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Sample records for low-dose combination preparation

  1. The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation.

    Science.gov (United States)

    Heinle, H; Tober, C; Zhang, D; Jäggi, R; Kuebler, W M

    2010-01-01

    Vertigo of various and often unknown aetiologies has been associated with and attributed to impaired microvascular perfusion in the inner ear or the vertebrobasilar system. Vertigoheel is a low-dose combination preparation of proven value in the symptomatic treatment of vertigo. In the present study we tested the hypothesis that Vertigoheel's anti-vertiginous properties may in part be due to a vasodilatory effect exerted via stimulation of the adenylate and/or guanylate cyclase pathways. Thus, the influence of Vertigoheel or its single constituents on synthesis and degradation of cyclic nucleotides was measured. Furthermore, vessel myography was used to observe the effect of Vertigoheel on the vasoreactivity of rat carotid arteries. Vertigoheel and one of its constituents, Anamirta cocculus, stimulated adenylate cyclase activity, while another constituent, Conium maculatum, inhibited phosphodiesterase 5, suggesting that the individual constituents of Vertigoheel contribute differentially to a synergistic stimulation of cyclic nucleotide signalling pathways. In rat carotid artery rings, Vertigoheel counteracted phenylephrine-induced tonic vasoconstriction. The present data demonstrate a vasorelaxant effect of Vertigoheel that goes along with a synergistic stimulation of cyclic nucleotide pathways and may provide a mechanistic basis for the documented anti-vertiginous effects of this combination preparation.

  2. 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 ...

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

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... patients undergoing transurethral surgery could reduce block duration and ... There was no evidence of higher risk of analgesic failure in the combination group. ... tumor (TURBT) are elderly people who have coexisting.

  4. Elotuzumab in combination with thalidomide and low-dose dexamethasone

    DEFF Research Database (Denmark)

    Mateos, Maria-Victoria; Granell, Miguel; Oriol, Albert

    2016-01-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-...

  5. Tibolone and low-dose continuous combined hormone treatment : vaginal bleeding pattern, efficacy and tolerability

    NARCIS (Netherlands)

    Hammar, M. L.; van de Weijer, P.; Franke, H. R.; Pornel, B.; von Mauw, E. M. J.; Nijland, E. A.

    2007-01-01

    Objectives The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E-2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. Design A randomised,

  6. Clinical investigation of 131I therapy combined with low-dose lithium carbonate for Graves disease

    International Nuclear Information System (INIS)

    Xu Haiqing; Wu Bian

    2006-01-01

    Objective: To investigate the clinical curative effects of 131 I therapy combined with low-dose lithium carbonate for Graves disease. Methods: Patients with Graves disease took lithium carbonate (250 mg, once per day) orally for 5 weeks. Then they were treated with 131 I (doses=3.15 MBq(80 uCi)/g, based on 60%-70% of the thyroid size). We kept track from 6 to 24 months (averaging 14 months) and classified the results into three: cured, improved or no effect. Results: After a single cycle of 131 I therapy combined with low-dose lithium carbonate, 106 patients with Graves disease were cured, 28 were improved and 8 saw no effects, respectively 74.6%, 19.7% and 5.6% among the 142 patients. We then treated 23 of them with another 131 I therapy (without lithium carbonate). 10 of such were cured (43.5%), 8 were improved (34.8%) and the other 5 saw no effects. Among all patients, hypothyroidism was observed from 25(17.6%), 6 months after the first 131 I therapy. Conclusions: Notable curative results were observed from 131 I therapy combined with low-dose lithium carbonate for Graves disease. Moreover, the dosage of 131 I was therefore decreased, which also lowered the toxicity response. (authors)

  7. [The best noise index combined with ASIR weighting selection in low-dose chest scanning].

    Science.gov (United States)

    Xiao, Huijuan; Hou, Ping; Liu, Jie; Gao, Jianbo; Tan, Hongna; Liang, Pan; Pu, Shi

    2015-10-06

    To discuss the best noise index combined with ASIR weighting selection in low-dose chest scanning based on BMI. 200 patients collected from May to December 2014 underwent non-contrast chest CT examinations, they were randomly assigned into standard dose group (Group A, NI15 combined with 30% ASIR) and low-dose groups (Group B, NI25 combined with 40% ASIR, Group C, NI30 combined with 50% ASIR, Group D, NI35 combined with 60% ASIR), 50 cases in each group; the patients were assigned into three groups based on BMI (kg/m2): BMI25. Signal-to-nosie ratio (SNR), contrast-to noise ratio (CNR), CT dose index volume (CTDIvol), dose-length product (DLP), effective dose (ED) and subjective scoring between the standard and low-dose groups were compared and analyzed statistically. Differences of SNR, CNR, CTDIvol, DLP and ED among groups were determined with ANOVA analysis and the consistency of diagnosis with Kappa test. SNR, CTDIvol, DLP and ED reduced with the increase of nosie index, the differences among the groups were statistically significant (P25 kg/m2 group. NI35 combined with 60% ASIR in BMIASIR in 18.5 kg/m2≤BMI≤25 kg/m2 group; NI25 combined with 40% ASIR in 18.5 kg/m2≤BMI≤25 kg/m2 group were the best parameters combination which both can significantly reduce the radiation dose and ensure the image quality.

  8. 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

    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...... 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...

  9. Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Johnson, D.W.; Kessler, J.F.; Ferrigni, R.G.; Anderson, J.D.

    1989-01-01

    The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma

  10. The Combination Very Low-Dose Naltrexone–Clonidine in the Management of Opioid Withdrawal

    Science.gov (United States)

    Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A.; Gorelick, David A.

    2013-01-01

    Background The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives We investigated the effects of a VLNTX–clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1–.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal. PMID:22233189

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

    Directory of Open Access Journals (Sweden)

    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

  12. Combination effect of low dose fentanyl and propofol on emergence agitation in children following sevoflurane anesthesia

    International Nuclear Information System (INIS)

    Bakhamees, Hassan S; Mercan, Arzu; ElHalafawy, Yasser M

    2009-01-01

    To investigate the combination effect of low dose fentanyl and subhypnotic dose of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure.After ethical approval, a prospective, randomized, clinical study was performed in Saad Specialist Hospital, Al-Khobar, Kingdom of Saudi Arabia in 2007-2008. One hundred and twenty children in physical status of I according to the American Society of Anesthesiologists, aged 2-6 years, scheduled for adentonsillectomy under general anesthesia were allocated into 3 groups randomly. Anesthesia was induced and maintained by sevoflurane in all groups. Children received 0.1 ml.kg-1 normal saline at the end of surgery in group C (n=40), 1.5 mcg.kg-1 fentanyl during induction, and 0.1 ml.kg-1 normal saline at the end of surgery in group F (n=40), and 1.5 mcg.kg-1 fentanyl during induction and 1 mg.kg-1 propofol at the end of surgery in group FP (n=40). Postoperative agitation was recorded, if any, for the first postoperative hour.Three groups were comparable with regard to demographic data. Twenty-one patients (53%) in the control group, 14 patients (35%) in group F and 7 (18%) patients in group FP experienced postoperative agitation.The combination of low dose fentanyl before surgery and propofol at the end of surgery decreases the incidence and level of emergence agitation in children after adenotonsillectomy procedure under sevoflurane anesthesia. (author)

  13. Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture effects in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Pedersen, Mikael; Skov, Kasper

    2016-01-01

    Humans are simultaneously exposed to several chemicals that act jointly to induce mixture effects. At doses close to or higher than no-observed adverse effect levels, chemicals usually act additively in experimental studies. However, we are lacking knowledge on the importance of exposure to complex...... real-world mixtures at more relevant human exposure levels. We hypothesised that adverse mixture effects occur at doses approaching high-end human exposure levels. A mixture (Mix) of 14 chemicals at a combined dose of 2.5 mg/kg bw/day was tested in combination with perfluorononanoic acid (PFNA...... pituitary-adrenal axis. In conclusion, our data suggest that mixtures of environmental chemicals at doses approaching high-end human exposure levels can cause a hormonal imbalance and disturb steroid hormones and their regulation. These effects may be non-monotonic and were observed at low doses. Whether...

  14. Central blood circulation in children at chronic combined low dose radiation and chemical action

    International Nuclear Information System (INIS)

    Arinchin, A.N.

    2000-01-01

    The state of central blood circulation and its hormonal regulation were studied in 1465 children living permanently under chronic low dose radiation and chemical action. Basic group consisted of 1093 children (579 boys and 514 girls) . 372 children (115 boys and 227 girls permanently living on 'clean' areas) were investigated in control group. Average age was 10,8 years old in basic group and 10,4 years old in the control group. Such parameters as arterial pressure, level of lead in blood and urine, adrenaline, noradrenaline and dophamine content in urine, thyroxine, iodothyronine, prostaglandins and cyclic AMP content in the blood serum has been controlled. Hypotensive states were determined to prevail in children living permanently under chronic low dose radiation and chemical action. The main pathogenic mechanism of this defeat is consider to be a reduction of the sympathoadrenal system activity combined with a decreasing of the thyroid system activity and of cyclic AMP level as well as predominance of prostaglandin depressive activity

  15. Study of morbidity in persons subjected to combined effect of low dose irradiation and alcohol

    International Nuclear Information System (INIS)

    Mashneva, N.I.; Zakharov, A.A.

    1990-01-01

    Materials related to study of morbidity in persons from one of the controled areas subjected to combined effect of low dose ionizing radiation and alcohol are presented. The group under control included persons living in the same area but not misusing alcohol. The morbidity analysis for the period of two years before the accident showed that the number of morbidity cases and days characterized by incapacity for work among 100 working persons was 1.2 and 1.35 times higher as compared to persons not misusing alcohol. Two years after the accident these values constitute 1.6 and 1.75 correspondingly. It is established on the basis of the dispensary examnations, that taking into account other equal conditions the number of morbidity cases related to cardiovasular deseases among the persons misusing alcohol increased (11 % against 6.8 % bycontrol). The number of other chronic morbidity cases does not differ from control values. 7 refs.; 2 tabs

  16. Preparation and determination of kerma for Iridium 192 sources of low dose rate for brachytherapy

    International Nuclear Information System (INIS)

    Tendilla, J.I.; Tovar M, V.; Mitsoura, E.; Aguilar H, F.; Alanis M, J.

    2000-01-01

    The practice of Brachytherapy with Iridium-192 sources of low dose rate (0.4 - 0.8 Gy/h) is a technique used in the treatment of diverse illnesses. in this work the preparation, quality control and calibration are presented in terms of kerma in air of Iridium-192 using as target these recycled Iridium-Platinum wires. The targets were obtained as decayed sources of different radio therapeutical centers in the country and they were characterized by Scanning electron microscopy in order to determine their chemical composition. Subsequently it was developed an experimental design to establish the effect of neutron flux, geometrical array and irradiation time over the activity and percentage of the sources homogeneity. The homogeneity was determined by auto radiography and by Gamma spectroscopy. Once the optimal irradiation conditions were established, it is determined the apparent activity and kerma in air using a well type ionization chamber with traceability to a primary laboratory. Iridium-192 sources were obtained with an average homogeneity 96 %, apparent activity 282.129 ± 0.531 M Bq and kerma in air 0.03200 ± 0.00006 m Gy m/h A. (Author)

  17. Combining Acceleration Techniques for Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction.

    Science.gov (United States)

    Huang, Hsuan-Ming; Hsiao, Ing-Tsung

    2017-01-01

    Over the past decade, image quality in low-dose computed tomography has been greatly improved by various compressive sensing- (CS-) based reconstruction methods. However, these methods have some disadvantages including high computational cost and slow convergence rate. Many different speed-up techniques for CS-based reconstruction algorithms have been developed. The purpose of this paper is to propose a fast reconstruction framework that combines a CS-based reconstruction algorithm with several speed-up techniques. First, total difference minimization (TDM) was implemented using the soft-threshold filtering (STF). Second, we combined TDM-STF with the ordered subsets transmission (OSTR) algorithm for accelerating the convergence. To further speed up the convergence of the proposed method, we applied the power factor and the fast iterative shrinkage thresholding algorithm to OSTR and TDM-STF, respectively. Results obtained from simulation and phantom studies showed that many speed-up techniques could be combined to greatly improve the convergence speed of a CS-based reconstruction algorithm. More importantly, the increased computation time (≤10%) was minor as compared to the acceleration provided by the proposed method. In this paper, we have presented a CS-based reconstruction framework that combines several acceleration techniques. Both simulation and phantom studies provide evidence that the proposed method has the potential to satisfy the requirement of fast image reconstruction in practical CT.

  18. Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer

    International Nuclear Information System (INIS)

    Fujita, Masahiro; Murayama, Shigeyuki; Matayoshi, Yoshinobu; Ikeda, Hiroshi; Shimizutani, Kimishige; Inoue, Toshihiko; Kozuka, Takahiro; Masaki, Norie.

    1990-01-01

    Serum concentrations of cisplatin (CDDP) and acute complications were studied in patients treated for head and neck cancer by radiotherapy combined with daily administration of low doses of CDDP (5 mg/m 2 or 6 mg/body) at Osaka University Hospital between March 1988 and December 1989. Serum concentrations of total-CDDP (6 patients) and free-CDDP (2 patients) were studied in cases injected intravenously with 5 mg/m 2 daily. Total-CDDP determined just before daily administration of CDDP was increased gradually (0.35 to 0.64 μg/ml by the 7th day, 0.42 to 0.91 μg/ml by the 14th day and 0.60 to 0.82 μg/ml by the 20th or 21st day) and still observed in the serum for more than two weeks after cessation of the chemotherapy. Serum concentrations of free-CDDP were about 0.35 μg/ml at 5 minutes and 0.15 μg/ml at 30 minutes after the intravenous injection of CDDP. Incidence of the acute complications more severe than grade 2 were nausea and vomiting: 4/52 (8%), leukopenia: 11/52 (21%) and thrombocytopenia: 4/52 (8%). Incidence of myelosuppression (leukopenia and/or thrombocytopenia) was 11/26(42%) when the total dose of CDDP exceeded 120 mg, and 3/26 (12%) when it was less than 120 mg. Transient renal dysfunction (increase of serum creatinine) of grade 1 was seen in only 3 patients. (author)

  19. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

    Science.gov (United States)

    Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

    2016-01-01

    at baseline. Accordingly, the combination with low dose of DXM was feasible to improve BP control in patients who failed to achieve the BP goal by standard AM monotherapy. The benefit effects might be significant especially in patients with impaired endothelial function. PMID:27015224

  20. Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

    Science.gov (United States)

    Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

    2008-10-01

    Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

  1. Combined administration of the GPVI-Fc fusion protein Revacept with low-dose thrombolysis in the treatment of stroke

    Directory of Open Access Journals (Sweden)

    Andreas Reimann

    2016-04-01

    Full Text Available BackgroundThrombolytic therapy with recombinant tissue plasminogen activator (rtPA remains the only approved medication for acute ischemic stroke, but incurs significant bleeding risks. Therefore, approaches to combine lower doses of thrombolytic therapy with other effective drugs aim at improving efficacy and reducing bleeding rates. We examined the safety and therapeutic effects of various dosings of rtPA, either alone or combined with glycoprotein VI-Fc fusion protein (GPVI-Fc, Revacept on experimental stroke in mice.Methods and resultsThe effect of filament-induced intracerebral thrombus formation and embolization was investigated after a one-hour occlusion of the middle cerebral artery.In accordance with previous studies, treatment with 10 mg/kg rtPA significantly improved functional outcome, cerebral infarct size and edema, but also resulted in markedly increased intracranial bleeding volumes. In contrast, low doses of rtPA (0.1 or 0.35 mg/kg body weight did not change outcome parameters. However, addition of 1 mg/kg Revacept to 0.35 mg/kg rtPA led to improved reperfusion compared to rtPA alone. Moreover, these combined treatments resulted in improved grip strength, compared to the respective dose of rtPA alone. Infarct-surrounding edema improved after combined treatments, but not after respective single rtPA dosings. Intracranial bleeding volumes were below controls after all low-dose rtPA therapies, given either alone or combined with Revacept.ConclusionsIn contrast to using the equally effective full dose of rtPA, intracranial bleeding was not increased by low-dose rtPA combined with Revacept. Therefore, addition of Revacept to low-dose rtPA does not incur safety risks, but improves efficacy of treatment.

  2. Combined action of low doses of Ionizing Radiation, Electromagnetic Fields, and Homeopathic Remedies of low dilution on Ionic Homeostasis of a Cell

    International Nuclear Information System (INIS)

    Nadareishvili, G.

    2006-01-01

    It is known fact that low doses of ionizing radiation, electromagnetic fields (EMF) of certain frequency, and a number of homeopathic remedies produce stimulating effect in the cellular ionic homeostasis. The objective of present study was investigation of combined, simultaneous action of these three factors. The mice fibroblasts served as cell source. With an aid of ion-selective electrodes the sum effect of the following factors was evaluated: low dose irradiation (0.05 Gy), EMF (45 Hz, 2 mT), and stimulated phosphoric acid (homeopathic preparation diluted at 10 -14 ). It was found that integral index of the ionic homeostasis during above action, was higher than after action of any of these factors separately. It is suggested that these data point at beneficial action of the homeopathic remedy and it should be considered when promoting the homeopathic means of therapy. (author)

  3. Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Tsuchida, Tetsuo; Hiragushi, Junji; Asano, Yoshihide

    1995-01-01

    Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

  4. In vitro therapy study combined with low doses of radiation (Rn-222) and chemotherapy (taxol)

    International Nuclear Information System (INIS)

    Soto, J.; Sainz, C.; Cos, S.; Gonzalez-Lamuno, D.

    2004-01-01

    A study was carried out to test the possibility that breast cancer cells show increased sensitivity to the chemotherapeutic agent taxol when they have been treated with low radiation doses from the gas radon. To this end, the cells were cultivated in a medium containing dissolved radon and then in a second medium containing a concentration of taxol. After the culture phase the surviving cells were counted and their viability was assessed. The results obtained indicate that the cells treated with low doses of radon exhibit increased sensitivity when treated with certain concentrations of taxol; in particular a lower survival rate and lower viability were observed in cells treated with radon and 50 nM of taxol in cells treated with the same concentration of taxol alone. These effects seem to result from the influence of the radon on the expression of apoptosis -related genes, which is complementary to the action of taxol on bcl-x related genes. (author)

  5. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy; Case report

    Directory of Open Access Journals (Sweden)

    Samaresh Das

    2016-08-01

    Full Text Available An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofol-fentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman.

  6. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

    Science.gov (United States)

    Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

    2016-01-01

    An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

  7. Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

    Science.gov (United States)

    Franchi, F; Lazzeri, C; Foschi, M; Tosti-Guerra, C; Barletta, G

    2002-08-01

    Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

  8. Combined exposure to low doses of pesticides causes decreased birth weights in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Christiansen, Sofie; Petersen, Marta Axelstad

    2017-01-01

    Decreased birth weight is a common effect of many pesticides in reproductive toxicity studies, but there are no empirical data on how pesticides act in combination on this endpoint. We hypothesized that a mixture of six pesticides (cyromazine, MCPB, pirimicarb, quinoclamine, thiram, and ziram) wo...... to avoid potentially serious impact of mixed exposure on prenatal development and pregnancy in humans....

  9. Chromosomal damage by low doses of radiation: protection by combination of dietary antioxidants

    International Nuclear Information System (INIS)

    Sarma, Lakshmi; Abraham, S.K.; Kesavan, P.C.

    1994-01-01

    Mice which were fed antioxidants, consisting of a combination of β-carotene, αtocopherol and ascorbic acid, or curcumin, ascorbic acid and chlorogenic acid are substantially protected against γ-ray induced micronuclei in polychromatic erythrocytes obtained from bone-marrow. In this context, the relevance of a more balanced intake of food material especially those with anti carcinogens/anti mutagenic principles for human health care needs no over-emphasis. (author). 9 refs., 1 tab., 1 fig

  10. Efficacy of the low-dose combined oral contraceptive chlormadinone acetate/ethinylestradiol: physical and emotional benefits.

    Science.gov (United States)

    Heskamp, Marie-Luise S; Schramm, Georg A K

    2010-01-01

    This study investigated the effects of the low-dose combined oral contraceptive (COC) 2.0 mg chlormadinone acetate (CMA)/0.03 mg ethinylestradiol (EE) (Belara, Balanca) on cycle-related physical and emotional disorders in women >or=25 years of age. A prospective, non-interventional, observational study of 3772 women over six cycles was conducted in 303 office-based gynecological centers throughout Germany. CMA/EE provided high contraceptive efficacy with a Pearl index of 0 (95% confidence interval=0.00-0.22) and was generally well tolerated, with no statistically significant weight changes during the observation period (p=.147). CMA/EE intake resulted in a statistically significant improvement in cycle-related physical and emotional symptoms, with a 67% overall reduction in sum score for number and intensity of cycle-related symptoms per patient. The results of this study in women >or=25 years of age support previous findings that 2.0 mg CMA/0.03 mg EE is an effective low-dose COC, with an excellent tolerability profile, with the additional benefits of significantly reducing both cycle-related physical and emotional symptoms (pcontraceptive treatment. Further research is warranted.

  11. The Combined Impact of Surgery and Immunomodulation With Low Dose Cytoxan and GM-CSF in the Early Treatment of Breast Cancer

    National Research Council Canada - National Science Library

    Kendra, Kari L

    2004-01-01

    The purpose of this study was to evaluate the combined impact of surgery and immunomodulation with low dose cytoxan and GM-CSF on the development of dendritic cells and the activation of T cells in vivo...

  12. Knowledge of users of low-dose oral combined contraceptives about the method

    Directory of Open Access Journals (Sweden)

    Camila Félix Américo

    2013-07-01

    Full Text Available OBJECTIVES: to identify the knowledge of users of combined oral contraceptive about correct use, side effects and complications; to verify the correlation between knowledge about the method with age, education, family income and time of use. METHOD: cross-sectional study performed in Fortaleza, Ceará, Brazil, from March to July 2010, with 294 women. Data were collected through interviews. RESULTS: 75% had substantial knowledge about the proper use and side effects and no knowledge about complications. The higher the educational level and family income, the higher the women's knowledge about the correct use of the method. Positive correlation suggests that women who used the method for longer knew more about its side effects. CONCLUSION: there are knowledge gaps about the method, which are influenced by socioeconomic variables and use time.

  13. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

    International Nuclear Information System (INIS)

    Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

    1993-01-01

    The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

  14. Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

    Science.gov (United States)

    Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

    2017-02-01

    Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

  15. Combined Impact of low dose Ionizing Radiation, Electromagnetic Field, and Homeopathic Remedy at low Dilution on the Transmembrane Transport of Na+, K+ and Ca2+ in Tumor Cells

    International Nuclear Information System (INIS)

    Nadareishvili, G.

    2006-01-01

    Influence of different agents on the ionic homeostasis of the tumor cells has its specificity - transmembrane transport is faster and these cells are more sensitive to various agents. It is known fact that low doses of ionizing radiation, electromagnetic fields (EMF) of certain frequency, and a number of homeopathic remedies produce stimulating effect in the cellular ionic homeostasis. The objective of present study was investigation of combined, simultaneous action of these three factors. The cell of Ehrlich carcinoma served as major material. With an aid of ion-selective electrodes the sum effect of the following factors was evaluated: low dose irradiation (0.05 Gy), EMF (45 Hz, 2 mT), and stimulated phosphoric acid (homeopathic preparation diluted at 10 -14 ). It was found that integral index of the ionic homeostasis during above action, was higher than after action of any of these factors separately. On the other hand, if dose of ionizing radiation was increased to 0.5 Gy, which is known to inhibit ionic transport, the sum effect was decreased. (author)

  16. Local superficial hyperthermia in combination with low-dose radiation therapy for palliation of superficially localized metastases

    International Nuclear Information System (INIS)

    Owczarek, G.; Miszczyk, L.

    2005-01-01

    Full text: The aim of this study is to evaluate the response of superficially located metastases and local toxicity to microwave hyperthermia combined with radiation therapy. From May 2003 through December 2004 58 patients (33 male, 25 female; mean age 60 years) with lymph nodes or skin metastases were treated with microwave superficial hyperthermia combined with low-dose radiation therapy. Hyperthermia was administered twice weekly with high frequency applicator (∼900 Mhz) with water bolus. The temperature was set to 43 o C for 45 minutes. Radiotherapy was performed daily with dose 2 Gy or 4 Gy per fraction, to a total dose 20 Gy. There were 47 patients with carcinoma, 4 with sarcoma, 7 with melanoma. Treated regions were: head and neck (37 patients), chest wall 8, abdomen wall and groins 4, upper and lower limb 2 and 8 patients respectively. Primary tumor sites were: head and neck region (9 patients), lung 15, alimentary tract 8, breast 5, soft tissue 8, urogenital 4 and 9 patients with primary tumor site unknown. The toxicity was evaluated using 6 step scale: 0-no skin reaction, 1-faint red mark, 2-distinct red mark, 3-blisters, 4-brown mark, 5-necrosis. Presence of pain and its intensity were also analyzed. Diameter of tumor after the treatment was observed. Complete response was achieved in 5 patients (8.5 %), and partial response in 29 patients (50 %), no response was observed in 12 patients (20 %) and progression of tumor in 7 patients (12 %). No skin reaction was observed in 3 patients, faint red mark in 14 patients, distinct red mark in 28 patients, blisters in 8 patients, brown mark in 4 patients and necrosis in 1 patient. The pain occurred in 9 patients but it was no the cause of stopping treatment. Local superficial hyperthermia combined with low-dose radiation therapy is an effective method of treatment in a proportion of patients with superficial metastases. This combination of treatment modalities is well tolerated and is useful for palliation

  17. Low dose combinations of 2-methoxyestradiol and docetaxel block prostate cancer cells in mitosis and increase apoptosis.

    Science.gov (United States)

    Reiner, Teresita; de las Pozas, Alicia; Gomez, Lourdes A; Perez-Stable, Carlos

    2009-04-08

    Clinical trials have shown that chemotherapy with docetaxel (Doc) combined with prednisone can improve survival of patients with androgen-independent prostate cancer (AI-PC). It is likely that the combination of Doc with other novel agents would also improve the survival of AI-PC patients. We investigated whether the combination of Doc and 2-methoxyestradiol (2ME2), an endogenous metabolite of estradiol promising for cancer therapy, can increase apoptotic cell death in prostate cancer cells. Low concentration 2ME2 (0.5-1 microM)+Doc (0.05-0.1 nM) combinations inhibit cell growth, increase G2/M cell cycle arrest, and increase apoptosis more effectively than the single concentrations in a variety of human AI-PC cells. Effects on apoptosis were associated with an increase in p53 protein and a decrease in cyclin A-dependent kinase activity. We then investigated whether the combination of 2ME2+Doc can increase apoptotic cell death and inhibit the growth of prostate tumors in the FG/Tag transgenic mouse model of AI-PC. Doses of 2ME2 and Doc that increase mitotic cell cycle arrest result in an increase in apoptosis and lower primary prostate tumor weights in FG/Tag mice. High dose 2ME2+Doc combinations did not increase G2/M cell cycle arrest or apoptosis in AI-PC cell lines and in the FG/Tag mice more than the single drugs. Overall, our data indicate that low dose 2ME2+Doc combinations may provide a treatment strategy that can improve therapeutic efficacy against AI-PC while reducing toxicity often seen in patients treated with Doc.

  18. Low doses of haloperidol combined with ondansetron are not effective for prophylaxis of postoperative nausea and vomiting in susceptible patients.

