubation, leading to a higher PDI efficacy.

  20. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Science.gov (United States)

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  1. Low-dose {gamma}-irradiation enhances the proliferation of myeloid leukemia (M1) cells

    Energy Technology Data Exchange (ETDEWEB)

    Ibuki, Yuko; Suzuki, Akifumi; Goto, Rensuke [Shizuoka Univ. (Japan). Graduate School of Nutritional and Environmental Sciences

    2001-10-01

    We examined the effect of low-dose {gamma}-irradiation on proliferation of myeloid leukemia, M1 cells. M1 cells irradiated with 4 cGy showed increased proliferation as determined by cell number, alamar Blue metabolism and DNA synthesis. The increase by low-dose irradiation was observed at every concentration of serum from 1% to 10%, showing the decrease of the serum requirement in irradiated cells. Furthermore, survival days of SL mice inoculated intraperitoneally with low-dose irradiated M1 cells were shorter than those with sham-irradiated cells. These results shown as the decrease of serum requirement and increase of transplantation ability, indicated the augmentation of leukemia malignancy by low-dose irradiation. (author)

  2. Design for low dose extrapolation of carcinogenicity data. Technical report No. 24

    Energy Technology Data Exchange (ETDEWEB)

    Wong, S C

    1979-06-01

    Parameters for modelling dose-response relationships in carcinogenesis models were found to be very complicated, especially for distinguishing low dose effects. The author concluded that extrapolation always bears the danger of providing misleading information. (PCS)

  3. Effects of low doses of alcohol on declarative memory in humans

    National Research Council Canada - National Science Library

    José Arturo Bríñez-Horta; Raúl Oyuela-Vargas

    2011-01-01

    This study assessed the effect of low doses of alcohol on two elements of explicit or declarative memory, in 16 participants, 8 women and 8 men, with The Weschler Memory Scale III Text Test. A factorial 2...

  4. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data

    Science.gov (United States)

    Da Silva, J A P; Jacobs, J W G; Kirwan, J R; Boers, M; Saag, K G; Inês, L B S; de Koning, E J P; Buttgereit, F; Cutolo, M; Capell, H; Rau, R; Bijlsma, J W J

    2006-01-01

    Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo. PMID:16107513

  5. Immediate and Delayed Drug Therapy Effects on Low Dose Sarin Exposed Mice Myocardial Performance

    Science.gov (United States)

    2011-03-01

    antiarrhythmic drug which acts as a β-adrenergic receptor blockade (Ramos, et al. 2003). Major benefits of propranolol are reduced heart rate, decrease...IMMEDIATE AND DELAYED DRUG THERAPY EFFECTS ON LOW DOSE SARIN EXPOSED MICE MYOCARDIAL PERFORMANCE THESIS Joshua T. Miller, Major, USA...IMMEDIATE AND DELAYED DRUG THERAPY EFFECTS ON LOW DOSE SARIN EXPOSED MICE MYOCARDIAL PERFORMANCE THESIS Presented to the Faculty Department of

  6. Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Seth, Isheeta [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States); Joiner, Michael C. [Department of Radiation Oncology, Wayne State University, Detroit, Michigan (United States); Tucker, James D., E-mail: jtucker@biology.biosci.wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, Michigan (United States)

    2015-01-01

    Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

  7. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

    OpenAIRE

    Jin Ok Kim; Dae Won Jun; Hye Jin Tae; Kang Nyeong Lee; Hang Lak Lee; Oh Young Lee; Ho Soon Choi; Byung Chul Yoon; Joon Soo Hahm

    2015-01-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The p...

  8. Low-dose cyclosporine treatment for sight-threatening uveitis: Efficacy, toxicity, and tolerance

    OpenAIRE

    Mathews D; Mathews John; Jones N

    2010-01-01

    Aim : To ascertain the effectiveness, tolerability, and safety of low-dose cyclosporine in the management of sight-threatening uveitis. Materials and Methods: This was a retrospective clinical case series of patients using oral low-dose cyclosporine for the management of sight-threatening uveitis in the uvea clinic (UC). Patients receiving cyclosporine were identified from the clinic database. Main outcome measures were degree of intraocular inflammation, visual acuity and dose reduction of...

  9. The benefit of low dose prophylaxis in the treatment of hemophilia: a focus on China.

    Science.gov (United States)

    Wu, Runhui; Luke, Koon Hung

    2017-11-01

    Currently full dose prophylaxis is the standard of care in the treatment of hemophilia (World Federation of Hemophilia). However, the high costs prevent the use of standard or intermediate dose prophylaxis in China and other developing countries. Low dose prophylaxis would be a viable alternative treatment. At present global research data on the use of low dose prophylaxis is limited. Areas covered: Since 2007, China has been developing low dose prophylaxis as a high priority (90 % of moderate and severe hemophilia boys suffer joint disease by age 6 - 9). 11 studies were successfully conducted and published results showing evidence of the benefits of low dose prophylaxis to reduce joint bleeding. This new knowledge has been implemented into clinical practice in China. However the long-term outcome of arthropathy remains unclear and obstacles in execution exist. Expert commentary: In 2016, the first phenotype-based individualized prophylaxis study using four escalating low dose regimens on severe Chinese hemophilia A boys (China Individualized Prophylaxis Study (CHIP China)) launched. Using the previously published and imminent CHIP data, the goal for China is to establish an effective escalating low dose prophylaxis protocol for use in China as a standard of care.

  10. Low-dose versus standard-dose CT protocol in patients with clinically suspected renal colic.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Platon, Alexandra; Rutschmann, Olivier T; Schmidlin, Franz R; Iselin, Christophe E; Becker, Christoph D

    2007-04-01

    The purpose of our study was to compare a low-dose abdominal CT protocol, delivering a dose of radiation close to the dose delivered by abdominal radiography, with standard-dose unenhanced CT in patients with suspected renal colic. One hundred twenty-five patients (87 men, 38 women; mean age, 45 years) who were admitted with suspected renal colic underwent both abdominal low-dose CT (30 mAs) and standard-dose CT (180 mAs). Low-dose CT and standard-dose CT were independently reviewed, in a delayed fashion, by two radiologists for the characterization of renal and ureteral calculi (location, size) and for indirect signs of renal colic (renal enlargement, pyeloureteral dilatation, periureteral or renal stranding). Results reported for low-dose CT, with regard to the patients' body mass indexes (BMIs), were compared with those obtained with standard-dose CT (reference standard). The presence of non-urinary tract-related disorders was also assessed. Informed consent was obtained from all patients. In patients with a BMI 3 mm. Low-dose CT was 100% sensitive and specific for depicting non-urinary tract-related disorders (n = 6). Low-dose CT achieves sensitivities and specificities close to those of standard-dose CT in assessing the diagnosis of renal colic, depicting ureteral calculi > 3 mm in patients with a BMI < 30, and correctly identifying alternative diagnoses.

  11. Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Nicolas Pelisch

    Full Text Available Multiple sclerosis (MS is characterized by inflammatory demyelination and deposition of fibrinogen in the central nervous system (CNS. Elevated levels of a critical inhibitor of the mammalian fibrinolitic system, plasminogen activator inhibitor 1 (PAI-1 have been demonstrated in human and animal models of MS. In experimental studies that resemble neuroinflammatory disease, PAI-1 deficient mice display preserved neurological structure and function compared to wild type mice, suggesting a link between the fibrinolytic pathway and MS. We previously identified a series of PAI-1 inhibitors on the basis of the 3-dimensional structure of PAI-1 and on virtual screening. These compounds have been reported to provide a number of in vitro and in vivo benefits but none was tested in CNS disease models because of their limited capacity to penetrate the blood-brain barrier (BBB. The existing candidates were therefore optimized to obtain CNS-penetrant compounds. We performed an in vitro screening using a model of BBB and were able to identify a novel, low molecular PAI-1 inhibitor, TM5484, with the highest penetration ratio among all other candidates. Next, we tested the effects on inflammation and demyelination in an experimental allergic encephalomyelitis mice model. Results were compared to either fingolimod or 6α-methylprednisolone. Oral administration of TM5484 from the onset of signs, ameliorates paralysis, attenuated demyelination, and axonal degeneration in the spinal cord of mice. Furthermore, it modulated the expression of brain-derived neurotrophic factor, which plays a protective role in neurons against various pathological insults, and choline acetyltransferase, a marker of neuronal density. Taken together, these results demonstrate the potential benefits of a novel PAI-1 inhibitor, TM5484, in the treatment of MS.

  12. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

    Science.gov (United States)

    Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

    2013-12-18

    Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo

  13. Dose Optimization for Computed Tomography Localizer Radiographs for Low-Dose Lung Computed Tomography Examinations.

    Science.gov (United States)

    Schmidt, Bernhard T; Hupfer, Martin; Saltybaeva, Natalia; Kolditz, Daniel; Kalender, Willi A

    2017-02-01

    , using the optimal settings instead of the standard settings on the ID scanner reduced LR dose from 53 μSv (120 kV, 30 mA) to 10 μSv (80 kV, 20 mA). The simulations for the different tube voltages show that effective dose and CTDIvol behave similarly for different views and patient sizes. However, the tube voltage level itself impacts the relationship between CTDIvol and effective dose, by up to a factor of 2. Dose from LRs may contribute significantly to the total effective dose of low-dose CT examinations such as lung cancer screening. Optimal LR settings can reduce LR dose substantially, but adaptations have to consider scanner characteristics, detector technology, and patient size. Thus, for low-dose CT examinations, such as cardiac examinations and lung cancer screening, LR optimization may result in a significant dose reduction and thereby in a substantial reduction of total dose.

  14. Extracting gene networks for low-dose radiation using graph theoretical algorithms.

    Directory of Open Access Journals (Sweden)

    Brynn H Voy

    2006-07-01

    Full Text Available Genes with common functions often exhibit correlated expression levels, which can be used to identify sets of interacting genes from microarray data. Microarrays typically measure expression across genomic space, creating a massive matrix of co-expression that must be mined to extract only the most relevant gene interactions. We describe a graph theoretical approach to extracting co-expressed sets of genes, based on the computation of cliques. Unlike the results of traditional clustering algorithms, cliques are not disjoint and allow genes to be assigned to multiple sets of interacting partners, consistent with biological reality. A graph is created by thresholding the correlation matrix to include only the correlations most likely to signify functional relationships. Cliques computed from the graph correspond to sets of genes for which significant edges are present between all members of the set, representing potential members of common or interacting pathways. Clique membership can be used to infer function about poorly annotated genes, based on the known functions of better-annotated genes with which they share clique membership (i.e., "guilt-by-association". We illustrate our method by applying it to microarray data collected from the spleens of mice exposed to low-dose ionizing radiation. Differential analysis is used to identify sets of genes whose interactions are impacted by radiation exposure. The correlation graph is also queried independently of clique to extract edges that are impacted by radiation. We present several examples of multiple gene interactions that are altered by radiation exposure and thus represent potential molecular pathways that mediate the radiation response.

  15. Comparison of the Effects of Low-Dose Midazolam, Magnesium Sulfate, Remifentanil and Low-Dose Etomidate on Prevention of Etomidate-Induced Myoclonus in Orthopedic Surgeries.

    Science.gov (United States)

    Sedighinejad, Abbas; Naderi Nabi, Bahram; Haghighi, Mohammad; Biazar, Gelareh; Imantalab, Vali; Rimaz, Siamak; Zaridoost, Zahra

    2016-04-01

    Etomidate is a potent hypnotic agent with several desirable advantages such as providing a stable cardiovascular profile with minimal respiratory adverse effects and better hemodynamic stability compared with other induction agents. This drug is associated, however, with myoclonic movements which is characterized by a sudden, brief muscle contractions as a disturbing side-effect. The present study was designed to compare the effectiveness of low- dose midazolam, magnesium sulfate, remifentanil and low-dose etomidate to suppress etomidate-induced myoclonus in orthopedic surgery. A double-blind clinical trial study was conducted in an academic hospital from September 2014 to August 2015. Two hundred and eighty-four eligible patients, American society of anesthesiologists class I - II, scheduled for elective orthopedic surgery were randomly allocated into four equal groups (n = 71). They received premedication with intravenous low-dose midazolam 0.015 mg/kg, magnesium sulfate 30 mg/kg, remifentanil 1 μg/kg and low-dose etomidate 0.03 mg/kg two minutes before induction of anesthesia with 0.3 mg/kg intravenous etomidate. Then the incidence and intensity of myoclonus were evaluated on a scale of 0 - 3; 0 = no myoclonus; 1 = mild (movement at wrist); 2 = moderate (movement at arm only, elbow or shoulder); and 3 = severe, generalized response or movement in more than one extremity, within ninety seconds. Any adverse effect due to these premedication agents was recorded. The incidence and intensity of myoclonus were significantly lower in the low-dose etomidate group. The incidence rates of myoclonus were 51 (71.85%), 61 (85.9%), 30 (42.3%) and 41 (57.7%), and the percentages of patients who experienced grade III of myoclonus were 30 (58.8%), 32 (52.5%), 9 (30%) and 14 (34.1%) in the midazolam, magnesium sulfate, etomidate and remifentanil groups, respectively. The incidence and intensity of myoclonus were significantly lower in the low-dose etomidate group (P = 0

  16. Burden of upper gastrointestinal symptoms in patients receiving low-dose acetylsalicylic acid for cardiovascular risk management

    DEFF Research Database (Denmark)

    Bytzer, Peter; Pratt, Stephen; Elkin, Eric

    2013-01-01

    Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users.......Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users....

  17. Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

    Science.gov (United States)

    Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

    2016-03-01

    Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

  18. Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

    DEFF Research Database (Denmark)

    Nicoletti, F; Di Marco, R; Conget, I

    2000-01-01

    was prevented by a neutralizing monoclonal antibody (mAb) against IFN-gamma, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-gamma. The data provide...... other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice...... having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent...

  19. Pomalidomide Plus Low-Dose Dexamethasone Improves Survival for Patients with Multiple Myeloma

    Science.gov (United States)

    ... on this post. All comments must follow our comment policy . National Cancer Institute at the National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION About This Website Cancer.gov ...

  20. Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

    Science.gov (United States)

    2012-06-13

    humidity (Tempera- ture Stick, Testo, Sparta , NJ, USA) and one 1/4 inch diameter port to measure the differential pressure within the exposure cham...a human anthrax vaccine in guinea pigs, rab- bits, and rhesus macaques against challenge by Bacillus anthracis iso- lates of diverse geographical

  1. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Veigl, Martina L. [Environmental Mutagen Society (EMS), Reston, VA (United States); Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Morgan, William F. [Univ. of Maryland, College Park, MD (United States); Schwartz, Jeffrey L. [Univ. of Washington, Seattle, WA (United States)

    2009-11-11

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.

  2. Low-Dose Paclitaxel Inhibits Tumor Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chaoxiang Lv

    2017-05-01

    Full Text Available Paclitaxel (PTX is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle. There was a significant decrease of pH in culture media with 0.3 nM PTX for 3 days. Also, lactate production was significantly increased in a dose- and time-dependent manner. Furthermore, expression of glutaminolysis-related genes GLS, SLC7A11 and SLC1A5 were significantly decreased in the colorectal carcinoma cells treated with low-dose PTX. Meanwhile, protein expression levels of p53 and p21 increased significantly in colorectal carcinoma cells so treated. In summary, low-dose PTX down-regulated glutaminolysis-related genes and increased their lactate production, resulting in decreased pH of tumor microenvironments and inhibition of tumor cell growth. Up-regulation of p53 and p21 in colorectal carcinoma cells treated with low-dose PTX also contributed to inhibition of tumor cell growth.

  3. Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available Great controversy exists regarding the biologic responses of osteoblasts to X-ray irradiation, and the mechanisms are poorly understood. In this study, the biological effects of low-dose radiation on stimulating osteoblast proliferation, differentiation and fracture healing were identified using in vitro cell culture and in vivo animal studies. First, low-dose (0.5 Gy X-ray irradiation induced the cell viability and proliferation of MC3T3-E1 cells. However, high-dose (5 Gy X-ray irradiation inhibited the viability and proliferation of osteoblasts. In addition, dynamic variations in osteoblast differentiation markers, including type I collagen, alkaline phosphatase, Runx2, Osterix and osteocalcin, were observed after both low-dose and high-dose irradiation by Western blot analysis. Second, fracture healing was evaluated via histology and gene expression after single-dose X-ray irradiation, and low-dose X-ray irradiation accelerates fracture healing of closed femoral fractures in rats. In low-dose X-ray irradiated fractures, an increase in proliferating cell nuclear antigen (PCNA-positive cells, cartilage formation and fracture calluses was observed. In addition, we observed more rapid completion of endochondral and intramembranous ossification, which was accompanied by altered expression of genes involved in bone remodeling and fracture callus mineralization. Although the expression level of several osteoblast differentiation genes was increased in the fracture calluses of high-dose irradiated rats, the callus formation and fracture union were delayed compared with the control and low-dose irradiated fractures. These results reveal beneficial effects of low-dose irradiation, including the stimulation of osteoblast proliferation, differentiation and fracture healing, and highlight its potential translational application in novel therapies against bone-related diseases.

  4. Usefulness of low-dose CT in the detection of pulmonary metastasis of gestational trophoblastic tumours

    Energy Technology Data Exchange (ETDEWEB)

    Xu, X.J. [Department of Radiology, First Affiliated Hospital, Woman Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Lou, F.L. [Department of Radiology, Woman Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Zhang, M.M. [Department of Radiology, First Affiliated Hospital, Woman Hospital, School of Medicine, Zhejiang University, Hangzhou (China)], E-mail: zhangminming@163.com; Pan, Z.M. [Department of Radiology, Woman Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Zhang, L. [Department of Radiology, First Affiliated Hospital, Woman Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

    2007-10-15

    Aim: To determine whether a low-dose spiral chest computed tomography (CT) examination could replace standard-dose chest CT in detecting pulmonary metastases in patients with gestational trophoblastic tumour (GTT). Materials and methods: In a prospective investigation, 67 chest CT examinations of 39 GTT patients were undertaken. All the patients underwent CT examinations using standard-dose (150 mAs, pitch 1, standard reconstruction algorithm) and low-dose (40 mAs, pitch 2, bone reconstruction algorithm) protocols. Two radiologists interpreted images independently. A metastasis was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of metastases detected with each protocol was recorded. The size of each lesion was measured and categorized as <5, 5-9.9, and {>=}10 mm. Wilcoxon's signed rank test was used to assess the difference between the numbers of lesion detected by the two protocols. Results: The CT dose index (CTDI) for the standard-dose and low-dose CT protocols was 10.4 mGy and 1.4 mGy, respectively. One thousand, six hundred, and eighty-two metastases were detected by standard-dose CT, and 1460 lesions by the low-dose protocol. The numbers detected by low-dose CT were significantly less than those detected by standard-dose CT (Z = -3.776, p < 0.001), especially for nodules smaller than 5 mm (Z = -4.167, p < 0.001). However, the disease staging and risk score of the patients were not affected by use of the low-dose protocol. Conclusion: Low-dose chest CT can be used as a staging and follow-up procedure for patients with GTT.

  5. Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for extrahepatic bile duct cancer.

    Science.gov (United States)

    Kim, Sang-Won; Noh, O Kyu; Kim, Ji Hun; Chun, Mison; Oh, Young-Taek; Kang, Seok Yun; Lee, Hyun Woo; Park, Rae Woong; Yoon, Dukyong

    2017-06-01

    We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC). From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens. Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5-205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756). Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.

  6. Clofarabine plus Low-Dose Cytarabine Followed by Clofarabine plus Low-Dose Cytarabine Alternating with Decitabine in AML Frontline Therapy of Older Patients

    Science.gov (United States)

    Faderl, Stefan; Ravandi, Farhad; Huang, Xuelin; Wang, Xuemei; Jabbour, Elias; Garcia-Manero, Guillermo; Kadia, Tapan; Ferrajoli, Alessandra; Konopleva, Marina; Borthakur, Gautam; Burger, Jan; Feliu, Jennie; Kantarjian, Hagop M.