    Science.gov (United States)

    Veiga-Gil, Leonor; López-Olaondo, Luis; Pueyo, Javier; Callejas, Raquel; Duque, Paula; Carrascosa, Francisco

    2015-02-01

    In this observational study we reviewed the efficacy and side effects of different antiemetic combinations used in our hospital for postoperative nausea and vomiting (PONV) prophylaxis in high-risk women undergoing highly emetogenic surgery. After reviewing retrospectively the medical records of patients undergoing highly emetogenic elective surgeries under general anaesthesia, we selected 368 women whose Apfel risk score was ≥ 3 and receiving a combination of 2 antiemetics for PONV prophylaxis. We analysed the incidence of PONV at 2, 6, 12 and 24h after surgery, antiemetic rescue requirements, pattern of occurrence of PONV, side effects and level of sedation were also assessed. The main goal was complete response defined as no PONV within 24h after surgery. Ondansetron 4mg i.v. plus dexamethasone 8mg i.v. (O&Dex), haloperidol 1mg i.v. (O&Hal1), haloperidol 2mg i.v. (O&Hal2) or droperidol 1.25mg i.v. (O&Dro) were the combinations most frequently used. The complete response was better in groups O&Dex: 68.5% (CI: 58-78), O&Hal2: 64.1% (CI: 53-74) and O&Dro 63% (CI: 52-73) than in group O&Hal1: 41.3% (CI: 31-52) (p<0,01). Peak incidence of PONV occurred within the 2-6h period. The incidence of side effects was higher in group O&Hal2. In high risk patients for PONV who underwent highly emetogenic surgeries, the efficacy of low-dose haloperidol (1mg) in combination is limited. Higher doses (2mg) are more effective but its use is associated with a high incidence of side effects. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Feasibility and effectiveness of unintended pregnancy prevention with low-dose mifepristone combined with misoprostol before expected menstruation.

    Science.gov (United States)

    Li, Cui-Lan; Chen, Dun-Jin; Deng, Yi-Fan; Song, Li-Ping; Mo, Xue-Tang; Liu, Kai-Jie

    2015-12-01

    What is the efficacy of maintaining or restoring non-pregnant status with low-dose mifepristone combined with misoprostol administered before expected menstruation? Low-dose mifepristone and misoprostol administered at the time of expected menstruation was effective and safe in maintaining or restoring non-pregnant status, with no obvious menstrual disturbance. Menstrual regulation involves the medical or mechanical stimulation of uterine sloughing in women with up to 2-3 weeks of menstrual delay. Low-dose mifepristone plus misoprostol is efficacious for termination of ultra-early pregnancy (≤ 35 days of amenorrhoea) with no obvious menstrual disturbance. A total of 678 women fulfilled all criteria and were recruited. Seventeen women dropped out after deciding to remain pregnant and 11 others were lost to follow-up. Thus, data from 650 women who completed the procedure were included in analyses. Participants were enrolled at any time during their menstrual cycle and administered medication 1 day before expected menstruation. The end of the study was defined on a per-patient basis as the date of completion of the post-treatment menstrual cycle. The primary outcome was the efficacy of abortion induction (for pregnant women) or menstrual regulation (for non-pregnant women). Women with regular menstrual cycles (25-35 days) were voluntarily recruited for this study between February 2012 and December 2014. Serum β-hCG was measured before mifepristone intake. Mifepristone (50 mg) was administered orally 1 day before expected menstruation and 200 µg misoprostol was administered orally on the day of expected menstruation. Efficacy, disturbance in bleeding patterns in the treatment and post-treatment cycles, satisfaction with the treatment, and subsequent contraception preference were analysed. Retrospective analysis of serum β-hCG levels at admission indicated that 23.3% (158/678) of the women were pregnant. The success rate for pregnancy termination was 98.6% (136

  20. Low-dose-rate intraoperative brachytherapy combined with external beam irradiation in the conservative treatment of soft tissue sarcoma

    International Nuclear Information System (INIS)

    Delannes, M.; Thomas, L.; Martel, P.; Bonnevialle, P.; Stoeckle, E.; Chevreau, Ch.; Bui, B.N.; Daly-Schveitzer, N.; Pigneux, J.; Kantor, G.

    2000-01-01

    Purpose: Conservative treatment of soft tissue sarcomas most often implies combination of surgical resection and irradiation. The aim of this study was to evaluate low-dose-rate intraoperative brachytherapy, delivered as a boost, in the local control of primary tumors, with special concern about treatment complications. Methods and Materials: Between 1986 and 1995, 112 patients underwent intraoperative implant. This report focuses on the group of 58 patients with primary sarcomas treated by combination of conservative surgery, intraoperative brachytherapy, and external irradiation. Most of the tumors were located in the lower limbs (46/58--79%). Median size of the tumor was 10 cm, most of the lesions being T2-T3 (51/58--88%), Grade 2 or 3 (48/58--83%). The mean brachytherapy dose was 20 Gy and external beam irradiation dose 45 Gy. In 36/58 cases, iridium wires had to be placed on contact with neurovascular structures. Results: With a median follow-up of 54 months, the 5-year actuarial survival was 64.9%, with a 5-year actuarial local control of 89%. Of the 6 patients with local relapse, 3 were salvaged. Acute side effects, essentially wound healing problems, occurred in 20/58 patients, late side effects in 16/58 patients (7 neuropathies G2 to G4). No amputation was required. The only significant factor correlated with early side effects was the location of the tumor in the lower limb (p = 0.003), and with late side effects the vicinity of the tumor with neurovascular structures (p = 0.009). Conclusion: Brachytherapy allows early delivery of a boost dose in a reduced volume of tissue, precisely mapped by the intraoperative procedure. Combined with external beam irradiation, it is a safe and efficient treatment technique leading to high local control rates and limited functional impairment

  1. Low-dose narrow-band UVB phototherapy combined with topical therapy is effective in psoriasis and does not inhibit systemic T-cell activation

    NARCIS (Netherlands)

    de Rie, M. A.; Out, T. A.; Bos, J. D.

    1998-01-01

    Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined

  2. Clinical application of low-dose CT combined with computer-aided detection in lung cancer screening

    International Nuclear Information System (INIS)

    Xu Zushan; Hou Hongjun; Xu Yan; Ma Daqing

    2010-01-01

    Objective: To investigate the clinical value of chest low-dose CT (LDCT) combined with computer-aided detection (CAD) system for lung cancer screening in high risk population. Methods: Two hundred and nineteen healthy candidates underwent 64-slice LDCT scan. All images were reviewed in consensus by two radiologists with 15 years of thoracic CT diagnosis experience. Then the image data were analyzed with CAD alone. Finally images were reviewed by two radiologists with 5 years of CT diagnosis experience with and without CT Viewer software. The sensitivity, false positive rate of CAD for pulmonary nodule detection were calculated. SPSS 11.5 software and Chi-square test were used for the statistics. Results: Of 219 candidates ,104(47.5% ) were detected with lung nodules. There were 366 true nodules confirmed by the senior radiologists. The CAD system detected 271 (74.0%) true nodules and 424 false-positive nodules. The false-positive rate was 1.94/per case. The two junior radiologists indentifid 292 (79.8%), 286(78.1%) nodules without CAD and 336 (91.8%), 333 (91.0%) nodules with CAD respectively. There were significant differences for radiologists in indentifying nodules with or without CAD system (P<0.01). Conclusions: CAD is more sensitive than radiologists for indentifying the nodules in the central area or in the hilar region of the lung. While radiologists are more sensitive for the peripheral and sub-pleural nodules,or ground glass opacity nodules, or nodules smaller than 4 mm. CAD can not be used alone. The detection rate can be improved with the combination of radiologist and CAD in LDCT screen. (authors)

  3. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Jan Susilo

    2011-08-01

    patients in the fluconazole group (2/80 = 2.5%.Conclusion: The present study showed that the efficacy and safety of ketoconazole 100 mg and fluconazole 40 mg combination was not inferior compared to fluconazole 150 mg in single doses for the treatment of vaginal candidiasis. (Med J Indones 2011; 20:205-11Keywords: fluconazole, low-dose ketoconazole-fluconazole combination, single dose, vaginal candidiasis

  4. Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

    2007-12-01

    Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

  5. Combining automatic tube current modulation with adaptive statistical iterative reconstruction for low-dose chest CT screening.

    Directory of Open Access Journals (Sweden)

    Jiang-Hong Chen

    Full Text Available To reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT by combining adaptive statistical iterative reconstruction (ASIR and automatic tube current modulation (ATCM.Patients undergoing cancer screening (n = 200 were subjected to 64-slice multidetector chest CT scanning with ASIR and ATCM. Patients were divided into groups 1, 2, 3, and 4 (n = 50 each, with a noise index (NI of 15, 20, 30, and 40, respectively. Each image set was reconstructed with 4 ASIR levels (0% ASIR, 30% ASIR, 50% ASIR, and 80% ASIR in each group. Two radiologists assessed subjective image noise, image artifacts, and visibility of the anatomical structures. Objective image noise and signal-to-noise ratio (SNR were measured, and effective dose (ED was recorded.Increased NI was associated with increased subjective and objective image noise results (P<0.001, and SNR decreased with increasing NI (P<0.001. These values improved with increased ASIR levels (P<0.001. Images from all 4 groups were clinically diagnosable. Images with NI = 30 and 50% ASIR had average subjective image noise scores and nearly average anatomical structure visibility scores, with a mean objective image noise of 23.42 HU. The EDs for groups 1, 2, 3 and 4 were 2.79 ± 1.17, 1.69 ± 0.59, 0.74 ± 0.29, and 0.37 ± 0.22 mSv, respectively. Compared to group 1 (NI = 15, the ED reductions were 39.43%, 73.48%, and 86.74% for groups 2, 3, and 4, respectively.Using NI = 30 with 50% ASIR in the chest CT protocol, we obtained average or above-average image quality but a reduced ED.

  6. Combining automatic tube current modulation with adaptive statistical iterative reconstruction for low-dose chest CT screening.

    Science.gov (United States)

    Chen, Jiang-Hong; Jin, Er-Hu; He, Wen; Zhao, Li-Qin

    2014-01-01

    To reduce radiation dose while maintaining image quality in low-dose chest computed tomography (CT) by combining adaptive statistical iterative reconstruction (ASIR) and automatic tube current modulation (ATCM). Patients undergoing cancer screening (n = 200) were subjected to 64-slice multidetector chest CT scanning with ASIR and ATCM. Patients were divided into groups 1, 2, 3, and 4 (n = 50 each), with a noise index (NI) of 15, 20, 30, and 40, respectively. Each image set was reconstructed with 4 ASIR levels (0% ASIR, 30% ASIR, 50% ASIR, and 80% ASIR) in each group. Two radiologists assessed subjective image noise, image artifacts, and visibility of the anatomical structures. Objective image noise and signal-to-noise ratio (SNR) were measured, and effective dose (ED) was recorded. Increased NI was associated with increased subjective and objective image noise results (PASIR levels (PASIR had average subjective image noise scores and nearly average anatomical structure visibility scores, with a mean objective image noise of 23.42 HU. The EDs for groups 1, 2, 3 and 4 were 2.79 ± 1.17, 1.69 ± 0.59, 0.74 ± 0.29, and 0.37 ± 0.22 mSv, respectively. Compared to group 1 (NI = 15), the ED reductions were 39.43%, 73.48%, and 86.74% for groups 2, 3, and 4, respectively. Using NI = 30 with 50% ASIR in the chest CT protocol, we obtained average or above-average image quality but a reduced ED.

  7. Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study

    OpenAIRE

    Pan, Guang-hui; Chen, Zheng; Xu, Lu; Zhu, Jing-hui; Xiang, Peng; Ma, Jun-jie; Peng, Yan-wen; Li, Guang-hui; Chen, Xiao-yong; Fang, Jia-li; Guo, Yu-he; Zhang, Lei; Liu, Long-shan

    2016-01-01

    Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppr...

  8. A randomized trial of a low-dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease.

    Science.gov (United States)

    Olanow, C Warren; Kieburtz, Karl; Leinonen, Mika; Elmer, Lawrence; Giladi, Nir; Hauser, Robert A; Klepiskaya, Olga S; Kreitzman, David L; Lew, Mark F; Russell, David S; Kadosh, Shaul; Litman, Pninit; Friedman, Hadas; Linvah, Nurit; The P B Study Group, For

    2017-05-01

    Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo-controlled study to determine whether 2 doses of a novel slow-release, low-dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD. Previously untreated patients with early PD were randomized (1:1:1) to once-daily treatment with P2B001 (0.3 mg pramipexole/0.75 mg rasagiline), P2B001 (0.6 mg pramipexole/0.75 mg rasagiline) or placebo in a 12-week multicenter double-blind, placebo-controlled trial. The primary endpoint was the change from baseline to final visit in Total-UPDRS score versus placebo. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in Parkinson Disease Quality of Life Scale-39 and UPDRS activities of daily living and motor scores. A total of 149 participants were randomized and 136 (91.3%) completed the study. Adjusted mean change from baseline to final visit versus placebo in Total-UPDRS score was -4.67 ± 1.28 points for the P2B001 0.6/0.75 mg group (P = .0004) and -3.84 ± 1.25 points for the 0.3/0.75 mg group (P = .003). Significant benefits were also observed for both doses in the responder analysis (P = .0002 and P = .0001), Parkinson Disease Quality of Life Scale-39 scores (P = .05 and P = .01), and the UPDRS motor (P = .02 and P = .006) and activities of daily living (P = .005 and P = .0004) subscores. Adverse events of P2B001 were comparable to placebo apart from transient nausea and somnolence, which were more common with P2B001 treatment. P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder

  9. Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

    Science.gov (United States)

    Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

    2016-04-01

    Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition

  10. A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

    Science.gov (United States)

    Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

    2017-02-28

    Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

  11. The DSA diagnosis, artery embolization combined with low dose of vasopressin infusion treatment for lower digestive tract hemorrhage

    International Nuclear Information System (INIS)

    Huang Guoxin; Dou Yongchong; Zhang Yanfang; Shen Xinying; Xu Jianmin

    2005-01-01

    Objective: To evaluate the clinical value of digital subtraction angiography (DSA) diagnosis and interventional treatment for lower digestive tract hemorrhage of unknown reasons. Methods: DSA was performed in 32 patients with unknown etiologic lower digestive tract hemorrhage. The locations and causes of hemorrhage were determined by angiography according to the demonstration of contrast medium extravasation, abnormal vasculature and tumor staining. Superselective arterial embolization was performed with retaining catheter of low dose vasopressin infusion for 12 hours of hemostasis. Results: Seventy-five percent of the lesions were identified by DSA with 2 cases of intestinal typhoid, 1 intestinal tuberculosis, 14 cases of vascular malformation and 7 cases of tumor. Hemostasis was succeeded in 20 of 24 patients. The rate of success was 83.3%. Conclusions: DSA and interventional therapy are of great value in diagnosing and treating patients with lower digestive tract hemorrhage of unknown reasons and even those undergone unsuccessful conservative treatment. Low dose vasopressin infusion through retained catheter is safe and efficient after superselective arterial embolization. (authors)

  12. A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms

    Directory of Open Access Journals (Sweden)

    Jirath Wichianpitaya

    2013-01-01

    Full Text Available Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG with drospirenone (DRSP in the changes of premenstrual symptoms. Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE/150 micrograms DSG (DSG group or 20 micrograms EE/3 mg DRSP (DRSP group in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases. Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction.

  13. Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease

    International Nuclear Information System (INIS)

    Pace, L.; Cuocolo, A.; Salvatore, M.; Perrone-Filardi, P.; Prastaro, M.; Vezzuto, P.; Crisci, T.; Dellegrottaglie, S.; Piscione, F.; Chiariello, M.; Mainenti, P.P.; Varrone, A.

    1998-01-01

    The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201 Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201 Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40±20) after myocardial revascularization. Discriminant analysis was applied to the results of 201 Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201 Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P 201 Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined. (orig.)

  14. 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.)

  15. Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.

    Science.gov (United States)

    Kobayashi, Shigeki; Susa, Takehisa; Tanaka, Takeo; Murakami, Wakako; Fukuta, Seiko; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

    2012-01-01

    The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

  16. Low doses effects

    International Nuclear Information System (INIS)

    Tubiana, M.

    1997-01-01

    In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

  17. Meta-analysis: low-dose intake of vitamin E combined with other vitamins or minerals may decrease all-cause mortality.

    Science.gov (United States)

    Jiang, Shan; Pan, Zhenyu; Li, Hui; Li, Fenglan; Song, Yanyan; Qiu, Yu

    2014-01-01

    It has been suggested that vitamin E alone or combined with other vitamins or minerals can prevent oxidative stress and slow oxidative injury-related diseases, such as cardiovascular disease and cancer. A comprehensive search of PubMed/MEDLINE, EMBASE and the Cochrane Library was performed. Relative risk was used as an effect measure to compare the intervention and control groups. A total of 33 trials were included in the meta-analysis. Neither vitamin E intake alone (RR=1.01; 95% CI, 0.97 to 1.04; p=0.77) nor vitamin E intake combined with other agents (RR=0.97; 95% CI, 0.89 to 1.06; p=0.55) was correlated with all-cause mortality. Subgroup analyses revealed that low-dose vitamin E supplementation combined with other agents is associated with a statistically significant reduction in all-cause mortality (RR=0.92; 95% CI, 0.86 to 0.98; p=0.01), and vitamin E intake combined with other agents is associated with a statistically significant reduction in mortality rates among individuals without probable or confirmed diseases (RR=0.92; 95% CI, 0.86 to 0.99; p=0.02). Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. But a low dose (vitamin E combined with other agents is correlated with a reduction in all-cause mortality, and vitamin E intake combined with other agents is correlated with a reduction in the mortality rate among individuals without probable or confirmed diseases.

  18. Effects of low dose radiation combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation of bone marrow in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2004-01-01

    Objective: To study the effect of low dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle, and proliferation of bone marrow in mice tumor-bearing mice. Methods: Kunming strain male mice were implanted with S180 sarcoma cells in the left hind leg subcutaneously as an experimental animal model. Five and 8 days after implantation, the mice were given 75 mGy whole-body γ-ray radiation and CTX(300 mg/kg) by intraperitoneal injection 36 hour after LDR. All mice were sacrificed to measure the tumor volume, tumor cell apoptosis, and cell cycle; the proliferation of bone marrow was analyzed by flow cytometry. Results: Tumor growth was significantly slowed down in the treated groups. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G 1 phase in CTX and CTX+LDR groups, more significantly in the latter group than in the former group. Concentration of bone marrow cells and proliferation index in CTX + LDR group were higher than those in CTX group, although concentration of bone marrow cells in CTX and CTX+LDR groups were much lower than that in normal mice. Conclusion: Low dose radiation combined with cyclophosphamide causes more significant G 1 -phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. At the same time LDR significantly protects hematopoietic function of bone marrow, which is of practical significance as an adjuvant chemotherapy

  19. [Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

    Science.gov (United States)

    Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

    2018-04-25

    Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all Pdensity of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

  20. Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.

    Science.gov (United States)

    Biason, Talita Poli; Goldberg, Tamara Beres Lederer; Kurokawa, Cilmery Suemi; Moretto, Maria Regina; Teixeira, Altamir Santos; Nunes, Hélio Rubens de Carvalho

    2015-04-03

    Low-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs. This was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 μg ethinylestradiol/150 μg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann-Whitney test with the significance level fixed at 5% or p variations in the median percentages for bone mass variables. The COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p variation between COC users and non-users. Use of a low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) was associated with lower bone mass acquisition in adolescents during the study period. Registry Number, RBR-5h9b3c.

  1. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

    Science.gov (United States)

    Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-08-01

    Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

  2. Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

    DEFF Research Database (Denmark)

    Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

    2015-01-01

    , whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing......Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential...... consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0...

  3. Low-dose X-ray computed tomography image reconstruction with a combined low-mAs and sparse-view protocol.

    Science.gov (United States)

    Gao, Yang; Bian, Zhaoying; Huang, Jing; Zhang, Yunwan; Niu, Shanzhou; Feng, Qianjin; Chen, Wufan; Liang, Zhengrong; Ma, Jianhua

    2014-06-16

    To realize low-dose imaging in X-ray computed tomography (CT) examination, lowering milliampere-seconds (low-mAs) or reducing the required number of projection views (sparse-view) per rotation around the body has been widely studied as an easy and effective approach. In this study, we are focusing on low-dose CT image reconstruction from the sinograms acquired with a combined low-mAs and sparse-view protocol and propose a two-step image reconstruction strategy. Specifically, to suppress significant statistical noise in the noisy and insufficient sinograms, an adaptive sinogram restoration (ASR) method is first proposed with consideration of the statistical property of sinogram data, and then to further acquire a high-quality image, a total variation based projection onto convex sets (TV-POCS) method is adopted with a slight modification. For simplicity, the present reconstruction strategy was termed as "ASR-TV-POCS." To evaluate the present ASR-TV-POCS method, both qualitative and quantitative studies were performed on a physical phantom. Experimental results have demonstrated that the present ASR-TV-POCS method can achieve promising gains over other existing methods in terms of the noise reduction, contrast-to-noise ratio, and edge detail preservation.

  4. Effect of transcervical resection of adhesion combined with low-dose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue

    Directory of Open Access Journals (Sweden)

    Qian-Wen Chen

    2016-11-01

    Full Text Available Objective: To study the effect of transcervical resection of adhesion combined with lowdose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue. Methods: A total of 78 patients with severe intrauterine adhesions who received transcervical resection of adhesion in our hospital between June 2012 and October 2014 were prospectively studied and randomly divided into two groups, observation group received postoperative estrogenprogestogen combined with low-dose aspirin therapy, and control group received postoperative estrogen-progestogen therapy. Ultrasound examination was conducted before and after treatment to determine uterine artery and endometrial blood flow parameters, intrauterine adhesion tissue was collected to detect the expression levels of Smad2 and Smad3 as well as downstream molecules, and serum was collected to determine the levels of cytokines. Results: On the ovulation day after 3 cycles of treatment, uterine artery RI and PI of observation group were significantly lower than those of control group, and endometrial VI, FI and VFI were significantly higher than those of control group; uPA expression level in intrauterine adhesion tissue of observation group was significantly higher than that of control group, Smad2, Smad3, PAI-1, ADAM15 and ADAM17 expression levels were significantly lower than those of control group, and serum TGF-β, VEGF, CTGF, IGF-I and TNF-α levels were significantly lower than those of control group. Conclusions: Transcervical resection of adhesion combined with low-dose aspirin therapy can improve the postoperative uterine artery and endometrial blood flow state, inhibit extracellular matrix deposition mediated by Smad2/3 signaling pathway and prevent intrauterine re-adhesion in patients with intrauterine adhesions.

  5. A Study on Epidural Tramadol Compared with Epidural Fentanyl Combined with Low Dose Bupivacaine for the Control of Metastatic Cancer Pain

    Directory of Open Access Journals (Sweden)

    Resham Bahadur Rana

    2010-04-01

    Full Text Available Background: Despite advances in the knowledge of pathophysiology of pain and its management, patients continue to suffer from pain in many terminal stage cancer. Tramadol hydrochloride is a weak opioid with analgesic properties, and can be tried for cancer pain management. Objectives: This study was performed to find out the efficacy of the analgesic property of Tramadol through epidural route in cancer patients as an combination with low dose(.125% Bupivacaine and to compare with Fentanyl, a μ opioid agonist. Methods: 50 Cancer patients with or without previous pain management were randomly allocated to one of the two study regime- Group-A (tramadol 50 mg and Group-B (Fentanyl 50 mgm in combination with .125% Bupivacaine. Drugs were administered epidurally 6 hourly, 8 hourly and 12 hourly respectively for the 1st, 2nd and 3rd day. Low dose bupivacaine was added to both groups to enhance quality. Pain scores, blood pressure, respiratory rate, heart rate, side effects and patients' satisfaction score was recorded 6 hourly for 72 hrs. The data yielded from this study were compiled and analyzed by unpaired and paired ‘t' test with 95% confidence limit. A value of P< 0.05 was considered to be significant. ÷ square test was done for some of the data. Results: Pain scores were significantly decreased in both the groups but were not significantly different. The incidence of side effects including nausea and vomiting was found in both the groups and was not significantly different between the two groups. Conclusion: The use of epidural Tramadol in selected cancer pain patients (especially pain in lower abdomen and lower back may be very useful and is comparable to opioid in certain situations. Key words: Metastatic cancer pain; Epidural tramadol. DOI: 10.3329/bsmmuj.v2i2.4760 BSMMU J 2009; 2(2: 66-72

  6. Low dose epidemiologic studies

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    In this chapter the BEIR committee has reviewed low-dose irradiation studies since the BEIR III report. They have considered the carcinogenic effectiveness of low-LET in populations exposed to radiation from a number of different sources: diagnostic radiography; fallout from nuclear weapons testing; nuclear installations; radiation in the workplace and high levels of natural background radiation

  7. Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients

    International Nuclear Information System (INIS)

    Loven, David; B e'Ery, Einat; Yerushalmi, Rinat; Koren, Claude; Sulkes, Aaron; Fenig, Eyal; Lavi, Idit; Shaked, Yuval

    2008-01-01

    Metronomic low-dose chemotherapy regimen was found to have an antiangiogenic effect in tumors. However, its effect on levels of circulating pro-angiogenic and anti-angiogenic factors is not fully explored. Materials and methods. The levels of both VEGF and PDGF-BB were measured in three time points, in the serum of 32 rectal carcinoma patients receiving daily reduced-dose/continuous capecitabine in combination with preoperative pelvic irradiation. Results. We found a significant decrease in VEGF and PDGF-BB serum levels during the combination treatment (p<0.0001), followed by an increase in the successive rest-period (p<0.0001). In addition, substantial changes in platelets counts were observed during treatment in correlation with the changes of VEGF and PDGF-BB serum levels. Discussion. These results suggest that combined chemo-irradiation affect levels of pro-angiogenic factors during treatment, and may reflect an anti-angiogenic window induced during this treatment. The potential implications of this inducible phenomenon, including a possible clinical benefit from the administration of long lasting metronomic chemotherapy immediately following combined chemo-irradiation, would warrant further investigation

  8. Weekly, low-dose docetaxel combined with estramustine for Japanese castration-resistant prostate cancer: its efficacy and safety profile compared with tri-weekly standard-dose treatment.

    Science.gov (United States)

    Nakai, Yasutomo; Nishimura, Kazuo; Nakayama, Masashi; Uemura, Motohide; Takayama, Hitoshi; Nonomura, Norio; Tsujimura, Akira

    2014-02-01

    We retrospectively investigated the efficacy and safety profile of weekly low-dose docetaxel (DTX) with estramustine in comparison with triweekly standard-dose DTX treatment for Japanese patients with castration-resistant prostate cancer (CRPC). Between April 2002 and January 2011, 75 CRPC patients were treated with triweekly DTX (60-75 mg/m(2) every 3 weeks) (standard-dose group), and 76 CRPC patients were treated with weekly low-dose DTX (20-30 mg/m(2) on days 2 and 9 with estramustine 560 mg on days 1-3 and 8-10) every 3 weeks (low-dose group). Prostate-specific antigen (PSA) response and progression-free and overall survival were analyzed in each group. Median serum PSA level of the standard-dose group and low-dose group was 25.0 and 35.5 ng/ml, respectively. In the standard-dose and low-dose groups, 57.8 and 65.2 % of patients, respectively, achieved a PSA decline ≥ 50 %. There was no significant difference in either median time to progression between the standard-dose group (10.0 months) and low-dose group (7.1 months) or in median duration of survival between the standard-dose group (24.2 months) and low-dose group (30.6 months). Multivariate analysis with a Cox proportional hazards regression model showed that DTX treatment protocol did not influence the risk of death. Incidences of grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia were significantly higher in the standard-dose versus low-dose group (58.7 vs. 7.9 %, 16.0 vs. 3.9 %, and 8.0 vs. 0 %, respectively). For Japanese CRPC patients, weekly low-dose DTX combined with estramustine has similar efficacy to standard-dose DTX but with fewer adverse events.

  9. Effects of low doses

    International Nuclear Information System (INIS)

    Le Guen, B.

    2001-01-01

    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.)

  10. Effects of letrozole in combination with low-dose intramuscular injection of human menopausal gonadotropin on ovulation and pregnancy of 156 patients with polycystic ovary syndrome.

    Science.gov (United States)

    Chen, Zhihua; Zhang, Mengzhen; Qiao, Yuhuan; Yang, Junjuan

    2016-01-01

    To explore the effects of letrozole (LE) in combination with low-dose intramuscular injection of human menopausal gonadotropin (HMG) on the ovulation induction and pregnancy of patients with polycystic ovary syndrome (PCOS). A total of 156 patients with PCOS infertility were randomly divided into an LE group, a clomiphene citrate (CC) group and an LE + HMG group (n= 52). LE and CC were orally taken according to the prescribed dosage on the 3rd-5th days of menstruation respectively, and 75 IU HMG was given through intramuscular injection. The ovulation induction parameters and pregnancy outcomes were observed. The number of ovulation cycle of LE + HMG group was significantly higher than that of LE group (χ 2 =8.451, Pmedication cycle of clinically pregnant patients was (2.9 ± 0.3) weeks, which was significantly shorter than those of CC and LE groups (F=17.241, Pmedication cycle and high clinical pregnancy rate, which is promising for treating patients with PCOS infertility.

  11. Insulin Sensitizing and Antioxidant Effects of Hesperidin and Low Dose Gamma Irradiation in Combination with Rosiglitazone in Type 2 Diabetic Rats

    International Nuclear Information System (INIS)

    Morcos, N.Y.; Abdel-Ghaffar, A.B.; Osman, S.A.; Mohamed, M.Kh.; Arbid, M.S.; El-Eraky, W.I.

    2012-01-01

    The present study was designed to investigate the possible ameliorative effect of hesperidin and low dose fÁ-irradiation (LDR) in combination with rosiglitazone in an experimental model of insulin resistance. Type 2 diabetes mellitus (T2DM) was induced in rats by single intraperitoneal injection of streptozotocin (STZ) followed by nicotinamide (NIC) (65 and 110 mg/kg b.wt; i.p respectively). After verifying T2DM in rats, they were subjected to LDR (50 cGy) and then treated with rosiglitazone (4 mg/kg b.wt; p.o) and hesperidin (100 mg/kg b.wt; p.o) for 30 days. Results showed that STZ injection significantly elevated blood glucose, glycosylated hemoglobin (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid peroxides (TBARS; MDA) accompanied with a reduction in adiponectin plasma level, reduced glutathione (GSH) and superoxide dismutase (SOD) serum level. Treatment of diabetic rats with rosiglitazone, hesperidin and LDR significantly reduced blood glucose, HbA1c, insulin, HOMA-IR and MDA levels. Whereas, plasma adiponectin, SOD in serum and GSH plasma level were significantly elevated. Therefore, our data suggest that hesperidin and LDR might be useful adjuvants with rosiglitazone and attenuate insulin resistance and oxidative stress in T2DM.

  12. Restaging of patients with lymphoma. Comparison of low dose CT (20 mAs) with contrast enhanced diagnostic CT in combined [18F]-FDG PET/CT

    International Nuclear Information System (INIS)

    Fougere, C. la; Pfluger, T.; Schneider, V.; Hacker, M.; Broeckel, N.; Bartenstein, P.; Tiling, R.; Morhard, D.; Hundt, W.; Becker, C.

    2008-01-01

    Aim: assessment of the clinical benefit of i.v. contrast enhanced diagnostic CT (CE-CT) compared to low dose CT with 20 mAs (LD-CT) without contrast medium in combined [ 18 F]-FDG PET/CT examinations in restaging of patients with lymphoma. Patients, methods: 45 patients with non-Hodgkin lymphoma (n = 35) and Hodgkin's disease (n = 10) were included into this study. PET, LD-CT and CE-CT were analyzed separately as well as side-by-side. Lymphoma involvement was evaluated separately for seven regions. Indeterminate diagnoses were accepted whenever there was a discrepancy between PET and CT findings. Results for combined reading were calculated by rating indeterminate diagnoses according the suggestions of either CT or PET. Each patient had a clinical follow-up evaluation for > 6 months. Results: region-based evaluation suggested a sensitivity/specificity of 66/93% for LD-CT, 87%/91% for CE-CT, 95%/96% for PET, 94%/99% for PET/LD-CT and 96%/99% for PET/CE-CT. The data for PET/CT were obtained by rating indeterminate results according to the suggestions of PET, which turned out to be superior to CT. Lymphoma staging was changed in two patients using PET/CE-CT as compared to PET/LD-CT. Conclusion: overall, there was no significant difference between PET/LD-CT and PET/CE-CT. However, PET/CE-CT yielded a more precise lesion delineation than PET/LD-CT. This was due to the improved image quality of CE-CT and might lead to a more accurate investigation of lymphoma. (orig.)

  13. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy.

    Science.gov (United States)

    Wu, Rui-Yi; Wang, Guo-Min; Xu, Lei; Zhang, Bo-Heng; Xu, Ye-Qing; Zeng, Zhao-Chong; Chen, Bing

    2011-05-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P = 0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P = 0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

  14. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H

    1998-01-01

    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5

  15. Optimal low-dose radiosurgery combined with and without intervention for unruptured arteriovenous malformations. A long-term follow-up study

    International Nuclear Information System (INIS)

    Inoue, Hiroshi K.; Naitou, Isao

    2006-01-01

    Treatment indication for unruptured arteriovenous malformations (AVMs) of the brain was investigated based on long-term results of low-dose Gamma Knife (GK) surgery. Thirty-nine patients with unruptured AVMs treated with GK surgery were followed more than 7 years. These AVMs were found due to seizure and steal symptoms in 22 and 4 patients, respectively, and incidentally in 13. Embolization was performed in 6 patients before GK surgery. Total obliteration was obtained in 83.3% after initial treatment and 95.8% after additional treatment. Bleeding before total obliteration occurred in 2 patients and adverse effect on the internal capsule in 1. It is concluded that low-dose GK surgery is safe and effective for the treatment of unruptured AVMs, especially symptomatic AVMs in functional areas. (author)

  16. Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

    Science.gov (United States)

    Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

    2017-11-01

    During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

  17. High frequencies of chromatid aberrations produced during G/sub 2/ in human lymphocytes by very low doses (0. 025-0. 4 Gy) of X-rays in combination with inhibitors of DNA synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, H.C.; Kihlman, B.A. (Uppsala Univ. (Sweden). Dept. of Genetics)

    1984-09-01

    Whole-blood cultures of human lymphocytes were exposed in the G/sub 2/-phase (3.5 h before harvesting) to various doses of X-rays and post-treated for 3 h with inhibitors of DNA synthesis. The inhibitors used were 2'-deoxyadenosine (dAdo), hydroxyurea (HU) and 1-..beta..-D-arabinofuranosylcytosine (ara-C). To prevent deamination of dAdo by adenosine deaminase (ADA), the dAdo treatments were carried out in the presence of the ADA inhibitor coformycin. HU and ara-C were used either alone or in combination. After the 3-h inhibitor treatments, the cultures were harvested and slides prepared and analyzed for chromatid aberrations in metaphase. When the inhibitors were used at concentrations high enough to cause marked chromosome damage by themselves, very low doses of X-rays (0.025-0.2 Gy) were sufficient to produce a dramatic increase in the frequency of chromatid aberrations. High frequencies of chromatid aberrations were also obtained when cultures that had received moderate doses of X-rays (0.4-0.8 Gy) were post-treated with low inhibitor concentrations that produce no or only a few aberrations by themselves.

  18. Low doses effects and gamma radiations low dose rates

    International Nuclear Information System (INIS)

    Averbeck, D.

    1999-01-01

    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.)

  19. Reduced oxygen enhancement ratio at low doses

    International Nuclear Information System (INIS)

    Palcic, B.; Skarsgard, L.D.

    1984-01-01

    The oxygen depletion rate in cell suspensions was measured using a Clark electrode. It was found that under experimental conditions used in this laboratory for hypoxic irradiations, the oxygen levels before the start of irradiation are always below 0.1μm, the levels which could give any significant enhancement to radiation inactivation by x-rays. The measured O/sub 2/ depletion rates were comparable to those reported in the literature. Chinese hamster cells (CHO) were made hypoxic by gas exchange, combined with metabolic consumption of oxygen by cells at 37 0 C. Full survival curves were determined in the dose range 0 to 3Gy using the low dose survival assay. The results confirmed the authors' earlier finding that the OER decreases at low doses. The authors therefore believe that the dose-dependent OER is a true radiobiological phenomenon and not an artifact of the experimental method used in the low dose survival assay

  20. Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer

    Directory of Open Access Journals (Sweden)

    Zhang L

    2017-03-01

    Full Text Available Lianru Zhang, Rutian Li, Hong Chen, Jia Wei, Hanqing Qian, Shu Su, Jie Shao, Lifeng Wang, Xiaoping Qian, Baorui Liu The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China Abstract: Cell membrane-derived nanoparticles are becoming more attractive because of their ability to mimic many features of their source cells. This study reports on a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this system, the surface of poly-lactic-co-glycolic acid nanoparticles was camouflaged using T-lymphocyte membranes, and local low-dose irradiation (LDI was used as a chemoattractant for nanoparticle targeting. The T-lymphocyte membrane coating was verified using dynamic light scattering, transmission electron microscopy, and confocal laser scanning microscopy. This new platform reduced nanoparticle phagocytosis by macrophages to 23.99% (P=0.002. Systemic administration of paclitaxel-loaded T-lymphocyte membrane-coated nanoparticles inhibited the growth of human gastric cancer by 56.68% in Balb/c nude mice. Application of LDI at the tumor site significantly increased the tumor growth inhibition rate to 88.50%, and two mice achieved complete remission. Furthermore, LDI could upregulate the expression of adhesion molecules in tumor vessels, which is important in the process of leukocyte adhesion and might contribute to the localization of T-lymphocyte membrane-encapsulated nanoparticles in tumors. Therefore, this new drug-delivery platform retained both the long circulation time and tumor site accumulation ability of human cytotoxic T lymphocytes, while local LDI could significantly enhance tumor localization. Keywords: cell membrane, drug delivery system, gastric cancer, low-dose irradiation, nanoparticles

  1. A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Shigeki Kobayashi

    Full Text Available OBJECTIVES: The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. BACKGROUND: The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+ handling in heart failure remains unclear. METHODS: We investigated the effect of milrinone plus landiolol on intracellular Ca(2+ transient (CaT, cell shortening (CS, the frequency of diastolic Ca(2+ sparks (CaSF, and sarcoplasmic reticulum Ca(2+ concentration ({Ca(2+}SR in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2 and phospholamban (PLB. RESULTS: In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808 in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17. Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz in failing cardiomyocytes. CONCLUSION: A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+ leak.

  2. A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum.

    Science.gov (United States)

    Kobayashi, Shigeki; Susa, Takehisa; Ishiguchi, Hironori; Myoren, Takeki; Murakami, Wakako; Kato, Takayoshi; Fukuda, Masakazu; Hino, Akihiro; Suetomi, Takeshi; Ono, Makoto; Uchinoumi, Hitoshi; Tateishi, Hiroki; Mochizuki, Mamoru; Oda, Tetsuro; Okuda, Shinichi; Doi, Masahiro; Yamamoto, Takeshi; Yano, Masafumi

    2015-01-01

    The purpose of this study was to investigate whether adding a low-dose β1-blocker to milrinone improves cardiac function in failing cardiomyocytes and the underlying cardioprotective mechanism. The molecular mechanism underlying how the combination of low-dose β1-blocker and milrinone affects intracellular Ca(2+) handling in heart failure remains unclear. We investigated the effect of milrinone plus landiolol on intracellular Ca(2+) transient (CaT), cell shortening (CS), the frequency of diastolic Ca(2+) sparks (CaSF), and sarcoplasmic reticulum Ca(2+) concentration ({Ca(2+)}SR) in normal and failing canine cardiomyocytes and used immunoblotting to determine the phosphorylation level of ryanodine receptor (RyR2) and phospholamban (PLB). In failing cardiomyocytes, CaSF significantly increased, and peak CaT and CS markedly decreased compared with normal myocytes. Administration of milrinone alone slightly increased peak CaT and CS, while CaSF greatly increased with a slight increase in {Ca(2+)}SR. Co-administration of β1-blocker landiolol to failing cardiomyocytes at a dose that does not inhibit cardiomyocyte function significantly decreased CaSF with a further increase in {Ca(2+)}SR, and peak CaT and CS improved compared with milrinone alone. Landiolol suppressed the hyperphosphorylation of RyR2 (Ser2808) in failing cardiomyocytes but had no effect on levels of phosphorylated PLB (Ser16 and Thr17). Low-dose landiolol significantly inhibited the alternans of CaT and CS under a fixed pacing rate (0.5 Hz) in failing cardiomyocytes. A low-dose β1-blocker in combination with milrinone improved cardiac function in failing cardiomyocytes, apparently by inhibiting the phosphorylation of RyR2, not PLB, and subsequent diastolic Ca(2+) leak.

  3. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    Science.gov (United States)

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. © 2014 Wiley Periodicals, Inc.

  4. Combination therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea and low dose rate radiation in the 9L rat brain tumor and spheroid models: implications for brain tumor brachytherapy

    International Nuclear Information System (INIS)

    Gutin, P.H.; Bernstein, M.; Sano, Y.; Deen, D.F.

    1984-01-01

    The effects of combination treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and low dose rate radiation were studied in the 9L rat brain tumor in vivo model and the 9L multicellular tumor spheroid model. F-344 rats bearing intracerebral 9L gliosarcomas were implanted with removable 125 I sources. Minimal (peripheral) tumor doses of 6387 rad produced an increased life-span (ILS) of 28% over that of control rats implanted with dummy sources, BCNU alone (13.3 mg/kg) produced in an ILS of 67%, and combination treatment with BCNU and implanted 125 I sources produced an ILS of 167%. As measured by a colony-forming efficiency assay, the greatest cell kill in 9L spheroids occurred when BCNU was administered 24 hours before irradiation from a 137 Cs source at a low dose rate of 5 rad/minute. At a higher dose rate of 210 rad/minute, the time dependence of the effects of combination treatment was identical and therefore independent of dose rate

  5. Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

    International Nuclear Information System (INIS)

    Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

    1979-01-01

    Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

  6. Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section

    Directory of Open Access Journals (Sweden)

    Ahmed Sobhy Basuni

    2016-01-01

    Conclusion: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS.

  7. A rationally designed combined treatment with an alphavirus-based cancer vaccine, sunitinib and low-dose tumor irradiation completely blocks tumor development

    NARCIS (Netherlands)

    Draghiciu, Oana; Boerma, Annemarie; Hoogeboom, Baukje Nynke; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The clinical efficacy of therapeutic cancer vaccines remains limited. For effective immunotherapeutic responses in cancer patients, multimodal approaches capable of both inducing antitumor immune responses and bypassing tumor-mediated immune escape seem essential. Here, we report on a combination

  8. Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

    Science.gov (United States)

    Zent, Clive S.; Taylor, Ronald P.; Lindorfer, Margaret A.; Beum, Paul V.; LaPlant, Betsy; Wu, Wenting; Call, Timothy G.; Bowen, Deborah A.; Conte, Michael J.; Frederick, Lori A.; Link, Brian K.; Blackwell, Sue E.; Veeramani, Suresh; Baig, Nisar A.; Viswanatha, David S.; Weiner, George J.; Witzig, Thomas E.

    2014-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a phase II trial testing the efficacy and tolerability of a short duration regimen combining pentostatin, alemtuzumab, and low dose high frequency rituximab (PAR) designed to decrease the risk of treatment associated infections and limit loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n=36) or previously untreated with 17p13 deletion (17p13-)(n=3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional and eight patients had purine analogue refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy with only five (13%) patients having treatment limiting toxicity, and no treatment related deaths. Twenty-two (56%) patients responded to treatment with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression free survival was 7.2 months, time to next treatment 9.1 months, and overall survival 34.1 months. The majority of deaths (82%) were caused by progressive disease including transformed diffuse large B cell lymphoma (n=6). Correlative studies showed that low dose rituximab activates complement and NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR is a tolerable and effective therapy for CLL and that low dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  9. Health effect of low dose/low dose rate radiation

    International Nuclear Information System (INIS)

    Kodama, Seiji

    2012-01-01

    The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

  10. Mixture effects at very low doses with combinations of anti-androgenic pesticides, antioxidants, industrial pollutant and chemicals used in personal care products

    Energy Technology Data Exchange (ETDEWEB)

    Orton, Frances; Ermler, Sibylle; Kugathas, Subramaniam [Institute for the Environment, Brunel University, Kingston Lane, Uxbridge UB8 3PH (United Kingdom); Rosivatz, Erika [Institute of Chemical Biology, Imperial College London, Exhibition Road, London SW7 2AZ (United Kingdom); Scholze, Martin [Institute for the Environment, Brunel University, Kingston Lane, Uxbridge UB8 3PH (United Kingdom); Kortenkamp, Andreas, E-mail: andreas.kortenkamp@brunel.ac.uk [Institute for the Environment, Brunel University, Kingston Lane, Uxbridge UB8 3PH (United Kingdom)

    2014-08-01

    Many xenobiotics have been identified as in vitro androgen receptor (AR) antagonists, but information about their ability to produce combined effects at low concentrations is missing. Such data can reveal whether joint effects at the receptor are induced at low levels and may support the prioritisation of in vivo evaluations and provide orientations for the grouping of anti-androgens in cumulative risk assessment. Combinations of 30 AR antagonists from a wide range of sources and exposure routes (pesticides, antioxidants, parabens, UV-filters, synthetic musks, bisphenol-A, benzo(a)pyrene, perfluorooctane sulfonate and pentabromodiphenyl ether) were tested using a reporter gene assay (MDA-kb2). Chemicals were combined at three mixture ratios, equivalent to single components' effect concentrations that inhibit the action of dihydrotesterone by 1%, 10% or 20%. Concentration addition (CA) and independent action were used to calculate additivity expectations. We observed complete suppression of dihydrotestosterone effects when chemicals were combined at individual concentrations eliciting 1%, 10% or 20% AR antagonistic effect. Due to the large number of mixture components, the combined AR antagonistic effects occurred at very low concentrations of individual mixture components. CA slightly underestimated the combined effects at all mixture ratios. In conclusion, large numbers of AR antagonists from a wide variety of sources and exposure routes have the ability of acting together at the receptor to produce joint effects at very low concentrations. Significant mixture effects are observed when chemicals are combined at concentrations that individually do not induce observable AR antagonistic effects. Cumulative risk assessment for AR antagonists should apply grouping criteria based on effects where data are available, rather than on criteria of chemical similarity. - Highlights: • Mixtures of AR antagonists at low individual concentrations cause complete inhibition

  11. The addition of low-dose leucovorin to the combination of 5-fluorouracil-levamisole does not improve survival in the adjuvant treatment of Dukes' C colon cancer

    NARCIS (Netherlands)

    Bleeker, WA; Mulder, NH; Hermans, J; Otter, R; Plukker, JT

    Purpose: To assess the effect of the addition of leucovorin to the combination of 5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in patients after a resection with curative intent of a Dukes' C colon cancer. Patients and methods: Five hundred patients with Dukes' C colon

  12. Development of new chemical dosimeter for low dose range

    International Nuclear Information System (INIS)

    Mhatre, Sachin G.V.; Adhikari, S.

    2012-01-01

    Accurate measurement of low dose radiation in complex systems is of utmost importance in radiation biology and related areas. Ferrous Benzoic acid Xylenol orange (FBX) system is being widely used for measurement of low dose gamma radiation because of its reproducibility and precision. However, an additional step, i.e., dissolution of benzoic acid in water at higher temperature followed by cooling at room temperature is involved for the preparation of this dosimeter. This makes it inconvenient as a ready to use dosimeter. In the present work, the organic molecule, sorbitol has been used for measurement of low doses of radiation. The advantages of using sorbitol are its ready availability and instantaneous water solubility. Owing to its dissolution at room temperature, possible errors those are involved in calculation of dose due to thermal oxidation of ferrous ions during preparation of the FBX dosimetric solution could be made insignificant in the proposed dosimeter. In the present system, sorbitol acts as radiolytic sensitizer for the oxidation of ferrous ion, and xylenol orange forms a 1:1 complex specifically with ferric ions. Thus, the analytical detection limit of ferric ions is enhanced compared to other systems. Final composition of the dosimetric solution is; 0.5 mol/m 3 xylenol orange, 10 mol/m 3 sorbitol and 0.2 mol/m 3 ferrous ion in 50 mol/m 3 sulfuric acid. Radiolytic sensitization in combination with analytical enhancement of the ferrous based system, allows us to measure radiation dose in the range of 0.05 Gy–12 Gy with ease and high reproducibility.

  13. Feasibility of low-dose contrast medium high pitch CT angiography for the combined evaluation of coronary, head and neck arteries.

    Directory of Open Access Journals (Sweden)

    Zhiwei Wang

    Full Text Available PURPOSE: To evaluate the image quality and radiation dose of combined heart, head, and neck CT angiography (CTA using prospectively electrocardiography (ECG-triggered high-pitch spiral scan protocol, compared with single coronary CTA. MATERIALS AND METHODS: 151 consecutive patients were prospectively included and randomly divided into three groups. Group 1 (n = 47 underwent combined heart, neck, and head CTA using prospectively ECG-triggered high-pitch spiral (Flash scan protocol with a single-phase intravenous injection of iodinated contrast and saline flush; Group 2 (n = 51 underwent single coronary CTA with Flash scan protocol; and Group 3 (n = 53 underwent single coronary CTA with prospective sequence scan protocol. All patients were examined on a dual source CT (Definition FLASH. The image quality was determined for each CT study. RESULTS: Patients of scanning protocol Group 1, 2, and 3 showed no significant differences in age, sex, heart rates, and BMI. Evaluation of coronary artery image quality showed comparable results in the three scanning protocol groups on a per patient-based analysis. In group 1, image quality was found to be sufficient to be diagnostic in all arterial segments of carotid arteries. The mean dose-length product (DLP for group 1 was 256.3±24.5 mGy×cm and was significantly higher in comparison with group 2 (93.4±19.9 mGy×cm; p < 0.001. However, there was no significant difference of DLP between group 1 and group 3 (254.1±69.9 mGy×cm. CONCLUSIONS: The combined heart, neck, and head arteries scan using prospectively electrocardiography (ECG-triggered high-pitch spiral scan protocol in 1 single examination resulted in an excellent opacification of the aorta, the carotid arteries, and the coronary arteries and provided a good image quality with low radiation dose.

  14. Effect of low-dose cyclophosphamide, ACTH, and IVIG combination immunotherapy on neuroinflammation in pediatric-onset OMS: A retrospective pilot study.

    Science.gov (United States)

    Pranzatelli, Michael R; Allison, Tyler J; Tate, Elizabeth D

    2018-03-05

    Flow cytometric cerebrospinal fluid (CSF) lymphocyte subset analysis has improved the diagnosis of neuroinflammation and identified multiple markers of inflammation in opsoclonus-myoclonus syndrome (OMS). The aim of this exploratory, retrospective study was to analyze the effect of immunotherapy on these markers to determine which agents are disease modifying. Cross-sectional immunological observations were made in an IRB-approved case-control study, and patients were treated empirically. Ten different CSF lymphocyte subpopulations from 18 children with persistent OMS had been measured by flow cytometry before and after clinical treatment with cyclophosphamide/ACTH/IVIG combination (n = 7) or ACTH/IVIG alone (n = 11). Clinical severity of OMS was scored from videotapes by a blinded observer using the OMS Evaluation Scale. Only cyclophosphamide combination therapy (mean dose 26 ± 3 mg/kg or 922 ± 176 mg/m 2 x 6 cycles) significantly decreased the percentage of CSF B cells. The mean reduction was 65%, with CSF B cell frequency normalized at 7-8 months in 70%. Other abnormalities of the CSF immunophenotype, such as the low CD4/CD8 T cell ratio, persisted, and there were no therapeutic changes in T cell activation/maturation markers. Effects on relative and absolute size of PBMC subsets were similar. Clinical improvement was 70% and 55% in respective treatment groups. The relapse rates of the two groups did not significantly differ. The main effect of cyclophosphamide combination therapy on neuroinflammation in OMS was moderate reduction in CSF B cell expansion. Though exploratory, it may provide a steroid sparer option in partially-responsive OMS. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Detection of pulmonary embolism with combined ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector CT angiography

    DEFF Research Database (Denmark)

    Gutte, Henrik; Mortensen, Jann; Jensen, Claus Verner

    2009-01-01

    The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer testing, and imaging with either pulmonary ventilation-perfusion (V/Q) scintigraphy or pulmonary multidetector CT (MDCT) angiography. Both V/Q SPECT and MDCT angiography seem to have...... high diagnostic accuracy. However, only limited data directly comparing these 2 modalities are available. Hybrid gamma-camera/MDCT systems have been introduced and allow simultaneous 3-dimensional lung V/Q SPECT and MDCT angiography, suitable for diagnosing PE. The aim of our study was to compare...

  16. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  17. 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.

  18. Combined use of low dose gamma irradiation and fenoxycarb, as a means of protection against infestation of wheat grains with khapra beetle Trogoderma granarium, Everts

    International Nuclear Information System (INIS)

    Ghanem, I; Al-Ek, H.

    2006-04-01

    Larvae of khapra beetle were exposed to one of the following treatments: Rearing on wheat grains treated with varying concentrations of fenoxycarb. Irradiation with varying doses of gamma rays followed by rearing on non-treated wheat grains. Irradiation with varying doses of gamma rays followed by rearing on fenoxycarb-treated wheat grains. The development of these larvae was followed and the percentage of each developmental stage was recorded. Results indicate that the combined use of radiation and fenoxycarb resulted in a accumulative effect that leads to the reduction in the doses of both treatments needed to achieve a complete abolition of adult emergence. Within five weeks of commencement about 85% of the larvae in the control treatment have reached adulthood, eggs laid by these adults have hatched into life larvae. When larvae were irradiated with gamma ray, development was disrupted and percentages of emerging adults decreased with the increase in irradiation dose. At a dose of 100 Gy adult emergence was abolished and no adults were found five weeks from the start of the experiment. Likewise, Rearing of larvae on fenoxycarb-treated grains resulted in a disruption of development and a dose of 1ppm was necessary to achieve total abolishment of adult emergence. However, when a combination of gamma ray and fenoxycarb treatment was applied a accumulative effect was observed resulting in a reduction in the doses of irradiation and fenoxycarb needed to achieve similar results. The doses needed to achieve a total absence of adult emergence were reduced to 50Gy and 0.063 ppm for irradiation and fenoxycarb treatment respectively. The significance of the above results is discussed, and an explanation to the observed accumulative effect is offered. (author)

  19. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.

    Science.gov (United States)

    Jensterle, Mojca; Kravos, Nika Aleksandra; Goričar, Katja; Janez, Andrej

    2017-01-31

    Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m 2 ) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1.2 mg QD (N = 15) or liraglutide 3 mg (LIRA3) QD alone (N = 15) for 12 weeks. The primary outcome was change in anthropometric measures of obesity. Both treatments led to significant weight loss (-3.6 ± 2.5 kg, p = 0.002 in COMBO vs -6.3 ± 3.7 kg, p = 0.001 in LIRA3). BMI and waist circumference reduction in LIRA3 was greater than in COMBO (-2.2 ± 1.3 vs -1.3 ± 0.9 kg/m 2 , p = 0.05 and -4.2 ± 3.4 vs -2.2 ± 6.2 cm, p = 0.014, respectively). Both interventions resulted in a significant decrease of post-OGTT glucose levels. COMBO significantly reduced total testosterone and was associated with less nausea. Short-term interventions with COMBO and LIRA3 both led to significant improvement of measures of obesity in obese PCOS, LIRA3 being superior to COMBO. However, COMBO further improved androgen profile beyond weight reduction and was associated with better tolerability. The study was retrospectively registered with ClinicalTrials.gov ( NCT02909933 ) on 16 th of September 2016.

  20. Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low-dose streptozotocin.