    2014-01-01

    Background Standard therapy for older patients with AML has a poor outcome. We have designed a combination of clofarabine plus low-dose cytarabine followed by a prolonged consolidation alternating with decitabine. Methods Sixty patients with a median age of 70 years (range 60-81) with newly diagnosed AML were included. They received clofarabine 20mg/m2 intravenously daily × 5 days plus cytarabine 20mg subcutaneously twice daily × 10 days. Responding patients continued for up to 17 courses of consolidation therapy including decitabine. Results Forty of 59 evaluable patients responded (66%). Complete remission rate was 58%. Median relapse-free survival (RFS) was 14.1 (95% CI: 6.9-not estimable) and median overall survival (OS) 12.7 months (95% CI: 8.8-not estimable). Median OS of responding patients (CR/CRp) was 24.2 months (95% CI: 17-not estimable). Compared to a historical group of patients who received clofarabine plus low-dose cytarabine with a shorter consolidation, RFS was not statistically different. Induction mortality was low (7% at 8 weeks) and toxicities manageable. Conclusions Clofarabine plus low-dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven. PMID:22282348

  7. Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice

    Science.gov (United States)

    Mathias, Daniel; Mitchel, Ronald E. J.; Barclay, Mirela; Wyatt, Heather; Bugden, Michelle; Priest, Nicholas D.; Scholz, Markus; Hildebrandt, Guido; Kamprad, Manja; Glasow, Annegret

    2015-01-01

    Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  8. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    Directory of Open Access Journals (Sweden)

    Marie S A Palmnäs

    Full Text Available Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat or high fat (HF, 60% kcal fat and further into ad libitum water control (W or low-dose aspartame (A, 5-7 mg/kg/d in drinking water treatments for 8 week (n = 10-12 animals/treatment. Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05. Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

  9. Low-dose CT of the lung: potential value of iterative reconstructions.

    Science.gov (United States)

    Baumueller, Stephan; Winklehner, Anna; Karlo, Christoph; Goetti, Robert; Flohr, Thomas; Russi, Erich W; Frauenfelder, Thomas; Alkadhi, Hatem

    2012-12-01

    To prospectively assess the impact of sinogram-affirmed iterative reconstruction (SAFIRE) on image quality of nonenhanced low-dose lung CT as compared to filtered back projection (FBP). Nonenhanced low-dose chest CT (tube current-time product: 30 mAs) was performed on 30 patients at 100 kVp and on 30 patients at 80 kVp. Images were reconstructed with FBP and SAFIRE. Two blinded, independent readers measured image noise; two readers assessed image quality of normal anatomic lung structures on a five-point scale. Radiation dose parameters were recorded. Image noise in datasets reconstructed with FBP (57.4 ± 15.9) was significantly higher than with SAFIRE (31.7 ± 9.8, P vol) and effective doses were 1.5 ± 0.7 mGy·cm and 0.7 ± 0.2 mSv at 100 kVp, and 1.4 ± 2.8 mGy · cm and 0.5 ± 0.2 mSv at 80 kVp (P < 0.001, both). Use of SAFIRE in low-dose lung CT reduces noise, improves image quality, and renders more studies diagnostic as compared to FBP. Low-dose computed tomography is an important thoracic investigation tool. Radiation dose can be less than 1 mSv with iterative reconstructions. Iterative reconstructions render more low-dose lung CTs diagnostic compared to conventional reconstructions.

  10. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective.

    Science.gov (United States)

    Lanas, Angel; Gargallo, Carla J

    2015-06-01

    Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance.

  11. The short term effects of Low-dose-rate Radiation on EL4 Lymphoma Cell

    Energy Technology Data Exchange (ETDEWEB)

    Bong, Jin Jong; Kang, Yu Mi; Shin, Suk Chull; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Seoul (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    To determine the biological effects of low-dose-rate radiation ({sup 137}Cs, 2.95 mGy/h) on EL4 lymphoma cells during 24 h, we investigated the expression of genes related to apoptosis, cell cycle arrest, DNA repair, iron transport, and ribonucleotide reductase. EL4 cells were continuously exposed to low-dose-rate radiation (total dose: 70.8 mGy) for 24 h. We analyzed cell proliferation and apoptosis by trypan blue exclusion and flow cytometry, gene expression by real-time PCR, and protein levels with the apoptosis ELISA kit. Apoptosis increased in the Low-dose-rate irradiated cells, but cell number did not differ between non- (Non-IR) and Low-dose-rate irradiated (LDR-IR) cells. In concordance with apoptotic rate, the transcriptional activity of ATM, p53, p21, and Parp was upregulated in the LDR-IR cells. Similarly, Phospho-p53 (Ser15), cleaved caspase 3 (Asp175), and cleaved Parp (Asp214) expression was upregulated in the LDR-IR cells. No difference was observed in the mRNA expression of DNA repair-related genes (Msh2, Msh3, Wrn, Lig4, Neil3, ERCC8, and ERCC6) between Non-IR and LDR-IR cells. Interestingly, the mRNA of Trfc was upregulated in the LDR-IR cells. Therefore, we suggest that short-term Low-dose-rate radiation activates apoptosis in EL4 lymphoma cells.

  12. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  13. Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

    2016-10-15

    Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

  14. Treatment of Cancer and Inflammation With Low-Dose Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Shuji Kojima

    2017-03-01

    Full Text Available There is considerable evidence from experimental studies in animals, as well as from clinical reports, that low-dose radiation hormesis is effective for the treatment of cancer and ulcerative colitis. In this study, we present 3 case reports that support the clinical efficacy of low-dose radiation hormesis in patients with these diseases. First, a patient with prostate cancer who had undergone surgical resection showed a subsequent increase in prostate-specific antigen (PSA. His PSA value started decreasing immediately after the start of repeated low-dose X-ray irradiation treatment and remained low thereafter. Second, a patient with prostate cancer with bone metastasis was treated with repeated low-dose X-ray irradiation. His PSA level decreased to nearly normal within 3 months after starting the treatment and remained at the low level after the end of hormesis treatment. His bone metastasis almost completely disappeared. Third, a patient with ulcerative colitis showed a slow initial response to repeated low-dose irradiation treatment using various modalities, including drinking radon-containing water, but within 8 months, his swelling and bleeding had completely disappeared. After 1 year, the number of bowel movements had become normal. Interest in the use of radiation hormesis in clinical practice is increasing, and we hope that these case reports will encourage further clinical investigations.

  15. Treatment of Cancer and Inflammation With Low-Dose Ionizing Radiation: Three Case Reports.

    Science.gov (United States)

    Kojima, Shuji; Tsukimoto, Mitsutoshi; Shimura, Noriko; Koga, Hironobu; Murata, Akishisa; Takara, Tsuyoshi

    2017-01-01

    There is considerable evidence from experimental studies in animals, as well as from clinical reports, that low-dose radiation hormesis is effective for the treatment of cancer and ulcerative colitis. In this study, we present 3 case reports that support the clinical efficacy of low-dose radiation hormesis in patients with these diseases. First, a patient with prostate cancer who had undergone surgical resection showed a subsequent increase in prostate-specific antigen (PSA). His PSA value started decreasing immediately after the start of repeated low-dose X-ray irradiation treatment and remained low thereafter. Second, a patient with prostate cancer with bone metastasis was treated with repeated low-dose X-ray irradiation. His PSA level decreased to nearly normal within 3 months after starting the treatment and remained at the low level after the end of hormesis treatment. His bone metastasis almost completely disappeared. Third, a patient with ulcerative colitis showed a slow initial response to repeated low-dose irradiation treatment using various modalities, including drinking radon-containing water, but within 8 months, his swelling and bleeding had completely disappeared. After 1 year, the number of bowel movements had become normal. Interest in the use of radiation hormesis in clinical practice is increasing, and we hope that these case reports will encourage further clinical investigations.

  16. Treatment of Cancer and Inflammation With Low-Dose Ionizing Radiation

    Science.gov (United States)

    Tsukimoto, Mitsutoshi; Shimura, Noriko; Koga, Hironobu; Murata, Akishisa; Takara, Tsuyoshi

    2017-01-01

    There is considerable evidence from experimental studies in animals, as well as from clinical reports, that low-dose radiation hormesis is effective for the treatment of cancer and ulcerative colitis. In this study, we present 3 case reports that support the clinical efficacy of low-dose radiation hormesis in patients with these diseases. First, a patient with prostate cancer who had undergone surgical resection showed a subsequent increase in prostate-specific antigen (PSA). His PSA value started decreasing immediately after the start of repeated low-dose X-ray irradiation treatment and remained low thereafter. Second, a patient with prostate cancer with bone metastasis was treated with repeated low-dose X-ray irradiation. His PSA level decreased to nearly normal within 3 months after starting the treatment and remained at the low level after the end of hormesis treatment. His bone metastasis almost completely disappeared. Third, a patient with ulcerative colitis showed a slow initial response to repeated low-dose irradiation treatment using various modalities, including drinking radon-containing water, but within 8 months, his swelling and bleeding had completely disappeared. After 1 year, the number of bowel movements had become normal. Interest in the use of radiation hormesis in clinical practice is increasing, and we hope that these case reports will encourage further clinical investigations. PMID:28539853

  17. A comparison of statistical methods for low dose extrapolation utilizing time-to-tumor data.

    Science.gov (United States)

    Krewski, D; Crump, K S; Farmer, J; Gaylor, D W; Howe, R; Portier, C; Salsburg, D; Sielken, R L; Van Ryzin, J

    1983-01-01

    The assessment of health risks due to low levels of exposure to potential environmental hazards based on the results of toxicological experiments necessarily involves extrapolation of results obtained at relatively high doses to the low dose region of interest. In this paper, different statistical extrapolation procedures which take into account both time-to-response and the presence of competing risks are compared using a large simulated data base. The study was designed to cover a range of plausible dose response models as well as to assess the effects of competing risks, background response, latency and experimental design on the performance of the different extrapolation procedures. It was found that point estimates of risk in the low dose region may differ from the actual risk by a factor of 1000 or more in certain situations, even when precise information on the time of occurrence of the particular lesion of interest is available. Although linearized upper confidence limits on risk can be highly conservative when the underlying dose response curve is sublinear in the low dose region, they were found not to exceed the actual risk in the low dose region by more than a factor of 10 in those cases where the underlying dose response curve was linear at low doses.

  18. The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipid.

    Science.gov (United States)

    Gale, P

    2006-08-01

    The issue of whether the mechanism of infection is independent or co-operative for low doses of transmissible spongiform encephalopathy (TSE) agent is critical for risk assessment. The susceptibility (and hence ID(50)) of individuals with the same prion protein (PrP) genotype may vary considerably with a small proportion being very susceptible. Assuming independent action, the incubation period (IP) would continue to increase until the dose is below the ID(50) of the most susceptible individuals in the experiment, at which point it would become constant. This may explain the observed increase in IP with decreasing dose below the apparent ID(50) in experiments with untreated TSE agent. In contrast, IPs for autoclaved or NaOH-treated TSE agent increase greatly at doses treatment destroys the PL breaking up the nucleation seeds, which require long IPs to reform at low doses. Replenishing those inactivated PLs with host PL would explain how the phenotypic effect of long IP at low dose is lost on subpassage. It is proposed here that strain thermostability is controlled by the nature and strength of the PrP/PL interactions, which are independent of the host PrP genotype. Although repeated oral exposure to low doses of scrapie is less harmful than a single large exposure, this effect may reflect interference by competition rather than diminished risks due to a co-operative effect, and is of little importance for 'one-off' low-dose environmental exposures.

  19. Optimization of SPECT-CT Hybrid Imaging Using Iterative Image Reconstruction for Low-Dose CT: A Phantom Study.

    Directory of Open Access Journals (Sweden)

    Oliver S Grosser

    Full Text Available Hybrid imaging combines nuclear medicine imaging such as single photon emission computed tomography (SPECT or positron emission tomography (PET with computed tomography (CT. Through this hybrid design, scanned patients accumulate radiation exposure from both applications. Imaging modalities have been the subject of long-term optimization efforts, focusing on diagnostic applications. It was the aim of this study to investigate the influence of an iterative CT image reconstruction algorithm (ASIR on the image quality of the low-dose CT images.Examinations were performed with a SPECT-CT scanner with standardized CT and SPECT-phantom geometries and CT protocols with systematically reduced X-ray tube currents. Analyses included image quality with respect to photon flux. Results were compared to the standard FBP reconstructed images. The general impact of the CT-based attenuation maps used during SPECT reconstruction was examined for two SPECT phantoms. Using ASIR for image reconstructions, image noise was reduced compared to FBP reconstructions for the same X-ray tube current. The Hounsfield unit (HU values reconstructed by ASIR were correlated to the FBP HU values(R2 ≥ 0.88 and the contrast-to-noise ratio (CNR was improved by ASIR. However, for a phantom with increased attenuation, the HU values shifted for low X-ray tube currents I ≤ 60 mA (p ≤ 0.04. In addition, the shift of the HU values was observed within the attenuation corrected SPECT images for very low X-ray tube currents (I ≤ 20 mA, p ≤ 0.001.In general, the decrease in X-ray tube current up to 30 mA in combination with ASIR led to a reduction of CT-related radiation exposure without a significant decrease in image quality.

  20. Optimization of SPECT-CT Hybrid Imaging Using Iterative Image Reconstruction for Low-Dose CT: A Phantom Study

    Science.gov (United States)

    Grosser, Oliver S.; Kupitz, Dennis; Ruf, Juri; Czuczwara, Damian; Steffen, Ingo G.; Furth, Christian; Thormann, Markus; Loewenthal, David; Ricke, Jens; Amthauer, Holger

    2015-01-01

    Background Hybrid imaging combines nuclear medicine imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) with computed tomography (CT). Through this hybrid design, scanned patients accumulate radiation exposure from both applications. Imaging modalities have been the subject of long-term optimization efforts, focusing on diagnostic applications. It was the aim of this study to investigate the influence of an iterative CT image reconstruction algorithm (ASIR) on the image quality of the low-dose CT images. Methodology/Principal Findings Examinations were performed with a SPECT-CT scanner with standardized CT and SPECT-phantom geometries and CT protocols with systematically reduced X-ray tube currents. Analyses included image quality with respect to photon flux. Results were compared to the standard FBP reconstructed images. The general impact of the CT-based attenuation maps used during SPECT reconstruction was examined for two SPECT phantoms. Using ASIR for image reconstructions, image noise was reduced compared to FBP reconstructions for the same X-ray tube current. The Hounsfield unit (HU) values reconstructed by ASIR were correlated to the FBP HU values(R2 ≥ 0.88) and the contrast-to-noise ratio (CNR) was improved by ASIR. However, for a phantom with increased attenuation, the HU values shifted for low X-ray tube currents I ≤ 60 mA (p ≤ 0.04). In addition, the shift of the HU values was observed within the attenuation corrected SPECT images for very low X-ray tube currents (I ≤ 20 mA, p ≤ 0.001). Conclusion/Significance In general, the decrease in X-ray tube current up to 30 mA in combination with ASIR led to a reduction of CT-related radiation exposure without a significant decrease in image quality. PMID:26390216

  1. Severe hyperpigmentation and scarring following glycolic acid peel treatment in combination with low-dose isotretinoin.

    Science.gov (United States)

    Gerber, Peter Arne; Kukova, Gabriela; Bölke, Edwin; Homey, Bernhard; Diedrichson, Evelyn

    2014-11-07

    The application of systemic isotretinoin in the treatment of cutaneous photoaging has been well investigated. In addition, well-recognized topical antiaging therapies such as superficial chemical peeling (CP) with α-hydroxy acids have been shown to be more helpful when combined with low-dose oral isotretinoin. Even though the combination of systemic isotretinoin and medium to deep CP has been associated with serious side effects such as delayed wound healing and enlarged incidence of scarring, to date superficial CP and concomitant systemic isotretinoin have been considered safe. In this report, we present the case of a patient receiving low-dose oral isotretinoin therapy who developed severe painful erythema and erosions that led to permanent hyperpigmentation and scarring of her face and neck after undergoing superficial CP with glycolic acid. There is a potential risk of hyperpigmentation and scarring with the use of a combination of low-dose oral isotretinoin and glycolic acid peeling.

  2. Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

    Directory of Open Access Journals (Sweden)

    Junko Shibato

    2009-03-01

    Full Text Available We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot and secondary metabolites (LC-MS/MS in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (g rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s.

  3. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

    Purpose Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case–control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. Methods We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000–2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75–150 mg) or nonaspirin NSAID use, adjusted for potential confounders. Results Use of low-dose aspirin...

  4. Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

    Science.gov (United States)

    Rakwal, Randeep; Agrawal, Ganesh Kumar; Shibato, Junko; Imanaka, Tetsuji; Fukutani, Satoshi; Tamogami, Shigeru; Endo, Satoru; Sahoo, Sarata Kumar; Masuo, Yoshinori; Kimura, Shinzo

    2009-01-01

    We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (γ) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s. PMID:19399245

  5. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  6. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  7. 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.

  8. Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice.

    Science.gov (United States)

    Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse; Bromley, Susan; García Rodríguez, Luis A

    2017-11-28

    To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom. A cohort of new users of low-dose aspirin (75-300 mg; n = 199,079) aged 40-84 years and a 1:1 matched cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95% confidence intervals (CIs) were calculated for current low-dose aspirin use (0-7 days before the index date [ICB date for cases, random date for controls]); reference group was never used. There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH], and n = 385 for subarachnoid hemorrhage [SAH]). RRs (95% CI) were 0.98 (0.84-1.13) for all ICB, 0.98 (0.80-1.20) for ICH, 1.23 (0.95-1.59) for SDH, and 0.77 (0.58-1.01) for SAH. No duration of use or dose-response association was apparent. RRs (95% CI) for ≥1 year of low-dose aspirin use were 0.90 (0.72-1.13) for ICH, 1.20 (0.91-1.57) for SDH, and 0.69 (0.50-0.94) for SAH. Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year. © 2017 American Academy of Neurology.

  9. Is bacterial luminescence response to low-dose radiation associated with mutagenicity?

    Science.gov (United States)

    Rozhko, T V; Guseynov, O A; Guseynova, V E; Bondar, A A; Devyatlovskaya, A N; Kudryasheva, N S

    2017-10-01

    Luminous marine bacteria are widely used in bioassays with luminescence intensity being a physiological parameter tested. The purpose of the study was to determine whether bacterial genetic alteration is responsible for bioluminescence kinetics change under low-dose radiation exposure. The alpha-emitting radionuclide 241Am and beta-emitting radionuclide 3H were used as the sources of low-dose ionizing radiation. Changes of bioluminescence kinetics of Photobacterium phosphoreum in solutions of 241Am(NO3)3, 7 kBq/L, and tritiated water, 100 MBq/L, were studied; bioluminescence kinetics stages (absence of effect, activation, and inhibition) were determined. Bacterial suspension was sampled at different stages of the bioluminescent kinetics; the doses accumulated by the samples were close or a little higher than a tentative limit of a low-dose interval: 0.10 and 0.85 Gy for 241Am, or 0.11 and 0.18 Gy for 3H. Sequence analysis of the 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose alpha and beta radiation in the bacterial samples. Previous results on bacterial DNA exposed to low-dose gamma radiation (0.25 Gy) were analyzed and compared to those for alpha and beta irradiation. It is concluded that bioluminescence activation and/or inhibition under the applied conditions of low-dose alpha, beta and gamma radioactive exposure is not associated with DNA mutations in the gene sequences tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Low-dose CT coronary angiography for the prediction of myocardial ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Stolzmann, Paul; Donati, Olivio F.; Scheffel, Hans; Baumueller, Stephan; Leschka, Sebastian; Marincek, Borut; Alkadhi, Hatem [University Hospital Zurich (Switzerland). Institute of Diagnostic Radiology; Azemaj, Naim; Plass, Andre; Gruenenfelder, Juerg [University Hospital Zurich, Clinic for Cardiovascular Surgery, Zurich (Switzerland); Kozerke, Sebastian; Boesiger, Peter [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland)

    2010-01-15

    The purpose of this study was to prospectively determine the accuracy of low-dose computed tomography coronary angiography (CTCA) for the diagnosis of functionally relevant coronary artery disease (CAD) using cardiac magnetic resonance (CMR) as a standard of reference. Forty-one consecutive patients (age 64 {+-} 10 years) underwent k-space and time broad-use linear acquisition speed-up technique accelerated CMR (1.5 T) and dual-source CTCA using prospective electrocardiography gating within 1 day. CTCA lesions were analysed and diameter stenoses of more than 50% and more than 75% were compared with CMR findings taken as the reference standard for assessing the functional relevance of CAD. CMR revealed perfusion defects in 21/41 patients (51%). A total of 569 coronary segments were analysed with low-dose CTCA. The image quality of low-dose CTCA was diagnostic in 566/569 segments (99.5%) in 39/41 patients (95%). Low-dose CTCA revealed stenoses of more than 50% in 58/123 coronary arteries (47.2%) in 24/41 patients (59%) and more than 75% stenoses in 46/123 coronary arteries (37.4%) in 23/41 patients (56%). Using a greater than 50% diameter stenosis, low-dose CTCA yielded the following per artery sensitivity, specificity, positive and negative predictive values, and accuracy for the detection of perfusion defects: 89%, 79%, 72%, 92% and 83%, respectively. Low-dose CTCA is reliable for ruling out functionally relevant CAD, but is a poor predictor of myocardial ischaemia. (orig.)