    Science.gov (United States)

    Manaer, Tabusi; Yu, Lan; Zhang, Yi; Xiao, Xue-Jun; Nabi, Xin-Hua

    2015-07-01

    Shubat, probiotic fermented camel milk, has been used both as a drink with ethnic flavor and a medicine among Kazakh population for diabetic patients. Kazakh people have lower diabetic prevalence and impaired fasting glucose (IFG) than do other ethnic groups living in Xinjiang China, which might be related to the beneficial properties of shubat. We therefore prepared shubat in laboratory and tested anti-diabetic activity and evaluated its possible hypolipidemic and renoprotective effects in type 2 diabetic rats. Type 2 diabetic rats were induced by an administration of high-glucose-fat diet for 6 weeks and an intraperitoneal injection of streptozotocin (STZ, 30mg/kg). Diabetic rats were divided randomly into four groups and treated for 28 days with sitagliptin (30mg/kg) or shubat (6.97×10(6) lactic acid bacteria+2.20×10(4) yeasts) CFU/mL, (6.97×10(7) lactic acid bacteria+2.20×10(5) yeasts) CFU/mL and (6.97×10(8) lactic acid bacteria+2.20×10(6) yeasts) CFU/mL. In addition, a normal control group and a diabetic control group were used for comparison. All drugs were given orally once daily 10mL/kg for 4 weeks. Fasting blood glucose (FBG) and body weight (BW) were measured before treatment and every week thereafter. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), serum creatinine (SCr), blood urea nitrogen (BUN), C-peptide, glycated hemoglobin (HbAlc), glucagon-like peptide-1 (GLP-1) levels and pancreas tissue sections were tested after 4 weeks. Shubat demonstrated positive hypoglycemic activity on FBG, HbAlc, C-peptide and GLP-1 levels, high dose shubat decreased FBG (Pdiabetic controls. Histological analysis showed shubat protected the function of islets of type 2 diabetic rats. The results of this study indicate that shubat has significant hypoglycemic potential in T2D rats and may modulate lipid metabolism and protect renal function in the type 2 diabetic condition, which

  1. Synergistic induction of tumors in NMRI mice by combined fetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.

    1988-08-01

    Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumor pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumor frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumors and ovary tumors. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy fetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumors of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumors suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus.

  2. Statistical and low dose response

    International Nuclear Information System (INIS)

    Thorson, M.R.; Endres, G.W.R.

    1981-01-01

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  3. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    International Nuclear Information System (INIS)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-01-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m 2 /day) was continuously infused over 24 hours, and CDDP (3-7 mg/m 2 /day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  4. Multidisciplinary European Low Dose Initiative (MELODI). Strategic research agenda for low dose radiation risk research

    Energy Technology Data Exchange (ETDEWEB)

    Kreuzer, M. [Federal Office for Radiation Protection, BfS, Department of Radiation Protection and Health, Neuherberg (Germany); Auvinen, A. [University of Tampere, Tampere (Finland); STUK, Helsinki (Finland); Cardis, E. [ISGlobal, Barcelona Institute for Global Health, Barcelona (Spain); Durante, M. [Institute for Fundamental Physics and Applications, TIFPA, Trento (Italy); Harms-Ringdahl, M. [Stockholm University, Centre for Radiation Protection Research, Stockholm (Sweden); Jourdain, J.R. [Institute for Radiological Protection and Nuclear Safety, IRSN, Fontenay-aux-roses (France); Madas, B.G. [MTA Centre for Energy Research, Environmental Physics Department, Budapest (Hungary); Ottolenghi, A. [University of Pavia, Physics Department, Pavia (Italy); Pazzaglia, S. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome (Italy); Prise, K.M. [Queens University Belfast, Belfast (United Kingdom); Quintens, R. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Sabatier, L. [French Atomic Energy Commission, CEA, Paris (France); Bouffler, S. [Public Health England, PHE, Chilton (United Kingdom)

    2018-03-15

    MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html). (orig.)

  5. Preparation and determination of kerma for Iridium 192 sources of low dose rate for brachytherapy; Preparacion y determinacion del kerma de fuentes de iridio-192 de baja tasa de dosis para braquiterapia

    Energy Technology Data Exchange (ETDEWEB)

    Tendilla, J.I.; Tovar M, V.; Mitsoura, E.; Aguilar H, F.; Alanis M, J. [Instituto Nacional de Investigaciones Nucleares, C.P. 52045-1, Salazar, Esrado de Mexico, D.F. (Mexico)

    2000-07-01

    The practice of Brachytherapy with Iridium-192 sources of low dose rate (0.4 - 0.8 Gy/h) is a technique used in the treatment of diverse illnesses. in this work the preparation, quality control and calibration are presented in terms of kerma in air of Iridium-192 using as target these recycled Iridium-Platinum wires. The targets were obtained as decayed sources of different radio therapeutical centers in the country and they were characterized by Scanning electron microscopy in order to determine their chemical composition. Subsequently it was developed an experimental design to establish the effect of neutron flux, geometrical array and irradiation time over the activity and percentage of the sources homogeneity. The homogeneity was determined by auto radiography and by Gamma spectroscopy. Once the optimal irradiation conditions were established, it is determined the apparent activity and kerma in air using a well type ionization chamber with traceability to a primary laboratory. Iridium-192 sources were obtained with an average homogeneity 96 %, apparent activity 282.129 {+-} 0.531 M Bq and kerma in air 0.03200 {+-} 0.00006 m Gy m/h A. (Author)

  6. 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.

  7. 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

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  8. Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice

    Directory of Open Access Journals (Sweden)

    Fatih M. Uckun

    2015-04-01

    Full Text Available In high-risk remission B-precursor acute lymphoblastic leukemia (BPL patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT even after the use of very intensive total body irradiation (TBI-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL” fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI combined with CD19L–sTRAIL was highly effective against (1 xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2 radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT.

  9. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

    Science.gov (United States)

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

    2011-01-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

  10. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  11. Clinical value of a one-stop-shop low-dose lung screening combined with 18F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer

    International Nuclear Information System (INIS)

    Han, Yeon Hee; Lim, Seok Tae; Jeong, Hwan Jeong; Sohn, Myung Hee

    2016-01-01

    The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with 18F-fluoro-2-deoxyglucose positron emission tomography with CT (18F-FDG PET/CT) compared with conventional lung setting image of 18F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with 18F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had  >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of 18F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of 18F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of 18F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional

  12. Clinical value of a one-stop-shop low-dose lung screening combined with {sup 18}F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yeon Hee; Lim, Seok Tae; Jeong, Hwan Jeong; Sohn, Myung Hee [Dept. of Nuclear Medicine, Research Institute of Clinical Medicine, Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2016-06-15

    The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with 18F-fluoro-2-deoxyglucose positron emission tomography with CT (18F-FDG PET/CT) compared with conventional lung setting image of 18F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with 18F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had  >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of 18F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of 18F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of 18F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional

  13. Clinical Value of a One-Stop-Shop Low-Dose Lung Screening Combined with (18)F-FDG PET/CT for the Detection of Metastatic Lung Nodules from Colorectal Cancer.

    Science.gov (United States)

    Han, Yeon-Hee; Lim, Seok Tae; Jeong, Hwan-Jeong; Sohn, Myung-Hee

    2016-06-01

    The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with (18)F-fluoro-2-deoxyglucose positron emission tomography with CT ((18)F-FDG PET/CT) compared with conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with (18)F-FDG PET/CT. Forty-five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had ≤5 metastatic lung nodules and the other 20 patients had >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with ≤5 nodules were evaluated by conventional lung setting image of (18)F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of (18)F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. Of the 120 nodules in the 25 patients with ≤5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of (18)F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were LD-HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional lung setting image and additional LD-HRCT were 0.712 and 0.827 respectively. Additional LD-HRCT with maximum inspiration was superior to conventional lung setting image of (18)F-FDG PET

  14. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

    Sugahara, Tsutomu; Sagan, L.A.; Aoyama, Takashi

    1992-01-01

    It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

  15. Low-dose dental CT

    International Nuclear Information System (INIS)

    Rustemeyer, P.; Eich, H.T.; John-Mikolajewski, V.; Mueller, R.D.

    1999-01-01

    Purpose: The intention of this study was to reduce patient dose during dental CT in the planning for osseointegrated implants. Methods and Materials: Dental CTs were performed with a spiral CT (Somatom Plus 4, Siemens) and a dental software package. Use of the usual dental CT technique (120 kVp; 165 mA, 1 s rotation time, 165 mAs; pitch factor 1) was compared with a new protocol (120 kVp; 50 mA; 0.7 s rotation time; 35 mAs; pitch factor 2) which delivered the best image quality at the lowest possible radiation dose, as tested in a preceding study. Image quality was analysed using a human anatomic head preparation. Four radiologists analysed the images independently. A Wilcoxon rank pair-test was used for statistic evaluation. The doses to the thyroid gland, the active bone marrow, the salivary glands, and the eye lens were determined in a tissue-equivalent phantom (Alderson-Rando Phantom) with lithium fluoride thermoluminescent dosimeters at the appropriate locations. Results: By mAs reduction from 165 to 35 and using a pitch factor of 2, the radiation dose could be reduced by a factor of nine (max.) (e.g., the bone marrow dose could be reduced from 23.6 mSv to 2.9 mSv, eye lens from 0.5 mSv to 0.3 mSv, thyroid gland from 2.5 mSv to 0.5 mSv, parotid glands from 2.3 mSv to 0.4 mSv). The dose reduction did not lead to an actual loss of image quality or diagnostic information. Conclusion: A considerable dose reduction without loss of diagnostic information is achievable in dental CT. Dosereducing examination protocols like the one presented may further expand the use of preoperative dental CT. (orig.) [de

  16. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  17. Exposure to low doses of ionizing radiations

    International Nuclear Information System (INIS)

    Le Guen, B.

    2008-01-01

    The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

  18. Biological influence from low dose and low-dose rate radiation

    International Nuclear Information System (INIS)

    Magae, Junji

    2007-01-01

    Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

  19. 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.

  20. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    Lawson, Helen

    1976-05-01

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  1. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    2000-01-01

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on lung cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from 60 Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows helper T-cells to activate killer cells and antibody producing cells

  2. Mammography-oncogenecity at low doses

    International Nuclear Information System (INIS)

    Heyes, G J; Mill, A J; Charles, M W

    2009-01-01

    Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 ± 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 ± 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

  3. New risk estimates at low doses

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1992-01-01

    The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

  4. Cytogenetic effects of low-dose radiation

    International Nuclear Information System (INIS)

    Metalli, P.

    1983-01-01

    The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

  5. 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.’

  6. Radiation effects of high and low doses

    International Nuclear Information System (INIS)

    El-Naggar, A.M.

    1998-01-01

    The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

  7. Estimation of radiation risks at low dose

    International Nuclear Information System (INIS)

    1990-04-01

    The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

  8. Low doses of gamma radiation in soybean

    International Nuclear Information System (INIS)

    Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C.; Arthur, Valter; Arthur, Paula B.; Franco, Caio H.

    2017-01-01

    The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

  9. Modification of damage following low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Nelson, J.M.; Metting, N.F.

    1988-01-01

    At very low doses the damage-interaction mechanism is responsible for very little lethal or potentially lethal damage, and repair of the latter should essentially disappear. An alternative model suggests that potentially lethal damage is either repaired with a constant half time or misrepaired at a rate which is proportional to the square of the damage concentration. In this case, as the dose decreases, the probability of misrepair decreases faster than the probability of repair, and repair becomes a more pronounced feature of the cell response. Since the consequence of unrepaired damage is an important question in determining the effects of low doses of radiation delivered at low dose rates, we have attempted to determine which of these two types of models is consistent with the response of plateau-phase CHO cells. In the earlier experiments, there was no indication of repair after a 50-rad exposure with a 24-hour split dose or plating delay; in fact, immediate plating resulted in survival slightly above control and delayed plating in survival slightly below the control value

  10. Low doses of gamma radiation in soybean

    Energy Technology Data Exchange (ETDEWEB)

    Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C., E-mail: zegilmar60@gmail.com, E-mail: gilmita@uol.com.br, E-mail: villavic@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil); Arthur, Valter; Arthur, Paula B., E-mail: arthur@cena.usp.br [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil); Franco, Caio H. [Universidade Federal de São Paulo (UNIFESP), SP (Brazil). Departamento de Microbiologia, Imunologia e Parasitologia

    2017-07-01

    The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

  11. Biological effects of low doses of radiation at low dose rate

    International Nuclear Information System (INIS)

    1996-05-01

    The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

  12. Preparation, characterization and in vitro release kinetics of polyaspartamide-based conjugates containing antimalarial and anticancer agents for combination therapy

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2016-09-01

    Full Text Available Malaria is treated by combination of two drugs in order to overcome drug resistance. Antimalarials have been found to be more effective by combining them with low doses of anticancer drugs. Polymer-drug conjugates containing aminoquinoline...

  13. Bioavailability of diclofenac potassium at low doses

    Science.gov (United States)

    Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

    2005-01-01

    Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

  14. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    Ionizing radiation of cosmic or terrestrial origin is part of the environment in which all living things have evolved since the creation of the universe. The artificial radioactivity generated by medical diagnostic and treatment techniques, some industrial activities, radioactive fallout, etc. has now been added to this natural radioactivity. This article reviews the biological effects of the low doses of ionizing radiation to which the population is thus exposed. Their carcinogenic risk cannot simply be extrapolated from what we know about high-dose exposure. (author)

  15. Low dose radiation and diabetes mellitus

    International Nuclear Information System (INIS)

    Zhao Hongguang; Gong Shouliang; Cai Lu

    2006-01-01

    Induction of hormesis and adaptive response by low-dose radiatio (LDR) has been extensively indicated. It's mechanism may be related with the protective protein and antioxidants that LDR induced, which take effects on the diabetes mellitus (DM) and other diseases. This review will summarize available dat with emphasis on three points: the preventive effect of LDR on the development of diabetes, the therapeutic effect of LDR on diabetic complications and possible mechanisms by which LDR prevents the development of diabetes and diabetic complications. Finally, the perspectives of LDR clinical, diabetes-related implication are discussed. (authors)

  16. Low-dose effect on blood chromosomes

    International Nuclear Information System (INIS)

    Pohl-Rueling, J.

    1992-01-01

    Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

  17. Low and very low doses, new recommendations?

    International Nuclear Information System (INIS)

    Foucher, N.

    1999-01-01

    The topic of the seminar organized by the world council of nuclear workers (WONUC) was the effects of low or very low doses on human health. Discussions centred round the linearity of the relation between dose and effect in the evaluation and management of the health hazard. The recommendations proposed by ICPR (international commission for radiological protection) are based on this linearity as a precaution. On the one hand it is remembered that low dose irradiation might be beneficial. It has been proved that the irradiation of the whole body is efficient in case of Hodgkin lymphoma. On the other hand it is remembered that doses as low as 10 mSv in utero have led to an excess of cancer in children. Studies based on experimentally radio-induced cancers have been carried out in Japan, China, Canada and France.Their results seem to be not consistent with the hypothesis of linearity. During the last decade a lot of work has been made but a conclusion is far to be reached, it is said that the American department of energy (DOE) has invited bids in 1999 to launch research programs in order to clarify the situation. (A.C.)

  18. The usage and efficacy of a combination analgesic preparation ...

    African Journals Online (AJOL)

    Combination analgesics are frequently prescribed for the treatment of a multitude of conditions. Many of these preparations contain agents with no proven analgesic efficacy. We examined 3059 patients using a new combination agent containing only paracetamol, codeine, and ibuprofen. It appears that despite a wide ...

  19. 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...

  20. Low Dose Ionizing Radiation Modulates Immune Function

    International Nuclear Information System (INIS)

    Nelson, Gregory A.

    2016-01-01

    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

  1. 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

  2. Thermal stability of low dose Ga+ ion irradiated spin valves

    International Nuclear Information System (INIS)

    Qi Xianjin; Wang Yingang; Zhou Guanghong; Li Ziquan

    2009-01-01

    The thermal stability of low dose Ga + ion irradiated spin valves has been investigated and compared with that of the as-prepared ones. The dependences of exchange field, measured using vibrating sample magnetometer at room temperature, on magnetic field sweep rate and time spent at negative saturation of the pinned ferromagnetic layer, and training effect were explored. The training effect is observed on both the irradiated spin valves and the as-prepared ones. The magnetic field sweep rate dependence of the exchange bias field of the irradiated spin valves is nearly the same as that of the as-prepared ones. For the as-prepared structure thermal activation has been observed, which showed that holding the irradiated structure at negative saturation of the pinned ferromagnetic layer for up to 28 hours results in no change in the exchange field. The results indicate that the thermal stability of the ion irradiated spin valves is the same as or even better than the as-prepared ones.

  3. The use of a combined regimen of GnRH agonist plus a low-dose oral contraceptive improves the spontaneous pulsatile LH secretory characteristics in patients with polycycstic ovary disease after discontinuation of treatment.

    Science.gov (United States)

    Genazzani, A D; Battaglia, C; Gamba, O; Petraglia, F; Malavasi, B; Genazzani, A R

    2000-05-01

    The fertility rate in women with polycystic ovary disease (PCOD) is influenced by the type of treatment received. The present study evaluated the possible correlation between treatment and pulsatile release of gonadotropins. Spontaneous episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and hormonal parameters were monitored before and after 1, 3, and 6 months after treatments suspension. Twenty-four PCOD patients were randomly divided into two groups of 12 subjects. Group A was treated with gonadotropin-releasing hormone (GnRH)-analogue plus oral contraceptive (OC). Group B was treated only with OC. Both groups were treated for 6 months and followed up for 6 months. In all subjects the therapeutic regimens reduced the androgenic milieau and the gonadotropin plasma levels. Spontaneous pulsatile secretion of LH and FSH was significantly modified in both groups, but patients who received the combined regimen showed a significantly greater reduction of LH plasma levels and a significantly greater decrease of LH pulse amplitude throughout the 6 months after treatment suspension. Ferriman-Gallway score and ovarian volumes were significantly reduced in patients who received the combined treatment than in the OC-treated patients. These data support the evidence of a higher efficacy of the combination of GnRH-a + OC than OC alone in restoring a normal and adequate spontaneous episodic gonadotropin discharge and in decreasing Ferriman-Gallway score and ovarian volumes in patients with PCOD.

  4. Long term administration of low doses of mycotoxins in poultry. 2. Residues of ochratoxin A and aflatoxins in broilers and laying hens after combined administration of ochratoxin A and aflatoxin B1.

    Science.gov (United States)

    Micco, C; Miraglia, M; Benelli, L; Onori, R; Ioppolo, A; Mantovani, A

    1988-01-01

    The effects of combined administration of ochratoxin A (OA) and aflatoxin B1 (AFB1) on the occurrence and the levels of residues of mycotoxins in poultry have been investigated. Male broilers and laying hens were fed from 14 days old with standard diets contaminated with 50 micrograms/kg OA and 50 micrograms/kg AFB1. Two groups of broilers and hens were withdrawn from contaminated feed at 37 and 88 days, respectively. At the time of sacrifice no significant lesions were found. Residues were compared with those found after administration of either toxin alone in former trials. Combined treatment resulted in higher content of OA in broiler livers (40 versus 5.0 micrograms/kg) and, to a lesser extent, in kidneys and skin, and of AFB1 in broiler liver and kidney (0.15 versus 0.02 microgram/kg and 0.40 versus 0.05 microgram/kg respectively). Laying hens showed smaller differences (0.20 versus 0.10 microgram/kg in liver and 0.32 versus 0.08 in kidneys). Withdrawal from treatment led to the almost complete disappearance of OA residues in broilers and in hens. These results show a synergistic effect of OA and AFB1, particularly in broilers.

  5. Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

    Science.gov (United States)

    Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

    2018-03-24

    Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

  6. low dose irradiation growth in zirconium

    International Nuclear Information System (INIS)

    Fortis, A.M.

    1987-01-01

    Low dose neutron irradiation growth in textured and recrystallized zirconium, is studied, at the Candu Reactors Calandria temperature (340 K) and at 77 K. It was necessary to design and build 1: A facility to irradiate at high temperatures, which was installed in the Argentine Atomic Energy Commission's RA1 Reactor; 2: Devices to carry out thermal recoveries, and 3: Devices for 'in situ' measurements of dimensional changes. The first growth kinetics curves were obtained at 365 K and at 77 K in a cryostat under neutron fluxes of similar spectra. Irradiation growth experiments were made in zirconium doped with fissionable material (0,1 at % 235 U). In this way an equivalent dose two orders of magnitude greater than the reactor's fast neutrons dose was obtained, significantly reducing the irradiation time. The specimens used were bimetallic couples, thus obtaining a great accuracy in the measurements. The results allow to determine that the dislocation loops are the main cause of irradiation growth in recrystallized zirconium. Furthermore, it is shown the importance of 'in situ' measurements as a way to avoid the effect that temperature changes have in the final growth measurement; since they can modify the residual stresses and the overconcentrations of defects. (M.E.L.) [es

  7. Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

    International Nuclear Information System (INIS)

    Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

    2008-01-01

    Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

  8. Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women

    Directory of Open Access Journals (Sweden)

    Momoeda M

    2014-12-01

    Full Text Available Mikio Momoeda,1 Masakane Hayakawa,2 Yukio Shimazaki,3 Hideki Mizunuma,4 Yuji Taketani5 1Department of Integrated Women's Health, St Luke's International Hospital, Tokyo, 2Medical Affairs, 3Product Development, Bayer Yakuhin, Ltd, Osaka, 4Department of Obstetrics and Gynecology, Faculty of Medicine, Hirosaki University, Hirosaki, 5Japan Labour Health and Welfare Organization, Kawasaki, JapanBackground: The purpose of this study was to investigate the effectiveness of a combination of ethinylestradiol (EE and 0.02 mg/drospirenone (DRSP 3 mg in Japanese women with dysmenorrhea and in particular to determine whether or not the presence of specific coexisting organic diseases (eg, endometriosis, uterine fibroids, uterine adenomyosis has an impact on treatment.Methods and results: Four hundred and ten patients with dysmenorrhea aged 20 years or older (315 without coexisting organic disease, 28 with endometriosis, 37 with uterine fibroids, and 46 with uterine adenomyosis [some patients had multiple coexisting organic diseases] were enrolled and treated with EE/DRSP in either a 16-week comparator study or a 52-week long-term safety study. Evaluations included changes in total dysmenorrhea score, visual analog scale for dysmenorrhea, severity of symptoms, hormone levels, endometrial thickness, and safety outcomes. In both studies, the total dysmenorrhea score was significantly (P<0.001 decreased from baseline during treatment with EE/DRSP. Time-dependent changes in visual analog score for dysmenorrhea and alleviation of symptoms, such as lower abdominal pain, low back pain (lumbago, headache, and nausea/vomiting, were similar in all patient groups with and without any specific coexisting organic diseases. These improvements with EE/DRSP were observed for both short-term (16 weeks and long-term (52 weeks use. These effects were associated with suppressed increases in serum estradiol and progesterone levels and decreased endometrial thickness. The safety

  9. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Masse, R.

    2006-01-01

    Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

  10. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Metting, N.F.; Nelson, J.M.

    1987-01-01

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  11. 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

  12. Effects of low dose mitomycin C on experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Yang Jianzheng; Liang Shuo; Qu Yaqin; Pu Chunji; Zhang Haiying; Wu Zhenfeng; Wang Xianli

    2001-01-01

    Objective: To evaluate the possibility of low dose mitomycin C(MMC) as an adjunct therapy for radiotherapy. Methods: Change in tumor size tumor-bearing mice was measured. Radioimmunoassay was used to determine immune function of mice. Results: Low dose Mac's pretreatment reduced tumor size more markedly than did radiotherapy only. The immune function in mice given with low dose MMC 12h before radiotherapy was obviously higher than that in mice subjected to radiotherapy only (P<0.05), and was close to that in the tumor-bearing mice before radiotherapy. Conclusion: Low dose MMC could improve the radiotherapy effect. Pretreatment with low dose MMC could obviously improve the immune suppression state in mice caused by radiotherapy. The mechanism of its improvement of radiotherapeutic effect by low dose of MMC might be due to its enhancement of immune function and induction of adaptive response in tumor-bearing mice

  13. 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.

  14. 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 ...

  15. 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

    low dose radiation exposure. Cells viability/cytotoxicity analysis data are currently being analyzed to determine how these endpoints are affected under our experimental conditions. The results from this study will be translatable to risk assessment for assigning limits to radiation workers, pre-dosing for more effective radiotherapy and the consequences of long duration space flight. The data from this study has been presented a various scientific meetings/workshops and a manuscript, containing the findings, is currently being prepared for publication. Due to unforeseen challenges in collecting the data and standardizing experimental procedures, the second and third aims have not been completed. However, attempts will be made, based on the availability of funds, to continue this project so that these aims can be satisfied.

  16. Combination could be another tool for bowel preparation?

    Science.gov (United States)

    Soh, Jae Seung; Kim, Kyung-Jo

    2016-01-01

    Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol (PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents (e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents (e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents (e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients’ adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies. PMID:26973388

  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 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....

  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 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....

  19. Study of genomic instability induced by low dose ionizing radiation

    International Nuclear Information System (INIS)

    Seoane, A.; Crudeli, C.; Dulout, F.

    2006-01-01

    The crews of commercial flights and services staff of radiology and radiotherapy from hospitals are exposed to low doses of ionizing radiation. Genomic instability includes those adverse effects observed in cells, several generations after the exposure occurred. The purpose of this study was to analyze the occurrence of genomic instability by very low doses of ionizing radiation [es

  20. The Myocardial Performance Index During Low Dose Dobutamine Echocardiography in Normals and Patients With a Recent Myocardial Infarction

    DEFF Research Database (Denmark)

    Nørager, Betina; Husic, Mirza; Møller, Jacob E

    2004-01-01

    BACKGROUND: Wall-motion analysis during low-dose dobutamine echocardiography (LDDE) is a semiquantitative measure of left ventricular contractile reserve after myocardial infarction (MI). The Doppler echocardiographic myocardial performance index (MPI) is a quantitative measure of combined left...

  1. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 5

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Imanaka, Kazufumi; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

    1982-01-01

    We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. This active specific immunotherapy was performed on the thirteenth day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the thirteenth day to the seventeenth day. The inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432 compared with that received this active specific immunotherapy alone. (author)

  2. Biological responses to low dose rate gamma radiation

    International Nuclear Information System (INIS)

    Magae, Junji; Ogata, Hiromitsu

    2003-01-01

    Linear non-threshold (LNT) theory is a basic theory for radioprotection. While LNT dose not consider irradiation time or dose-rate, biological responses to radiation are complex processes dependent on irradiation time as well as total dose. Moreover, experimental and epidemiological studies that can evaluate LNT at low dose/low dose-rate are not sufficiently accumulated. Here we analyzed quantitative relationship among dose, dose-rate and irradiation time using chromosomal breakage and proliferation inhibition of human cells as indicators of biological responses. We also acquired quantitative data at low doses that can evaluate adaptability of LNT with statistically sufficient accuracy. Our results demonstrate that biological responses at low dose-rate are remarkably affected by exposure time, and they are dependent on dose-rate rather than total dose in long-term irradiation. We also found that change of biological responses at low dose was not linearly correlated to dose. These results suggest that it is necessary for us to create a new model which sufficiently includes dose-rate effect and correctly fits of actual experimental and epidemiological results to evaluate risk of radiation at low dose/low dose-rate. (author)

  3. Response of human and rabbit lymphocytes to low doses of X-rays

    International Nuclear Information System (INIS)

    Fabry, L.

    1982-01-01

    The response of human and rabbit lymphocytes to low doses of X-rays was studied by the yields of dicentrics in first division metaphases. For both species, the dose-response curve was best fitted to the linear-quadratic model with a linear component predominating up to 67 and 42 rad respectively for man and rabbit. A calibration curve (5-400 rad) was obtained by combining the present results on man with previous data at higher doses. On the other hand, it appears that, at low doses, the radiosentivity of human lymphocytes is significantly higher than that of rabbit lymphocytes [fr

  4. 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.

  5. Clinical characteristic of epidemic hepatitis in case of the effect of low dose irradiation

    International Nuclear Information System (INIS)

    Geras'kov, O.P.; Shubik, V.M.

    1990-01-01

    Clinical course of infections hepatitics B, developed on the background of pulmonary tuberculosis in people, who were subjected to chronic low dose ionizing radiation, indicated more frequent cases of severe and medium-severe forms of morbidity as compared to non-irradiated patients and those with no comitant pulmonary tuberculosis. However the reconvalescence terms, hepatitis size normalization, urine colour in different group patients did not differ essentially. The data obtained testify to the absence of significant peculiarities in the course of infections hepatitis B, combined with pulmonar tuberculosis under conditions of chronic low dose ionizing radiation. 3 refs.; 3 tabs

  6. Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

    International Nuclear Information System (INIS)

    Ogata, Hiromitsu; Magae, Junji

    2008-01-01

    Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

  7. Risk of cancer subsequent to low-dose radiation

    International Nuclear Information System (INIS)

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

  8. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  9. Topics on study of low dose-effect relationship

    International Nuclear Information System (INIS)

    Yamada, Takeshi; Ohyama, Harumi

    1999-01-01

    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)

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

    Science.gov (United States)

    2011-01-01

    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. PMID:22114930

  11. 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.

  12. 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.

  13. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  14. Development of Plant Application Technique of Low Dose Radiation

    International Nuclear Information System (INIS)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek

    2007-07-01

    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

  15. Review of European research trends of low dose radiation risk

    International Nuclear Information System (INIS)

    Iwasaki, Toshiyasu; Yoshida, Kazuo

    2010-01-01

    Large research projects on low dose radiation effects in Europe and US over the past decade have provided limited scientific knowledge which could underpin the validation of radiation protection systems. Recently in Europe, there have been repeated discussions and dialogues to improve the situation, and as the consequence, the circumstances surrounding low dose radiation risks are changing. In 2009, Multidisciplinary European Low Dose Initiative (MELODI) was established as a trans-national organization capable of ensuring appropriate governance of research in the pursuit of a long term shared vision, and Low Dose Research towards Multidisciplinary Integration (DoReMi) network was launched in 2010 to achieve fairly short term results in order to prove the validity of the MELODI approach. It is expected to be very effective and powerful activities to facilitate the reduction of uncertainties in the understanding of low dose risks, but the regulatory requests rushing the reinforcement of radiological protection regulations based on the precautional principles are more increasing. To develop reasonable radiological protection systems based on scientific evidences, we need to accelerate to collect scientific evidences which could directly underpin more appropriate radiation protection systems even in Japan. For the purpose, we Japan need to develop from an independent standpoint and share as a multidisciplinary vision a long term and holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

  16. Evaluation of a low-dose neonatal chest radiographic system

    International Nuclear Information System (INIS)

    Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

    1988-01-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness

  17. Low-dose dual-energy cone-beam CT using a total-variation minimization algorithm

    International Nuclear Information System (INIS)

    Min, Jong Hwan

    2011-02-01

    Dual-energy cone-beam CT is an important imaging modality in diagnostic applications, and may also find its use in other application such as therapeutic image guidance. Despite of its clinical values, relatively high radiation dose of dual-energy scan may pose a challenge to its wide use. In this work, we investigated a low-dose, pre-reconstruction type of dual-energy cone-beam CT (CBCT) using a total-variation minimization algorithm for image reconstruction. An empirical dual-energy calibration method was used to prepare material-specific projection data. Raw data at high and low tube voltages are converted into a set of basis functions which can be linearly combined to produce material-specific data using the coefficients obtained through the calibration process. From much fewer views than are conventionally used, material specific images are reconstructed by use of the total-variation minimization algorithm. An experimental study was performed to demonstrate the feasibility of the proposed method using a micro-CT system. We have reconstructed images of the phantoms from only 90 projections acquired at tube voltages of 40 kVp and 90 kVp each. Aluminum-only and acryl-only images were successfully decomposed. We evaluated the quality of the reconstructed images by use of contrast-to-noise ratio and detectability. A low-dose dual-energy CBCT can be realized via the proposed method by greatly reducing the number of projections

  18. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2008-01-01

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

  19. 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.

  20. Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

    Science.gov (United States)

    García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

    2016-01-01

    Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

  1. 舒芬太尼复合小剂量布比卡因蛛网膜下腔麻醉在老年患者手术中的应用%The application of sufentanil combined with low-dose bupivacaine for spinal an~thesia in elderly patients

    Institute of Scientific and Technical Information of China (English)

    项小兵; 马美娜; 柳兆芳

    2012-01-01

    目的 观察舒芬太尼复合小剂量布比卡因蛛网膜下腔注射在老年患者麻醉中的临床效果.方法 60例择期行下腹部或下肢手术患者,随机分为三组,每组20例.Ⅰ组:0.5%布比卡因7.5 mg+舒芬太尼5μg,Ⅱ组:0.5%布比卡因7.5 mg+舒芬太尼2.5 μg,Ⅲ组:0.5%布比卡因10mg行蛛网膜下腔麻醉.观察感觉阻滞起效时间、感觉阻滞平面上界、镇痛维持时间、运动阻滞起效时间、运动阻滞程度、血流动力学影响及不良反应发生情况.结果 Ⅰ、Ⅱ组给药后血流动力学影响小,运动阻滞恢复时间短于Ⅲ组,恶心、头晕发生率明显低于Ⅲ组(P<0.05);Ⅰ组感觉阻滞起效时间,达T10时间明显短于Ⅱ组和Ⅲ组,T10镇痛维持时间明显长于Ⅱ组和Ⅲ组(P<0.05).结论 舒芬太尼2.5、5μg复合小剂量布比卡因蛛网膜下腔注射用于老年患者均可产生良好的感觉和运动阻滞,且对血流动力学影响小.%Objective To investigate the effect of spinal anesthesia with different doses of sufentanil combined with low-dose bupivacaine in elderly patients. Methods Sixty patients undergoing abdominal or leg surgery were randomly divided into three groups with 20 cases each, all patients were received spinal anesthesia. Group I : 0. 5% bupivacaine 7.5 mg + sufentanil 5 μg; groupⅡ : 0. 5% bupivacaine 7. 5 mg + sufentanil 2. 5 μg; group Ⅲ : 0. 5% bupivacaine 10 mg. The onset time of sensory and motor block, the upper sensory block level, post-operative analgesia, the degree of motor block, hemodynamics and side effects were recorded. Results In group I and U the hemodynamics were more stable, the time of regression motor block were faster and nausea and dizziness were lower than that in group HI (P<0. 05). In group I the onset time of sensory block, reaching to the T10 dermatomes of time were shorter, and post-operative analgesia was longer than in groups Ⅱ , Ⅲ (P<0. 05). Conclusion Sufentanil combined with low-dose

  2. A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

    Science.gov (United States)

    Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony; Suh, K Stephen

    2015-10-01

    The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

  3. Effects of low dose radiation on tumor-bearing mice

    International Nuclear Information System (INIS)

    Feng Li; Hou Dianjun; Huang Shanying; Deng Daping; Wang Linchao; Cheng Yufeng

    2007-01-01

    Objective: To explore the effects of low-dose radiation on tumor-bearing mice and radiotherapy induced by low-dose radiation. Methods: Male Wistar mice were implanted with Walker-256 sarcoma cells in the right armpit. On day 4, the mice were given 75 mGy whole-body X-ray radiation. From the fifth day, tumor volume was measured, allowing for the creation of a graph depicting tumor growth. Lymphocytes activity in mice after whole-body X-ray radiation with LDR was determinned by FCM. Cytokines level were also determined by ELISA. Results: Compared with the radiotherapy group, tumor growth was significantly slower in the mice pre-exposed to low-dose radiation (P<0.05), after 15 days, the average tumor weight in the mice pre- exposed to low-dose radiation was also significantly lower (P<0.05). Lymphocytes activity and the expression of the CK in mice after whole-body y-ray radiation with LDR increased significantly. Conclusions: Low-dose radiation can markedly improve the immune function of the lymphocyte, inhibit the tumor growth, increase the resistant of the high-dose radiotherapy and enhance the effect of radiotherapy. (authors)

  4. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  5. Comparison of radiosensitization by 41 deg. C hyperthermia during low dose rate irradiation and during pulsed simulated low dose rate irradiation in human glioma cells

    International Nuclear Information System (INIS)

    Raaphorst, G. Peter; Ng, Cheng E.; Shahine, Bilal

    1999-01-01

    Purpose: Long duration mild hyperthermia has been shown to be an effective radiosensitizer when given concurrently with low dose rate irradiation. Pulsed simulated low dose rate (PSLDR) is now being used clinically, and we have set out to determine whether concurrent mild hyperthermia can be an effective radiosensitizer for the PSLDR protocol. Materials and Methods: Human glioma cells (U-87MG) were grown to plateau phase and treated in plateau phase in order to minimize cell cycle redistribution during protracted treatments. Low dose rate (LDR) irradiation and 41 deg. C hyperthermia were delivered by having a radium irradiator inside a temperature-controlled incubator. PSLDR was given using a 150 kVp X-ray unit and maintaining the cells at 41 deg. C between irradiations. The duration of irradiation and concurrent heating depended on total dose and extended up to 48 h. Results: When 41 deg. C hyperthermia was given currently with LDR or PSLDR, the thermal enhancement ratios (TER) were about the same if the average dose rate for PSLDR was the same as for LDR. At higher average dose rates for PSLDR the TERs became less. Conclusions: Our data show that concurrent mild hyperthermia can be an effective sensitizer for PSLDR. This sensitization can be as effective as for LDR if the same average dose rate is used and the TER increases with decreasing dose rate. Thus mild hyperthermia combined with PSLDR may be an effective clinical protocol

  6. Risks to health from radiation at low dose rates

    International Nuclear Information System (INIS)

    Gentner, N.E.; Osborne, R.V.

    1997-01-01

    Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

  7. Biological effects of low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

    2009-01-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  8. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ganapathy, Suthakar, E-mail: s.ganapathy@neu.edu [Center for Drug Development, Northeastern University, Boston (United States); Li, Ping [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Fagman, Johan [The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Yu, Tianqi; Lafontant, Jean [Center for Drug Development, Northeastern University, Boston (United States); Zhang, Guojun [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); Chen, Changyan [Center for Drug Development, Northeastern University, Boston (United States); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden)

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  9. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    International Nuclear Information System (INIS)

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-01-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  10. Regulatory aspects of low doses control in Albania

    International Nuclear Information System (INIS)

    Dollani, K.; Kushe, R.

    1997-01-01

    In the present paper are described the status of regulatory aspects of low doses control as well as the existing procedures for their implementation in Albania. According to new Radiological Protection Act, approved by Parliament in 1995, the establishment of the infrastructures in radiation protection area is in course, accompanied by the installation and functioning of new equipment for low dose control. Based in many years experience it is concluded that personal doses of the workers added by practices in Albania are 1/10 of dose Emits. Some particular cases of overexposured workers were investigated. Last times the elements of the optimisation procedures (QA and QC) are outlined in the frame of improving regulatory aspects of low doses control. (author)

  11. Low-Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James; Slovic, Paul

    2001-01-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email and internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  12. Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

    Science.gov (United States)

    Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

    2016-01-01

    We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

  13. Effects of low dose radiation and epigenetic regulation

    International Nuclear Information System (INIS)

    Jiao Benzheng; Ma Shumei; Yi Heqing; Kong Dejuan; Zhao Guangtong; Gao Lin; Liu Xiaodong

    2010-01-01

    Purpose: To conclude the relationship between epigenetics regulation and radiation responses, especially in low-dose area. Methods: The literature was examined for papers related to the topics of DNA methylation, histone modifications, chromatin remodeling and non-coding RNA modulation in low-dose radiation responses. Results: DNA methylation and radiation can regulate reciprocally, especially in low-dose radiation responses. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase (HDAC) inhibitors show a promising application to enhance radiation sensitivity, no matter whether in low-dose or high-dose areas; the connection between γ-H2AX and LDR has been remained unknown, although γ-H2AX has been shown no radiation sensitivities with 1-15 Gy irradiation; histone ubiquitination play an important role in DNA damage repair mechanism. Moreover, chromatin remodeling has an integral role in DSB repair and the chromatin response, in general, may be precede DNA end resection. Finally, the effect of radiation on miRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. Conclusion: Although the advance of epigenetic regulation on radiation responses, which we are managing to elucidate in this review, has been concluded, there are many questions and blind blots deserved to investigated, especially in low-dose radiation area. However, as progress on epigenetics, we believe that many new elements will be identified in the low-dose radiation responses which may put new sights into the mechanisms of radiation responses and radiotherapy. (authors)

  14. Low-dose vaporized cannabis significantly improves neuropathic pain.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  15. The researches on the effects of low doses irradiation

    International Nuclear Information System (INIS)

    2009-02-01

    All research conducted as part of 'Risc-Rad' and those conducted by actors in international programs on low doses allow progress in understanding mechanisms of carcinogenesis associated with irradiation. The data do not question the use in radiation protection, risk estimation models based on a linear increase of the risk with the dose of radiation. Nevertheless, they show that the nature of biological responses induced by low doses of radiation has differences with the responses induced by high doses of radiation. They also show the diversity of effects/dose relationships as the mechanism observed and the importance of genetic predisposition in the individual sensitivity to low doses of radiation. It is therefore essential to continue to bring new data to better understand the complex biological effects and their impact on the establishment of radiation protection standards. In addition, the results have often been at the cellular level. The diversity of responses induced by radiations is also a function of cell types observed, the aging of cells and tissue organization. It is essential to strengthen researches at the tissue and body level, involving in vitro and in vivo approaches while testing the hypothesis in epidemiology with a global approach to systems biology. Over the past four years, the collaboration between partners of 'Risc-Rad' using experimental biology approaches and those using mathematical modeling techniques aimed at developing a new model describing the carcinogenesis induced by low radiation doses. On an other hand, The High level expert group on European low dose risk research (H.L.E.G.) develop programmes in the area of low dose irradiation (Germany, Finland, France, Italy and United Kingdom). It proposed a structure of trans national government called M.E.L.O.D.I. ( multidisciplinary european low dose initiative). Its objective is to structure and integrate European research by gathering around a common programme of multidisciplinary

  16. Review and Evaluation of Updated Research on the Health Effects Associated with Low-Dose Ionizing Radiation

    International Nuclear Information System (INIS)

    Dauer, Lawrence T.; Brooks, Antone L.; Hoel, David G.; Morgan, William F.; Stram, Daniel; Tran, Phung

    2010-01-01

    Potential health effects of low levels of radiation have predominantly been based on those effects observed at high levels of radiation. The authors have reviewed more than 200 percent publications in radiobiology and epidermiology related to low dose radiation and concluded that recent radiobiological studies at low-doses; that doses <100 mSv in a single exposure appear to be too small to allow epidermiological detection of statistically significant excess cancers in the presence of naturally occurring cancers; that low dose radiation research should to holistic, systems-based approaches to develop models that define the shape of the dose-response relationships at low doses; and that these results should be combined with the latest epidermiology to produce a comprehensive understanding of radiation effects that addresses both damage, likely with a linear effect, and response, possibly with non-linear consequences.

  17. Some remarks on the significance of low doses

    International Nuclear Information System (INIS)

    Cigna, A.A.

    1989-12-01

    The criteria of the present system of individual dose limitation are considered as well as the evolution of the limiting values. The assumption of the linearity of the dose-effect relationship without any threshold is probably the best approach to adopt for recommendations in radiation protection and for accounting the doses acquired by exposure to ionizing radiation. On the other hand the present evaluation of the natural background could imply a different dose-effect relationship in the low doses region and perhaps the existence of a threshold. Therefore the extrapolations which are usually made after exposures of different groups of people to low doses cannot be considered as scientifically sound. (author)

  18. [Influence of low doses of ionizing radiation on tenascin expression in hybridoma cell systems].

    Science.gov (United States)

    Lunga, I N

    2003-01-01

    One of the achievements of the modern radiation ecology is the preparation and application of stable eukariotic cell lines to solve various problems occurring under exposure to ionizing radiation, especially to low doses. The detection of onco-fetal protein--tenascin in different embryonic and tumor cells of humans and animals supposes the probability of appropriate gene expression in lymphoid cells, including hybridomal cells. Using the immunochemical method, the study of tenascin expression in two mouse hybridomal lines was carried out. Tenascin was revealed in hybridomal lines MLC-1 and K-48. Further hybridomal cell lines were exposed to X-ray radiation (120 KV) with doses 2.10,15 cGy. The obtained results demonstrated the sensitivity of tenascin expression to low doses of ionizing radiation, that may be used as a convenient model of studying of genotoxic effects of various damaging ionizing agents on a cell level.

  19. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

  20. Detection of lung nodules with low-dose spiral CT: comparison with conventional dose CT

    International Nuclear Information System (INIS)

    Zhu Tianzhao; Tang Guangjian; Jiang Xuexiang

    2004-01-01

    Objective: To investigate the effect of reducing scan dose on the lung nodules detection rate by scanning a lung nodule model at low dose and conventional dose. Methods: The lung and the thoracic cage were simulated by using a cyst filled with water surrounded by a roll bandage. Flour, butter, and paraffin wax were mixed together by a certain ratio to simulate lung nodules of 10 mm and 5 mm in diameter with the CT values ranging from -10 to 50 HU. Conventional-dose scan (240 mA, 140 kV) and low-dose scan of three different levels (43 mA, 140 kV; 50 mA, 120 kV; 75 mA, 80 kV) together with three different pitches (1.0, 1.5, and 2.0) were performed. The images of the simulated nodules were combined with the CT images of a normal adult's upper, middle, and inferior lung. Three radiologists read the images and the number of the nodules they detected including both the real ones and the false-positive ones was calculated to investigate weather there was any difference among different doses, pitch groups, and different locations. Results: The detection rate of the 10 mm and 5 mm nodules was 100% and 89.6% respectively by the low-dose scan. There was no difference between low-dose and conventional-dose CT (χ 2 =0.6907, P>0.70). The detection rate of 5 mm nodules declined when large pitch was used. Conclusion: The detection rates of 10 mm and 5 mm nodules had no difference between low-dose CT and conventional-dose CT. As the pitch augmented, the detection rate for the nodules declined

  1. Generative Adversarial Networks for Noise Reduction in Low-Dose CT.

    Science.gov (United States)

    Wolterink, Jelmer M; Leiner, Tim; Viergever, Max A; Isgum, Ivana

    2017-12-01

    Noise is inherent to low-dose CT acquisition. We propose to train a convolutional neural network (CNN) jointly with an adversarial CNN to estimate routine-dose CT images from low-dose CT images and hence reduce noise. A generator CNN was trained to transform low-dose CT images into routine-dose CT images using voxelwise loss minimization. An adversarial discriminator CNN was simultaneously trained to distinguish the output of the generator from routine-dose CT images. The performance of this discriminator was used as an adversarial loss for the generator. Experiments were performed using CT images of an anthropomorphic phantom containing calcium inserts, as well as patient non-contrast-enhanced cardiac CT images. The phantom and patients were scanned at 20% and 100% routine clinical dose. Three training strategies were compared: the first used only voxelwise loss, the second combined voxelwise loss and adversarial loss, and the third used only adversarial loss. The results showed that training with only voxelwise loss resulted in the highest peak signal-to-noise ratio with respect to reference routine-dose images. However, CNNs trained with adversarial loss captured image statistics of routine-dose images better. Noise reduction improved quantification of low-density calcified inserts in phantom CT images and allowed coronary calcium scoring in low-dose patient CT images with high noise levels. Testing took less than 10 s per CT volume. CNN-based low-dose CT noise reduction in the image domain is feasible. Training with an adversarial network improves the CNNs ability to generate images with an appearance similar to that of reference routine-dose CT images.

  2. Late effects of low-dose ionizing radiation on man

    International Nuclear Information System (INIS)

    Brilliant, M.D.; Vorob'ev, A.I.; Gogin, E.E.

    1987-01-01

    One of the most important problems, being stated before the medicine by the accident, which took place in Chernobyl in 1986- the problem of the so-called ionizing radiation low dose effect on a man's organism, is considered because a lot of people were subjected to low dose action. The concept of low doses of radiaion action and specificity of its immediate action in comparison with high dose action is considered. One of the most important poit while studying low dose action is the necessity to develop a system including all irradiated people and dosimetry, and espicially to study frequencies and periods of tumor appearance in different irradiated tissues. The results obtained when examining people who survived the atomic explosion in Japan and on the Marshall islands are analyzed. They testify to the fact that radiation affets more tissues than the clinical picture about the acute radiation sickness tells, and that tumors developing in them many years after radiation action tell about radiosensitivity in some tissues

  3. Low-dose aspirin and risk of intracranial bleeds

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...

  4. Biological effects of very low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Evseev, V.S.

    1987-01-01

    The paper deals with a qualitative microdosimetric analysis of a new radiobiological phenomenon (physiological reaction of the cell as a whole to very low doses of ionizing radiations). The analysis is aimed at identifying the type of the primary interaction of radiation with the cell and finding its place in the cell

  5. Advance of study on hormesis of low dose radiation

    International Nuclear Information System (INIS)

    Su Liaoyuan

    2003-01-01

    There have been growing interests in recent years over the effects of low doses of ionizing radiation on human. The paper gives a brief review on the LDR studies, which include LDR-induced hormesis and adaptive response, LDR experiments in vivo or in vitro and epidemiologic investigation, and clinical applications of LDR as well

  6. Low dose CT simulation using experimental noise model

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Satori; Zamyatin, Alexander A. [Toshiba Medical Systems Corporation, Tochigi, Otawarashi (Japan); Silver, Michael D. [Toshiba Medical Research Institute, Vernon Hills, IL (United States)

    2011-07-01

    We suggest a method to obtain system noise model experimentally without relying on assumptions on statistical distribution of the noise; also, knowledge of DAS gain and electronic noise level are not required. Evaluation with ultra-low dose CT data (5 mAs) shows good match between simulated and real data noise. (orig.)

  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. 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.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  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. Health hazards of low doses of ionizing radiations. Vo. 1

    International Nuclear Information System (INIS)

    El-Naggar, M.A.

    1996-01-01

    Exposure to high doses of ionizing radiation results in clinical manifestations of several disease entities that may be fatal. The onset and severity of these acute radiation syndromes are deterministic in relation to dose magnitude. Exposure to ionizing radiations at low doses and low dose rates could initiate certain damage in critical molecules of the cell, that may develop in time into serious health effects. The incidence of such delayed effects in low, and is only detectable through sophisticated epidemiological models carried out on large populations. The radiation damage induced in critical molecules of cells may develop by stochastic biochemical mechanisms of repair, residual damage, adaptive response, cellular transformation, promotion and progression into delayed health effects, the most important of which is carcinogenesis. The dose response relationship of probabilistic stochastic delayed effects of radiation at low doses and low dose rates, is very complex indeed. The purpose of this review is to provide a comprehensive understanding of the underlying mechanisms, the factors involved, and the uncertainties encountered. Contrary to acute deterministic effects, the occurrence of probabilistic delayed effects of radiation remains to be enigmatic. 7 figs

  12. 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

  13. Personal dosimetry statistics and specifics of low dose evaluation

    International Nuclear Information System (INIS)

    Avila, R.E.; Gómez Salinas, R.A.; Oyarzún Cortés, C.H.

    2015-01-01

    The dose statistics of a personal dosimetry service, considering 35,000+ readings, display a sharp peak at low dose (below 0.5 mSv) with skewness to higher values. A measure of the dispersion is that approximately 65% of the doses fall below the average plus 2 standard deviations, an observation which may prove helpful to radiation protection agencies. Categorizing the doses by the concomitant use of a finger ring dosimeter, that skewness is larger in the whole body, and ring dosimeters. The use of Harshaw 5500 readers at high gain leads to frequent values of the glow curve that are judged to be spurious, i.e. values not belonging to the roughly normal noise over the curve. A statistical criterion is shown for identifying those anomalous values, and replacing them with the local behavior, as fit by a cubic polynomial. As a result, the doses above 0.05 mSv which are affected by more than 2% comprise over 10% of the data base. The low dose peak of the statistics, above, has focused our attention on the evaluation of LiF(Mg,Ti) dosimeters exposed at low dose, and read with Harshaw 5500 readers. The standard linear procedure, via an overall reader calibration factor, is observed to fail at low dose, in detailed calibrations from 0.02 mSv to 1 Sv. A significant improvement is achieved by a piecewise polynomials calibration curve. A cubic, at low dose is matched, at ∼10 mSv, in value and first derivative, to a linear dependence at higher doses. This improvement is particularly noticeable below 2 mSv, where over 60% of the evaluated dosimeters are found. (author)

  14. Lateral topography for reducing effective dose in low-dose chest CT.

    Science.gov (United States)

    Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

    2013-06-01

    The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

  15. Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

    International Nuclear Information System (INIS)

    Malik, M.I.

    2013-01-01

    Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

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

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S.

    2000-01-01

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

  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. 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.

  19. 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.

  20. Repair and dose-response at low doses

    International Nuclear Information System (INIS)

    Totter, J.R.; Weinberg, A.M.

    1977-04-01

    The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis

  1. Response of human fibroblasts to low dose rate gamma irradiation

    International Nuclear Information System (INIS)

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-01-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to γ radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D 0 ) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury

  2. Low dose CT in early lung cancer diagnosis: prevalence data

    International Nuclear Information System (INIS)

    Cardinale, Luciano; Cortese, Giancarlo; Ferraris, Fabrizio; Perotto, Fabio; Fava, Cesare; Borasio, Piero; Dogliotti, Luigi; Novello, Silvia; Scagliotti, Giorgio

    2005-01-01

    Purpose. Lung cancer has a high mortality rate and its prognosis largely depends on early detection. We report the prevalence data of the study on early detection of lung cancer with low-dose spiral CT underway at our hospital. Materials and methods. Since the beginning of 2001, 519 asymptomatic volunteers have undergone annual blood tests, sputum tests, urinalyses and low-dose spiral CT. The inclusion criteria were age (55 years old), a history of cigarette smoking and a negative history for previous neoplastic disease. The diagnostic workup varied depending on the size and CT features of the nodules detected. Results. At baseline, the CT scan detected nodules> 5 mm in 22% of subjects; the nodules were single in 42 and multiple in 71. In 53% of cases the findings were completely negative, while in 122 (23.4%) nodules with a diameter [it

  3. Low-Dose Aspirin for the Prevention of Preeclampsia.

    Science.gov (United States)

    Fantasia, Heidi Collins

    2018-02-01

    Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  4. The assessment of the carcinogenic effects of low dose radiation

    International Nuclear Information System (INIS)

    Tubiana, M.; Lafuma, J.; Masse, R.; Latarjet, R.

    1991-01-01

    It is concluded that the exclusion of patients for the purposes of risk estimation, the choice of a particular relative risk projection model and of a dose reduction factor equal to 2 are all decisions which result in an overestimation of the actual risk. These choices can be understood when the aim is radiation protection and when it is safer to overestimate the risk; however, they are open to criticism if the aim is a realistic assessment of the risk. For low doses, below 50 mSv/year, and when all causes of uncertainty are added, the actual risk might be markedly lower than the risk estimated with the ICRP (1991) carcinogenic risk coefficient and the DRF estimated by ICRP. Future studies should aim at providing direct and more precise assessments of risk coefficients in the low dose region. (Author)

  5. Gamma regularization based reconstruction for low dose CT

    International Nuclear Information System (INIS)

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-01-01

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l 0 -norm and l 1 -norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. (paper)

  6. Low-dose effects hypothesis and observations on NPP personal

    Energy Technology Data Exchange (ETDEWEB)

    Georgieva, R.; Acheva, A.; Boteva, R.; Chobanova, N.; Djounova, J.; Gyuleva, I.; Ivanova, K.; Kurchatova, G.; Milchev, A.; Negoicheva, K.; Nikolov, V.; Panova, D.; Pejankov, I.; Rupova, I.; Stankova, K.; Zacharieva, E. [Radiobiology Department, National Centre of Radiobiology and Radiation Protection, Sofia (Bulgaria)

    2013-07-01

    In the modern world the use of various sources of ionizing radiation is nearly ubiquitous. They have numerous applications in industry, medicine, science, agriculture, etc. Radiation doses to workers nevertheless are commensurable to the natural background exposure. Published data on the health effects of occupational radiation exposure are often contradictory. Addressing the issue of „negative” (bystander effects, genomic instability) and „positive” (adaptive response, radiation hormesis) effects of low doses is important and has a significant social and economic impact. In this paper we summarize the results of our extensive monitoring of nuclear power plant (NPP) staff. We believe it is a cohort suitable for analysis of health effects at low doses, because of their good medical and dosimetric control. Our results rather support the idea of absence of adverse health effects in NPP workers. (author)

  7. Effect of low-dose radiation on ocular circulation

    International Nuclear Information System (INIS)

    Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro

    1999-01-01

    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)

  8. 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.