  11. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  12. Data integration reveals key homeostatic mechanisms following low dose radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Matzke, Melissa M. [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99338 (United States); Waters, Katrina M., E-mail: katrina.waters@pnnl.gov [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99338 (United States)

    2015-05-15

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time — with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24–72 h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. - Highlights: • Low dose ionizing radiation altered homeostasis in 3D skin tissue model. • Global gene/protein/metabolite data integrated using complementary statistical approaches • Time and location-specific change in matrix regulation

  13. Effects of low doses of alcohol on declarative memory in humans

    Directory of Open Access Journals (Sweden)

    José Arturo Bríñez-Horta

    2011-09-01

    Full Text Available This study assessed the effect of low doses of alcohol on two elements of explicit or declarative memory, in 16 participants, 8 women and 8 men, with The Weschler Memory Scale III Text Test. A factorial 2 * 4 counterbalanced with repeated measures design was used. There were no statistically significant differences by gender, but there were differences among doses, specially 0.150 g / Kg., which reduced episodic and semantic retrieval, between 43.9 and 62.9 % of effect strength, in intermediate term memory. These results provided evidence that alcohol in low doses has a more pronounced effect in semantic, rather than episodic memory, in the middle term

  14. Low-dose aspirin use and the risk of ovarian cancer in Denmark.

    Science.gov (United States)

    Baandrup, L; Kjaer, S K; Olsen, J H; Dehlendorff, C; Friis, S

    2015-04-01

    A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low-dose aspirin and the risk of ovarian cancer. We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. For 4103 ovarian cancer cases and 58 706 population controls, the adjusted OR for epithelial ovarian cancer associated with ever use (≥2 prescriptions) of low-dose aspirin was 0.94 (95% CI 0.85-1.05). ORs for epithelial ovarian cancer were lower with the use of 150 mg aspirin tablets (OR = 0.82; 95% CI 0.68-0.99) and with long-term use (≥5 years) of low-dose aspirin (OR = 0.77; 95% CI 0.55-1.08). Continuous long-term use of low-dose aspirin, defined as close consecutive prescriptions, was associated with a further reduction in OR (0.56; 95% CI 0.32-0.97). For histological types of epithelial ovarian cancer, the strongest inverse associations with low-dose aspirin use were seen for mucinous and endometrioid tumours. This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer. © The Author 2014. Published by Oxford

  15. Low-Dose Aspirin in Heart Failure Not Complicated by Atrial Fibrillation

    DEFF Research Database (Denmark)

    Madelaire, Christian; Gislason, Gunnar; Kristensen, Søren L

    2018-01-01

    OBJECTIVES: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. BACKGROUND: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease....... An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result. CONCLUSIONS: No association was detected between...

  16. Agonist trigger: what is the best approach? Agonist trigger and low dose hCG

    DEFF Research Database (Denmark)

    Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2012-01-01

    Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)......Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)...

  17. Degradation of physical and mechanical properties of steel G-91 under low-dose neutron irradiation

    Science.gov (United States)

    Kislitsin, Sergey; Dikov, Alexey; Maksimkin, Oleg; Merezhko, Mikhail; Rofman, Oleg; Turubarova, Lyudmila; Gorlachev, Igor; Sil'nagina, Nadezhda

    2017-12-01

    Changes in the structure and physicomechanical properties of steel G-91 were studied after low-dose neutron irradiation. The irradiation was carried out in the "wet" channel of the WWR-K research nuclear reactor of INP, Almaty, Kazakhstan, to the fast neutron fluencies 8.6×1019 n/cm2 at a temperature of dislocation density and appearance of radiation defects (black dots). The most significant consequence of low-dose irradiation during a long period (up to a year and a half) is severe corrosion, which leads to embrittlement of steel G-91.

  18. A model for low dose effects of low-LET radiation delivered at high dose rates

    Science.gov (United States)

    Schöllnberger, H.; Stewart, R.D.; Mitchel, R.E.J.

    2011-01-01

    In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA repair are related to temporal changes in the amount of DNA damage in a cell. The combined effects of endogenous DNA damage, background radiation and artificial irradiation are considered. PMID:22318364

  19. Incidence of intracranial bleeds in new users of low-dose aspirin

    DEFF Research Database (Denmark)

    Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse

    2017-01-01

    BACKGROUND: Low-dose aspirin protects against ischemic cardiovascular (CV) events as well as colorectal cancer (CRC). However, low-dose aspirin may be associated with a small increased risk of intracranial bleeds (ICB). OBJECTIVES: To obtain incidence rates of ICB overall and by patient subgroups...... per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (CI 0.06-0.07) and 0.09 (CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. CONCLUSIONS: Our results provide valuable...

  20. [Efficacy of low-dose tadalafil on ED assessed by Self-Esteem and Relationship Questionnaire].

    Science.gov (United States)

    Li, Jing-Ping; Li, Fei; Guo, Wen-Bin; Zhou, Qi-Zhao; Liu, Cun-Dong; Mao, Xiang-Ming; Tan, Wan-Long; Zheng, Shao-Bin

    2010-12-01

    To explore the effects of low-dose oral tadalafil on self-esteem, confidence and sexual relationship in ED patients. We treated 17 ED patients with oral tadalafil at the low dose of 5 mg once daily for 12 weeks, and used the paired t test to compare their scores on The Self-Esteem and Relationship Questionnaire (SEAR) and IIEF-5 and the results of nocturnal penile tumescence (NPT) obtained by nocturnal electrobioimpedance volumetric assessment (NEVA) before and after the medication. The scores on SEAR and IIEF-5 were significantly increased (P self-esteem, confidence, sexual relationship satisfaction and NPT of ED patients.

  1. Long term/low dose formalin exposure to small-scale recirculation aquaculture systems

    DEFF Research Database (Denmark)

    Pedersen, Lars-Flemming; Pedersen, Per Bovbjerg; Nielsen, Jeppe L.

    2010-01-01

    Repetitive long term formalin application at low dose was investigated to determine the effect on formaldehyde removal rate, biofilter nitrification and the microbial composition in small-scale recirculation aquaculture biofilters. Six pilot-scale recirculation aquaculture systems holding rainbow...... Nitrobacter sp. was not detected. The relative abundances of AOB and NOB in the untreated system were generally higher compared to the system exposed to formalin. Low dose formalin in recirculated aquaculture systems proved to be a possible treatment strategy, as the effect on nitrification was minimal. Since...

  2. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN.

    Science.gov (United States)

    Jabbour, Elias; Short, Nicholas J; Montalban-Bravo, Guillermo; Huang, Xuelin; Bueso-Ramos, Carlos; Qiao, Wei; Yang, Hui; Zhao, Chong; Kadia, Tapan; Borthakur, Gautam; Pemmaraju, Naveen; Sasaki, Koji; Estrov, Zeev; Cortes, Jorge; Ravandi, Farhad; Alvarado, Yesid; Komrokji, Rami; Sekeres, Mikkael A; Steensma, David P; DeZern, Amy; Roboz, Gail; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2017-09-28

    Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m2 intravenously/subcutaneously daily or decitabine 20 mg/m2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% (P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine (P = .2). Cytogenetic response rates were 61% and 25% (P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively (P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225). © 2017 by The American Society of Hematology.

  3. TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, A; Bostani, M [University of California, Los Angeles, Los Angeles, CA (United States); McMillan, K [Mayo Clinic, Rochester, MN (United States); Zankl, M [Helmholtz Zentrum Munchen, Neuherberg (Germany); Cagnon, C [UCLA Medical Center, Los Angeles, CA (United States); McNitt-Gray, M [UCLA School of Medicine, Los Angeles, CA (United States)

    2016-06-15

    Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generated using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical

  4. Clinical impact of model-based type iterative reconstruction with fast reconstruction time on image quality of low-dose screening chest CT.

    Science.gov (United States)

    Yuki, Hideaki; Oda, Seitaro; Utsunomiya, Daisuke; Funama, Yoshinori; Kidoh, Masafumi; Namimoto, Tomohiro; Katahira, Kazuhiro; Honda, Keiichi; Tokuyasu, Shinichi; Yamashita, Yasuyuki

    2016-03-01

    Model-based type iterative reconstruction algorithms with fast reconstruction times are now available. The clinical feasibility of their reconstruction has not been evaluated adequately. To investigate the effects of model-based type iterative reconstruction, i.e. iterative model reconstruction (IMR), with fast reconstruction time on the qualitative and quantitative image quality at low-dose chest computed tomography (CT). Thirty-one patients undergoing low-dose screening chest CT were enrolled. Images were reconstructed using filtered back projection (FBP), hybrid iterative reconstruction (HIR), and IMR algorithms. The CT attenuation and image noise for all reconstructions were calculated at the lung apex, middle, and base. Using a 4-point scale, two reviewers visually evaluated the image quality with respect to vessel sharpness, streak artifact, the mediastinum, and the overall image quality of each reconstruction method. The mean estimated effective dose was 1.0 ± 0.3 mSv. There was no significant difference in the CT attenuation among the three reconstructions. The mean image noise of FBP, HIR, and IMR images was 124.3 ± 57.3, 34.8 ± 10.2, and 22.9 ± 5.8 HU, respectively. There were significant differences for all comparison combinations among the three methods (P reconstruction time for IMR was within 3 min in all cases. At low-dose chest CT, IMR can improve the qualitative and quantitative visualization of both lung and mediastinal structures especially in the lung apex at a clinically acceptable reconstruction time. Its application may improve diagnostic performance. © The Foundation Acta Radiologica 2015.

  5. Potential drug interaction with opioid agonist in the setting of chronic low-dose opioid antagonist use.

    Science.gov (United States)

    Leonard, James B; Nair, Vidya; Diaz, Christopher J; Penoyar, Jonathan B; Goode, Penelope A

    2017-08-01

    Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Low dose decitabine in very high risk relapsed or refractory acute myeloid leukaemia in children and young adults.

    Science.gov (United States)

    Phillips, Christine L; Davies, Stella M; McMasters, Richard; Absalon, Michael; O'Brien, Maureen; Mo, Jun; Broun, Randall; Moscow, Jeffrey A; Smolarek, Teresa; Garzon, Ramiro; Blum, William; Schwind, Sebastian; Marcucci, Guido; Perentesis, John P

    2013-05-01

    Low-dose decitabine has encouraging activity and tolerability in adults with acute myeloid leukaemia (AML), but paediatric experience is lacking. We report our retrospective experience with decitabine in eight children and young adults (median age 4 years) with refractory/relapsed AML, who had failed multiple regimens or were not candidates for standard retrieval regimens due to prior toxicities. Three of eight patients (38%) had complete response (CR; 1 each of CR, CR with incomplete platelet recovery and CR with incomplete count recovery). Best responses were observed after a median of 2.5 cycles (range 1-4 cycles). Four patients received subsequent allogeneic stem cell transplant, and two remain in long-term CR. © 2013 Blackwell Publishing Ltd.

  7. More than lung cancer: Automated analysis of low-dose screening CT scans

    NARCIS (Netherlands)

    Mets, O.M.

    2012-01-01

    Smoking is a major health care problem and is projected to cause over 8 million deaths per year worldwide in the coming decades. To reduce lung cancer mortality in heavy smokers, several randomized screening trials were initiated in the past years using screening with low-dose Computed Tomography

  8. Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine

    NARCIS (Netherlands)

    de Gans, J.; Lange, J. M.; Derix, M. M.; de Wolf, F.; Eeftinck Schattenkerk, J. K.; Danner, S. A.; Ongerboer de Visser, B. W.; Cload, P.; Goudsmit, J.

    1988-01-01

    Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These

  9. Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil [Keimyung Univ., Daegu (Korea, Republic of)

    2013-12-15

    While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment.

  10. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    Directory of Open Access Journals (Sweden)

    Ravi Vachhani

    2010-06-01

    Full Text Available Ravi Vachhani1, Doumit Bouhaidar1, Alvin Zfass1, Bimaljit Sandhu1, Ali Nawras21Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298–0341, USA; 2Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Toledo Medical Center, Toledo, Ohio 43606-3390, USAAbstract: Low dose aspirin (≤325 mg is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two-to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior history of ulcer or upper gastrointestinal (GI bleeding, concomitant use of other nonsteroidal anti-inflammatory drugs, corticosteroid or warfarin, dual antiplatelet therapy, Helicobacter pylori (H. pylori infection, and advanced age. Esomeprazole, like other proton pump inhibitors (PPIs is very effective in decreasing the risk of aspirin induced gastrointestinal toxicity. Although evidence to support esomeprazole or other PPIs for primary prophylaxis in aspirin induced gastrointestinal toxicity is limited, its role in secondary prophylaxis is well established.Keywords: esomeprazole, proton pump inhibitors, low dose aspirin, gastrointestinal toxicity, gastrointestinal bleeding

  11. Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin.

    Science.gov (United States)

    Hsu, Ping-I; Tsai, Tzung-Jiun

    2015-01-01

    Low-dose aspirin, commonly defined as 75-325 mg daily, is widely used for cardiovascular (CV) protection. It reduced the risk of CV events and death in patients with coronary and cerebrovascular diseases and has the advantages of both low cost and long duration of antiplatelet action. However, low-dose aspirin therapy is associated with upper gastrointestinal (GI) side effects, which range from dyspepsia (point prevalence: 31%), gastroduodenal erosions (point prevalence: 60%), endoscopic peptic ulcer (3-month incidence: 7%) to symptomatic or complicated ulcers (annual incidence of upper GI bleeding: 0.6%; relative risk of upper GI bleeding: 2.6). The important factors that increase the risk of low-dose aspirin-related ulcer complications include a history of bleeding peptic ulcer, prior peptic ulcer, age > 70 years, H pylori infection, and concomitant drug therapy with non-steroidal anti-inflammatory drugs, other antiplatelet agents (e.g., clopidogrel) or anticoagulants. The use of enteric-coated or buffered preparations do not reduce the risk of upper GI complications. Assessment of GI risk for patients is a crucial step in preventing complications of antiplatelet agents. Patients with a high GI risk should prevent peptic ulcer or ulcer complications by co-therapy with an antisecretory agent, especially proton pump inhibitors. H pylori eradication is recommended for patients requiring long-term low-dose aspirin therapy who have a prior history of peptic ulcer or GI bleeding.

  12. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    DEFF Research Database (Denmark)

    Bitsch, M; Hermann, G G; Andersen, J P

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid......) bladder cancer....

  13. Preoperative low-dose steroid can prevent respiratory insufficiency after thymectomy in generalized myasthenia gravis.

    Science.gov (United States)

    Kataoka, Hiroshi; Kiriyama, Takao; Kawaguchi, Takeshi; Sawa, Nobuhiro; Sugie, Kazuma; Horikawa, Hirosei; Tojo, Takashi; Ueno, Satoshi

    2014-01-01

    Postoperative respiratory insufficiency (PRI) in myasthenia gravis (MG) often occurs within several days after thymectomy and remains problematic. In limited studies reporting that preoperative steroids prevented PRI in patients with MG, high doses of steroids were used and detailed information on the use of steroids is limited. Because high-dose steroids significantly increase the risk of adverse effects, we studied 37 patients with generalized MG to investigate whether low-dose steroids might prevent PRI. The low-dose steroids were started orally, and the dose was gradually increased to the maximum level (30 mg/day). Immediately before thymectomy, patients received the maximum dose of oral steroids daily. PRI was defined as the development of restrictive dysfunction requiring mechanical ventilation within 3 days after thymectomy and total postoperative mechanical ventilation support time of >24 h. The rate of PRI in the low-dose steroid use group was significantly lower than that in the no-steroid use group. The postoperative stay in the intensive care unit was shorter in the steroid use group. Extended thymectomy is a well-accepted surgical treatment for selected patients with MG. However, PRI remains problematic. Our results suggest that not only preoperative high-dose steroid treatment, but also low-dose steroid treatment can prevent PRI. © 2014 S. Karger AG, Basel.

  14. Low-dose computed tomography screening for lung cancer : Results of the first screening round

    NARCIS (Netherlands)

    Horeweg, Nanda; Nackaerts, Kristiaan; Oudkerk, Matthijs; de Koning, Harry J.

    Evaluation of: National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368, 1980-1991 (2013). In 2011, the US NLST trial demonstrated that mortality from lung cancer can be reduced

  15. Microdose acquisition in adolescent leg length discrepancy using a low-dose biplane imaging system

    DEFF Research Database (Denmark)

    Jensen, Janni; Mussmann, Bo Redder; Hjarbæk, John

    2017-01-01

    Background Children with leg length discrepancy often undergo repeat imaging. Therefore, every effort to reduce radiation dose is important. Using low dose preview images and noise reduction software rather than diagnostic images for length measurements might contribute to reducing dose. Purpose ...

  16. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  17. Fully Convolutional Architecture for Low-Dose CT Image Noise Reduction

    Science.gov (United States)

    Badretale, S.; Shaker, F.; Babyn, P.; Alirezaie, J.

    2017-10-01

    One of the critical topics in medical low-dose Computed Tomography (CT) imaging is how best to maintain image quality. As the quality of images decreases with lowering the X-ray radiation dose, improving image quality is extremely important and challenging. We have proposed a novel approach to denoise low-dose CT images. Our algorithm learns directly from an end-to-end mapping from the low-dose Computed Tomography images for denoising the normal-dose CT images. Our method is based on a deep convolutional neural network with rectified linear units. By learning various low-level to high-level features from a low-dose image the proposed algorithm is capable of creating a high-quality denoised image. We demonstrate the superiority of our technique by comparing the results with two other state-of-the-art methods in terms of the peak signal to noise ratio, root mean square error, and a structural similarity index.

  18. Effects of Low-Dose Mindfulness-Based Stress Reduction (MBSR-ld) on Working Adults

    Science.gov (United States)

    Klatt, Maryanna D.; Buckworth, Janet; Malarkey, William B.

    2009-01-01

    Mindfulness-based stress reduction (MBSR) has produced behavioral, psychological, and physiological benefits, but these programs typically require a substantial time commitment from the participants. This study assessed the effects of a shortened (low-dose [ld]) work-site MBSR intervention (MBSR-ld) on indicators of stress in healthy working…

  19. Effect of low-dose oral contraceptives on Lipid profile levels in ...

    African Journals Online (AJOL)

    Background: Oral contraceptives provide highly reliable contraceptive protection even though imperfect use is considered, and are widely used worldwide. Objective: This study aimed to assess the effect of low dose combined oral contraceptive pills use on lipid profile levels in Sudanese women, and to find its correlation ...

  20. The effect of Low-dose Gamma Radiation on the Bio-chemical ...

    African Journals Online (AJOL)

    Low-dose gamma radiation has been applied to intravenous fluids to enhance the sterility assurance levels. This study was undertaken to determine the stability of gamma irradiated 2.5 % dextrose, 2.5 % dextrose in saline, Ringers lactate and Gastrointestinal replacement fluid at doses of 0, 2, 4, 6, 8, 10 and 20 kGy.

  1. Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease

    NARCIS (Netherlands)

    Heitner, Rene; Elstein, Deborah; Aerts, Johannes; Weely, Sonja van; Zimran, Ari

    2002-01-01

    The objective of this study was to evaluate the efficacy and safety of low-dose substrate balance therapy with OGT 918 for the treatment of adults with Gaucher disease. Eighteen patients with Gaucher disease from two centers were enrolled in an open-label 6-month study of OGT 918, 50 mg taken three

  2. [The imaging principles and the structure of the low-dose digital radiographic device].

    Science.gov (United States)

    Kang, Q Z; Yu, H L; Zhang, H; Zhang, D S; Cao, H D

    2001-03-01

    This article introduced A new type of X-ray radiographic device, which uses MWPC as the low-dose detector with the machinery and computer to reconstruct the X-ray digital images. In this paper, the advantages and the disadvantages of the device are analysed, thus much improvement has been made to make it better and more efficient.

  3. Synergistic cancer growth-inhibitory effect of emodin and low-dose ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-cancer activity of emodin and its combination with low-dose cisplatin against human gastric cancer (SNU-5), including their effects on cell cycle phase distribution, apoptosis and cancer cell morphology. Methods: The anti-cancer activity of emodin, cisplatin and their combination against ...

  4. Effect of low dose Lead (Pb) administration on tail immersion test ...

    African Journals Online (AJOL)

    Lead (Pb) is cheap and there is a long tradition of its use, but its toxic effects have also been recognized. There is increased public health concern regarding the hazards of low dose Pb exposure to adults and children. Studies have shown the risks for hypertension, decrements in renal function, subtle decline in cognitive ...

  5. Low-dose antibiotics: current status and outlook for the future

    DEFF Research Database (Denmark)

    of the application of antibiotics for uses other than the treatment of patients and the association with such utilization with emerging drug resistance. This Research Topic “Low- dose antibiotics: current status and outlook for the future” in Frontiers in Microbiology: Antimicrobials, Resistance and Chemotherapy...

  6. use of combined paracetamol and low dose ketamine in pain control

    African Journals Online (AJOL)

    East African Medical Journal Vol 88 No. 3 March 2011. USE OF COMBINED PARACETAMOL AND LOW DOSE KETAMINE IN PAIN CONTROL DURING CHANGE OF. DRESSINGS IN BURN PATIENTS. K. P. Werunga, MBChB, MMed Anaesthesia(NBI), Diploma ICU and Pain, Lecturer, Moi University, School of Medicine,.

  7. Low dose lopinavir/ritonavir tablet achieves adequate pharmacokinetic parameters in HIV-infected Thai adolescents.

    NARCIS (Netherlands)

    Klinklom, A.; Puthanakit, T.; Gorowara, M.; Phasomsap, C.; Kerr, S.; Sriheara, C.; Ananworanich, J.; Burger, D.M.; Ruxrungtham, K.; Pancharoen, C.