  9. 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)

  10. Low-dose radiation-induced endothelial cell retraction

    International Nuclear Information System (INIS)

    Kantak, S.S.; Onoda, J.M.; Diglio, C.A.; Harper Hospital, Detroit, MI

    1993-01-01

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

  11. Late effects of low doses and dose rates

    International Nuclear Information System (INIS)

    Paretzke, H.G.

    1980-01-01

    This paper outlines the spectrum of problems and approaches used in work on the derivation of quantitative prognoses of late effects in man of low doses and dose rates. The origins of principal problems encountered in radiation risks assessments, definitions and explanations of useful quantities, methods of deriving risk factors from biological and epidemiological data, and concepts of risk evaluation and problems of acceptance are individually discussed

  12. 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.)

  13. Fruit-flies in low-dose exposure experiments

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Sheptyakova, A.I.

    2002-01-01

    In vivo exposure of fruit-flies of Drosophila melanogaster line to low doses provided new data indicating that mechanisms of induced genetic instability are involved in radiation-induced alteration of genotype. It is true for increase of genetic variance due to change in transposition number, for change in adaptation capabilities due to modification of gene expression, and for mutability-associated reparation and apoptosis. (author)

  14. 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.

  15. Biological effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    Osmak, M.

    1998-01-01

    A study was performed with the aim to examine whether the progeny of cells that had been repeatedly irradiated with low doses of gamma rays will change their sensitivity to cytotoxic agents. Four mammalian cell lines were used in the experiment. It was found that the progeny of cells irradiated in this way do not change their sensitivity to gamma rays but would change their sensitivity to various cytostatics drugs. (A.K.)

  16. Effect of low dose ionizing radiation upon concentration of

    International Nuclear Information System (INIS)

    Viliae, M.; Kraljeviae, P.; Simpraga, M.; Miljaniae, S.

    2004-01-01

    It is known that low dose ionizing radiation might have stimulating effects (Luckey, 1982, Kraljeviae, 1988). This fact has also been confirmed in the previous papers of Kraljeviae et al. (2000-2000a; 2001). Namely, those authors showed that irradiation of chicken eggs before incubation by a low dose of 0.15 Gy gamma radiation increases the activity aspartateaminotrasferases (AST) and alanine-aminotransferases (ALT) in blood plasma of chickens hatched from irradiated eggs, as well as growth of chickens during the fattening period. Low doses might also cause changes in the concentration of some biochemical parameters in blood plasma of the same chickens such as changes in the concentration of total proteins, glucose and cholesterol. In this paper, an attempt was made to investigate the effects of low dose gamma radiation upon the concentration of sodium and potassium in the blood plasma of chickens which were hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy. Obtained results were compared with the results from the control group (chickens hatched from nonirradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from heart, and later from the wing vein on days 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of sodium and potassium was determined spectrophotometrically by atomic absorbing spectrophotometer Perkin-Elmer 1100B. The concentration of sodium and potassium in blood plasma of chickens hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy indicated a statistically significant increase (P>0.01) only on the first day of the experiment. Obtained results showed that irradiation of eggs on the 19th day of incubation by dose of 0.15 Gy gamma radiation could have effects upon the metabolism of electrolytes in chickens. (Author)

  17. Low dose monitoring by double implant technique in IC fabrication

    International Nuclear Information System (INIS)

    Ahmad, I.B.; Weidemann, J.

    1995-01-01

    The utilisation of low dose implant monitoring (using Boron) in a manufacturing line has been discussed. The utilisation of phosphorus ions as the second implant dose were also studied as comparison. The technique relies on the fact that the sheet resistant of doped layer will increase significantly when damaged by relatively low implant dose. The technique is very sensitive and applicable for adjusting the channel dose so that an accurate threshold voltage in MOS device could be achieved

  18. adverse effects of low dose methotrexate in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    Gilani, S.T.; Khan, D.A.; Khan, F.A.; Ahmed, M.

    2012-01-01

    To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients. Study Design: Cross-sectional observational study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011. Methodology: One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer. Results: Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 mu mol/l with a sensitivity of 71% and specificity of 76%. Conclusion: Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 mu mol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy. (author)

  19. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    Newman, M.R.; Ormsby, R.J.; Blyth, B.J.; Sykes, P.J.; Bezak, E.

    2011-01-01

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  20. Exercise and Sport Performance with Low Doses of Caffeine

    OpenAIRE

    Spriet, Lawrence L.

    2014-01-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5–13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (

  1. MELODI: The 'Multidisciplinary European Low-Dose Initiative'

    International Nuclear Information System (INIS)

    Belli, M.; Salomaa, S.; Ottolenghi, A.

    2011-01-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European Low Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Multidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA. (authors)

  2. Low dose effects detected by micronucleus assay in lymphocytes

    International Nuclear Information System (INIS)

    Koeteles, G.J.; Bojtor, I.; Kubasova, T.; Horvath, G.

    1997-01-01

    The effects of low doses of X-rays between 0.01 and 1 Gy were studied on whole blood samples of various individuals using the cytokinesis-blocked lymphocyte micronucleus assay as an endpoint. The adaptive response could be induced in G 0 cells by 0.01 Gy followed by 1 Gy challenging dose within a time period of 8 hours, in vitro. The probability distribution of micronucleus increments in those samples which had received very low doses in the range 0.01-0.05 Gy proved to be of asymmetrical type (i.e. lognormal) -very likely to the same shape which has been verified for unirradiated (control) population - while the variable turned to be normally distributed at or above 1 Gy. Profound changes have been experienced in the main characteristics of the linear dose - response relationship and in regression parameters, as well, when successively lessened dose ranges were studied toward 0.01 Gy. In the range below ∼ 0.2 Gy the response were found to be unrelated to the absorbed dose. These findings suggest that in (very) low dose range a higher attention should be needed to biological parameters like repair, protective mechanisms and antioxidant capacities, rather than to the absorbed radiation energy only. (author)

  3. Problems linked to effects of ionizing radiations low doses

    International Nuclear Information System (INIS)

    Anon.

    1995-10-01

    The question of exposure to ionizing radiations low doses and risks existing for professional and populations has been asked again, with the recommendations of the International Commission of Radiation Protection (ICRP) to lower the previous standards and agreed as guides to organize radiation protection, by concerned countries and big international organisms. The sciences academy presents an analysis which concerned on epidemiological and dosimetric aspects in risk estimation, on cellular and molecular aspects of response mechanism to irradiation. The observation of absence of carcinogen effects for doses inferior to 200 milli-sieverts and a re-evaluation of data coming from Nagasaki and Hiroshima, lead to revise the methodology of studies to pursue, to appreciate more exactly the effects of low doses, in taking in part, particularly, the dose rate. The progress of molecular and cellular biology showed that the extrapolation from high doses to low doses is not in accordance with actual data. The acknowledge of DNA repair and carcinogenesis should make clearer the debate. (N.C.). 61 refs., 9 annexes

  4. Thermoluminescent dosimeters for low dose X-ray measurements

    International Nuclear Information System (INIS)

    Del Sol Fernández, S.; García-Salcedo, R.; Sánchez-Guzmán, D.; Ramírez-Rodríguez, G.; Gaona, E.; León-Alfaro, M.A. de; Rivera-Montalvo, T.

    2016-01-01

    The response of TLD-100, CaSO_4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm"2 at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO_4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO_4:Dy showed a linearity from 0.1 to 60 mGy - Highlights: • Low dose X-ray doses for personal dosimetry were measured. • Radiation dose (µGy ) for environmental dosimetry were determined. • Scattering radiation dose were measured by TLDs. • Linearity of pair TLD system was successful in the range of microgray. • Pair TLDs composed by CaSO_4:Dy and by LiF:Mg,Cu,P. is suggested for clinical dosimetry.

  5. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    International Nuclear Information System (INIS)

    Schoenfeld, Gordon O.; Amdur, Robert J.; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-01-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element

  6. Ageing effects of polymers at very low dose-rates

    International Nuclear Information System (INIS)

    Chenion, J.; Armand, X.; Berthet, J.; Carlin, F.; Gaussens, G.; Le Meur, M.

    1987-10-01

    The equipment irradiation dose-rate into the containment is variable from 10 -6 to 10 -4 gray per second for the most exposed materials. During qualification, safety equipments are submitted in France to dose-rates around 0.28 gray per second. This study purpose is to now if a so large irradiation dose-rate increase is reasonable. Three elastomeric materials used in electrical cables, o'rings seals and connectors, are exposed to a very large dose-rates scale between 2.1.10 -4 and 1.4 gray per second, to 49 KGy dose. This work was carried out during 3.5 years. Oxygen consumption measurement of the air in contact with polymer materials, as mechanical properties measurement show that: - at very low dose-rate, oxygen consumption is maximum at the same time (1.4 year) for the three elastomeric samples. Also, mechanical properties simultaneously change with oxygen consumption. At very low dose-rate, for the low irradiation doses, oxygen consumption is at least 10 times more important that it is showed when irradiation is carried out with usual material qualification dose-rate. At very low dose-rate, oxygen consumption decreases when absorbed irradiation dose by samples increases. The polymer samples irradiation dose is not still sufficient (49 KGy) to certainly determine, for the three chosen polymer materials, the reasonable irradiation acceleration boundary during nuclear qualification tests [fr

  7. Biochemical and cellular mechanisms of low-dose effects

    International Nuclear Information System (INIS)

    Feinendegen, L.E.; Booz, J.; Muehlensiepen, H.

    1988-01-01

    The question of health effects from small radiation doses remains open. Individual cells, when being hit by single elemental doses - in low-dose irradiation - react acutely and temporarily by altering control of enzyme activity, as is demonstrated for the case of thymidine kinase. This response is not constant in that it provides a temporary protection of enzyme activity against a second irradiation, by a mechanism likely to be via improved detoxification of intracellular radicals. It must be considered that in the low-dose region radiation may also exert protection against other challenges involving radicals, causing a net beneficial effect by temporarily shielding the hit cell against radicals produced by metabolism. Since molecular alterations leading to late effects are considered a consequence of the initial cellular response, late effects from small radiation doses do not necessarily adhere to a linear dose-effect relationship. The reality of the linear relationship between the risk of late effects from high doses to small doses is an assumption, for setting dose limits, but it must not be taken for predicting health detriment from low doses. (author)

  8. Exercise and sport performance with low doses of caffeine.

    Science.gov (United States)

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  9. Plants as warning signal for exposure to low dose radiation

    International Nuclear Information System (INIS)

    Rusli Ibrahim; Norhafiz Talib

    2012-01-01

    The stamen-hair system of Tradescantia for flower colour has proven to be one of the most suitable materials to study the frequency of mutations induced by low doses of various ionizing radiations and chemical mutagens. The system has also been used successfully for detecting mutagenic synergisms among chemical mutagens and ionizing radiations as well as for studying the variations of spontaneous mutation frequency. In this study of radiobiology, the main objective is to observe somatic mutation (occurrence of pink cells from blue cells) induced on stamen hairs of five Tradescantia sp. available in Malaysia after exposure to low doses of chronic gamma irradiation using Gamma Green House. Pink cells appeared only on Tradescantia Pallida Purpurea stamen hairs after 13 days of exposure to irradiation with different doses of gamma rays. The highest number of stamens with pink cells was recorded from flowers irradiated with the highest dose of 6.37 Gy with 0.07 Gy/ h of dose rate. The lowest number of stamens with pink cells was recorded with an average of 0.57, irradiated with the lowest dose of 0.91 Gy with 0.01 Gy/ h of dose rate. There were no pink cells observed on Tradescantia Spathaceae Discolor after exposure to different doses of gamma rays. Similar negative results were observed for the control experiments. The principal cells in this assay are the mitotic stamen hair cells developing in the young flower buds. After exposure to radiation, the heterozygous dominant blue character of the stamen hair cell is prevented, resulting in the appearance of the recessive pink color. Furthermore, no pink cell appears on all species of Tradescantia spathaceae after irradiated with different doses of gamma rays. The sensitivity of the Tradescantia has been used widely and has demonstrated the relation between radiation dose and frequency of mutation observed at low doses which can contribute to the effects of low doses and their consequences for human health. This system

  10. Intracranial germinomas: a case for low dose radiation therapy alone

    International Nuclear Information System (INIS)

    Harrigan, Patricia M.; Loeffler, Jay S.; Shrieve, Dennis; Tarbell, Nancy J.

    1995-01-01

    Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Materials and Methods: Between 1975 and 1995, 39 patients with a diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All but one pt received whole brain (WB) RT, (median dose: 3240 cGy range: 1500-4437 cGy) and a boost to the tumor volume (median total tumor volume dose: 5200 cGy, range: 3960-5950 cGy). Thirty-one pts received RT to the spine (median dose: 2500, range: 1875-3750). Eleven pts were treated with low dose RT and a tumor volume boost, (WB dose ≤ 2550 cGy, and spine dose ≤ 2160 cGy). Five pts were treated with cisplatin-based chemotherapy and low dose WB RT. Fifteen pts were biopsy-proven and 18 presented with multiple midline germinomas (MMG). Among all pts, 33% had serum or CSF positive for low levels of HCG and none of 19 (9 biopsy-proven) germinomas measured positive for AFP tumor marker. Six of 22 (27%) pts who had spine imaging or CSF cytology had evidence of tumor seeding. The male-to female-ratio was 1.4. Median age at diagnosis was 14 yrs for male pts and 9.5 yrs for females (p=.02, overall age range: 1-31 yrs). Median follow-up for survivors is 64 months (range: 1-226 months). Toxicity of treatment relative to dose was assessed. Results: The 5-yr. actuarial rate of disease-free survival (DFS) and overall survival for presumed germinomas was 97%. No pts died of germinoma. One pt died of a shunt infection who had received concurrent chemotherapy and low dose whole brain RT. Among the low dose RT alone group 6 pts received whole brain RT of ≤ 2550 cGy and 9 pts were treated with spinal RT of ≤ 2160 cGy without chemotherapy. Two of these pts had CSF cytology positive for tumor seeding. Additionally, 8 pts received a total dose to the tumor volume of ≤ 4800 cGy without chemotherapy. The 5-yr DFS was 100%. Five pts were treated with cisplatin-based chemotherapy followed

  11. Intracranial germinomas: a case for low dose radiation therapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Harrigan, Patricia M; Loeffler, Jay S; Shrieve, Dennis; Tarbell, Nancy J

    1995-07-01

    Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Materials and Methods: Between 1975 and 1995, 39 patients with a diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All but one pt received whole brain (WB) RT, (median dose: 3240 cGy range: 1500-4437 cGy) and a boost to the tumor volume (median total tumor volume dose: 5200 cGy, range: 3960-5950 cGy). Thirty-one pts received RT to the spine (median dose: 2500, range: 1875-3750). Eleven pts were treated with low dose RT and a tumor volume boost, (WB dose {<=} 2550 cGy, and spine dose {<=} 2160 cGy). Five pts were treated with cisplatin-based chemotherapy and low dose WB RT. Fifteen pts were biopsy-proven and 18 presented with multiple midline germinomas (MMG). Among all pts, 33% had serum or CSF positive for low levels of HCG and none of 19 (9 biopsy-proven) germinomas measured positive for AFP tumor marker. Six of 22 (27%) pts who had spine imaging or CSF cytology had evidence of tumor seeding. The male-to female-ratio was 1.4. Median age at diagnosis was 14 yrs for male pts and 9.5 yrs for females (p=.02, overall age range: 1-31 yrs). Median follow-up for survivors is 64 months (range: 1-226 months). Toxicity of treatment relative to dose was assessed. Results: The 5-yr. actuarial rate of disease-free survival (DFS) and overall survival for presumed germinomas was 97%. No pts died of germinoma. One pt died of a shunt infection who had received concurrent chemotherapy and low dose whole brain RT. Among the low dose RT alone group 6 pts received whole brain RT of {<=} 2550 cGy and 9 pts were treated with spinal RT of {<=} 2160 cGy without chemotherapy. Two of these pts had CSF cytology positive for tumor seeding. Additionally, 8 pts received a total dose to the tumor volume of {<=} 4800 cGy without chemotherapy. The 5-yr DFS was 100%. Five pts were treated with cisplatin-based chemotherapy

  12. 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.

  13. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

  14. The effect of low-dose X-irradiation on immune system

    International Nuclear Information System (INIS)

    Ishii, Keiichiro

    1996-01-01

    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 4 and IL-1 being inflammatory mediators. After 5 cGy irradiation the production of LTB 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-α 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. (author). 127 refs

  15. 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.

  16. Low-dose CT: new tool for screening lung cancer?

    International Nuclear Information System (INIS)

    Diederich, S.; Wormanns, D.; Heindel, W.

    2001-01-01

    Lung cancer is the leading cause of death from malignant tumours as it is very common and has a poor prognosis at advanced tumour stages. Prognosis could be improved by treatment at early stages. As these stages are usually asymptomatic, a diagnostic test that would allow detection of early tumour stages in a population at risk could potentially reduce mortality from lung cancer. Previous approaches using chest radiography and sputum cytology in smokers have been disappointing. Fluorescent bronchoscopy and molecular markers are not yet applicable in clinical routine. Because of its high sensitivity for small pulmonary nodules, which are the most common manifestation of early lung cancer, CT appears suitable as a screening test. Low-dose examination parameters can and should be used for this purpose. From clinical practice it is well known that chest CT often demonstrates small pulmonary nodules, which do not represent lung cancer. Therefore, non-invasive diagnostic algorithms are required to avoid unnecessary biopsies in benign lesions. In preliminary studies of low-dose CT using algorithms based on size and density of detected nodules a large proportion of asymptomatic lung cancers and a large proportion of early, resectable tumour stages were found with a small proportion of invasive procedures for benign nodules. Before this technology can be recommended for broad application, however, further information is required regarding appropriate inclusion criteria (smoking habits, age groups) and screening intervals. Most importantly, further data are required to clarify whether lung cancer screening using low-dose CT can actually reduce mortality from lung cancer. (orig.)

  17. Low-dose multislice CT in febrile neutropenic patients

    International Nuclear Information System (INIS)

    Wendel, F.; Jenett, M.; Hahn, D.; Sandstede, J.; Geib, A.

    2005-01-01

    Purpose: to define the value of low-dose multislice CT in a clinical setting for early detection of pneumonia in neutropenic patients with fever of unknown origin. Materials and methods: thirty-five neutropenic patients suffering from fever of unknown origin with normal chest X-ray underwent unenhanced low-dose CT of the chest (120 kV, 10 eff. mAs, collimation 4 x 1 mm) using a multislice CT scanner. Axial und frontal slices with a thickness of 5 mm were calculated. If no pneumonia was found, standard antibiotics were given and a repeated examination was performed if fever continued. In case of pneumonia, antimycotic therapy was added and a follow-up CT was performed within one week. Regression or progression of pneumonia at follow-up served as evidence of pneumonia; lowering of fever within 48 h or inconspicuous follow-up CT was regarded as absence of pneumonia. Results: ten of 35 patients had pneumonic infiltration, which decreased or increased on follow-up CT in 3 and 6 patients, respectively. One patient revealed leucemic infiltration by bronchoalveolar lavage. Twenty-five of 35 patients had no evidence of pneumonia. Twenty of these patients were free of fever within 48 h under antibiotics; one patient died due to his basic illness. Out of 4 patients with persisting fever, 3 patients had no pneumonia on repeated examination; one patient showed disseminated micronodular infiltration. Frontal reconstructions helped to differentiate infiltration from atelectasis in 4 patients. Sensitivity and specificity for the detection of pneumonia at the first examination were 90% and 96%, negative predictive value was 96%. Conclusion: low-dose multislice CT should be performed in neutropenic patients having a fever of unknown origin and normal chest X-ray. (orig.)

  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. 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.

  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. Effect of low doses of ionizing radiation on human health

    International Nuclear Information System (INIS)

    Kovalenko, A.N.

    1990-01-01

    Data are reported on the possible mechanism of biological effects of low doses of ionizing radiation on the human body. The lesioning effect of this radiation resulted in some of the persons in the development of disorders of the function of information and vegetative-regulatory systems determined as a desintegration syndrome. This syndrome is manifested in unspecific neuro-vegetative disorders of the function of most important physiological and homeostatic system of the body leading to weakening of the processes of compensation and adaptation. This condition is characterized by an unspecific radiation syndrome as distinct from acute or chronic radiation disease which is a specific radiation syndrome

  2. Low-Dose Radiation Induces Genes Promoting Cell Survival

    International Nuclear Information System (INIS)

    Liu, Shu-Zheng; Chen, Dong; Mu, Ying

    1999-01-01

    Apoptosis is an important process controlling homeostasis of the body. It is influenced by stimuli constantly arising from the external and internal environment of the organism. It is well known that radiation could induce apoptosis of cells in vitro and in vivo. However, the dose-effect relationship of apoptosis extending to the low-dose range has scarcely been studied. Here, the molecular basis of the phenomenon is explored by examining the changes in expression of some of the proapoptotic and antiapoptotic genes

  3. A consideration of low dose radiation effects on human health

    International Nuclear Information System (INIS)

    Shimada, Yoshiya; Nishimura, Mayumi; Imaoka, Tatsuhiko; Kakinuma, Shizuko

    2011-01-01

    On March 11, 2011, an earthquake categorized as 9 Mw occurred off the northeast coast of Japan. The subsequent destructive tsunami disabled emergency units of Fukushima Dai'ichi Nuclear Power Plant and caused partial meltdown of reactors and explosions. Resulting radiation releases forced large evacuations, bore concerns about food and water and fears against human health. In this manuscript, we described the effect of radiation, especially low dose radiation below 100 mSv, on cancer risk, focusing on fetuses and children. (author)

  4. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

  5. Uterine malignant degeneration after low-dose endometrial irradiation

    International Nuclear Information System (INIS)

    Nikkanen, V.; Salmi, T.; Groenroos, M.

    1980-01-01

    The effectiveness of low-dose intrauterine irradiation for benign diseases and its possible carcinogenic effect on the uterus was studied in 190 patients who were treated during the years 1952-1974. The indications for irradiation were premenopausal functional bleeding, leukemia, hemophilia, fibroids, endometriosis or other benign reason. Radiation was also performed on patients with severe neurologic diseases that contraindicated surgery and on some mentally retarded patients whose restlessness and epileptic seizures were aggravated premenstrually and during menstruation. The mean follow-up period was 15 years. Uterine bleeding recurred in 21 percent of the patients. No cases of uterine malignant degeneration were found. (author)

  6. From Chernobyl to Fukushima: the effect of low doses

    International Nuclear Information System (INIS)

    Aurengo, A.

    2011-01-01

    This Power Point presentation describes the Fukushima's reactors, recalls some data about the earthquake and tsunami, and indicates their consequences for the operation of the power station (notably the loss of cooling means). It identifies some design errors for the Chernobyl's and Fukushima's power stations, outlines differences between these two cases. It gives assessment of doses receives by external irradiation around Fukushima, of the dose rate evolution, of the sea contamination. It gives some data about the Chernobyl accident (radioactivity evolution). After some data about health consequences of Chernobyl, health risks and more particularly biological risks associated to low doses are described. Protection measures are evoked, as well as psycho-social impacts

  7. Application of low dose radiation for preservation of sea foods

    International Nuclear Information System (INIS)

    Venugopal, V.; Nair, P.M.

    1994-01-01

    Treatment of food with low doses of gamma radiation has been recognized to have two main advantages. These consist of: (1) improvement of food safety by elimination of pathogens and (2) reduction of microbial spoilage and extension of shelf life of perishable items by reducing the number of viable spoilage organisms. Studies during the last few decades have conclusively proved the beneficial effects of radiation with respect to fishery products. The three potential areas of application to fish products include: (i) radurization for shelf life extension (ii) radicidation to eliminate food borne pathogens in the products and (iii) radiation treatment to dried products to control insects

  8. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

  9. Low dose of donepezil improves gabapentin analgesia in the rat spared nerve injury model of neuropathic pain

    DEFF Research Database (Denmark)

    Folkesson, Anna; Honoré, Per Hartvig; Andersen, Lene Munkholm

    2010-01-01

    the effect of the cholinesterase inhibitor donepezil when administered (1) alone and (2) as low-dose in combination with the first-line recommendation gabapentin. The co-administration studies were performed following single and multiple dosing. Single, parenteral dosing of donepezil (1, 1.5 and 3 mg...

  10. Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

    DEFF Research Database (Denmark)

    Hadrup, Niels; Svingen, Terje; Egebjerg, Karen Mandrup

    2016-01-01

    of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid...

  11. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 9

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji

    1983-01-01

    We have already reported the remarkable effect of an active specific immunotherapy using cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with the active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumor cells were received local radiotherapy with a dose of 3,000 rads by high energy electron beams on the fifth day after inoculation. The tumor cells and infiltrating mononuclear cells cryopreserved for two months were thawed and treated with mitomycin-C at concentration of 20 μg/10 7 cells at 37 0 C for 30 min. Then, these cells were injected subcutaneously into the left hind paws as a mitomycin C-treated, cryopreserved active specific immunotherapy on the thirteenth day, and daily dose of 1 KE of OK-432 was injected intraperitoneally from the sixth to the tenth days. The inhibition of the tumor growth was similarly observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432. (author)

  12. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  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 doses of neutrons induce changes in gene expression

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following γ-ray exposure in fibroblasts. Our past work had shown differences in the expression of β-protein kinase C and c-fos genes, both being induced following γ-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not γ-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 γ 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

  15. Low dose iodine-131 therapy in solitary toxic thyroid nodules

    International Nuclear Information System (INIS)

    Prakash, Rajeev

    1999-01-01

    Forty patients with solitary hyperfunctioning thyroid nodules were treated with relatively low dose radioiodine therapy, 131 I doses were calculated taking into account thyroid mass and radioiodine kinetics to deliver 100 μCi/g of estimated nodule weight corrected for uptake. Patients remaining persistently hyperthyroid at four months after the initial therapy were retreated with a similarly calculated dose. Cure of the hyperthyroid state was achieved in all patients, total administered dose in individual cases ranging from 3-17 mCi. 28 of the 40 patients required a single therapy dose. 36 patients were euthyroid after a 4.5 year mean follow-up period. Four cases developed post therapy hypothyroidism requiring replacement therapy. Nodules regressed completely in nine cases following 131 I treatment, with partial regression in size in 19 patients. Control of hyperthyroid state in cases of solitary toxic thyroid nodules can be satisfactorily achieved using relatively low dose radioiodine therapy with low incidence of post therapy hypothyroidism. (author)

  16. Development of microcontroller based instrumentation for low dose implantation

    International Nuclear Information System (INIS)

    Suresh, K.; Saravanan, K.; Panigrahi, B.K.; Nair, K.G.M.

    2011-01-01

    In experiments like ion implantation based ion track formations, the sample is implanted to low doses of the order of 10 10 ions/cm 2 , limiting the ion beam currents to be less than 1-5 x 10 -12 A. However the standard current integrators available are not sensitive to very low currents, causing an unacceptable high level of error in dose measurement. Hence a low dose implantation measurement system has been developed. It consists of a very sensitive low current preamplifier with full scale input 1nA/100pA, a standard current integrator, a microcontroller based interface circuit, which are connected to a personal computer(PC) through USB. Two types of the software are developed for the system: the microcontroller firmware using C and windows based virtual instrument programs using LabVIEW 7.0. Necessary precautions associated with pA level measurement like rigidly fastened good quality cables, low ripple DC power supply, shielding, close mounting of the preamplifier to the sample are adopted. After necessary calibrations with an ECIL make low current source, the system has been put into regular use. Design and development details, salient features are discussed in this paper. (author)

  17. 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

    that will be useful in estimating human health risks due to radiation that may occur during exposures in the work environment, nuclear/radiological catastrophes, as well as radiotherapy. Several papers have been published, accepted for publication or are in preparation. A number of poster and oral presentations have been made at scientific conferences and workshops. Archived tissues of various types will continue to be evaluated via funding from other sources (the DoE Low Dose Radiation Research Program, Office of Science and this specific grant will be appropriately included in the Acknowledgements of all subsequent publications/presentations). A post-doc and several students have participated in this study. More detailed description of the accomplishments is described in attached file.

  18. 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

  19. Exposures at low doses and biological effects of ionizing radiations

    International Nuclear Information System (INIS)

    Masse, R.