    2012-01-01

    BACKGROUND: Lopinavir/ritonavir (LPV/r) is an effective and commonly used protease inhibitor in HIV-infected adolescents. Previous data showed high plasma concentrations of LPV in Thai patients. This study determined the pharmacokinetic (PK) parameters of a low-dose LPV/r tablet (70% of standard

  8. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed

  9. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  10. Bioassay in BALB/c mice exposed to low dose rate radiation

    Energy Technology Data Exchange (ETDEWEB)

    Km, Sung Dae; Gong, Eun Ji; Bae, Min Ji; Yang, Kwang Mo; Kim, Joong Sun [Dongnam Institute of Radiological and Medical Sciences, Suwon (Korea, Republic of)

    2012-09-15

    The present study was performed to investigate the toxicity of low-dose-rate irradiation in BALB/c mice. Twenty mice of each sex were randomly assigned to four groups of five mice each and were exposed to 0 (sham), 0.02, 0.2, or 2 Gy, equivalents to low-dose-rate irradiation to 3.49 mGy{center_dot}h{sup -1}. Urine, blood, and blood biochemistry were analyzed, and organ weight was measured. The low-dose-rate irradiation did not induce any toxicologically significant changes in mortality, clinical signs, body weight, food and water consumption, urinalysis, and serum biochemistry. However, the weights of reproductive organs including the testis, ovary, and uterus decreased in a dose-dependent manner. Irradiation at 2 Gy significantly decreased the testis, ovary, and uterus weights, but did not change the weights of other organs. There were no adverse effects on hematology in any irradiated group and only the number of neutrophils increased dose dependently. The low-dose-rate irradiation exposure did not cause adverse effects in mice at dose levels of 2 Gy or less, but the reproductive systems of male and female mice showed toxic effects.

  11. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  12. 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.

  13. The question of a 'New Era in the Low Dose Radiation Epidemiology' approach

    Directory of Open Access Journals (Sweden)

    Koterov A.N.

    2016-12-01

    Full Text Available The historical and recent years data on cancer and/or leukemia rate increasing after exposure of people in low dose (up to 100 mGy radiation with a low LET, attributiveness of effects and the possibility of their experimental confirmation were considered. Previously, information about the carcinogenic effects of low doses was not clearly interpreted due to the presence of uncertainty, biases and confounders. The biological mechanism was also absent. In the last 5-7 years the situation has changed dramatically: more significant data were obtained: irradiation at computed tomography in dentistry, for residents of a high natural background radiation, and others. Simultaneously it was obtained radiobio-logical data on increased DNA double strand breaks level after exposure to doses from few milligrays and it can be considered as a possible molecular mechanism of these effects. As a result, was declared 'New Era in the Low Dose Radiation Epidemiology' (Kitahara С M., et al., 2015, which can lead to costs in terms of tightening of radiation risks and to fear of medical exposure. The conducted in the review analysis of recent epidemiological and radiobiological evidence suggests, however, that there is no unambiguous evidence of attributed to radiation carcinogenic effects, identified during the 'New Epidemiology of Low Doses', and there is no a proven molecular mechanism that could provide biological plausibility of such effects.

  14. Levamisole and low-dose prednisolone in the treatment of reccurent aphthous stomatitis.

    Science.gov (United States)

    Sharda, Neelkamal; Shashikanth, M C; Kant, Priyanka; Jain, Manika

    2014-04-01

    Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease. However, the available therapies for RAS only relieve symptoms and do not provide a cure. This study assessed the response to treatment with levamisole and low-dose prednisolone drug combination in patients with RAS. Fifty RAS subjects were enrolled in the single-blind randomized placebo-controlled trial. Study medications were administered thrice daily for 3 consecutive days/week for 3 consecutive weeks. Patients in Group 1 received placebo, Group 2 received levamisole (50 mg) and Group 3 received levamisole (50 mg) and low-dose prednisolone (5 mg). Patients were followed up for 60 days after treatment. Response to treatment was assessed using the following clinical parameters: pain due to ulcers, number of ulcers/episode, size of ulcers, duration of ulcers, and frequency of ulcers (episodes/month). Mann–Whitney U-test. A statistically significant improvement was noted in all parameters except for the size of ulcers in patients treated with levamisole alone and with combination of levamisole and low-dose prednisolone. There was no statistically significant improvement in the placebo group. Both active groups had significantly better improvement when compared to placebo group, while there was no significant difference between the two active groups. Levamisole alone and combination of levamisole and low-dose prednisolone are effective modes of therapy for RAS.

  15. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability

    NARCIS (Netherlands)

    Wachters-Hagedoorn, R. E.; Priebe, M. G.; Heimweg, J. A. J.; Heiner, A. M.; Elzinga, H.; Stellaard, F.; Vonk, R. J.

    Aims Slowly digestible starch is associated with beneficial health effects. The glucose-lowering drug acarbose has the potential to retard starch digestion since it inhibits alpha-amylase and alpha-glucosidases. We tested the hypothesis that a low dose of acarbose delays the rate of digestion of

  16. 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

  17. Low dose radiotherapy for plantar fasciitis. Treatment outcome of 171 patients.

    Science.gov (United States)

    Badakhshi, Harun; Buadch, Volker

    2014-12-01

    Although the effectiveness of low-dose radiotherapy for chronic degenerative and inflammatory diseases has been documented in previous studies, patient-reported clinical outcomes are rarely available. This study aimed to determine the effect of low-dose radiotherapy on patients with painful plantar fasciitis. From 2002 to 2008, 200 patients older than 65 years of age with painful plantar fasciitis were treated in our hospital. Records from 171 of these patients were available for analysis. All patients were treated with an identical dose of 3Gy using identical equipment and techniques. Response was evaluated with patient-reported questionnaires and clinical visits. Minimum-term follow-up was 18 months, with mean follow-up at 54 months. Three months after receiving low-dose radiotherapy, 67.3% of patients had no or mild pain, and 57.9% had no or discrete mobility restriction. At a mean of 54 months, 61.4% of patients had no or mild pain and 64.9% of patients had no or discrete mobility restriction; 60.8% of patients reported improved quality of life. Low-dose radiotherapy is effective in most patients with painful plantar fasciitis. Due to minimal side effects and low costs, it represents an excellent treatment option compared to conventional therapies or surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Optimised low-dose multidetector CT protocol for children with cranial deformity

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, Jose Luis [Complejo Hospitalario Universitario de Vigo, Department of Radiology, Vigo, Pontevedra (Spain); Pombar, Miguel Angel [Complejo Hospitalario Universitario de Santiago, Department of Radiophysics, Santiago de Compostela, La Coruna (Spain); Pumar, Jose Manuel [Complejo Hospitalario Universitario de Santiago, Department of Radiology, Santiago de Compostela, La Coruna (Spain); Campo, Victor Miguel del [Complejo Hospitalario Universitario de Vigo, Department of Public Health, Vigo, Pontevedra (Spain)

    2013-08-15

    To present an optimised low-dose multidetector computed tomography (MDCT) protocol for the study of children with cranial deformity. Ninety-one consecutive MDCT studies were performed in 80 children. Studies were performed with either our standard head CT protocol (group 1, n = 20) or a low-dose cranial deformity protocol (groups 2 and 3). Group 2 (n = 38), initial, and group 3 (n = 33), final and more optimised. All studies were performed in the same 64-MDCT equipment. Cranial deformity protocol was gradationally optimised decreasing kVp, limiting mA range, using automatic exposure control (AEC) and increasing the noise index (NI). Image quality was assessed. Dose indicators such us CT dose index volume (CTDIvol), dose-length product (DLP) and effective dose (E) were used. The optimised low-dose protocol reached the following values: 80 kVp, mA range: 50-150 and NI = 23. We achieved a maximum dose reduction of 10-22 times in the 1- to 12-month-old cranium in regard to the 2004 European guidelines for MDCT. A low-dose MDCT protocol that may be used as the first diagnostic imaging option in clinically selected patients with skull abnormalities. (orig.)

  19. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because...

  20. Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Cristina Campos

    2014-01-01

    Full Text Available This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n=9/group were divided in three groups: (1 ovariectomized (Ovx, (2 ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg, and (3 high dose (HE; 0.5 mg 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD and catalase (CAT activities, redox ratio (GSH/GSSG, total radical-trapping antioxidant potential (TRAP, hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.

  1. Comparison of colloid preload versus coload under low dose spinal anesthesia for cesarean delivery.

    Science.gov (United States)

    Varshney, Rohit; Jain, Gaurav

    2013-01-01

    Although fluid bolus is considered as a conventional prophylactic measure to prevent spinal-induced hypotension; vasopressors are nevertheless required. Low dose spinal anesthetics could markedly reduce such episodes of hypotension, by minimizing sympathetic blockade. We chose to compare the relative efficacy of colloid preload versus coload under low dose spinal anesthesia, for elective cesarean delivery. A prospective, randomized, double-blinded study. In total, 42 parturients were randomized to receive a preload (Group P) of hydroxyl ethyl starch (10 ml/kg) over 20 min before initiation of low dose spinal anesthesia (hyperbaric bupivacaine 5.5 mg with fentanyl 25 μg) or coload (Group C) of an identical fluid over 5 min, starting at the time of identification of cerebrospinal fluid. Our primary outcome included hemodynamic parameters and the incidence of hypotension. The neonatal outcome and side-effects were also monitored. Mann-Whitney U test and Fisher's exact/Chi-square test, whichever appropriate. A P advantage over the coload strategy, in reducing hypotensive episodes under low dose spinal anesthesia. Preload is better under large hemodynamic fluctuations while coload is preferable for emergency scenarios.

  2. [Prevention of preeclampsia with low-dose acetyl salicylic acid: critical assessment].

    Science.gov (United States)

    Verrotti, C; Fieni, S; Gualdi, M; Cavatorta, E

    1999-01-01

    The Authors present a critical review of the published literature about the effect of low dose of acido acetilsalicilico on prevention and treatment of preeclampic. Beginning from the effects of low daily dose of acido acetilsalicilico on the pregnancy, the Authors present the published datas from 1970 until today, and suggest the present directions for use of acido acetilsalicilico in pregnancy.

  3. Low dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

    DEFF Research Database (Denmark)

    Nielsen, Mads; Raundahl, Jakob; Pettersen, Paola

    2009-01-01

    Objective: To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density or heterogeneity compared to raloxifene. Secondarily, if these changes relate to changes in bone formation/resorption markers, and if these findings indicate elevation of breast cancer...

  4. Effect of radioimmunosuppression on the development of low-dose streptozotocin diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, H.J.; Barnstorf, K.; Nadrowitz, R.; Besch, W.; Schmidt, W. (Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic); Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

    1982-12-01

    The effect of whole-body irradiation (6.0 Gy) on the development of low-dose streptozotocin diabetes in male C57 Bl/KsJ-mice was investigated. After induction of the process of diabetes development, irradiation failed to interfere with the development of hyperglycemia and did not modify the reduced pancreatic insulin content after exogenous diabetes induction.

  5. Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms

    NARCIS (Netherlands)

    Koivisto, J.H.; Wolff, J.E.; Kiljunen, T.; Schulze, D.; Kortesniemi, M.

    2015-01-01

    The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the

  6. LOW-DOSE APROTININ IN INTERNAL MAMMARY ARTERY BYPASS OPERATIONS CONTRIBUTES TO IMPORTANT BLOOD SAVING

    NARCIS (Netherlands)

    SCHONBERGER, JPAM; EVERTS, PAM; ERCAN, H; BREDEE, JJ; BAVINCK, JH; BERREKLOUW, E; WILDEVUUR, CRM

    1992-01-01

    The effect on postoperative blood loss and blood use of blood-saving treatment with or without 280 mg of low-dose aprotinin (2 million kallikrein inactivator units) was studied in 200 consecutive patients undergoing either unilateral or bilateral internal mammary artery bypass grafting.

  7. Convolutional auto-encoder for image denoising of ultra-low-dose CT

    Directory of Open Access Journals (Sweden)

    Mizuho Nishio

    2017-08-01

    Conclusion: Neural network with convolutional auto-encoder could be trained using pairs of standard-dose and ultra-low-dose CT image patches. According to the visual assessment by radiologists and technologists, the performance of our proposed method was superior to that of large-scale nonlocal mean and block-matching and 3D filtering.

  8. Low-dose aspirin and preterm birth: a randomized controlled trial.

    Science.gov (United States)

    Silver, Robert M; Ahrens, Katherine; Wong, Luchin F; Perkins, Neil J; Galai, Noya; Lesher, Laurie L; Faraggi, David; Wactawski-Wende, Jean; Townsend, Janet M; Lynch, Anne M; Mumford, Sunni L; Sjaarda, Lindsey; Schisterman, Enrique F

    2015-04-01

    To evaluate the association between low-dose aspirin initiated before conception and the risk of preterm birth. This was a secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial. Women with a history of pregnancy loss (original stratum: one loss less than 20 weeks of gestation during the previous year; expanded stratum: one or two losses with no restrictions on timing or gestational age of the losses) were randomized to either daily low-dose aspirin (81 mg, n=615) and folic acid or folic acid alone (placebo; n=613). Preterm birth was compared between groups using intent-to-treat analysis. Preterm birth rates were 4.1% (22/535 low-dose aspirin) and 5.7% (31/543 placebo) (relative risk [RR] 0.72, 95% confidence interval [CI] 0.42-1.23); spontaneous preterm birth rates were 1.1% (6/535 low-dose aspirin) and 2.2% (12/543 placebo) (RR 0.51, 95% CI 0.19-1.34); medically indicated preterm birth rates were 2.6% (14/535 low-dose aspirin) and 2.9% (16/543 placebo) (RR 0.89, 95% CI 0.44-1.80). After restriction to confirmed pregnancies using inverse probability weighting, preterm birth rates were 5.7% and 9.0% (RR 0.63, 95% CI 0.37-1.09) and spontaneous preterm birth rates were 1.4% and 3.2% (RR 0.44, 95% CI 0.17-1.18). In confirmed pregnancies in the original stratum, preterm birth occurred in 3.8% and 9.7% of the low-dose aspirin and placebo groups, respectively (RR 0.39, 95% CI 0.16-0.94). Preconception low-dose aspirin was not significantly associated with the overall rate of preterm birth. Although the study was underpowered for this secondary analysis, numeric trends in favor of benefit, particularly in the women with a recent, single early pregnancy loss, warrant further investigation. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00467363.

  9. Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

    Science.gov (United States)

    Imai, Rumi; Miyazaki, Osamu; Horiuchi, Tetsuya; Asano, Keisuke; Nishimura, Gen; Sago, Haruhiko; Nosaka, Shunsuke

    2017-06-01

    Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes)(-0.5), the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

  10. Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Yinghua [Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States); Chen, Guang-Hong [Department of Medical Physics and Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States); Hacker, Timothy A.; Raval, Amish N. [Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Van Lysel, Michael S.; Speidel, Michael A., E-mail: speidel@wisc.edu [Department of Medical Physics and Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53705 (United States)

    2014-07-15

    Purpose: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. Methods: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. Results: Forin vivo studies, the 500 mA FBP maps gave −88.4%, −96.0%, −76.7%, and −65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring −94.7%, −81.6%, −84.0%, and −72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, −11.8%, and −3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was −9.7%, 8.8%, −3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937

  11. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials

    Directory of Open Access Journals (Sweden)

    Audrey eCharlebois

    2014-04-01

    Full Text Available Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277. Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta 1-4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine (PNAG. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials.

  12. Exposure to low dose of gamma radiation enhances the excision repair in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, K.; Verma, N.C. [Bhabha Atomic Research Centre, Mumbai (India)

    1998-08-01

    The effect of low doses of ionizing and nonionizing radiation on the radiation response of yeast Saccharomyces cerevisiae toward ionizing and nonionizing radiation was studied. The wild-type strain D273-10B on exposure to 54 Gy gamma radiation (resulting in about 10% cell killing) showed enhanced resistance to subsequent exposure to UV radiation. This induced UV resistance increased with the incubation time between the initial gamma radiation stress and the UV irradiation. Exposure to low doses of UV light on the other hand showed no change in gamma or UV radiation response of this strain. The strains carrying a mutation at rad52 behaved in a way similar to the wild type, but with slightly reduced induced response. In contrast to this, the rad3 mutants, defective in excision repair, showed no induced UV resistance. Removal of UV-induced pyrimidine dimers in wild-type yeast DNA after UV irradiation was examined by analyzing the sites recognized by UV endonuclease from Micrococcus luteus. The samples that were exposed to low doses of gamma radiation before UV irradiation were able to repair the pyrimidine dimers more efficiently than the samples in which low gamma irradiation was omitted. The nature of enhanced repair was studied by scoring the frequency of induced gene conversion and reverse mutation at trp and ilv loci respectively in strain D7, which showed similar enhanced UV resistance induced by low-dose gamma irradiation. The induced repair was found to be essentially error-free. These results suggest that irradiation of strain D273-10B with low doses of gamma radiation enhances its capability for excision repair of UV-induced pyrimidine dimers. (author)

  13. Exposure to low-dose barium by drinking water causes hearing loss in mice.

    Science.gov (United States)

    Ohgami, Nobutaka; Hori, Sohjiro; Ohgami, Kyoko; Tamura, Haruka; Tsuzuki, Toyonori; Ohnuma, Shoko; Kato, Masashi

    2012-10-01

    We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice. We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry. Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups. Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

    Directory of Open Access Journals (Sweden)

    Ning Ma

    Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

  15. Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?

    Science.gov (United States)

    Shen, Fang-Zhen; Wang, Jing; Liang, Jun; Mu, Kun; Hou, Ji-Yuan; Wang, Yan-Tao

    2010-02-01

    Low-dose chemotherapy drugs can suppress tumours by restraining tumour vessel growth and preventing the repair of damaged vascular endothelial cells. Cisplatin is a broad-spectrum, cell cycle-non-specific drug, but has serious side effects if used at high doses. There have been few reports on the anti-angiogenic effects of low-dose cisplatin and hence the effect of low-dose metronomic (LDM) chemotherapy on the proliferation and neovascularization of H22 hepatocarcinoma cells is discussed in this research. The influence of LDM chemotherapy with cisplatin on human umbilical vascular endothelial cells (HUVECs) and proliferation of the HepG(2) human hepatocarcinoma cell line were measured using MTT assays. The LDM group was treated with cisplatin 0.6 mg/kg/day; the control group with saline 0.2 ml; the maximum tolerated dose (MTD) group with cisplatin 9 mg/kg/day. Vascular endothelial growth factor (VEGF) and matrix metallopeptidase 2 (MMP-2) were detected using immunohistochemical staining. A chicken chorio-allantoic membrane (CAM) model was used to check the inhibitory effect of LDM chemotherapy with cisplatin on neovascularization in vivo. Low-dose cisplatin inhibited HUVEC proliferation in a dose- and time-dependent manner, but was ineffective in inhibiting HepG(2) cell proliferation. Tumour growth was delayed in mice receiving LDM cisplatin, without apparent body weight loss, compared with mice that received MTD cisplatin. Microvessel density and expression of VEGF and MMP-2 were much lower in mice receiving LDM cisplatin than in the control and MTD groups. Continuous low-dose cisplatin suppressed CAM angiogenesis in vivo. LDM chemotherapy with cisplatin can inhibit the growth of blood vessel endothelial cells in vitro and shows anti-angiogenic ability in vivo.

  16. Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

    Science.gov (United States)

    Kim, Sae-Hoon; Park, Da-Eun; Lee, Hyun-Seung; Kang, Hye-Ryun; Cho, Sang-Heon

    2014-01-01

    Background Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR). Methods Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro. Results Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro. Conclusion Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways. PMID:25202911

  17. Toxicity bioassay in mice exposed to low dose-rate radiation

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    Kim, Joog Sun; Gong, Eun Ji; Heo, Kyu; Yang, Kwang Mo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2013-04-15

    The systemic effect of radiation increases in proportion to the dose amount and rate. The association between accumulated radiation dose and adverse effects, which is derived according to continuous low dose-rate radiation exposure, is not clearly elucidated. Our previous study showed that low dose-rate radiation exposure did not cause adverse effects in BALB/c mice at dose levels of ≤2 Gy, but the testis weight decreased at a dose of 2 Gy. In this study, we studied the effects of irradiation at the low dose rate (3.49 mGy/h) in the testes of C57BL/6 mice. Mice exposed to a total dose of 0.02, 0.2, and 2 Gy were found to be healthy and did not show any significant changes in body weight and peripheral blood components. However, mice irradiated with a dose of 2 Gy had significantly decreased testis weight. Further, histological studies and sperm evaluation also demonstrated changes consistent with the findings of decreased testis weight. In fertile patients found to have arrest of sperm maturation, the seminiferous tubules lack the DNMT1 and HDAC1 protein. The decrease of DNMT1 and HDAC1 in irradiated testis may be the part of the mechanism via which low dose-rate irradiation results in teticular injury. In conclusion, despite a low dose-rate radiation, our study found that when mice testis were irradiated with 2 Gy at 3.49 mGy/h dose rate, there was significant testicular and sperm damage with decreased DNMT1 and HDAC1 expression.

  18. AT cells are not radiosensitive for simple chromosomal exchanges at low dose

    Energy Technology Data Exchange (ETDEWEB)

    Hada, Megumi; Huff, Janice L.; Patel, Zarana S. [USRA Division of Life Sciences, Houston, TX 77058 (United States); Kawata, Tetsuya [Department of Radiology, School of Medicine, Keio University, Tokyo (Japan); Pluth, Janice M. [Lawrence Berkeley National Laboratory, Life Sciences Division, One Cyclotron Road, Building 74, Berkeley, CA 94720 (United States); George, Kerry A. [Wyle, 1290 Hercules Drive, Houston, TX 77058 (United States); Cucinotta, Francis A., E-mail: Francis.A.Cucinotta@nasa.gov [NASA, Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058 (United States)

    2011-11-01

    Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5 Gy) of ionizing radiation (X-rays or {gamma}-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5 Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1 Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1 Gy and higher, but were similar to wild type cells at 0.5 Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.

  19. Exposure of luminous marine bacteria to low-dose gamma-radiation.

    Science.gov (United States)

    Kudryasheva, N S; Petrova, A S; Dementyev, D V; Bondar, A A

    2017-04-01

    The study addresses biological effects of low-dose gamma-radiation. Radioactive 137Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Fasola, Carolina E. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Jones, Jennifer C. [Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (United States); Huang, Derek D. [Department of Internal Medicine, University of California-Los Angeles Olive View, Sylmar, California (United States); Le, Quynh-Thu; Hoppe, Richard T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

    2013-08-01

    Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

  1. Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

    2014-07-29

    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  2. Low-dose radiation employed in diagnostic imaging causes genetic effects in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Ponzinibbio, Maria V.; Peral-Garcia, Pilar; Seoane, Analia (Inst. de Genetica Veterinaria, Univ. Nacional de La Plata CONICET, La Plata (Argentina)), e-mail: aseoane@fcv.unlp.edu.ar; Crudeli, Cintia (Agencia Nacional de Promocion Cientifica y Tecnologica, La Plata (Argentina))

    2010-11-15

    Background: Exposure to environmental, diagnostic, and occupational sources of radiation frequently involves low doses. Although these doses have no immediately noticeable impact on human health there is great interest in their long-term biological effects. Purpose: To assess immediate and time-delayed DNA damage in two cell lines exposed to low doses of ionizing radiation by using the comet assay and micronucleus test, and to compare these two techniques in the analysis of low-dose induced genotoxicity. Material and Methods: CHO and MRC-5 cells were exposed to 50 milliSievert (mSv) of ionizing radiation and assayed immediately after irradiation and at 16 or 12 passages post-irradiation, respectively. Comet assay and micronucleus test were employed. Results: The comet assay values observed in 50 mSv-treated cells were significantly higher than in the control group for both sample times and cell lines (P < 0.001). Micronuclei frequencies were higher in treated cells than in the control group (P < 0.01, CHO cells passage 16; P < 0.05, MRC-5 cells immediately after exposure; P < 0.01 MRC-5 cells passage 12). Correlation analysis between the two techniques was statistically significant (correlation coefficient 0.82, P < 0.05 and correlation coefficient 0.86, P < 0.05 for CHO and MRC-5 cells, respectively). Cells scored at passages 12 or 16 showed more damage than those scored immediately after exposure in both cell lines (no statistically significant differences). Conclusion: Cytomolecular and cytogenetic damage was observed in cells exposed to very low doses of X-rays and their progeny. A single low dose of ionizing radiation was sufficient to induce such response, indicating that mammalian cells are exquisitely sensitive to it. Comet and micronucleus assays are sensitive enough to assess this damage, although the former seems to be more efficient

  3. Validation of a low dose simulation technique for computed tomography images.

    Directory of Open Access Journals (Sweden)

    Daniela Muenzel

    Full Text Available PURPOSE: Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT images from an original higher dose scan. MATERIALS AND METHODS: Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV of a swine were acquired (approved by the regional governmental commission for animal protection. Simulations of CT acquisition with a lower dose (simulated 10-80 mAs were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. RESULTS: Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was -1.2% (range -9% to 3.2% and -0.2% (range -8.2% to 3.2%, respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9-10.2 HU (noise and 1.9-13.4 HU (CT values, without significant differences (p>0.05. Subjective observer evaluation of image appearance showed no visually detectable difference. CONCLUSION: Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques.

  4. A low dose simulation tool for CT systems with energy integrating detectors.

    Science.gov (United States)

    Zabić, Stanislav; Wang, Qiu; Morton, Thomas; Brown, Kevin M

    2013-03-01

    This paper introduces a new strategy for simulating low-dose computed tomography (CT) scans using real scans of a higher dose as an input. The tool is verified against simulations and real scans and compared to other approaches found in the literature. The conditional variance identity is used to properly account for the variance of the input high-dose data, and a formula is derived for generating a new Poisson noise realization which has the same mean and variance as the true low-dose data. The authors also derive a formula for the inclusion of real samples of detector noise, properly scaled according to the level of the simulated x-ray signals. The proposed method is shown to match real scans in number of experiments. Noise standard deviation measurements in simulated low-dose reconstructions of a 35 cm water phantom match real scans in a range from 500 to 10 mA with less than 5% error. Mean and variance of individual detector channels are shown to match closely across the detector array. Finally, the visual appearance of noise and streak artifacts is shown to match in real scans even under conditions of photon-starvation (with tube currents as low as 10 and 80 mA). Additionally, the proposed method is shown to be more accurate than previous approaches (1) in achieving the correct mean and variance in reconstructed images from pure-Poisson noise simulations (with no detector noise) under photon-starvation conditions, and (2) in simulating the correct noise level and detector noise artifacts in real low-dose scans. The proposed method can accurately simulate low-dose CT data starting from high-dose data, including effects from photon starvation and detector noise. This is potentially a very useful tool in helping to determine minimum dose requirements for a wide range of clinical protocols and advanced reconstruction algorithms.

  5. Low-dose human menopausal gonadotrophin versus clomiphene citrate in subfertile couples treated with intrauterine insemination: a randomized controlled trial.

    Science.gov (United States)

    Peeraer, Karen; Debrock, Sophie; De Loecker, Peter; Tomassetti, C; Laenen, A; Welkenhuysen, M; Meeuwis, L; Pelckmans, S; Mol, B W; Spiessens, C; De Neubourg, D; D'Hooghe, T M

    2015-05-01

    Can controlled ovarian stimulation with low-dose human menopausal gonadotrophin (hMG) improve the clinical pregnancy rate when compared with ovarian stimulation with clomiphene citrate (CC) in an intrauterine insemination (IUI) programme for subfertile couples? Ovarian stimulation with low-dose hMG is superior to CC in IUI cycles with respect to clinical pregnancy rate. IUI after ovarian stimulation is an effective treatment for mild male subfertility, unexplained subfertility and minimal-mild endometriosis, but it is unclear which medication for ovarian stimulation is more effective. A total of 330 women scheduled for IUI during 657 cycles (September 2004-December 2011) were enrolled in an open-label randomized clinical trial to ovarian stimulation with low-dose hMG subcutaneous (n = 334, 37.5-75 IU per day) or CC per oral (n = 323, 50 mg/day from Day 3-7). Assuming a difference of 10% in 'clinical pregnancy with positive fetal heart beat', we needed 219 cycles per group (alpha-error 0.05, power 0.80). We studied subfertile couples with mild male subfertility, unexplained subfertility or minimal-mild endometriosis. Further inclusion criteria were failure to conceive for ≥12 months, female age ≤42 years, at least one patent Fallopian tube and a total motility count (TMC) ≥5.0 million spermatozoa after capacitation. The primary end-point was clinical pregnancy. Analysis was by intention to treat and controlled for the presence of multiple measures, as one couple could have more randomizations in multiple cycles. Linear mixed models were used for continuous measures. For binary outcomes we estimated the relative risk using a Poisson model with log link and using generalized estimating equations. When compared with ovarian stimulation with CC, hMG stimulation was characterized by a higher clinical pregnancy rate (hMG 48/334 (14.4%) versus CC 29/323 (9.0%), relative risk (RR) 1.6 (95% confidence interval (CI) 1.1-2.4)), higher live birth rate (hMG 46/334 (13

  6. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

    Directory of Open Access Journals (Sweden)

    Yen Chia-Hung

    2012-07-01

    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  7. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    Science.gov (United States)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  8. Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury-to-chronic kidney disease progression.

    Science.gov (United States)

    Tampe, Björn; Steinle, Ulrike; Tampe, Désirée; Carstens, Julienne L; Korsten, Peter; Zeisberg, Elisabeth M; Müller, Gerhard A; Kalluri, Raghu; Zeisberg, Michael

    2017-01-01

    Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is known that the antihypertensive drug hydralazine has demethylating activity, and that its optimum demethylating activity occurs at concentrations below blood pressure-lowering doses. Administration of low-dose hydralazine effectively induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter demethylation subsequently attenuated renal fibrosis and preserved excretory renal function independent of its blood pressure-lowering effects. In comparison, RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not detected upon administration of the angiotensin-converting enzyme inhibitor Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Final Report - Epigenetics of low dose radiation effects in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low

  10. Adding low dose rocuronium to local anesthetic mixture: Effect on quality of peribulbar blockade for vitreoretinal surgery

    Directory of Open Access Journals (Sweden)

    Mohamed T. Ghanem

    2016-04-01

    Conclusion: Adding low dose rocuronium to local anesthetics prolongs duration of peribulbar anesthesia and offers an optimal surgical condition without serious adverse effects for patients undergoing VR surgery.

  11. Influence of Ultra-Low-Dose and Iterative Reconstructions on the Visualization of Orbital Soft Tissues on Maxillofacial CT.

    Science.gov (United States)

    Widmann, G; Juranek, D; Waldenberger, F; Schullian, P; Dennhardt, A; Hoermann, R; Steurer, M; Gassner, E-M; Puelacher, W

    2017-08-01

    Dose reduction on CT scans for surgical planning and postoperative evaluation of midface and orbital fractures is an important concern. The purpose of this study was to evaluate the variability of various low-dose and iterative reconstruction techniques on the visualization of orbital soft tissues. Contrast-to-noise ratios of the optic nerve and inferior rectus muscle and subjective scores of a human cadaver were calculated from CT with a reference dose protocol (CT dose index volume = 36.69 mGy) and a subsequent series of low-dose protocols (LDPs I-4: CT dose index volume = 4.18, 2.64, 0.99, and 0.53 mGy) with filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR)-50, ASIR-100, and model-based iterative reconstruction. The Dunn Multiple Comparison Test was used to compare each combination of protocols (α = .05). Compared with the reference dose protocol with FBP, the following statistically significant differences in contrast-to-noise ratios were shown (all, P ≤ .012) for the following: 1) optic nerve: LDP-I with FBP; LDP-II with FBP and ASIR-50; LDP-III with FBP, ASIR-50, and ASIR-100; and LDP-IV with FBP, ASIR-50, and ASIR-100; and 2) inferior rectus muscle: LDP-II with FBP, LDP-III with FBP and ASIR-50, and LDP-IV with FBP, ASIR-50, and ASIR-100. Model-based iterative reconstruction showed the best contrast-to-noise ratio in all images and provided similar subjective scores for LDP-II. ASIR-50 had no remarkable effect, and ASIR-100, a small effect on subjective scores. Compared with a reference dose protocol with FBP, model-based iterative reconstruction may show similar diagnostic visibility of orbital soft tissues at a CT dose index volume of 2.64 mGy. Low-dose technology and iterative reconstruction technology may redefine current reference dose levels in maxillofacial CT. © 2017 by American Journal of Neuroradiology.

  12. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Neera Tewari-Singh

    Full Text Available Chemical warfare agent sulfur mustard (HD inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%, and activation of transcription factors NF-κB and AP-1 (complete reversal. Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  13. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    Science.gov (United States)

    Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  14. High-order noise analysis for low dose iterative image reconstruction methods: ASIR, IRIS, and MBAI

    Science.gov (United States)

    Do, Synho; Singh, Sarabjeet; Kalra, Mannudeep K.; Karl, W. Clem; Brady, Thomas J.; Pien, Homer

    2011-03-01

    Iterative reconstruction techniques (IRTs) has been shown to suppress noise significantly in low dose CT imaging. However, medical doctors hesitate to accept this new technology because visual impression of IRT images are different from full-dose filtered back-projection (FBP) images. Most common noise measurements such as the mean and standard deviation of homogeneous region in the image that do not provide sufficient characterization of noise statistics when probability density function becomes non-Gaussian. In this study, we measure L-moments of intensity values of images acquired at 10% of normal dose and reconstructed by IRT methods of two state-of-art clinical scanners (i.e., GE HDCT and Siemens DSCT flash) by keeping dosage level identical to each other. The high- and low-dose scans (i.e., 10% of high dose) were acquired from each scanner and L-moments of noise patches were calculated for the comparison.

  15. Low-dose aspirin use and the risk of ovarian cancer in Denmark

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kjaer, S K; Olsen, J H

    2015-01-01

    BACKGROUND: A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low......-dose aspirin and the risk of ovarian cancer. PATIENTS AND METHODS: We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using...... risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic...

  16. Growth factors, glucose and insulin kinetics after low dose growth hormone in HIV - lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Flyvbjerg, Allan

    2006-01-01

    OBJECTIVES: Low-dose growth hormone (GH) administration has been suggested as a treatment for HIV-lipodystrophy. METHODS: Postglucose GH-secretion, kinetics of insulin-like growth factors (IGFs), insulin, and glucose metabolism were examined in six male HIV-infected lipodystrophic patients (two...... during a 5h oral glucose-tolerance test. Near lower normal limits in all patients before GH-therapy, total and free IGF-I increased between 87 and 152% during the GH-therapy (P... on circulating IGF-I, glucose metabolism, and insulin kinetics, 0.7 mg/day of GH may be expedient for treatment of HIV-infected males with lipodystrophy. Whether the patients' glucose metabolic status matters for the IGF-response to low-dose GH-therapy awaits further investigation....

  17. Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT

    DEFF Research Database (Denmark)

    Ashraf, Haseem; Saghir, Zaigham; Dirksen, Asger

    2014-01-01

    to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening......BACKGROUND: We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised...... round were handled using two different models. RESULTS: There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p

  18. Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation

    Science.gov (United States)

    Liu, Shu-Zheng

    2007-01-01

    Previous studies showed that low dose radiation (LDR) could stimulate the immune system in both animal and human populations. This paper reviews the present status of relevant research as support to the use of LDR in clinical practice for cancer prevention and treatment. It has been demonstrated that radiation-induced changes in immune activity follows an inverse J-shaped curve, i.e., low dose stimulation and high dose suppression. The stimulation of immunity by LDR concerns most anticancer parameters, including antibody formation, natural killer activity, secretion of interferon and other cytokines as well as other cellular changes. Animal studies have revealed that LDR retards tumor growth, decreases cancer metastasis, and inhibits carcinogenesis induced by high dose radiation. These effects of LDR on cancer control were found to be related to its stimulation on immunity. The experimental data may well explain the efficacy of the clinical trial of LDR in the treatment of cancer. PMID:18648611

  19. A sub-sampled approach to extremely low-dose STEM

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, A. [OptimalSensing, Southlake, Texas 76092, USA; Duke University, ECE, Durham, North Carolina 27708, USA; Luzi, L. [Rice University, ECE, Houston, Texas 77005, USA; Yang, H. [Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA; Kovarik, L. [Pacific NW National Laboratory, Richland, Washington 99354, USA; Mehdi, B. L. [Pacific NW National Laboratory, Richland, Washington 99354, USA; University of Liverpool, Materials Engineering, Liverpool L69 3GH, United Kingdom; Liyu, A. [Pacific NW National Laboratory, Richland, Washington 99354, USA; Gehm, M. E. [Duke University, ECE, Durham, North Carolina 27708, USA; Browning, N. D. [Pacific NW National Laboratory, Richland, Washington 99354, USA; University of Liverpool, Materials Engineering, Liverpool L69 3GH, United Kingdom

    2018-01-22

    The inpainting of randomly sub-sampled images acquired by scanning transmission electron microscopy (STEM) is an attractive method for imaging under low-dose conditions (≤ 1 e-2) without changing either the operation of the microscope or the physics of the imaging process. We show that 1) adaptive sub-sampling increases acquisition speed, resolution, and sensitivity; and 2) random (non-adaptive) sub-sampling is equivalent, but faster than, traditional low-dose techniques. Adaptive sub-sampling opens numerous possibilities for the analysis of beam sensitive materials and in-situ dynamic processes at the resolution limit of the aberration corrected microscope and is demonstrated here for the analysis of the node distribution in metal-organic frameworks (MOFs).

  20. Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women

    DEFF Research Database (Denmark)

    Sturdee, D.W.; Archer, D.F.; Rakov, V.

    2008-01-01

    and informed consent were obtained prior to initiation and enrollment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound......: The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment......OBJECTIVE: To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding. METHODS: A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval...

  1. The Effects of Low Dose {gamma}-Irradiation on MIA Induced Joint Inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Seok Chan; Lee, Ko Eun; Kim, Eun-hea; Lee, Tae Woong; Lee, Won Ho; Kim, June Sun [Korea University, College of Health Science, Seoul (Korea, Republic of)

    2010-10-15

    Inflammation of the synovial membrane is associated with the progression of cartilage degeneration and unexpected pain in osteoarthritis (OA). Inflammation produces painful sensations which are largely divided into spontaneous (non-evoked) pain and evoked pain depending on the presence of external stimuli and are characterized by hyperalgesia and allodynia Nitric oxide (NO) is related to the pathogenesis of OA as inflammatory mediator. Inducible nitric oxide synthase (iNOS) is marker of enhanced NO production in arthritic pain. In previously, low dose irradiation can suppress pro-inflammatory cytokines. But, ray therapeutic effect is unclear. Thus, present study examined the preemptive effect of low dose irradiation on the development of inflammatory pain in MIA induced OA animal model

  2. Growth factors, glucose and insulin kinetics after low dose growth hormone in HIV - lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Flyvbjerg, Allan

    2006-01-01

    OBJECTIVES: Low-dose growth hormone (GH) administration has been suggested as a treatment for HIV-lipodystrophy. METHODS: Postglucose GH-secretion, kinetics of insulin-like growth factors (IGFs), insulin, and glucose metabolism were examined in six male HIV-infected lipodystrophic patients (two...... and temporary reduction in insulin sensitivity was caused by a reduction in non-oxidative glucose metabolism (n=5). GH-administration reduced hepatic extraction of insulin alleviating the demand for insulin secretion (n=5). No adverse effects of GH were detected. CONCLUSIONS: As judged from effects...... on circulating IGF-I, glucose metabolism, and insulin kinetics, 0.7 mg/day of GH may be expedient for treatment of HIV-infected males with lipodystrophy. Whether the patients' glucose metabolic status matters for the IGF-response to low-dose GH-therapy awaits further investigation....

  3. Issues in low dose radiation biology: the controversy continues. A perspective.

    Science.gov (United States)

    Morgan, William F; Bair, William J

    2013-05-01

    Both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. Much of this is unavoidable, e.g., natural background radiation, but as the use of radiation increases, so does the potential health risk and the public's concerns. This perspective reflects the authors' view of current issues in low dose radiation biology research, highlights some of the controversies therein, and suggests areas of future research to address both issues in low dose radiation research and the controversies. This is a critical time for the radiation sciences and the implications of future research will have a significant impact on radiation protection, medicine, national security, research and industry. The views expressed here are the authors' own and do not represent any institution, organization or funding body.

  4. Non-targeted effects of ionising radiation—Implications for low dose risk

    DEFF Research Database (Denmark)

    Kadhim, Munira; Salomaa, Sisko; Wright, Eric

    2013-01-01

    Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects an......) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. © 2012 Elsevier B.V. All rights reserved....... and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly...

  5. Simulating threshold voltage shift of MOS devices due to radiation in the low-dose range

    CERN Document Server

    Wan Xin Heng; Gao Wen Yu; Huang Ru; Wang Yang Yuan

    2002-01-01

    An analytical MOSFET threshold voltage shift model due to radiation in the low-dose range has been developed for circuit simulations. Experimental data in the literature shows that the model predictions are in good agreement. It is simple in functional form and hence computationally efficient. It can be used as a basic circuit simulation tool for analysing MOSFET exposed to a nuclear environment up to about 1 Mrad(Si). In accordance with common believe, radiation induced absolute change of threshold voltage was found to be larger in irradiated PMOS devices. However, if the radiation sensitivity is defined in the way authors did it, the results indicated NMOS rather than PMOS devices are more sensitive, specially at low doses. This is important from the standpoint of their possible application in dosimetry

  6. "EFFECT OF HIGH VERSUS LOW DOSES OF HUMAN RECOMBINANT ERYTHROPOIETIN ON THE ANEMIA OF PREMATURITY"

    Directory of Open Access Journals (Sweden)

    A. Mohammadzadeh

    2005-05-01

    Full Text Available Recombinant human erythropoietin (rh-EPO is known to accelerate erythropoiesis in preterm infants. The purpose of this study was to compare the effectiveness of early treatment with two doses of rh-EPO (high vs. low dose in the management of anemia of prematurity. Twenty preterm infants with hematocrit (Hct < 30% when infant’s age was between 2 to 3 weeks after birth or Hct <25% when infant’s age was more than 3 weeks after birth, were divided randomly in two groups, each group including 10 babies. Infants in high dose group received 500 u/kg rh-EPO twice per week and the low dose group received 500 u/kg rh-EPO weekly. All infants were fed human milk supplemented with enteral iron. Hematocrit and reticulocyte counts were determined for each infant at the start of the study, 3 days after start of treatment and one week after the end of treatment. The means of gestational age in high dose and low dose groups were 31.4 ± 2.2 and 31.3±2.0 weeks, respectively. Means of birth weight in high dose and low dose groups were 1366 ± 243 and 1438±249 gr, respectively. The two groups were significantly different in reticulocyte count at 3 days after treatment (P = 0.047 and in hematocrit at the end of study (P < 0.0001. We concluded the early treatment of anemia of prematurity with high dose rh-EPO with supplemental iron significantly increases hematocrit and reticulocyte in preterm infants and reduce the need for blood transfusion in these high risk neonates.