    2000-01-01

    Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

  20. Risk of radiation-induced cancer at low doses and low dose rates for radiation protection purposes

    International Nuclear Information System (INIS)

    1995-01-01

    The aim of this report is to provide an updated, comprehensive review of the data available for assessing the risk of radiation-induced cancer for radiation protection purposes. Particular emphasis is placed on assessing risks at low doses and low dose rates. The review brings together the results of epidemiological investigations and fundamental studies on the molecular and cellular mechanisms involved in radiation damage. Additionally, this information is supplemented by studies with experimental animals which provide further guidance on the form of the dose-response relationship for cancer induction, as well as on the effect of dose rate on the tumour yield. The emphasis of the report is on cancer induction resulting from exposure to radiations with a low linear energy transfer (LET). The work was performed under contract for the Institut de Protection et de Surete Nucleaire, Fontenay-aux-Roses, Paris, France, whose agreement to publish is gratefully ackowledged. It extends the advice on radiation risks given in Documents of the NRPB, 4 No. 4 (1993). (Author)

  1. The health effects of low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Dixit, A.N.; Dixit, Nishant

    2012-01-01

    It has been established by various researches, that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). Exposure to high levels of radiation can cause radiation injury, and these injuries can be relatively severe with sufficiently high radiation doses. Prolonged exposure to low levels of radiation may lead to cancer, although the nature of our response to very low radiation levels is not well known at this time. Many of our radiation safety regulations and procedures are designed to protect the health of those exposed to radiation occupationally or as members of the public. According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. Evidence indicates an inverse relationship between chronic low-dose radiation levels and cancer incidence and/or mortality rates. Examples are drawn from: 1) state surveys for more than 200 million people in the United States; 2) state cancer hospitals for 200 million people in India; 3) 10,000 residents of Taipei who lived in cobalt-60 contaminated homes; 4) high-radiation areas of Ramsar, Iran; 5) 12 million person-years of exposed and carefully selected control nuclear workers; 6) almost 300,000 radon measurements of homes in the United States; and 7) non-smokers in high-radon areas of early Saxony, Germany. This evidence conforms to the hypothesis that

  2. Low dose ionizing radiation responses and knockdown of ATM kinase activity in glioma stem cells

    International Nuclear Information System (INIS)

    Lim, Y.C.; Roberts, T.; Day, B.; Kozlov, S.; Walker, D.; Lavin, M.; Harding, A.

    2009-01-01

    Genesis of new cells in the mammalian brain has previously been regarded as a negligible event; an assumption that long limited our understanding in the development of neoplasias. The recent discovery of perpetual lineages derived from neural stem cells has resulted in a new approach to studying the cellular behaviour of potential cancer stem cells in the brain. Glioblastoma multiforme (GBM), the most aggressive and lethal brain tumour is derived from a group of cancerous stem cells known as glioma stem cells. GBM cells are impervious to conventional therapies such as surgical resection and ionizing radiation because of their pluripotent and radioresistant properties. Thus in our study, we aim to investigate whether a combination of chemo- and radio- therapies is an effective treatment for glioma stem cells. The study utilizes a specific kinase inhibitor (ATMi) of the ATM (Ataxia-telangiectasia mutated) protein which is an essential protein in DNA-damage responses. In the presence of both low dose radiation and ATMi, glioma stem cells have rapid onset of cell death and reduction in growth. Since DNA damage can be inherited through cell division, accumulated DNA breaks in later generations may also lead to cell death. The limitation of conventional radiation therapy is that administration of fractionated (low) doses to reduce any potential harm to the surrounding healthy cells in the brain outweighs the benefits of high radiation doses to induce actual arrest in the propagation of malignant cells. Our study demonstrates a benefit in using low dose radiation combined with chemotherapy resulting in a reduction in malignancy of glioma stem cells. (author)

  3. The spectrum of mutation produced by low dose radiation

    International Nuclear Information System (INIS)

    Morley, Alexander A.; Turner, David R.

    2004-01-01

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  4. Low dose response analysis through a cytogenetic end-point

    International Nuclear Information System (INIS)

    Bojtor, I.; Koeteles, G.J.

    1998-01-01

    The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

  5. Metabolomics: new prospects in low-dose radio-toxicology

    International Nuclear Information System (INIS)

    Souidi, Maamar; Grison, Stephane

    2014-01-01

    There is recurring public concern regarding the health impact of chronic exposure to low-dose ionizing radiation. This concern is further heightened when possible sources of exposure are identified, such as disused mines, the operation of nuclear facilities and radioactive waste disposal facilities, accidental release from fuel cycle facilities or the possible return of residents to areas contaminated following a reactor accident, such as the one that occurred at Fukushima. In keeping with the guidelines set out in the European strategic research agenda for MELODI, IRSN is conducting an extensive, largely experiment-based, research program to acquire scientific data to respond to this concern. The program has already revealed that chronic ingestion of cesium-137 or uranium induces many subtle, generally slight, metabolic changes, the overall biological effects of which remain to be studied. A recent 'broad-spectrum' analytical technique known as metabolomics was used to pinpoint these metabolic changes. (authors)

  6. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner

    2013-01-01

    ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...... selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). RESULTS: We identified a subset of transcripts (n = 988) where changes...

  7. The effect of low-dose spironolactone on resistant hypertension

    DEFF Research Database (Denmark)

    Engbaek, Mette; Hjerrild, Mette; Hallas, Jesper

    2010-01-01

    with three classes of antihypertensive drugs. The effect on blood pressure was estimated by office measurements together with serum potassium and adverse effects. The data were analyzed retrospectively. A total of 544 patients were identified; 200 were excluded because of secondary hypertension, other......Our objective was to estimate the effect of addition of low-dose spironolactone to previous antihypertensive therapy in patients with resistant hypertension. Patients had 25 to 50 mg of spironolactone once daily added to the treatment of hypertension that was uncontrolled despite previous treatment...... indications for spironolactone than hypertension, previous antihypertensive therapy with less than three drugs unless demonstrated intolerance to a third drug, insufficient compliance, and lack of follow-up data. Thus, 344 cases were included in the analysis. The population was 62.1 ± 12.8 years old, 45...

  8. Low-dose aripiprazole for refractory burning mouth syndrome.

    Science.gov (United States)

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    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.

  9. 'Reasonable' regulation of low doses in the Netherlands?

    International Nuclear Information System (INIS)

    Zuur, Ciska

    2002-01-01

    As long as it is not clear exactly what the risks of low doses are, exposures should be regulated to be 'as low as reasonably achievable' (ALARA). In radiation protection, for normal situations, this means that a projected dose reduction can only be obligatory when the efforts needed to achieve the reduction are 'reasonable' in comparison with it, economical and social aspects being taken into account. In the recent Dutch regulations, 'reasonable' values have been established for the relevant parameters used in the ALARA concept and the paper discusses the values required to calculate the doses for the critical group due to a source. In some cases, the effort expended in making the ALARA dose assessments might not be reasonable in comparison with the dose reduction to be expected. The system which has been developed in the Netherlands to avoid these 'unreasonable' dose calculations, measurements and assessments is explained. (author)

  10. State of human genome at low-doses ecological influences

    International Nuclear Information System (INIS)

    Mel'nov, S.B.; Rytik, P.G.; Kruchinskij, N.G.; Kovalev, V.A.; Palamar, L.A.; Senyuk, O.F.

    2005-01-01

    The results of analysis of the state of genome (amounts of single strand breaks in DNA) of the persons exposed to influence of complex 'Chernobyl factor' in remote terms after a failure on ChNPP are resulted. Findings allowed to expose the increase of level of single strand breaks in DNA at the chronically irradiated persons mainly carry adaptive character and probably can be related to instability of genome. Thus at organism level growth of mutational pressure and strengthening of instability of cellular genome is related to the change of spectrum of biological characteristics, in particular individual reaction of somatic cells of victims on additional mutagens influences. The indicated changes can testify to existence of potential risk of remote genetic consequences of long-term irradiation influence in low doses

  11. Low-dose irradiation for controlling prostate cancer

    International Nuclear Information System (INIS)

    Cuttler, J.M.

    2003-01-01

    Prostate cancer is the second most commonly diagnosed cancer among North American men and the second leading cause of death in those aged 65 and over. The American Cancer Society recommends testing those over age 50 who are expected to live at least 10 years, even though the ability of early detection to decrease prostate cancer mortality has not been demonstrated. So controversy exists about the appropriateness of screening because of the considerable economic and social burden of diagnosing and treating prostate cancer, coupled with the projected large increase in the number of new cases as the population ages. This very important public health issue could be addressed at low cost by total-body low-dose irradiation therapy to stimulate the patient's own defences to prevent and control most cancers, including prostate cancer, with no symptomatic side effects. (author)

  12. 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.

  13. Effect of low dose radiation on apoptosis in mouse spleen

    International Nuclear Information System (INIS)

    Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

    1999-01-01

    Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

  14. The effects of chronic low dose irradiation on drosophila melanogaster

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Yuraneva, I.N.; Taskaev, A.I.

    2001-01-01

    It was investigated the influence of the chronic gamma-irradiation in the dose rate of 0.17 cGy/h on the rate of genetic variability and on the life-span in the laboratory strains of Drosophila melanogaster with genotypic distinguishes in mobile genetic elements and defects in the DNA repair processes. It is shown that the radiation-induced alteration of the traits under study depends from genotype of investigated strains. In the different strains we have observed an increase as well as a decrease of the mutation rate and life-span. Also it was established that irradiation leads to the frequencies of the GD-sterility and mutability of the snw and h(w+) in the P-M and H-E dysgenic crosses. The obtained results suggest that mobile genetic elements play an important role in the forming of genetic effects in response to low dose irradiation. (author)

  15. Genetic effects of low-dose irradiation in Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Zajnulin, V.G.; Shaposhnikov, M.V.; Yuraneva, I.N.

    2000-01-01

    Influence of chronic γ-irradiation at the dose rate of 0.17 cGy/h on the rate of genetic variability in the laboratory strains of Drosophila Melanogaster with genotypic distinguishes by families of mobile genetic elements and of systems of hybrid disgenesis and also violations in reparation processes control mechanisms. It was shown that the rates of induction of recessive lethal mutations depended on genotype of investigated strains. In the different strains an increase as well as a decrease of the mutation rate were observed. Also in was established that irradiation leads to the increase in frequencies of the gonads sterility and mutability of the sn w and h(w + ) in the P-M and H-E dysgenic crosses. Obtained results suggest that mobile genetic elements play an important role in the forming of genetic effects in response to low dose irradiation [ru

  16. Low dose preoperative radiotherapy for carcinoma of the oesophagus

    International Nuclear Information System (INIS)

    Arnott, S.J.; Duncan, W.; Kerr, G.R.; Jack, W.J.L.; Mackillop, W.J.; Walbaum, P.R.; Cameron, E.

    1992-01-01

    Patients (176) with potentially operable squamous cell carcinoma or adenocarcinoma of middle or lower thirds of oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 moths, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumor grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone. (author). 9 refs.; 3 figs.; 6 tabs

  17. High and low dose-rate brachytherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Orton, C.G.

    1998-01-01

    For the brachytherapy component of the r[iation treatment of cervical carcinoma, high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due primarily to r[iation safety and other physical benefits attributed to the HDR modality. Many r[iation oncologists are reluctant to make this change because of perceived r[iobiological dis[vantages of HDR. However, in clinical practice HDR appears to be as effective as LDR but with a lower risk of late complications, as demonstrated by one randomized clinical trial and two comprehensive literature and practice surveys. The reason for this appears to be that the r[iobiological dis[vantages of HDR are outweighed by the physical [vantages. (orig.)

  18. Curative effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Fei Luo

    2017-01-01

    Conclusion: Surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage can improve neural nutritional status and reduce nerve injury degree, and it is beneficial to the recovery of neural function.

  19. Lung cancer screening with low-dose CT

    International Nuclear Information System (INIS)

    Diederich, S.; Wormanns, D.; Heindel, W.

    2003-01-01

    Screening for lung cancer is hoped to reduce mortality from this common tumour, which is characterised by a dismal overall survival, relatively well defined risk groups (mainly heavy cigarette smokers and workers exposed to asbestos) and a lack of early symptoms. In the past studies using sputum cytology and chest radiography have failed to demonstrate any reduction in lung cancer mortality through screening. One of the reasons is probably the relatively poor sensitivity of both these tests in early tumours. Low radiation dose computed tomography (CT) has been shown to have a much higher sensitivity for small pulmonary nodules, which are believed to be the most common presentation of early lung cancer. As, however, small pulmonary nodules are common and most are not malignant, non-invasive diagnostic algorithms are required to correctly classify the detected lesions and avoid invasive procedures in benign nodules. Nodule density, size and the demonstration of growth at follow-up have been shown to be useful in this respect and may in the future be supplemented by contrast-enhanced CT and positron emission tomography. Based on these diagnostic algorithms preliminary studies of low-dose CT in heavy smokers have demonstrated a high proportion of asymptomatic, early, resectable cancers with good survival. As, however, several biases could explain these findings in the absence of the ultimate goal of cancer screening, i.e. mortality reduction, most researchers believe that randomised controlled trials including several 10000 subjects are required to demonstrate a possible mortality reduction. Only then general recommendations to screen individuals at risk of lung cancer with low-dose CT should be made. It can be hoped that international cooperation will succeed in providing results as early as possible

  20. 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

  1. Varicose Vein Stripping Under Low-Dose Spinal Anaesthesia

    Directory of Open Access Journals (Sweden)

    Nalan Muhammedoğlu

    2014-03-01

    Full Text Available Aim: Spinal anesthesia is frequently used for procedures involving the lower limbs. Compared with general anesthesia, low-dose spinal anesthesia is a cost-effective method and has advantages such as avoiding hypotension, longer duration of anesthesia and increased length of hospitalization. The aim of this trial was to compare two different low-dose bupivacaine drug regimens. Methods: Sixty unpremedicated patients were randomly allocated into two groups (n=30. There were no differences between the groups in age, weight, the American Society of Anesthesiologists (ASA physical status classification, gender, and duration of surgery. We performed spinal anesthesia at the L3-4 interspace with the patient in the lateral decubitus position. We administered 6.5 mg (group 1 and 8 mg (group 2 0.5% heavy bupivacaine into the subarachnoid space. We positioned the patient laterally to the operation side for 15 minutes, then, turned to supine position. Motor and sensory block was assessed by the Bromage scale and pinprick test. Results: There were significant differences between the two groups in duration of motor block, but no significant differences in hemodynamic response to spinal anesthesia. None of the patients had intraoperative pain. Five patients in group 1 and 2 patients in group 2 had urinary retention. Conclusion: Our observations suggest that 6.5 mg heavy bupivacaine is efficient and suitable for unilateral varicose veins stripping operation. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 25-8

  2. 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.

  3. Clinical application of low-dose spiral CT for orthodontics

    International Nuclear Information System (INIS)

    Xie Na; Gan Yungen; Shu Huang; Lin FeiFei; Li Zhiyong; Sun Jie

    2009-01-01

    Objective: To determine the effect of reducing the value of mA or kV on the image quality and the radiation dose of the patients undergoing low-dose spiral CT for orthodontics. Methods: Thirty patients were divided into three groups, each group has 10 patients. They were group 1 (80 kV and 200 mA), group 2 (120 kV and 80 mA), group 3 (120 kV and 200 mA) The volume CT dose index (CTDI) was recorded and the average dose-length produce (DLP) was calculated in three groups,respectively. Image quality of three groups were compared and scored by two radiologists, and the results were statistically analysed. Results: The CTDI and DLP of 80 kV group (group 2) were 8.7 mGy and (36.80 ± 3.60) mGy · cm, respectively, those of 80 mA group (group 3) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively, and those of conventional-dose group (group 1) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively. There was no significant difference among three groups in diagnostic image quality. Conclusions: Low-dose spiral CT for orthodontics, especially the low-kV scan, may decrease the radiation exposure and guarantee the image quality. (authors)

  4. 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

  5. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    Jacob, P

    2006-01-01

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

  6. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry

    International Nuclear Information System (INIS)

    Metz-Flamant, Camille

    2011-01-01

    exposure. Our study finds a risk of leukemia associated with chronic external exposure and allows taking into account modifying factors of this relation. Additional follow-up allows to improve the precision of the estimated dose-response relationship. A combined analysis including the present cohort and other nuclear cohorts could quantify more precisely the risks associated with low doses at low dose rates, in order to validate current underlying hypotheses of the radiation protection system. (author)

  7. Low-dose-rate interstitial brachytherapy preserves good quality of life in buccal mucosa cancer patients

    International Nuclear Information System (INIS)

    Tayier, A.; Hayashi, Keiji; Yoshimura, Ryoichi

    2011-01-01

    The purpose of this study was to determine the results and long-term changes in radiation toxicity of stage I-II buccal mucosa cancer patients treated by low-dose-rate (LDR) brachytherapy with 198 Au grains. A total of 133 stage I-II buccal mucosa carcinomas patients received 198 Au grain implantation brachytherapy between January 1982 and July 2005: 75 of them were treated by 198 Au grain implantation alone and 58 were treated by 198 Au implantation in combination with external irradiation. The average 198 Au-grain dose was 70 Gy in 7 days. Gross tumor areas ranged from 2.4 cm 2 to 9 cm 2 , and the clinical target areas ranged from 6 cm 2 to 15 cm 2 . The follow-up periods ranged from 3 months to 20 years (mean: 5 years 11 months and median: 5 years 1 months). Failure at the site of the primary lesion occurred in 17 patients. Post-treatment mucosal ulceration developed in 15 patients, and all were cured within 25 months by conservative treatment. Osteoradionecrosis was diagnosed in 8 patients, but only one patient required surgical treatment. No severe complications or aggravation of complications developed more than 10 years after treatment. The results of low-dose-rate (LDR)-brachytherapy (BT) alone and LDR-BT in combination with external irradiation at a total dose of 25 Gy were acceptable from the standpoint of cure rate and quality of life (QOL). (author)

  8. The special cell effects and somatic consequences of exposure to low dose radiation

    International Nuclear Information System (INIS)

    Regina Fedortseva; Sergei Aleksanin; Eugene Zheleznyakov; Irina Bychkovskaya

    2007-01-01

    Complete text of publication follows. Objective: The experimental data presented in the report put some clarity into the ongoing polemics about possibility of induction of harmful non-carcinogenic effects in human body as a result of exposure to low doses of radiation. The denial of this possibility is based on the fact that traditionally studied genotoxic effects cannot be the cause of this pathology: the incidence of these effects in exposure to low doses of radiation is fairly low; the effects are not overt in critical slowly regenerating tissues, since they can only be morphologically manifested in actively growing cell populations. Methods: Endothelium of myocardial and alveolar capillaries were studied ultra-structurally in 236 rats irradiated by a wide range of X-ray doses (0,25;0,5;2,25;4,5;9;30;48;100) and 28 intact control animals. Studies were conducted during 12-18 months. The material consisted of 2-3 portions from various parts of myocardium and lung. From each portion, sections were prepared, in which all capillary sections were analyzed and ultra-structure of all lining capillary endotheliocytes (their number most often was more than 100) was studied. In each animal the percentage of non-viable endotheliocytes with signs of generalized organoid destruction, damage of plasmalemma and nuclear structures was accounted. Results: Irradiation of rat to low and higher doses caused significant (up to 7 times) increase number of endothelial cells with various ultra-structural damages (from relatively light ones to in the cell death). Even the lowest dose - 0,25 Gy produce an increasing degeneration, intracellular lysis and defects of mitochondria. We found unusual features of postradiational endothelium changes: dose independence, necessity of revealing the long-term, non-mutational cellular effects, massive involvement of cells, early development of the maximum effect already after the low dose irradiation. These special somatic effects, unlike genotoxic

  9. Investigation of the dose rate dependency of the PAGAT gel dosimeter at low dose rates

    International Nuclear Information System (INIS)

    Zehtabian, M.; Faghihi, R.; Zahmatkesh, M.H.; Meigooni, A.S.; Mosleh-Shirazi, M.A.; Mehdizadeh, S.; Sina, S.; Bagheri, S.

    2012-01-01

    Medical physicists need dosimeters such as gel dosimeters capable of determining three-dimensional dose distributions with high spatial resolution. To date, in combination with magnetic resonance imaging (MRI), polyacrylamide gel (PAG) polymers are the most promising gel dosimetry systems. The purpose of this work was to investigate the dose rate dependency of the PAGAT gel dosimeter at low dose rates. The gel dosimeter was used for measurement of the dose distribution around a Cs-137 source from a brachytherapy LDR source to have a range of dose rates from 0.97 Gy h −1 to 0.06 Gy h −1 . After irradiation of the PAGAT gel, it was observed that the dose measured by gel dosimetry was almost the same at different distances (different dose rates) from the source, although the points nearer the source had been expected to receive greater doses. Therefore, it was suspected that the PAGAT gel is dose rate dependent at low dose rates. To test this further, three other sets of measurements were performed by placing vials containing gel at different distances from a Cs-137 source. In the first two measurements, several plastic vials were exposed to equal doses at different dose rates. An ionization chamber was used to measure the dose rate at each distance. In addition, three TLD chips were simultaneously irradiated in order to verify the dose to each vial. In the third measurement, to test the oxygen diffusion through plastic vials, the experiment was repeated again using plastic vials in a nitrogen box and glass vials. The study indicates that oxygen diffusion through plastic vials for dose rates lower than 2 Gy h −1 would affect the gel dosimeter response and it is suggested that the plastic vials or (phantoms) in an oxygen free environment or glass vials should be used for the dosimetry of low dose rate sources using PAGAT gel to avoid oxygen diffusion through the vials.

  10. 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.)

  11. Low doses effects of ionizing radiation on Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Durand, J.; Broock, M. van; Gillette, V.H.

    2000-01-01

    The exposure of living cells to low doses of ionizing radiation induce in response the activation of cellular protection mechanisms against subsequent larger doses of radiation. This cellular adaptive response may vary depending on radiation intensity and time of exposure, and also on the testing probes used whether they were mammalian cells, yeast, bacteria and other organisms or cell types. The mechanisms involved are the genome activation, followed by DNA repair enzymes synthesis. Due to the prompt cell response, the cell cycle can be delayed, and the secondary detoxification of free radicals and/or activation of membrane bound receptors may proceed. All these phenomena are submitted to intense scientific research nowadays, and their elucidation will depend on the complexity of the organism under study. In the present work, the effects of low doses of ionizing radiation (gamma rays) over a suspension of the yeast Saccharomyces cerevisiae (Baker's yeast) was studied, mainly in respect to survival rate and radio-adaptive response. At first, the yeast surviving curve was assessed towards increasing doses, and an estimation of Lethal Dose 50 (LD50) was made. The irradiation tests were performed at LINAC (electrons Linear Accelerator) where electron energy reached approximately 2.65 MeV, and gamma-radiation was produced for bremsstrahlung process over an aluminium screen target. A series of experiments of conditioning doses was performed and an increment surviving fraction was observed when the dose was 2.3 Gy and a interval time between this and a higher dose (challenging dose) of 27 Gy was 90 minutes. A value of 58 ± 4 Gy was estimated for LD50, at a dose rate of 0.44 ± 0.03 Gy/min These quantities must be optimized. Besides data obtained over yeast survival, an unusual increasing amount of tiny yeast colonies appeared on the agar plates after incubation, and this number increased as increasing the time exposure. Preliminary results indicate these colonies as

  12. Suppression of carcinogenesis in mice by adaptive responses to low dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Kazuo; Iwasaki, Toshiyasu; Hoshi, Yuko; Nomura, Takaharu; Ina, Yasuhiro; Tanooka, Hiroshi [Central Research Institute of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

    2003-07-01

    Effects of prolonged low-dose-rate irradiation on the process of carcinogenesis were examined in mice treated with chemical carcinogen or irradiated with high doses of X-rays. Female ICR mice, 5 week-old, 35 in each group, were exposed to gamma-rays from a {sup 137}Cs source in the long-term low dose rate irradiation facility at CRIEPI. The dose rate was 2.6 mGy/hr (A), 0.96 mGy/hr (B), or 0.30 mGy/hr (C). Thirty-five days later, the mice were injected into the groin with 0.5 mg of methylcholanthrene (MC) dissolved in olive oil and irradiation was continued. Cumulative tumor incidences after 216 days following MC injection were 89% in group A, 76% in group B, and 94% in group C. That in non-irradiated control group was 94%. The difference in the tumor incidence between the control and position B was statistically significant, indicating the suppressive effect of the low dose rate irradiation on the process of MC-induced carcinogenesis with an optimum dose rate around 1 mGy/hr. In B6C3F1 mice, although the suppression of tumor incidence was not observed, there was a significant delay in tumor appearance in the irradiated mice between 100-150 days after MC injection. A group of 20 female C57BL/6N mice, 5 weeks old, were exposed to gamma-rays at 0.95 mGy/hr for 5 weeks. Then, they were exposed weekly to 1.8 Gy whole body X-irradiation (300 kVp) for consecutive 4 weeks to induce thymic lymphoma. Another group received only the fractionated irradiation. The first mouse died from thymic lymphoma appeared 89 days after the last irradiation in the group received only the fractionated irradiation, while 110 days in the group combined with the low dose rate irradiation. (author)

  13. 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.

  14. Effect of low doses gamma irradiation of cotton seeds

    International Nuclear Information System (INIS)

    Al-Oudat, M.; Khalifa, Kh.

    1996-01-01

    Field experiments and then large scale application of irradiated cotton seeds (C.V. Aleppo-40) were carried out during three seasons (1986, 1987 and 1988) for field experiment at ACSAD Station in Dier-Ezzor and 1988, 1989 and 1990 for large scale application at Euphrate's Basin, Al-Ghab and Salamia, farmers farms. The above areas were selected as they represent major cotton production areas in Syria. The aims of the experiments were to study the effect of low doses of gamma irradiation 0, 5, 10, 20, 30, 40 and 50 Gy on cotton yield and to look for the optimum dose of gamma irradiation to obtain best results. The results show that, there were positive effect (P<0.95) for doses 5-30 Gy in increasing cotton yield. The highest increase was at dose of 10 Gy. which as 19.5% higher than control. For the large scale application using 10 Gy the increase in cotton yield varied from 10-39% compared to control. (author). 11 refs., 6 figs

  15. Sensitivity to low-dose radiation in radiosensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-01-01

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells

  16. Medical effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    Coggle, J.E.

    1990-01-01

    Ionising radiation is genotoxic and causes biological effects via a chain of events involving DNA strand breaks and 'multiply damaged sites' as critical lesions that lead to cell death. The acute health effects of radiation after doses of a few gray, are due to such cell death and consequent disturbance of cell population kinetics. Because of cellular repair and repopulation there is generally a threshold dose of about 1-2 Gy below which such severe effects are not inducible. However, more subtle, sub-lethal mutational DNA damage in somatic cells of the body and the germ cells of the ovary and testis cause the two major low dose health risks -cancer induction and genetic (heritable) effects. This paper discusses some of the epidemiological and experimental evidence regarding radiation genetic effects, carcinogenesis and CNS teratogenesis. It concludes that current risk estimates imply that about 3% of all cancers; 1% of genetic disorders and between 0% and 0.3% of severe mental subnormality in the UK is attributable to the ubiquitous background radiation. The health risks associated with the medical uses of radiation are smaller, whilst the nuclear industry causes perhaps 1% of the health detriment attributable to background doses. (author)

  17. Carcinogenesis in mice after low doses and dose rates

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1979-01-01

    The results from the experimental systems reported here indicate that the dose-response curves for tumor induction in various tissues cannot be described by a single model. Furthermore, although the understanding of the mechanisms involved in different systems is incomplete, it is clear that very different mechanisms for induction are involved. For some tumors the mechanism of carcinogenesis may be mainly a result of direct effects on the target cell, perhaps involving one or more mutations. While induction may occur, in many instances, through such direct effects, the eventual expression of the tumor can be influenced by a variety of host factors including endocrine status, competence of the immune system, and kinetics of target and interacting cell populations. In other tumors, indirect effects may play a major role in the initiation or expression of tumors. Some of the hormone-modulated tumors would fall into this class. Despite the complexities of the experimental systems and the lack of understanding of the types of mechanisms involved, in nearly every example the tumorigenic effectiveness per rad of low-LET radiation tends to decrease with decreasing dose rate. For some tumor types the differences may be small or may appear only with very low dose rates, while for others the dose-rate effects may be large

  18. Fully automated gynecomastia quantification from low-dose chest CT

    Science.gov (United States)

    Liu, Shuang; Sonnenblick, Emily B.; Azour, Lea; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2018-02-01

    Gynecomastia is characterized by the enlargement of male breasts, which is a common and sometimes distressing condition found in over half of adult men over the age of 44. Although the majority of gynecomastia is physiologic or idiopathic, its occurrence may also associate with an extensive variety of underlying systemic disease or drug toxicity. With the recent large-scale implementation of annual lung cancer screening using low-dose chest CT (LDCT), gynecomastia is believed to be a frequent incidental finding on LDCT. A fully automated system for gynecomastia quantification from LDCT is presented in this paper. The whole breast region is first segmented using an anatomyorientated approach based on the propagation of pectoral muscle fronts in the vertical direction. The subareolar region is then localized, and the fibroglandular tissue within it is measured for the assessment of gynecomastia. The presented system was validated using 454 breast regions from non-contrast LDCT scans of 227 adult men. The ground truth was established by an experienced radiologist by classifying each breast into one of the five categorical scores. The automated measurements have been demonstrated to achieve promising performance for the gynecomastia diagnosis with the AUC of 0.86 for the ROC curve and have statistically significant Spearman correlation r=0.70 (p early detection as well as the treatment of both gynecomastia and the underlying medical problems, if any, that cause gynecomastia.