  7. Edge enhancement algorithm for low-dose X-ray fluoroscopic imaging.

    Science.gov (United States)

    Lee, Min Seok; Park, Chul Hee; Kang, Moon Gi

    2017-12-01

    Low-dose X-ray fluoroscopy has continually evolved to reduce radiation risk to patients during clinical diagnosis and surgery. However, the reduction in dose exposure causes quality degradation of the acquired images. In general, an X-ray device has a time-average pre-processor to remove the generated quantum noise. However, this pre-processor causes blurring and artifacts within the moving edge regions, and noise remains in the image. During high-pass filtering (HPF) to enhance edge detail, this noise in the image is amplified. In this study, a 2D edge enhancement algorithm comprising region adaptive HPF with the transient improvement (TI) method, as well as artifacts and noise reduction (ANR), was developed for degraded X-ray fluoroscopic images. The proposed method was applied in a static scene pre-processed by a low-dose X-ray fluoroscopy device. First, the sharpness of the X-ray image was improved using region adaptive HPF with the TI method, which facilitates sharpening of edge details without overshoot problems. Then, an ANR filter that uses an edge directional kernel was developed to remove the artifacts and noise that can occur during sharpening, while preserving edge details. The quantitative and qualitative results obtained by applying the developed method to low-dose X-ray fluoroscopic images and visually and numerically comparing the final images with images improved using conventional edge enhancement techniques indicate that the proposed method outperforms existing edge enhancement methods in terms of objective criteria and subjective visual perception of the actual X-ray fluoroscopic image. The developed edge enhancement algorithm performed well when applied to actual low-dose X-ray fluoroscopic images, not only by improving the sharpness, but also by removing artifacts and noise, including overshoot. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Low-Dose X-ray CT Reconstruction via Dictionary Learning

    Science.gov (United States)

    Xu, Qiong; Zhang, Lei; Hsieh, Jiang; Wang, Ge

    2013-01-01

    Although diagnostic medical imaging provides enormous benefits in the early detection and accuracy diagnosis of various diseases, there are growing concerns on the potential side effect of radiation induced genetic, cancerous and other diseases. How to reduce radiation dose while maintaining the diagnostic performance is a major challenge in the computed tomography (CT) field. Inspired by the compressive sensing theory, the sparse constraint in terms of total variation (TV) minimization has already led to promising results for low-dose CT reconstruction. Compared to the discrete gradient transform used in the TV method, dictionary learning is proven to be an effective way for sparse representation. On the other hand, it is important to consider the statistical property of projection data in the low-dose CT case. Recently, we have developed a dictionary learning based approach for low-dose X-ray CT. In this paper, we present this method in detail and evaluate it in experiments. In our method, the sparse constraint in terms of a redundant dictionary is incorporated into an objective function in a statistical iterative reconstruction framework. The dictionary can be either predetermined before an image reconstruction task or adaptively defined during the reconstruction process. An alternating minimization scheme is developed to minimize the objective function. Our approach is evaluated with low-dose X-ray projections collected in animal and human CT studies, and the improvement associated with dictionary learning is quantified relative to filtered backprojection and TV-based reconstructions. The results show that the proposed approach might produce better images with lower noise and more detailed structural features in our selected cases. However, there is no proof that this is true for all kinds of structures. PMID:22542666

  9. Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

    Science.gov (United States)

    Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

    2017-10-07

    We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

  10. Low dose radiation risks for women surviving the a-bombs in Japan: generalized additive model.

    Science.gov (United States)

    Dropkin, Greg

    2016-11-24

    Analyses of cancer mortality and incidence in Japanese A-bomb survivors have been used to estimate radiation risks, which are generally higher for women. Relative Risk (RR) is usually modelled as a linear function of dose. Extrapolation from data including high doses predicts small risks at low doses. Generalized Additive Models (GAMs) are flexible methods for modelling non-linear behaviour. GAMs are applied to cancer incidence in female low dose subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to test for linearity, explore interactions, adjust for the skewed dose distribution, examine significance below 100 mGy, and estimate risks at 10 mGy. For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20 mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low doses, RR increases with age-at-exposure and decreases with time-since-exposure, the preferred covariate. Using the empirical cumulative distribution of dose improves model fit, and capacity to detect non-linear responses. RR is elevated over wide ranges of covariate values. Results are stable under simulation, or when removing exceptional data cells, or adjusting neutron RBE. Estimates of Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times higher than extrapolations from a linear model fitted to the full cohort. Below 100 mGy, quasipoisson models find significant effects for all solid, squamous, uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at-exposure > 35 yrs. Results for the thyroid are compatible with studies of children treated for tinea capitis, and Chernobyl survivors. Results for the uterus are compatible with studies of UK nuclear workers and the Techa River cohort. Non-linear models find large, significant cancer risks for Japanese women exposed to low dose radiation from the atomic bombings. The risks should be reflected in protection standards.

  11. PERIOPERATIVE LOW-DOSE KETAMINE DIMINISHES POST-OPERATIVE CAESAREAN PAIN, NAUSEA & VOMITING AFTER SPINAL ANAESTHESIA

    OpenAIRE

    EDİPOĞLU, İpek Saadet; ÇELİK, Fatma Sevinç; Omaygenç, Derya Özden

    2017-01-01

    Objective: Despite various developments in the treatment ofpost-operative caesarean pain, there are still difficulties in satisfyingpatients due to individual differences. Ketamine is used as a potentanaesthetic and an effective analgesic since 1960’s. The purpose of our studyis to observe the effects of low-dose ketamine applied following spinalanaesthesia for postoperative analgesia and  nausea & vomiting in pregnant patients.Materıal and Method: We examined the Visual Anal...

  12. Evaluation of low dose ionizing radiation effect on some blood components in animal model

    OpenAIRE

    H. El-Shanshoury; G. El-Shanshoury; A. Abaza

    2016-01-01

    Exposure to ionizing radiation is known to have lethal effects in blood cells. It is predicted that an individual may spend days, weeks or even months in a radiation field without becoming alarmed. The study aimed to discuss the evaluation of low dose ionizing radiation (IR) effect on some blood components in animal model. Hematological parameters were determined for 110 animal rats (divided into 8 groups) pre- and post-irradiation. An attempt to explain the blood changes resulting from both ...

  13. Initial evaluation of low-dose phenobarbital as an indicator of compliance with antimalarial drug treatment.

    OpenAIRE

    Karbwang, J.; Fungladda, W.; Pickard, C. E.; Shires, S.; Hay, A.; Feely, M.

    1998-01-01

    Since poor compliance with antimalarial therapy is often suspected but difficult to prove, this study attempted to establish a model for predicting the plasma concentration of phenobarbital (given in low doses in conjunction with the drug) as an indicator of compliance. Phenobarbital was chosen because its value had been demonstrated as a marker of compliance in long-course therapies, any significant departure from steady-state concentrations (achieved with full compliance) indicating one or ...

  14. Low-Dose CT of the Paranasal Sinuses: Minimizing X-Ray Exposure with Spectral Shaping.

    Science.gov (United States)

    Wuest, Wolfgang; May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael

    2016-11-01

    Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192x0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 × 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDIvol 1.2 mGy vs. 4.4 mGy, p image quality at a very low radiation exposure. • Spectral optimization (tin filtration) is beneficial to low-dose parasinus CT • Tin filtration at 100 kV yields sufficient image quality for pre-operative planning • Diagnostic parasinus CT can be performed with an effective dose <0.05 mSv.

  15. The treatment of autism with low-dose phenytoin: a case report.

    Science.gov (United States)

    Bird, Philip D

    2015-01-16

    The drug treatment of autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions (such as inattention or irritability) that frequently coexist, with limited benefit for the core social deficits. Here, I describe the novel use of a low dose of the anti-epileptic phenytoin to enhance social functioning in a patient with an autism spectrum disorder. I present the case of a 19-year-old Caucasian man with autism spectrum disorder treated with stimulant medication since early childhood. He experienced long-standing difficulties in establishing and maintaining relationships and reading social cues, and was socially isolated. Within 10 minutes of a single sublingual low dose of phenytoin there was an immediate observable improvement in his eye contact and integration of both verbal and non-verbal communication. This enhanced social functioning associated with his adherence to the low-dose phenytoin therapy was maintained for over 18 months of follow-up. These clinical observations were supported by ratings using the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales, recorded pre-treatment and after seven months on 5mg phenytoin. This case report provides the first potential evidence that a low dose of phenytoin, a widely used and well tolerated anti-epileptic medication, may be capable of modifying the core social cognitive deficits associated with autism spectrum disorders. While acknowledging this is a single case study, the lack of availability of safe and effective treatments to address the important core deficits associated with autism spectrum disorders makes this case noteworthy.

  16. Renoprotective immunosuppression by pioglitazone with low-dose cyclosporine in rat heart transplantation.

    Science.gov (United States)

    Tanaka, Yosuke; Hasegawa, Tomomi; Chen, Zhi; Okita, Yutaka; Okada, Kenji

    2009-09-01

    The peroxisome proliferator-activated receptor gamma activator pioglitazone has recently been reported to possess pleiotropic cardioprotective and renoprotective actions. We hypothesized that pioglitazone would reduce a dose of the immunosuppressant cyclosporine after heart transplantation, resulting in beneficial protective effects for both cardiac allografts and recipient kidneys. Experiments were performed by using an allomismatched rat heterotopic heart transplantation model. Recipients were treated with cyclosporine with or without pioglitazone and were divided into one of 4 groups: group I, no treatment; group II, low-dose cyclosporine (2 mg x kg(-1) x d(-1)); group III, high-dose cyclosporine (5 mg x kg(-1) x d(-1)); and group IV, low-dose cyclosporine with pioglitazone (3 mg x kg(-1) x d(-1)). Cyclosporine-treated rats showed significantly longer graft survival and less graft rejection but severe renal damage in a dose-dependent manner. Compared with group II, treatment with pioglitazone with low-dose cyclosporine (group IV) significantly suppressed graft infiltration of CD4/CD8 T lymphocytes and serum concentrations of interleukin 2 and interferon gamma, leading to extended graft survival up to 60 days. These immunosuppressive effects in group IV were equivalent to those in group III. In addition, recipient kidneys in group IV had few apoptotic cells, possibly through upregulation of peroxisome proliferator-activated receptor gamma and downregulation of transforming growth factor beta1, and maintained stable renal functions, as evidenced by a normalization of blood urea nitrogen, creatinine, and creatinine clearance values. In vitro experiments also confirmed the renoprotective effects of pioglitazone on cyclosporine-induced toxicity. Collectively, pioglitazone can reduce a dose of cyclosporine with sufficient immunosuppressive effects. Pioglitazone treatment with low-dose cyclosporine has synergistic protective effects for cardiac allografts and recipient

  17. Radiation doses in low-dose pelvimetry using rare-earth screens.

    Science.gov (United States)

    Axelsson, B; Ohlsén, H

    1979-01-01

    A 'low-dose technique' of obstetric pelvimetry, using rare-earth screens and a reduced ambition level of image quality, yields an estimated absorbed dose to the maternal and foetal gonads of 0.9 and 0.01 mGy, respectively. The resulting risk for 'hereditary ill health' and the risk for induction of leukemia from the absorbed dose to the foetal red bone marrow, have been calculated to be at a very low level.

  18. Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses.

    Science.gov (United States)

    Rotiroti, Giuseppina; Shamji, Mohamed; Durham, Stephen R; Till, Stephen J

    2012-10-01

    Subcutaneous immunotherapy with high-dose grass pollen was first described more than 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. In contrast, low-dose subcutaneous immunotherapy has not shown clinical benefit. Uncontrolled reports from the early 20th century describe low-dose allergen inoculation directly into the dermis, an immunologically active area containing abundant dendritic cells and lymphatics. We sought to investigate the effect of low-dose intradermal grass pollen administration on cutaneous reactivity to allergen. Thirty adults sensitized to grass and tree pollens were randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single intradermal injection at 10 weeks. At the end of the study, cutaneous early and late responses were measured after double-blind intradermal injection with grass and birch pollen. Participants who received 6 fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than control subjects who received 2 injections separated by 10 weeks (P pollen-specific IgG antibodies. Suppression was observed whether late responses were measured on the arms or the back. However, early responses were equivalent in all groups. Low-dose intradermal allergen, like conventional subcutaneous high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in a manner that is allergen specific, systemic, and associated with induction of IgG antibodies. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion

    OpenAIRE

    Yaqi eYou; Silbergeld, Ellen K.

    2014-01-01

    Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance. Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome ...

  20. Effect of low-dose naloxone infusion on fentanyl requirements in critically ill children.

    Science.gov (United States)

    Darnell, Cindy Maria; Thompson, Jennifer; Stromberg, Daniel; Roy, Lonnie; Sheeran, Paul

    2008-05-01

    Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance. Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation. The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children. We conducted a double-blinded, randomized, placebo-control trial from December 2002 through July 2004 in a university PICU. We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for >4 days were eligible for enrollment. Those receiving additional oral analgesia or sedation, having a history of drug dependence or withdrawal, or having significant neurologic, renal, or hepatic disease were excluded. In addition to fentanyl infusions, patients received low-dose naloxone or placebo infusions. Medications were adjusted using the Modified Motor Activity Assessment Scale. Withdrawal was monitored using the Modified Narcotic Withdrawal Scale. Intervention was a low-dose naloxone infusion (0.25 microg/kg per hour) and the main outcome variable was the maximum cumulative daily fentanyl dose (micrograms per kilogram per day). There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone (N = 37) or those receiving placebo (N = 35). Adjustment for the starting fentanyl dose also failed to reveal group differences. Total fentanyl dose received throughout the study in the naloxone group (360 microg/kg) versus placebo (223 microg/kg) was not statistically different. Placebo patients trended toward fewer rescue midazolam boluses (10.7 vs 17.8), lower total midazolam dose (11.6 mg/kg vs 23.9 mg/kg), and fewer rescue fentanyl boluses (18.5 vs 23.9). We conclude that administration of low-dose naloxone (0.25 microg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically

  1. Cutaneous leishmaniasis: treatment with low-dose oral fluconazole with an excellent cosmetic result.

    Science.gov (United States)

    Aerts, Olivier; Duchateau, Nathalie; Willemse, Peter; Lambert, Julien

    2015-01-01

    We report the successful treatment of cutaneous leishmaniasis in a 6-year-old girl who presented with a solitary lesion on the cheek. A low dose of 3 mg/kg/day of fluconazole was used, with remarkable improvement at 6 weeks and complete regression at 12 weeks, excellent cosmetic results, and no relapse during a follow-up of 1 year. © 2014 Wiley Periodicals, Inc.

  2. Low dose vitamin C, vitamin E or L-arginine supplementation and ...

    African Journals Online (AJOL)

    The effect of chronic low-dose supplementation with vitamin C (300mg/day for 6 weeks in adults or 100mg/day for 6 weeks in children) or vitamin E (100 IU/day for 6 weeks in adults) or L-Arginine (1g/day for 6 weeks in adults) in ameliorating the pathophysiology and combating the deleterious effects of sickle cell disease in ...

  3. Exit wave reconstruction of radiation-sensitive materials from low-dose data

    Science.gov (United States)

    Huang, C.; Borisenko, K. B.; Kirkland, A. I.

    2014-06-01

    We report exit wave reconstruction using a focal series of low-dose images for ZSM-5, a zeolite which has a wide range of industrial applications. The exit wave phase was successfully reconstructed showing the structure of ZSM-5 at a near-atomic resolution even though the dose in the individual images in the focal series was as low as 26 electrons/Å2. This implementation shows the method's potential for application to other radiation-sensitive materials.

  4. Resource Letter EIRLD-2: Effects of Ionizing Radiation at Low Doses

    Science.gov (United States)

    Wilson, Richard

    2012-04-01

    This Resource Letter provides a guide to the literature on the effects of ionizing radiation on people at low doses. Journal articles, books and web pages are provided for the following: data at high dose levels, effects of moderate to high doses (leukemia, solid cancer, lung cancer, childhood cancer, and non-cancer outcomes), effects of dose rate, relationship to background, supra linearity and hormesis, and policy implications.

  5. Data Integration Reveals Key Homeostatic Mechanisms Following Low Dose Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tilton, Susan C.; Matzke, Melissa M.; Sowa, Marianne B.; Stenoien, David L.; Weber, Thomas J.; Morgan, William F.; Waters, Katrina M.

    2015-05-01

    The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time - with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24 – 72 hr). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress were measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 were experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation.

  6. Proteomic Analysis of Low Dose Arsenic and Ionizing Radiation Exposure on Keratinocytes

    OpenAIRE

    Berglund, Susanne R.; Santana, Alison R.; Li, Dan; Rice, Robert H.; Rocke, David M; Goldberg, Zelanna

    2009-01-01

    Human exposure to arsenic and ionizing radiation occur environmentally at low levels. While the human health effects of arsenic and ionizing radiation have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent ionizing radiation especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic an...

  7. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model.

    Science.gov (United States)

    Li, Qi; Ma, Zhuang; Liu, Yinhua; Kan, Xiaoxi; Wang, Changjun; Su, Bingnan; Li, Yuchen; Zhang, Yingmei; Wang, Pingzhang; Luo, Yang; Na, Daxiang; Wang, Lanlan; Zhang, Guoying; Zhu, Xiaoxin; Wang, Lu

    2016-08-01

    Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumor-supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose-specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF-κB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment. Gene expression microarray data are available in the GEO database under accession number GSE82048. © 2016 Federation of European Biochemical Societies.

  8. Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure.

    Science.gov (United States)

    Zhong, Jiang-hua; Chen, Xiao-pan; Yun, Mei-ling; Li, Wei-jing; Chen, Yan-fang; Yao, Zhen

    2007-08-01

    To study the effects of carvedilol on the transmural heterogeneity of ventricular repolarization in rabbits with congestive heart failure (CHF). Rabbits were randomly divided into 3 groups: control, CHF and carvedilol treated CHF group. Monophasic action potential duration (MAPD) in the 3 myocardial layers was simultaneously recorded. All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resistance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold (VFT) was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization (TDR) was significantly increased in CHF. Low-dose carvedilol (0.25 mg/kg, twice daily) had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Although the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. In the present study, the transmural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological property rather than its effect on ventricular remodeling.

  9. Report on FY16 Low-dose Metal Fuel Irradiation and PIE

    Energy Technology Data Exchange (ETDEWEB)

    Edmondson, Philip D.

    2016-09-01

    This report gives an overview of the efforts into the low-dose metal fuel irradiation and PIE as part of the Fuel Cycle Research & Development (FCRD) Advanced Fuels Campaign (AFC) milestone M3FT-16OR020303031. The current status of the FCT and FCRP irradiation campaigns are given including a description of the materials that have been irradiated, analysis of the passive temperature monitors, and the initial PIE efforts of the fuel samples.

  10. Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine.

    Science.gov (United States)

    Alburges, Mario E; Hoonakker, Amanda J; Cordova, Nathaniel M; Robson, Christina M; McFadden, Lisa M; Martin, Amber L; Hanson, Glen R

    2014-08-01

    Administration of high doses of methamphetamine (METH) in a manner mimicking the binging patterns associated with abuse reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied. The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported. Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50, or 1.00 mg/kg/subcutaneously (s.c.)). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5-48 h after the last injection. METH at doses of 0.25 and 0.50, but not 1.00 mg/kg, rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions. A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed.

  11. Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis.

    Science.gov (United States)

    Vitale, A T; Rodriguez, A; Foster, C S

    1996-03-01

    To describe the authors' approach to the management of patients with recalcitrant, chronic, endogenous uveitis using low-dose Cyclosporin A (CSA) alone or in combination with other immunosuppressive agents with attention to the anti-inflammatory efficacy, visual outcome, and side effects of therapy. The authors reviewed the records of 50 patients (92 eyes) with uveitis of various etiologies who had been treated with low-dose CSA (2.5-5.0 mg/kg daily) alone or in combination with prednisone and/or azathioprine (1.5-2.0 mg/kg daily). The median follow-up on low-dose CSA was 16 months (range, 6-64 months). Inflammatory control was achieved in 68 (73.9%) eyes, while persistent inflammatory activity was observed in 14 (15.2%). Thirty-eight (41%) eyes improved two Snellen lines or more, 43 (47.0%) stabilized, and 11 (12.0%) lost two lines or more. The CSA was discontinued because of nephrotoxicity in three patients and in each of two with systemic hypertension and constitutional intolerance to the drug, respectively. Thirteen patients enjoy inflammatory remission with this regimen. Low-dose CSA used alone or in combination with other immunosuppressive agents is effective in achieving inflammatory control with a favorable visual outcome and provides a useful steroid-sparing strategy in the management of chronic endogenous uveitis. The CSA-associated toxicity may be reduced by initiating therapy at very low initial doses, with incremental dosage escalation to the desired target range.

  12. Parkinson's disease: low-dose haloperidol increases dopamine receptor sensitivity and clinical response.

    Science.gov (United States)

    Hudson, Craig J; Seeman, Philip; Seeman, Mary V

    2014-01-01

    Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson's disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson's disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson's disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson's disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

  13. Prolonged exposure to low-dose microcystin induces nonalcoholic steatohepatitis in mice: a systems toxicology study.

    Science.gov (United States)

    He, Jun; Li, Guangyu; Chen, Jun; Lin, Juan; Zeng, Cheng; Chen, Jing; Deng, Junliang; Xie, Ping

    2017-01-01

    Microcystin-LR (MCLR), a cyanotoxin widely present in freshwater, has been shown to have potent acute hepatotoxicity. However, the chronic toxicity of low-dose MCLR remains confusing by traditional measurements of toxicity. This has impeded understanding of the chronic liver damage of low-dose MCLR and corresponding safety risks of the human exposure guideline value. Here, iTRAQ-based proteomics and NMR-based metabonomics were used to decipher the molecular toxicological signatures of low doses of MCLR in mice exposed to this agent for 90 days. Low levels of MCLR, even under the reported no observed adverse effect level, significantly altered hepatic protein expression, especially of proteins associated with lipid metabolism, transport, immune and proteolysis. Coherently, MCLR induced marked perturbations in lipid metabolites in both liver and serum. Integrated analysis of proteomic, metabolic, histological and cytokine profiles revealed that MCLR significantly inhibited fatty acid β-oxidation and hepatic lipoprotein secretion and promoted hepatic inflammation, resulting in nonalcoholic steatohepatitis disease (NASH). These findings for the first time provide compelling evidence that chronic exposure to low-level MCLR can induce NASH. These results also indicate that current guidelines for MCs in drinking water may be inadequate and associated with risks to human health.

  14. Response to low-dose herbicide selection in self-pollinated Avena fatua.

    Science.gov (United States)

    Busi, Roberto; Girotto, Marcelo; Powles, Stephen B

    2016-03-01

    When applied at the correct plant stage and dose, herbicides are highly toxic to plants. At reduced, low herbicide doses (below the recommended dose) plants can survive and display continuous and quantitative variation in dose-survival responses. Recurrent (directional) selection studies can reveal whether such a phenotypic variation in plant survival response to low herbicide dose is heritable and leads to herbicide resistance. In a common experimental garden study, we have subjected a susceptible population of self-pollinated hexaploid Avena fatua to low-dose recurrent selection with the ACCase-inhibiting herbicide diclofop-methyl for three consecutive generations. Significant differences in response to low-dose diclofop-methyl selection were observed between the selected progenies and parent plants, with a twofold diclofop-methyl resistance and cross-resistance to ALS-inhibiting herbicides. Thus, the capacity of self-pollinated A. fatua to respond to low-dose herbicide selection is marginal, and it is much lower than in cross-pollinated L. rigidum. Lolium rigidum in the same experiment evolved 40-fold diclofop-methyl resistance by progressive enrichment of quantitative resistance-endowing traits. Cross-pollination rate, genetic variation and ploidy levels are identified as possible drivers affecting the contrasting capacity of Avena versus Lolium plants to respond to herbicide selection and the subsequent likelihood of resistance evolution at low herbicide dose usage. © 2015 Society of Chemical Industry.

  15. Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

    Directory of Open Access Journals (Sweden)

    Chantelau Ernst A

    2011-12-01

    Full Text Available Abstract Introduction Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus. Case presentation We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion with the insulin analogue lispro (Humalog® in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog®. Conclusion Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog®, triggered by an unknown endogenous mechanism.

  16. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  17. Investigation of Iterative Image Reconstruction in Low-dose Breast CT

    Science.gov (United States)

    Bian, Junguo; Yang, Kai; Boone, John M.; Han, Xiao; Sidky, Emil Y.

    2014-01-01

    Interest exists in developing computed tomography (CT) dedicated for breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence exists suggesting that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image-total-variation (TV) minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with focuses on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics. PMID:24786683

  18. Metabolomic Response of Human Skin Tissue to Low Dose Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zeping; Kim, Young-Mo; Sowa, Marianne B.; Robinson, Robert J.; Gao, Xiaoli; Metz, Thomas O.; Morgan, William F.; Zhang, Qibin

    2012-05-18

    Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomics analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 hr) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, a comparable number of metabolites were detected to have significant change 48 hr after exposure to 3 and 10 cGy of irradiation, when compared with the high dose of 200 cGy. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.

  19. Robust low-dose dynamic cerebral perfusion CT image restoration via coupled dictionary learning scheme.

    Science.gov (United States)

    Tian, Xiumei; Zeng, Dong; Zhang, Shanli; Huang, Jing; Zhang, Hua; He, Ji; Lu, Lijun; Xi, Weiwen; Ma, Jianhua; Bian, Zhaoying

    2016-11-22

    Dynamic cerebral perfusion x-ray computed tomography (PCT) imaging has been advocated to quantitatively and qualitatively assess hemodynamic parameters in the diagnosis of acute stroke or chronic cerebrovascular diseases. However, the associated radiation dose is a significant concern to patients due to its dynamic scan protocol. To address this issue, in this paper we propose an image restoration method by utilizing coupled dictionary learning (CDL) scheme to yield clinically acceptable PCT images with low-dose data acquisition. Specifically, in the present CDL scheme, the 2D background information from the average of the baseline time frames of low-dose unenhanced CT images and the 3D enhancement information from normal-dose sequential cerebral PCT images are exploited to train the dictionary atoms respectively. After getting the two trained dictionaries, we couple them to represent the desired PCT images as spatio-temporal prior in objective function construction. Finally, the low-dose dynamic cerebral PCT images are restored by using a general DL image processing. To get a robust solution, the objective function is solved by using a modified dictionary learning based image restoration algorithm. The experimental results on clinical data show that the present method can yield more accurate kinetic enhanced details and diagnostic hemodynamic parameter maps than the state-of-the-art methods.

  20. Measurement of Fertility Benefits with Low Dose Thyroxine in Sub-fertile women

    Directory of Open Access Journals (Sweden)

    Upendra Pandit

    2016-12-01

    Full Text Available Introduction: High prevalence rate of thyroid dysfunction associated infertility is identified by a number of studies in Nepal. Thyroid dysfunction not only affects fertility but is also associated with miscarriage and fetal death. The objective of this study was to measure the fertility rate after low dose Thyroxine, 12.5 microgram, in women with subfertility. Methods: This was a descriptive and observational study done among women visiting infertility and in-vitro fertilization (IVF center at Nepalgunj Medical College, Nepal. After undergoing baseline investigations for infertility, all women diagnosed with primary or secondary infertility were enrolled in the study. Male factor and tubal factor infertility was excluded. All 136 women who were enrolled in the study received 12.5 microgram of thyroxine supplementation for a period of three months and subsequently followed up until the same time period. Results: Out of 136 women, 83 (61.02% women achieved pregnancy within three months of supplementation with low dose thyroxine. Among them, 34 (40.9% women with primary infertility achieved pregnancy within three months. Similarly 14 (16.8% women with previous miscarriage, 20 (24.09% women with previous caesarean section within past five years back, and 15 (18.07% with previous IUFD achieved pregnancy within three months. Conclusion: Low dose thyroxine supplementation would be beneficial and recommended to subfertile women of reproductive age group in the endemic regions of hypothyroidism. Dose adjustment would give extended benefits as soon as pregnancy is achieved.

  1. An optimized colony forming assay for low-dose-radiation cell survival measurement

    Energy Technology Data Exchange (ETDEWEB)

    Zhu J.; Sutherland B.; Hu W.; Ding N.; Ye C.; Usikalu M.; Li S.; Hu B.; Zhou G.

    2011-11-01

    The aim of this study is to develop a simple and reliable method to quantify the cell survival of low-dose irradiations. Two crucial factors were considered, the same number of cells plated in each flask and an appropriate interval between cell plating and irradiation. For the former, we optimized cell harvest with trypsin, diluted cells in one container, and directly seeded cells on the bottom of flasks in a low density before irradiation. Reproducible plating efficiency was obtained. For the latter, we plated cells on the bottom of flasks and then monitored the processing of attachment, cell cycle variations, and the plating efficiency after exposure to 20 cGy of X-rays. The results showed that a period of 4.5 h to 7.5 h after plating was suitable for further treatment. In order to confirm the reliability and feasibility of our method, we also measured the survival curves of these M059K and M059J glioma cell lines by following the optimized protocol and obtained consistent results reported by others with cell sorting system. In conclusion, we successfully developed a reliable and simple way to measure the survival fractions of human cells exposed to low dose irradiation, which might be helpful for the studies on low-dose radiation biology.

  2. Radiation-Induced Bystander Effects: Evidence for an Adaptive Response to Low Dose Exposures?

    Science.gov (United States)

    Mothersill, Carmel; Seymour, Colin

    2006-01-01

    This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response appears to require a quorum in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. While a death response might appear to be adverse, the position is argued in this paper that it is in fact protective and removes damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation, so called “background damage”, it is possible that low doses exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of “U-shaped” dose response curves. In this scenario, the level of “adaptive” or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors. PMID:18648593

  3. Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

    Science.gov (United States)

    Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

    2017-03-04

    Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl 4 )-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl 4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl 4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl 4 -induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl 4 -induced liver damage in rats.

  4. The bovine tuberculosis burden in cattle herds in zones with low dose radiation pollution in Ukraine

    Directory of Open Access Journals (Sweden)

    Svitlana Pozmogova

    2009-06-01

    Full Text Available The authors describe a study of the tuberculosis (TB incidence in cattle exposed to low doses of radiation resulting from the Chernobyl (pronounced ‘Chornobyl’ in Ukrainian nuclear plant catastrophe in 1986. The purpose of the study was to determine if ionising radiation influences the number of outbreaks of bovine TB and their severity on farms in the Kyiv, Cherkasy and Chernigiv regions of Ukraine. These farms are all located within a 200 km radius of Chernobyl and have had low-dose radiation pollution. Pathological and blood samples were taken from cattle in those regions that had positive TB skin tests. Mycobacterium spp. were isolated, differentiated by PCR, analysed and tested in guinea-pigs and rabbits. Species differentiation showed a significant percentage of atypical mycobacteria, which resulted in the allergic reactions to tuberculin antigen in the skin test. Mixed infection of M. bovis and M. avium subsp. hominissuis was found in three cases. The results concluded that low-dose radiation plays a major role in the occurrence of bovine TB in regions affected by the Chernobyl nuclear disaster.

  5. Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes.

    Science.gov (United States)

    Berglund, Susanne R; Santana, Alison R; Li, Dan; Rice, Robert H; Rocke, David M; Goldberg, Zelanna

    2009-04-01

    Human exposure to arsenic and ionizing radiation (IR) occur environmentally at low levels. While the human health effects of arsenic and IR have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent IR especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic and/or low dose IR exposure, resulting in differential proteomic expression based on 2-DE, immunoblotting and statistical analysis. Seven proteins were identified that passed a rigorous statistical screen for differential expression in 2-DE and also passed a strict statistical screen for follow-up immunoblotting. These included: alpha-enolase, epidermal-fatty acid binding protein, heat shock protein 27, histidine triad nucleotide-binding protein 1, lactate dehydrogenase A, protein disulfide isomerase precursor, and S100A9. Four proteins had combined effects that were different than would be expected based on the response to either individual toxicant. These data demonstrate a possible reaction to the combined insult that is substantially different from that of either separate treatment. Several proteins had different responses than what has been seen from high dose exposures, adding to the growing literature suggesting that the cellular responses to low dose exposures are distinct.

  6. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people

    Directory of Open Access Journals (Sweden)

    DiSilvestro Robert A

    2012-09-01

    Full Text Available Abstract Background Curcumin extracts of turmeric are proposed to produce health benefits. To date, human intervention studies have focused mainly on people with existing health problems given high doses of poorly absorbed curcumin. The purpose of the current study was to check whether in healthy people, a low dose of a lipidated curcumin extract could alter wellness-related measures. Methods The present study was conducted in healthy middle aged people (40–60 years old with a low dose of curcumin (80 mg/day in a lipidated form expected to have good absorption. Subjects were given either curcumin (N = 19 or placebo (N = 19 for 4 wk. Blood and saliva samples were taken before and after the 4 weeks and analyzed for a variety of blood and saliva measures relevant to health promotion. Results Curcumin, but not placebo, produced the following statistically significant changes: lowering of plasma triglyceride values, lowering of salivary amylase levels, raising of salivary radical scavenging capacities, raising of plasma catalase activities, lowering of plasma beta amyloid protein concentrations, lowering of plasma sICAM readings, increased plasma myeloperoxidase without increased c-reactive protein levels, increased plasma nitric oxide, and decreased plasma alanine amino transferase activities. Conclusion Collectively, these results demonstrate that a low dose of a curcumin-lipid preparation can produce a variety of potentially health promoting effects in healthy middle aged people.

  7. Low-dose CT of the paranasal sinuses. Minimizing X-ray exposure with spectral shaping

    Energy Technology Data Exchange (ETDEWEB)

    Wuest, Wolfgang [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany); Radiological Institute, Erlangen (Germany); May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany)

    2016-11-15

    Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192 x 0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 x 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDI{sub vol} 1.2 mGy vs. 4.4 mGy, p < 0.001). Spectral optimization (tin filtration at 100 kV) allows for visualization of the paranasal sinus with sufficient image quality at a very low radiation exposure. (orig.)

  8. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  9. Low-Dose CT with a Residual Encoder-Decoder Convolutional Neural Network (RED-CNN).

    Science.gov (United States)

    Chen, Hu; Zhang, Yi; Kalra, Mannudeep K; Lin, Feng; Chen, Yang; Liao, Peixo; Zhou, Jiliu; Wang, Ge

    2017-06-13

    Given the potential risk of X-ray radiation to the patient, low-dose CT has attracted a considerable interest in the medical imaging field. Currently, the main stream low-dose CT methods include vendor-specific sinogram domain filtration and iterative reconstruction algorithms, but they need to access raw data whose formats are not transparent to most users. Due to the difficulty of modeling the statistical characteristics in the image domain, the existing methods for directly processing reconstructed images cannot eliminate image noise very well while keeping structural details. Inspired by the idea of deep learning, here we combine the autoencoder, deconvolution network, and shortcut connections into the residual encoder-decoder convolutional neural network (RED-CNN) for low-dose CT imaging. After patch-based training, the proposed RED-CNN achieves a competitive performance relative to the-state-of-art methods in both simulated and clinical cases. Especially, our method has been favorably evaluated in terms of noise suppression, structural preservation, and lesion detection.

  10. Low-dose growth hormone therapy reduces inflammation in HIV-infected patients

    DEFF Research Database (Denmark)

    Lindboe, Johanne Bjerre; Langkilde, Anne; Eugen-Olsen, Jesper

    2016-01-01

    BACKGROUND: Combination antiretroviral therapy (cART) has drastically increased the life expectancy of HIV-infected patients. However, HIV-infected patients exhibit increased inflammation and 33-58% exhibit a characteristic fat re-distribution termed HIV-associated lipodystrophy syndrome (HALS......). Recombinant human growth hormone (rhGH) has been tested as treatment of HALS. Low-dose rhGH therapy improves thymopoiesis and fat distribution in HIV-infected patients and appears to be well tolerated. However, since high-dose rhGH is associated with adverse events related to inflammation, we wanted...... to investigate the impact of low-dose rhGH therapy on inflammation in HIV-infected patients. METHODS: Forty-six cART-treated HIV-infected men were included in the HIV-GH low-dose (HIGH/Low) study: a randomized, placebo-controlled, double-blinded trial. Subjects were randomized 3:2 to 0.7 mg/day rhGH, or placebo...

  11. Effects of low-dose niacin on dyslipidemia and serum phosphorus in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Hyo Jin Kang

    2013-03-01

    Conclusion: Low-dose niacin had a low frequency of adverse effects and also improved dyslipidemia, lowered serum phosphorus level, and increased GFR in patients with CKD. Further studies are needed to evaluate the long-term effects of low-dose niacin for renal progression of CKD.

  12. Effects of low-dose dopamine on renal and systemic hemodynamics during incremental norepinephrine infusion in healthy volunteers

    NARCIS (Netherlands)

    Hoogenberg, K; Smit, AJ; Girbes, ARJ

    Objectives: To assess the effects of low-dose dopamine on norepinephrine induced renal and systemic vasoconstriction in normotensive healthy subjects. Design: On separate days, either a low-dose dopamine (4 mu g/kg/min) or a placebo (5% glucose) infusion was added in a single, blinded, randomized

  13. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted...

  14. Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young [Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd., Daejeon (Korea, Republic of)

    2017-04-15

    Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

  15. A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Reneman, Liesbeth; Jager, Gerry; Vlieger, Erik-Jan P.; Olabarriaga, Sílvia D.; Lavini, Cristina; Bisschops, Ivo; Majoie, Charles B. L. M.; Booij, Jan; den Heeten, Gerard J.; van den Brink, Wim

    2007-01-01

    It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR

  16. Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.) following mixed exposure to copper and aluminum combined with low-dose gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mothersill, Carmel; Seymour, Colin B. [McMaster University, Medical Physics and Applied Radiation Sciences Department, Hamilton, ON (Canada); Norwegian University of Life Sciences, Department of Plant and Environmental Sciences, Aas (Norway); Smith, Richard W. [McMaster University, Medical Physics and Applied Radiation Sciences Department, Hamilton, ON (Canada); Heier, Lene Soerlie; Teien, Hans-Christian; Land, Ole Christian; Oughton, Deborah; Salbu, Brit [Norwegian University of Life Sciences, Department of Plant and Environmental Sciences, Aas (Norway)

    2014-03-15

    Very little is known about the combined effects of low doses of heavy metals and radiation. However, such ''multiple stressor'' exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water. Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 μg/L for the same time period. The aluminum dose was 250 μg/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 μg/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects. (orig.)

  17. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  18. Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

    Science.gov (United States)

    Matsuo, Koji; Cahoon, Sigita S; Yoshihara, Kosuke; Shida, Masako; Kakuda, Mamoru; Adachi, Sosuke; Moeini, Aida; Machida, Hiroko; Garcia-Sayre, Jocelyn; Ueda, Yutaka; Enomoto, Takayuki; Mikami, Mikio; Roman, Lynda D; Sood, Anil K

    2016-07-01

    To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all Pcancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all Pendometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative

  19. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  20. The effect of low-dose X-irradiation on immune system

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Keiichiro [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.

    1996-06-01

    The hypothesis of radiation hormesis has been proposed. To elucidate the hormetic effect on the immune system, we studied the mitogen-induced proliferation of splenocytes of F344/NSlc rat and BALB/c mouse after low-dose X-irradiation. Con A, PHA or LPS-induced proliferation of rat splenocytes prepared at 4 hr after irradiation was augmented with 5 cGy. This augmentation was observed within a few hours after irradiation, being a temporary effect. In case of mice, the proliferation of splenocytes induced by Con A, PHA or LPS was augmented by irradiation with 2.5 cGy. Thus, some phenomena of hormetic effect on the immune system were observed. However, the mechanism of augmentation of immune splenocytes is uncertainty. Therefore, we examined changes in production of LTB{sub 4} and IL-1 being inflammatory mediators. After 5 cGy irradiation the production of LTB{sub 4} of rat splenocyte showed a significant increase. Furthermore, 2.5 cGy irradiation also enhanced, the biological activity of intracellular IL-1 of LPS-stimulated mouse splenocytes. Additionally, to elucidate the stimulative effect on the antitumor immunity by low-dose X-irradiation, we studied the changes in the incidence of thymic lymphoma using AKR mice and of spontaneous metastasis to lung using tumor bearing mice. The incidence of thymic lymphoma was significantly decreased and the life span was significantly prolonged by periodical low-dose X-irradiation in terms of breeding of AKR mice. By an irradiation with 15 cGy, numbers of lung colony in the tumor bearing mice were decreased by 57% relative to the sham-irradiated controls. Then, IL-6 and TNF-{alpha} production of tumor bearing mice splenocytes were enhanced. These findings suggest that the low-dose X-irradiation might have caused a light inflammation and might have induced an augmentation of immune splenocytes. Furthermore, these results indicate that an augmentation of the antitumor immunity was induced by low-dose X-irradiation. 127 refs.

  1. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    Energy Technology Data Exchange (ETDEWEB)

    Gridley, Daila S.

    2008-10-31

    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

  2. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  3. Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI).

    LENUS (Irish Health Repository)

    Gleeson, T G

    2009-03-01

    The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard.

  4. Accuracy of low dose CT in the diagnosis of appendicitis in childhood and comparison with USG and standard dose CT.

    Science.gov (United States)

    Yi, Dae Yong; Lee, Kyung Hoon; Park, Sung Bin; Kim, Jee Taek; Lee, Na Mi; Kim, Hyery; Yun, Sin Weon; Chae, Soo Ahn; Lim, In Seok

    Computed tomography should be performed after careful consideration due to radiation hazard, which is why interest in low dose CT has increased recently in acute appendicitis. Previous studies have been performed in adult and adolescents populations, but no studies have reported on the efficacy of using low-dose CT in children younger than 10 years. Patients (n=475) younger than 10 years who were examined for acute appendicitis were recruited. Subjects were divided into three groups according to the examinations performed: low-dose CT, ultrasonography, and standard-dose CT. Subjects were categorized according to age and body mass index (BMI). Low-dose CT was a contributive tool in diagnosing appendicitis, and it was an adequate method, when compared with ultrasonography and standard-dose CT in terms of sensitivity (95.5% vs. 95.0% and 94.5%, p=0.794), specificity (94.9% vs. 80.0% and 98.8%, p=0.024), positive-predictive value (96.4% vs. 92.7% and 97.2%, p=0.019), and negative-predictive value (93.7% vs. 85.7% and 91.3%, p=0.890). Low-dose CT accurately diagnosed patients with a perforated appendix. Acute appendicitis was effectively diagnosed using low-dose CT in both early and middle childhood. BMI did not influence the accuracy of detecting acute appendicitis on low-dose CT. Low-dose CT is effective and accurate for diagnosing acute appendicitis in childhood, as well as in adolescents and young adults. Additionally, low-dose CT was relatively accurate, irrespective of age or BMI, for detecting acute appendicitis. Therefore, low-dose CT is recommended for assessing children with suspected acute appendicitis. Copyright © 2017. Published by Elsevier Editora Ltda.

  5. Screening of illegal intracorporeal containers ("body packing"): is abdominal radiography sufficiently accurate? A comparative study with low-dose CT.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Canel, Laurent; Becker, Christoph D; Wolff, Hans; Elger, Bernice; Lock, Eric; Sarasin, François; Bonfanti, Monica S; Dupuis-Lozeron, Elise; Perneger, Thomas; Platon, Alexandra

    2012-12-01

    To evaluate the diagnostic performance of abdominal radiography in the detection of illegal intracorporeal containers (hereafter, packets), with low-dose computed tomography (CT) as the reference standard. This study was approved by the institutional ethical review board, with written informed consent. From July 2007 to July 2010, 330 people (296 men, 34 women; mean age, 32 years [range, 18-55 years]) suspected of having ingested drug packets underwent supine abdominal radiography and low-dose CT. The presence or absence of packets at abdominal radiography was reported, with low-dose CT as the reference standard. The density and number of packets (≤ 12 or >12) at low-dose CT were recorded and analyzed to determine whether those variables influence interpretation of results at abdominal radiography. Packets were detected at low-dose CT in 53 (16%) suspects. Sensitivity of abdominal radiography for depiction of packets was 0.77 (41 of 53), and specificity was 0.96 (267 of 277). The packets appeared isoattenuated to the bowel contents at low-dose CT in 16 (30%) of the 53 suspects with positive results. Nineteen (36%) of the 53 suspects with positive low-dose CT results had fewer than 12 packets. Packets that were isoattenuated at low-dose CT and a low number of packets (≤12) were both significantly associated with false-negative results at abdominal radiography (P = .004 and P = .016, respectively). Abdominal radiography is mainly limited by low sensitivity when compared with low-dose CT in the screening of people suspected of carrying drug packets. Low-dose CT is an effective imaging alternative to abdominal radiography. © RSNA, 2012.

  6. Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception.

    Science.gov (United States)

    Bang, S; Yoo, S; Yang, T J; Cho, H; Kim, Y G; Hwang, S W

    2010-10-01

    Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in primary sensory neurons and skin keratinocytes play a crucial role as peripheral pain detectors. Many natural and synthetic ligands have been found to act on thermoTRPs, but little is known about endogenous compounds that inhibit these TRPs. Here, we asked whether resolvin D1 (RvD1), a naturally occurring anti-inflammatory and pro-resolving lipid molecule is able to affect the TRP channel activation. We examined the effect of RvD1 on the six thermoTRPs using Ca(2+) imaging and whole cell electrophysiology experiments using the HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. We also checked changes in agonist-specific acute licking/flicking or flinching behaviours and TRP-related mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems with or without inflammation. RvD1 inhibited the activities of TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent attenuations in agonist-specific acute pain behaviours by immediate peripheral administration with RvD1 were also observed. Furthermore, local pretreatment with RvD1 significantly reversed mechanical and thermal hypersensitivity in inflamed tissues. RvD1 was a novel endogenous inhibitor for several sensory TRPs. The results of our behavioural studies suggest that RvD1 has an analgesic potential via these TRP-related mechanisms.

  7. Protective effects of low-dose rosuvastatin on isoproterenol-induced chronic heart failure in rats by regulation of DDAH-ADMA-NO pathway.

    Science.gov (United States)

    Zhou, Ru; Ma, Ping; Xiong, Aiqin; Xu, Yehua; Wang, Yang; Xu, Qingbin

    2017-04-01

    Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms. Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection. Simultaneously, low-dose rosuvastatin (5 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by hemodynamic parameter, histopathological variables, serum asymmetric dimethylarginine (ADMA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and myocardial nitric oxide (NO), and the levels of dimethylarginine dimethylaminohydrolase 2 (DDAH2), arginine methyltransferases 1 (PRMT1) and endothelial nitric oxide synthase (eNOS) expression were analyzed. Therapeutic rosuvastatin (5 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of ventricle, reduced the increased serum content of ADMA, cTnI, and BNP, and elevated myocardial NO in rats (Pheart failure in rats by modulating DDAH-ADMA-NO pathway, and it may present the new therapeutic value in ameliorating chronic heart failure. © 2016 John Wiley & Sons Ltd.

  8. Ultra-Low-Dose CT of the Thorax Using Iterative Reconstruction: Evaluation of Image Quality and Radiation Dose Reduction.

    Science.gov (United States)

    Kim, Yookyung; Kim, Yoon Kyung; Lee, Bo Eun; Lee, Seok Jeong; Ryu, Yon Ju; Lee, Jin Hwa; Chang, Jung Hyun

    2015-06-01

    The purpose of this study is to assess the image quality and radiation dose reduction of ultra-low-dose CT using sinogram-affirmed iterative reconstruction (SAFIRE). This prospective study enrolled 25 patients who underwent three consecutive unenhanced CT scans including low-dose CT (120 kVp and 30 mAs) and two ultra-low-dose CT protocols (protocol A, 100 kVp and 20 mAs; protocol B, 80 kVp and 30 mAs) with image reconstruction using SAFIRE. The image quality and radiation dose reduction were assessed. The mean (± SD) effective radiation dose was 1.06 ± 0.11, 0.44 ± 0.05, and 0.31 ± 0.03 mSv for low-dose CT, ultra-low-dose CT protocol A, and ultra-low-dose CT protocol B, respectively. Overall image quality was determined as diagnostic in 100% of low-dose CT scans, 96% of ultra-low-dose CT protocol A scans, and 88% of ultra-low-dose CT protocol B scans. All patients with nondiagnostic quality images had a body mass index (weight in kilograms divided by the square of height in meters) greater than 25. There was no statistically significant difference in detection frequencies of 14 lesion types among the three CT protocols, but pulmonary emphysema was detected in fewer patients (3/25) in ultra-low-dose CT protocol B scans compared with ultra-low-dose CT protocol A scans (5/25) or low-dose CT scans (6/25). We measured the longest dimensions of 33 small solid nodules (3.8-12.4 mm in long diameter) and found no statistically significant difference in the values afforded by the three CT protocols (p = 0.135). Iterative reconstruction allows ultra-low-dose CT and affords acceptable image quality, allowing size measurements of solid pulmonary nodules to be made.

  9. Low dose radiation hypersensitivity and clustered DNA damages in human fibroblasts exposed to low dose and dose rate protons or 137CS y-rays

    Energy Technology Data Exchange (ETDEWEB)

    Bennett P. V.; Bennett, P.V.; Keszenman, D.J.; Johnson, A.M.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Effective radioprotection for human space travelers hinges upon understanding the individual properties of charged particles. A significant fraction of particle radiation astronauts will encounter in space exploratory missions will come from high energy protons in galactic cosmic radiation (GCR) and/or possible exposures to lower energy proton flux from solar particle events (SPEs). These potential exposures present major concerns for NASA and others, in planning and executing long term space exploratory missions. We recently reported cell survival and transformation (acquisition of anchorage-independent growth in soft agar) frequencies in apparently normal NFF-28 primary human fibroblasts exposed to 0-30 cGy of 50MeV, 100MeV (SPE-like), or 1000 MeV (GCR-like) monoenergetic protons. These were modeled after 1989 SPE energies at an SPE-like low dose-rate (LDR) of 1.65 cGy/min or high dose rate (HDR) of 33.3 cGy/min delivered at the NASA Space Radiation Laboratory (NSRL) at BNL.

  10. [Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives].

    Science.gov (United States)

    Cianci, A; De Leo, V

    2007-08-01

    The contraceptive pill has been a revolution of the last 40 years. In Italy, however, it is much less widely used than in other countries. Explanations for this phenomenon range from religious implications and customs to misinformation and word-of-mouth communication of negative experiences. The oral contraceptive pill is often used to correct menstrual disorders, leading to poor results and side-effects. Recent advances in oral contraception have led to a substantial reduction in doses and side-effects. Low-dose pills contain minimal doses of progesterones and estrogens and ensure good control of the menstrual cycle. Although reduction of ethinyl estradiol (EE) concentrations has reduced the incidence of negative systemic side effects such as water retention, edema and swollen breasts, the low estrogen dose may be associated with spotting and hypomenorrhea or amenorrhea in the long term, as well as dyspareunia due to reduced vaginal trophism, which may induce women to suspend use of the drug. It is also true that only one type of estrogen is used in the pill, albeit at different doses, whereas the progesterone may differ and in many cases is the cause of common side-effects. The choice of progesterone therefore involves not only its effect on the endometrium in synergy with estrogen, but also possible residual androgenic activity which may have negative metabolic repercussions. Indeed, addition of a progesterone, especially androgen-derived, attenuates the positive metabolic effects of estrogen. Two new monophasic oral contraceptives were recently released. They contain 30 microg (Yasmin) or 20 muicrog (Yasminelle) EE and a new progesterone, drospirenone, derived from spirolactone, which has antiandrogenic and antimineralcorticoid activity similar to endogenous progesterone. Like progesterone, the drospirenone molecule is an aldosterone antagonist and has a natriuretic effect that opposes the sodium retention effect of EE. It may, therefore, help to prevent the

  11. An investigation of low-dose 3D scout scans for computed tomography

    Science.gov (United States)

    Gomes, Juliana; Gang, Grace J.; Mathews, Aswin; Stayman, J. Webster

    2017-03-01

    Purpose: Commonly 2D scouts or topograms are used prior to CT scan acquisition. However, low-dose 3D scouts could potentially provide additional information for more effective patient positioning and selection of acquisition protocols. We propose using model-based iterative reconstruction to reconstruct low exposure tomographic data to maintain image quality in both low-dose 3D scouts and reprojected topograms based on those 3D scouts. Methods: We performed tomographic acquisitions on a CBCT test-bench using a range of exposure settings from 16.6 to 231.9 total mAs. Both an anthropomorphic phantom and a 32 cm CTDI phantom were scanned. The penalized-likelihood reconstructions were made using Matlab and CUDA libraries and reconstruction parameters were tuned to determine the best regularization strength and delta parameter. RMS error between reconstructions and the highest exposure reconstruction were computed, and CTDIW values were reported for each exposure setting. RMS error for reprojected topograms were also computed. Results: We find that we are able to produce low-dose (0.417 mGy) 3D scouts that show high-contrast and large anatomical features while maintaining the ability to produce traditional topograms. Conclusions: We demonstrated that iterative reconstruction can mitigate noise in very low exposure CT acquisitions to enable 3D CT scout. Such additional 3D information may lead to improved protocols for patient positioning and acquisition refinements as well as a number of advanced dose reduction strategies that require localization of anatomical features and quantities that are not provided by simple 2D topograms.

  12. Low-dose CT of the lung: potential value of iterative reconstructions

    Energy Technology Data Exchange (ETDEWEB)

    Baumueller, Stephan; Winklehner, Anna; Karlo, Christoph; Goetti, Robert; Frauenfelder, Thomas; Alkadhi, Hatem [University Hospital Zurich, Institute for Diagnostic and Interventional Radiology, Zurich (Switzerland); Flohr, Thomas [Siemens Healthcare, Computed Tomography Division, Forchheim (Germany); Russi, Erich W. [University Hospital Zurich, Pulmonary Division, Department of Internal Medicine, Zurich (Switzerland)

    2012-12-15

    To prospectively assess the impact of sinogram-affirmed iterative reconstruction (SAFIRE) on image quality of nonenhanced low-dose lung CT as compared to filtered back projection (FBP). Nonenhanced low-dose chest CT (tube current-time product: 30 mAs) was performed on 30 patients at 100 kVp and on 30 patients at 80 kVp. Images were reconstructed with FBP and SAFIRE. Two blinded, independent readers measured image noise; two readers assessed image quality of normal anatomic lung structures on a five-point scale. Radiation dose parameters were recorded. Image noise in datasets reconstructed with FBP (57.4 {+-} 15.9) was significantly higher than with SAFIRE (31.7 {+-} 9.8, P < 0.001). Image quality was significantly superior with SAFIRE than with FBP (P < 0.01), without significant difference between FBP at 100 kVp and SAFIRE at 80 kVp (P = 0.68). Diagnostic image quality was present with FBP in 96% of images at 100 kVp and 88% at 80 kVp, and with SAFIRE in 100% at 100 kVp and 98% at 80 kVp. There were significantly more datasets with diagnostic image quality with SAFIRE than with FBP (P < 0.01). Mean CTDI{sub vol} and effective doses were 1.5 {+-} 0.7 mGy.cm and 0.7 {+-} 0.2 mSv at 100 kVp, and 1.4 {+-} 2.8 mGy.cm and 0.5 {+-} 0.2 mSv at 80 kVp (P < 0.001, both). Use of SAFIRE in low-dose lung CT reduces noise, improves image quality, and renders more studies diagnostic as compared to FBP. (orig.)

  13. The risk of lower gastrointestinal bleeding in low-dose aspirin users.

    Science.gov (United States)

    Chen, W-C; Lin, K-H; Huang, Y-T; Tsai, T-J; Sun, W-C; Chuah, S-K; Wu, D-C; Hsu, P-I

    2017-06-01

    Aspirin increases the risk of gastrointestinal bleeding. To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers. A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, PAspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB. The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB. © 2017 John Wiley & Sons Ltd.

  14. Accurate tissue characterization in low-dose CT imaging with pure iterative reconstruction.

    Science.gov (United States)

    Murphy, Kevin P; McLaughlin, Patrick D; Twomey, Maria; Chan, Vincent E; Moloney, Fiachra; Fung, Adrian J; Chan, Faimee E; Kao, Tafline; O'Neill, Siobhan B; Watson, Benjamin; O'Connor, Owen J; Maher, Michael M

    2017-04-01

    We assess the ability of low-dose hybrid iterative reconstruction (IR) and 'pure' model-based IR (MBIR) images to maintain accurate Hounsfield unit (HU)-determined tissue characterization. Standard-protocol (SP) and low-dose modified-protocol (MP) CTs were contemporaneously acquired in 34 Crohn's disease patients referred for CT. SP image reconstruction was via the manufacturer's recommendations (60% FBP, filtered back projection; 40% ASiR, Adaptive Statistical iterative Reconstruction; SP-ASiR40). MP data sets underwent four reconstructions (100% FBP; 40% ASiR; 70% ASiR; MBIR). Three observers measured tissue volumes using HU thresholds for fat, soft tissue and bone/contrast on each data set. Analysis was via SPSS. Inter-observer agreement was strong for 1530 datapoints (rs > 0.9). MP-MBIR tissue volume measurement was superior to other MP reconstructions and closely correlated with the reference SP-ASiR40 images for all tissue types. MP-MBIR superiority was most marked for fat volume calculation - close SP-ASiR40 and MP-MBIR Bland-Altman plot correlation was seen with the lowest average difference (336 cm(3) ) when compared with other MP reconstructions. Hounsfield unit-determined tissue volume calculations from MP-MBIR images resulted in values comparable to SP-ASiR40 calculations and values that are superior to MP-ASiR images. Accuracy of estimation of volume of tissues (e.g. fat) using segmentation software on low-dose CT images appears optimal when reconstructed with pure IR. © 2016 The Royal Australian and New Zealand College of Radiologists.

  15. Impact of iterative reconstruction on image quality of low-dose CT of the lumbar spine.

    Science.gov (United States)

    Alshamari, Muhammed; Geijer, Mats; Norrman, Eva; Lidén, Mats; Krauss, Wolfgang; Jendeberg, Johan; Magnuson, Anders; Geijer, Håkan

    2017-06-01

    Background Iterative reconstruction (IR) is a recent reconstruction algorithm for computed tomography (CT) that can be used instead of the standard algorithm, filtered back projection (FBP), to reduce radiation dose and/or improve image quality. Purpose To evaluate and compare the image quality of low-dose CT of the lumbar spine reconstructed with IR to conventional FBP, without further reduction of radiation dose. Material and Methods Low-dose CT on 55 patients was performed on a Siemens scanner using 120 kV tube voltage, 30 reference mAs, and automatic dose modulation. From raw CT data, lumbar spine CT images were reconstructed with a medium filter (B41f) using FBP and four levels of IR (levels 2-5). Five reviewers scored all images on seven image quality criteria according to the European guidelines on quality criteria for CT, using a five-grade scale. A side-by-side comparison was also performed. Results There was significant improvement in image quality for IR (levels 2-4) compared to FBP. According to visual grading regression, odds ratios of all criteria with 95% confidence intervals for IR2, IR3, IR4, and IR5 were: 1.59 (1.39-1.83), 1.74 (1.51-1.99), 1.68 (1.46-1.93), and 1.08 (0.94-1.23), respectively. In the side-by-side comparison of all reconstructions, images with IR (levels 2-4) received the highest scores. The mean overall CTDIvol was 1.70 mGy (SD 0.46; range, 1.01-3.83 mGy). Image noise decreased in a linear fashion with increased strength of IR. Conclusion Iterative reconstruction at levels 2, 3, and 4 improves image quality of low-dose CT of the lumbar spine compared to FPB.

  16. Low dose X-irradiation mitigates diazepam induced depression in rat brain.

    Science.gov (United States)

    Kaur, Amandeep; Singla, Neha; Dhawan, D K

    2016-10-01

    Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. What Role for Biologically Based Dose–Response Models in Estimating Low-Dose Risk?

    Science.gov (United States)

    Crump, Kenny S.; Chen, Chao; Chiu, Weihsueh A.; Louis, Thomas A.; Portier, Christopher J.; Subramaniam, Ravi P.; White, Paul D.

    2010-01-01

    Background Biologically based dose–response (BBDR) models can incorporate data on biological processes at the cellular and molecular level to link external exposure to an adverse effect. Objectives Our goal was to examine the utility of BBDR models in estimating low-dose risk. Methods We reviewed the utility of BBDR models in risk assessment. Results BBDR models have been used profitably to evaluate proposed mechanisms of toxicity and identify data gaps. However, these models have not improved the reliability of quantitative predictions of low-dose human risk. In this commentary we identify serious impediments to developing BBDR models for this purpose. BBDR models do not eliminate the need for empirical modeling of the relationship between dose and effect, but only move it from the whole organism to a lower level of biological organization. However, in doing this, BBDR models introduce significant new sources of uncertainty. Quantitative inferences are limited by inter- and intraindividual heterogeneity that cannot be eliminated with available or reasonably anticipated experimental techniques. BBDR modeling does not avoid uncertainties in the mechanisms of toxicity relevant to low-level human exposures. Although implementation of BBDR models for low-dose risk estimation have thus far been limited mainly to cancer modeled using a two-stage clonal expansion framework, these problems are expected to be present in all attempts at BBDR modeling. Conclusions The problems discussed here appear so intractable that we conclude that BBDR models are unlikely to be fruitful in reducing uncertainty in quantitative estimates of human risk from low-level exposures in the foreseeable future. Use of in vitro data from recent advances in molecular toxicology in BBDR models is not likely to remove these problems and will introduce new issues regarding extrapolation of data from in vitro systems. PMID:20056564

  18. Protein expression profile changes in human fibroblasts induced by low dose energetic protons

    Science.gov (United States)

    Zhang, Ye; Clement, Jade Q.; Gridley, Daila S.; Rodhe, Larry H.; Wu, Honglu

    2009-12-01

    Extrapolation of known radiation risks to the risks from low dose and low dose-rate exposures of human population, especially prolonged exposures of astronauts in the space radiation environment, relies in part on the mechanistic understanding of radiation induced biological consequences at the molecular level. While some genomic data at the mRNA level are available for cells or animals exposed to radiation, the data at the protein level are still lacking. Here, we studied protein expression profile changes using Panorama antibody microarray chips that contain antibodies to 224 proteins (or their phosphorylated forms) involved in cell signaling that included mostly apoptosis, cytoskeleton, cell cycle and signal transduction. Normal human fibroblasts were cultured until fully confluent and then exposed to 2 cGy o