  19. Low dose radiation prevents doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-02

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

  20. Risk at Low Doses: Scientific knowledge, uncertainties and management

    International Nuclear Information System (INIS)

    Giusssani, A.; Ballarini, F.; Ottolenghi, A.

    2002-01-01

    Most of the applications of ionizing radiation in the medical field, for the exposed workers as well as the majority of patients undergoing diagnostic examinations, can be seen as low situations. Epidemiological information is however available for dose and dose rates higher than the values typical of most medical situation. Main source of information is the Life Span Study (LSS) of Japanese. A-bomb survivors, supplemented by studies of selected groups of exposed workers (uranium miners, radium painters) or radiotherapy patients with a detailed follow-up history. All of these group studies, however, suffer from one or more of the following limitations: - lack of adequate dosimetry - lack of a reliable control group for the necessary comparison - influence of concomitant factors (not always easy to find out) - influence of social conditions. In addition exposed study populations are different than the population of patients for which the risk estimates are needed in the medical situation. Recent studies aimed to evaluate the available data on the cohorts of the inhabitants of the Techa river settlements as well as of the workers of the Mayak nuclear facilities may provide in the future useful information on large populations chronically exposed to relatively low doses. (Author)

  1. International Conference on Low Doses of Ionising Radiation

    International Nuclear Information System (INIS)

    McEwan, A.C.

    1998-01-01

    Is there a threshold? and is a little radiation good for you? were two questions raised at the International Conference on Low Doses of Ionising Radiation : Biological Effects and Regulatory Control, jointly organised by the IAEA and WHO, and convened in Seville, Spain, over 17-21 November 1997. The answer to both these questions appears to be 'Maybe', but the answer has no present implications for radiation protection practice and regulation. The conference which had over 500 participants from 65 countries, was organised around ten fora which explored basic molecular mechanisms of radiation effects, through to radiation protection principles and implementation in practices and interventions. Each forum was introduced by an overview presentation by an invited keynote speaker. Brief presentations of a few of the proffered papers followed, and then open discussion. There was opportunity for all proffered papers to be presented as posters. The fora, which occupied 3 full days, were preceded by reports on biological effects of radiation from international orgnaisations, and on related international conferences held in the recent past. The fora were followed by round table presentations of regulatory control and scientiFic research, and a summary session drawing together conclusions on the topic areas of the conference. (author)

  2. Bayesian approach in MN low dose of radiation counting

    International Nuclear Information System (INIS)

    Serna Berna, A.; Alcaraz, M.; Acevedo, C.; Navarro, J. L.; Alcanzar, M. D.; Canteras, M.

    2006-01-01

    The Micronucleus assay in lymphocytes is a well established technique for the assessment of genetic damage induced by ionizing radiation. Due to the presence of a natural background of MN the net MN is obtained by subtracting this value to the gross value. When very low doses of radiation are given the induced MN is close even lower than the predetermined background value. Furthermore, the damage distribution induced by the radiation follows a Poisson probability distribution. These two facts pose a difficult task to obtain the net counting rate in the exposed situations. It is possible to overcome this problem using a bayesian approach, in which the selection of a priori distributions for the background and net counting rate plays an important role. In the present work we make a detailed analysed using bayesian theory to infer the net counting rate in two different situations: a) when the background is known for an individual sample, using exact value value for the background and Jeffreys prior for the net counting rate, and b) when the background is not known and we make use of a population background distribution as background prior function and constant prior for the net counting rate. (Author)

  3. Dynamic low dose I-123-iodophenylpentadecanoic acid metabolic cardiac imaging

    International Nuclear Information System (INIS)

    Murray, G.L.; Magill, H.L.; Schad, N.C.

    1993-01-01

    Recognition of stunned and hibernating myocardium is essential in this era of cardiac revascularization. Positron emission tomography (PET) accurately identifies viability but is costly and unavailable to most patients. Dynamic low dose I-123-iodophenylpentadecanoic acid (IPPA) metabolic cardiac imaging is a potentially cost-effective alternative to PET. Using transmural myocardial biopsies obtained during coronary bypass surgery as the viability gold standard, resting IPPA imaging agreed with 39/43 (91%) biopsies, with a sensitivity for viability of 33/36(92%) and a specificity of 6/7 (86%) in patients with severe ischemic cardiomyopathy. Eighty percent of IPPA viable, infarcted segments improved wall motion postoperatively. Furthermore, when compared to reinjection thallium (SPECT-Tl) scans after myocardial infarction, there was IPPA-Tl concordance in 27/35 (77%)(Kappa=0.536, p=0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-Tl, 26/35 (74%) vs. 18/35 (51%)(p=0.047). Finally, when compared to transvenous endomyocardial biopsy for detecting rejection following cardiac transplantation, IPPA sensitivity for ≥Grade II rejection was 100%, and IPPA screening assessment for the necessity of biopsy could result in a 31% cost-savings. Therefore, IPPA metabolic cardiac imaging is a safe, inexpensive technique with a promising future. (author)

  4. Low-dose caffeine physical dependence in humans.

    Science.gov (United States)

    Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

    1990-12-01

    This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

  5. Biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Gonzalez, A.J.

    1994-01-01

    Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

  6. Health Effects of Exposure to Low Dose of Radiation

    International Nuclear Information System (INIS)

    Alatas, Zubaidah

    2003-01-01

    Human beings are exposed to natural radiation from external sources include radionuclides in the earth and cosmic radiation, and by internal radiation from radionuclides, mainly uranium and thorium series, incorporated into the body. Living systems have adapted to the natural levels of radiation and radioactivity. But some industrial practices involving natural resources enhance these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Biological effects of ionizing radiation are the outcomes of physical and chemical processes that occur immediately after the exposure, then followed by biological process in the body. These processes will involve successive changes in the molecular, cellular, tissue and whole organism levels. Any dose of radiation, no matter how small, may produce health effects since even a single ionizing event can result in DNA damage. The damage to DNA in the nucleus is considered to be the main initiating event by which radiation causes damage to cells that results in the development of cancer and hereditary disease. It has also been indicated that cytogenetic damage can occur in cells that receive no direct radiation exposure, known as bystander effects. This paper reviews health risks of low dose radiation exposure to human body causing stochastic effects, i.e. cancer induction in somatic cells and hereditary disease in genetic cells. (author)

  7. Low dose CT perfusion in acute ischemic stroke

    International Nuclear Information System (INIS)

    Murphy, Amanda; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I.; So, Aaron; Lee, Ting-Yim

    2014-01-01

    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). 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.)

  8. Low dose CT perfusion in acute ischemic stroke.

    Science.gov (United States)

    Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

    2014-12-01

    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 test post hoc analysis (p 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 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.

  9. Low dose radiation damage effects in silicon strip detectors

    International Nuclear Information System (INIS)

    Wiącek, P.; Dąbrowski, W.

    2016-01-01

    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.

  10. 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.

  11. Radiation crosslinking of CMC-Na at low dose and its application as substitute for hydrogel

    International Nuclear Information System (INIS)

    Liu Pengfei; Peng Jing; Li Jiuqiang; Wu Jilan

    2005-01-01

    The slight radiation-crosslinked CMC-Na as a substitute for hydrogel was prepared by gamma irradiation below gelation dose. The effects of various parameters such as absorbed dose, concentration of inorganic salts, pH, swelling temperature and swelling time on the swelling ratio in water were investigated in detail. This kind of slight crosslinked CMC-Na showed good water absorption below 60 deg. C, whereas, it became solution when heated up to 70 deg. C. Such CMC-Na gel is different from the true gel that is insoluble in boiled water; nevertheless, it can be used as hydrogel at room temperature and produced at low dose. Due to its low cost, it might be useful for its application in agriculture or others

  12. A Shearlet-based algorithm for quantum noise removal in low-dose CT images

    Science.gov (United States)

    Zhang, Aguan; Jiang, Huiqin; Ma, Ling; Liu, Yumin; Yang, Xiaopeng

    2016-03-01

    Low-dose CT (LDCT) scanning is a potential way to reduce the radiation exposure of X-ray in the population. It is necessary to improve the quality of low-dose CT images. In this paper, we propose an effective algorithm for quantum noise removal in LDCT images using shearlet transform. Because the quantum noise can be simulated by Poisson process, we first transform the quantum noise by using anscombe variance stabilizing transform (VST), producing an approximately Gaussian noise with unitary variance. Second, the non-noise shearlet coefficients are obtained by adaptive hard-threshold processing in shearlet domain. Third, we reconstruct the de-noised image using the inverse shearlet transform. Finally, an anscombe inverse transform is applied to the de-noised image, which can produce the improved image. The main contribution is to combine the anscombe VST with the shearlet transform. By this way, edge coefficients and noise coefficients can be separated from high frequency sub-bands effectively. A number of experiments are performed over some LDCT images by using the proposed method. Both quantitative and visual results show that the proposed method can effectively reduce the quantum noise while enhancing the subtle details. It has certain value in clinical application.

  13. Investigations of putative reproductive toxicity of low-dose exposures to vinclozolin in Wistar rats.

    Science.gov (United States)

    Flick, Burkhard; Schneider, Steffen; Melching-Kollmuss, Stephanie; Fussell, Karma C; Gröters, Sibylle; Buesen, Roland; Strauss, Volker; van Ravenzwaay, Bennard

    2017-04-01

    The current investigation examines whether the fungicide vinclozolin, which has an anti-androgenic mode of action, is capable of disrupting endocrine homeostasis at very low doses. The data generated clarify whether a non-monotonic dose-response relationship exists to enhance the current debate about the regulation of endocrine disruptors. Moreover, it is part of a series of investigations assessing the dose-response relationship of single and combined administration of anti-androgenic substances. A pre-postnatal in vivo study design was chosen which was compliant with regulatory testing protocols. The test design was improved by additional endpoints addressing hormone levels, morphology and histopathological examinations. Doses were chosen to represent an effect level (20 mg/kg bw/d), the current NOAEL (4 mg/kg bw/d), and a dose close to the "ADI" (0.005 mg/kg bw/d) for the detection of a possible non-monotonic dose-response curve. Anti-androgenic changes were observable at the effect level but not at lower exposures. Nipple/areola counts appeared to be the most sensitive measure of effect, followed by male sex organ weights at sexual maturation, and finally gross and histopathological findings. The results indicate the absence of evidence for effects at low or very low dose levels. A non-monotonic dose-response relationship was not evident.

  14. New validated recipes for double-blind placebo-controlled low-dose food challenges.

    Science.gov (United States)

    Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

    2013-05-01

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  15. Low-dose spinal-epidural anesthesia for Cesarean section in a parturient with uncontrolled hyperthyroidism and thyrotoxic heart disease.

    Science.gov (United States)

    Liao, Zhimin; Xiong, Yaqin; Luo, Linli

    2016-08-01

    A 29-year-old woman at 34 weeks' gestation with uncontrolled hyperthyroidism and thyrotoxic heart disease was admitted to urgency Cesarean section. After preoperative sedation and good communication, low-dose spinal anesthesia (7.5 mg 0.5 % bupivacaine) combined with epidural anesthesia (6 ml 2 % lidocaine) was performed through L3-4 inter-vertebral. Opioids were given intravenously to the mother for sedation after delivery of the baby. Satisfactory anesthesia and sedation was provided during surgery. The mother and the neonate were safe and no special complication was found after surgery. Our case demonstrated that low-dose spinal anesthesia combined with epidural anesthesia with intravenous opioids can provide satisfactory anesthesia and sedation, and reduce the risk of heart failure and thyroid storm.

  16. Effect of low-dose irradiation on pregnant mouse haemopoiesis

    International Nuclear Information System (INIS)

    Weinberg, S.R.; McCarthy, E.G.; MacVittie, T.J.; Baum, S.J.

    1981-01-01

    The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to assess burst-forming uniterythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. Four days after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy. (author)

  17. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    Science.gov (United States)

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. High versus low-dose rate brachytherapy for cervical cancer.

    Science.gov (United States)

    Patankar, Sonali S; Tergas, Ana I; Deutsch, Israel; Burke, William M; Hou, June Y; Ananth, Cande V; Huang, Yongmei; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2015-03-01

    Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (Puse of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Relationship to carcinogenesis of repetitive low-dose radiation exposure

    International Nuclear Information System (INIS)

    Ootsuyama, Akira

    2016-01-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

  20. 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.

  1. A new study on the effects of low doses

    International Nuclear Information System (INIS)

    Dousset, M.; Jammet, H.

    1986-01-01

    A study conducted by prof. Rose has investigated mortality among 39540 employees of the UKAEA, from 1946 to 1978. The three main points are: 1. General mortality and mortality from malignant diseases are lower than in the population of England and Wales (74 and 79 per cent respectively), thus showing no major difference between workers monitored for exposure to radiation and other workers. 2. For monitored workers, the only death cause for which there is a statistically significant correlation with radiation exposure is prostate cancer; there are many cases especially in workers with doses exceeding 0.05 Sv (5 rem) and monitored for tritium. Such a correlation has never been found in any other epidemiologic survey of workers exposed to low-level doses, Hanford (USA) workers especially; conversely, mortality from either multiple myeloma or pancreas cancer is not found here. These facts plead for a cautious interpretation of the results as a whole. 3. A linear representation of the variations of leukemia and cancer mortality vs exposure results in lines, the slopes of which are 3 times higher than those of the lines adopted by ICRP; however, the 95% confidence intervals (-2.7 + 12.4 and -22 + 52.5) are such that the results are compatible with a null effect (slope 0) and even with a benefic effect (negative slope). They are therefore compatible with ICRP estimations. A recent attempt to evaluate the two main investigations on low-dose occupational exposures (UKAEA and Hanford) suggests a dose-response relationship very near that of ICRP [fr

  2. Lung cancer risk at low doses of alpha particles

    International Nuclear Information System (INIS)

    Hofmann, W.; Katz, R.; Zhang, C.X.

    1986-01-01

    A survey of inhabitant exposures arising from the inhalation of 222 Rn and 220 Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the high background and the control area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 2 ]2'' 2 Rn and 220 Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli

  3. 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.)

  4. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Rodda, Sree [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Vancouver, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Island Centre, Vancouver, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Morton, Gerard [Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

    2017-06-01

    Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

  5. A chewable low-dose oral contraceptive: a new birth control option?

    Directory of Open Access Journals (Sweden)

    Weisberg E

    2012-04-01

    Full Text Available Edith Weisberg1,21Sydney Centre for Reproductive Health Research, Research Division of Family Planning NSW, 2Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, AustraliaAbstract: A new chewable combined oral contraceptive pill containing ethinyl estradiol (EE 0.025 mg and norethindrone (NE 0.8 mg in a 24/4 regimen was approved for marketing in December 2010. Each of the four inactive tablets contains 75 mg ferrous fumarate, which has no therapeutic benefit. The tablet can be taken with food but not water as this affects the absorption of EE. The Pearl index based on intention to treat women aged 18–35 years has been reported at 2.01 (confidence interval [CI] 1.21, 3.14 and for the whole population 1.65 (CI 1.01, 2.55. The effect of a body mass index of >35 was not studied. Regular withdrawal bleeding occurred for 78.6% of women in Cycle 1, but by Cycle 13 almost half the women failed to have a withdrawal bleed. This new formulation provides an intermediate dose of an EE/NE combination that will be useful for women experiencing breakthrough bleeding on the lower-dose EE/NE pill. The convenience of a low-dose pill, which can be chewed without the need for water, will be useful to enable women who have forgotten a pill to take one whenever they remember, provided they carry it with them. The advantage of a 24/4 regimen is better suppression of follicular development in the pill-free interval and may be beneficial for women who experience menstrual cycle-related problems, such as heavy bleeding or dysmenorrhea.Keywords: combined oral contraceptive, low dose, ethinyl estradiol, norethindrone

  6. U.S.Department of energy low dose radiation research program: potential impact on Human health risk from Chornobyl

    International Nuclear Information System (INIS)

    Brooks, A.

    2002-01-01

    Radiation risks from low levels of radiation exposure, cannot be predicted with epidemiological studies alone. Combining advances in technology with those in cell and molecular biology make it possible to detect biological changes after low doses and dose-rates of radiation exposure, such as Chornobyl. Understanding the role of these biological changes in cancer risk may or may not impact radiation protection standards. However, they will help ensure that the standards are both adequate and appropriate

  7. Standard and Low-dose Hormone Therapy for Postmenopausal Women—Focus on the Breast

    Directory of Open Access Journals (Sweden)

    Peng-Hui Wang

    2007-06-01

    Full Text Available Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT

  8. Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dypiridamole

    International Nuclear Information System (INIS)

    Petrasinovic, Z.; Ostojic, M.; Beleslin, B.; Stojkovic, S.; Nedeljkovic, M.; Stankovic, G.; Dikic, A.; Pavlovic, S.; Sobic, D.

    2002-01-01

    Background. Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. Methods. The study group consisted of 20 consecutive patients (52±10 years, 17 male) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for >5% (inferoapical and posterolateral regions) or >10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the follow up period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. Results. Out of the 180 analyzed segments (20x9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34±12% to 42±14% in the follow-up period (p=0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51

  9. 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

  10. Experience with the low-dose in Bangladesh.

    Science.gov (United States)

    1982-03-01

    Condom sales (brand name Raja) have grown dramatically in Bangladesh and presently, sales account for over 50% of condoms distributed and represent more than 500,000 couple-years of protection (CYP). By contrast, sales of Maya, Noriday's brand name, accounts for only 8.5% of the total oral contraceptive (OC) distribution in Bangladesh and accounts for less than 50,000 CYP. According to the Director of the Bangladesh Social Marketing Program, poor performance of Maya is attributable to marketing factors. The mass media program was ineffectual in motivating new acceptors but it did make Maya a "household word" and it is now almost synonymous with the pill. Despite the nonuse, the number of potential OC users is high and therefore the CSM Project management decided that a new product with a distinct name, a new price, and a new marketing strategy was necessary. Norminest, a low-dose 0.35 mg ethinyl estradiol became available through AID and it was seen as a real alternative to those hormonal contraceptive products already available. The name selected was Ovacon and its packaging (which included goldleaf to signify high quality) was quite different than what came before. The price was set at 4.00 taka/cycle ($.21 in U.S.) which was higher than the Maya but lower than other commercially available OCs. Distribution of this new product was to center around physicians and other medical professionals in urban areas and promotion was to be limited to professional publications. This strategy had 2 objectives: establish personal contact with users and overcome the common practice of blaming the health of clients for the complaints heard. Ovacon was launched in June 1980 and now it is being detailed to rural practitioners. It is still not available in high traffic shops or through panwallahs. While sales have grown to 20-25,000 cycles/month, they are still about 1/2 of Maya sales. Together, these 2 methods represent 50,000 CYP. What was not anticipated was the magnitude of

  11. Spectroscopic characterization of low dose rate brachytherapy sources

    Science.gov (United States)

    Beach, Stephen M.

    The low dose rate (LDR) brachytherapy seeds employed in permanent radioactive-source implant treatments usually use one of two radionuclides, 125I or 103Pd. The theoretically expected source spectroscopic output from these sources can be obtained via Monte Carlo calculation based upon seed dimensions and materials as well as the bare-source photon emissions for that specific radionuclide. However the discrepancies resulting from inconsistent manufacturing of sources in comparison to each other within model groups and simplified Monte Carlo calculational geometries ultimately result in undesirably large uncertainties in the Monte Carlo calculated values. This dissertation describes experimentally attained spectroscopic outputs of the clinically used brachytherapy sources in air and in liquid water. Such knowledge can then be applied to characterize these sources by a more fundamental and metro logically-pure classification, that of energy-based dosimetry. The spectroscopic results contained within this dissertation can be utilized in the verification and benchmarking of Monte Carlo calculational models of these brachytherapy sources. This body of work was undertaken to establish a usable spectroscopy system and analysis methods for the meaningful study of LDR brachytherapy seeds. The development of a correction algorithm and the analysis of the resultant spectroscopic measurements are presented. The characterization of the spectrometer and the subsequent deconvolution of the measured spectrum to obtain the true spectrum free of any perturbations caused by the spectrometer itself is an important contribution of this work. The approach of spectroscopic deconvolution that was applied in this work is derived in detail and it is applied to the physical measurements. In addition, the spectroscopically based analogs to the LDR dosimetry parameters that are currently employed are detailed, as well as the development of the theory and measurement methods to arrive at these

  12. Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

    Science.gov (United States)

    Banyard, Ashley C; Healy, Derek M; Brookes, Sharon M; Voller, Katja; Hicks, Daniel J; Núñez, Alejandro; Fooks, Anthony R

    2014-03-06

    The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and

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

    International Nuclear Information System (INIS)

    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.

    2011-01-01

    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

  14. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    Science.gov (United States)

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  15. Systemic effects of low-dose dopamine during administration of cytarabine.

    Science.gov (United States)

    Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

    2017-09-01

    Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

  16. Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

    Science.gov (United States)

    Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

    2008-06-01

    Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  17. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    International Nuclear Information System (INIS)

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-01-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

  18. Plants ecotoxicology. A case of low doses and multi pollutant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' Kin, S.; Kim, J.; Evseeva, T.; Oudalova, A.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic {gamma}-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

  19. Lipid peroxidation in microsomes of murine bone marrow after low-dose γ-irradiation

    International Nuclear Information System (INIS)

    Schwenke, K.; Coslar, S.; Muehlensiepen, H.; Altman, K.I.; Feinendegen, L.E.

    1994-01-01

    The principal aim of the study was to investigate the effect of low-dose γ-irradiation on lipid peroxidation (LPO) in murine bone marrow. To this end, the degree of LPO in suspensions of microsomes of murine bone marrow cells (BMC) was determined in terms of malondialdehyde (MDA) formation after whole-body or in vitro exposure to various doses of γ-radiation. These effects were compared to some extent with similar effects in liver and spleen preparations. As to the effect of γ-irradiation on LPO in BMC, the response depends on the dose level and on whether whole-body or in vitro exposures are involved. Whole-body irradiation did not result in an increase in LPO in BMC microsomes, even at such high doses as 15 Gy, although hepatic microsomes showed a marked increase. In contrast, in vitro irradiation of BMC microsomes with 0.1, 10 and 50 Gy brought about an increase in LPO. This increase was already significant (P < 0.05) at 0.1 Gy following a post-irradiation incubation and substantial at 50 Gy, even without subsequent incubation. The results show that low doses of γ-irradiation are able to induce an elevation of LPO in murine BMC microsomes, but only after in vitro irradiation. In the case of whole-body irradiation cellular radical scavengers and other metabolic reactions may prevent a measurable increase in LPO. This is partly illustrated by the case of vitamin-E deficiency, where a substantial increase in LPO in BMC microsomes is observed even without γ-irradiation in comparison with euvitaminotic mice because normally occurring radicals are not scavenged sufficiently. (orig.)

  20. Printable organometallic perovskite enables large-area, low-dose X-ray imaging

    Science.gov (United States)

    Kim, Yong Churl; Kim, Kwang Hee; Son, Dae-Yong; Jeong, Dong-Nyuk; Seo, Ja-Young; Choi, Yeong Suk; Han, In Taek; Lee, Sang Yoon; Park, Nam-Gyu

    2017-10-01

    Medical X-ray imaging procedures require digital flat detectors operating at low doses to reduce radiation health risks. Solution-processed organic-inorganic hybrid perovskites have characteristics that make them good candidates for the photoconductive layer of such sensitive detectors. However, such detectors have not yet been built on thin-film transistor arrays because it has been difficult to prepare thick perovskite films (more than a few hundred micrometres) over large areas (a detector is typically 50 centimetres by 50 centimetres). We report here an all-solution-based (in contrast to conventional vacuum processing) synthetic route to producing printable polycrystalline perovskites with sharply faceted large grains having morphologies and optoelectronic properties comparable to those of single crystals. High sensitivities of up to 11 microcoulombs per air KERMA of milligray per square centimetre (μC mGyair-1 cm-2) are achieved under irradiation with a 100-kilovolt bremsstrahlung source, which are at least one order of magnitude higher than the sensitivities achieved with currently used amorphous selenium or thallium-doped cesium iodide detectors. We demonstrate X-ray imaging in a conventional thin-film transistor substrate by embedding an 830-micrometre-thick perovskite film and an additional two interlayers of polymer/perovskite composites to provide conformal interfaces between perovskite films and electrodes that control dark currents and temporal charge carrier transportation. Such an all-solution-based perovskite detector could enable low-dose X-ray imaging, and could also be used in photoconductive devices for radiation imaging, sensing and energy harvesting.

  1. Printable organometallic perovskite enables large-area, low-dose X-ray imaging.

    Science.gov (United States)

    Kim, Yong Churl; Kim, Kwang Hee; Son, Dae-Yong; Jeong, Dong-Nyuk; Seo, Ja-Young; Choi, Yeong Suk; Han, In Taek; Lee, Sang Yoon; Park, Nam-Gyu

    2017-10-04

    Medical X-ray imaging procedures require digital flat detectors operating at low doses to reduce radiation health risks. Solution-processed organic-inorganic hybrid perovskites have characteristics that make them good candidates for the photoconductive layer of such sensitive detectors. However, such detectors have not yet been built on thin-film transistor arrays because it has been difficult to prepare thick perovskite films (more than a few hundred micrometres) over large areas (a detector is typically 50 centimetres by 50 centimetres). We report here an all-solution-based (in contrast to conventional vacuum processing) synthetic route to producing printable polycrystalline perovskites with sharply faceted large grains having morphologies and optoelectronic properties comparable to those of single crystals. High sensitivities of up to 11 microcoulombs per air KERMA of milligray per square centimetre (μC mGy air -1 cm -2 ) are achieved under irradiation with a 100-kilovolt bremsstrahlung source, which are at least one order of magnitude higher than the sensitivities achieved with currently used amorphous selenium or thallium-doped cesium iodide detectors. We demonstrate X-ray imaging in a conventional thin-film transistor substrate by embedding an 830-micrometre-thick perovskite film and an additional two interlayers of polymer/perovskite composites to provide conformal interfaces between perovskite films and electrodes that control dark currents and temporal charge carrier transportation. Such an all-solution-based perovskite detector could enable low-dose X-ray imaging, and could also be used in photoconductive devices for radiation imaging, sensing and energy harvesting.

  2. Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

    1997-01-01

    The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

  3. Influence of low dose ionizing radiation on amplification and antitumor activity of LAK/TIL cells

    International Nuclear Information System (INIS)

    Liu Wei; Hou Dianjun; Qiao Jianwei; Shang Ximei; Li Jieqing

    2000-01-01

    Objective: To study the influence of low dose ionization on amplification and antitumor activity of LAK/TIL cells. Methods: TIL cells isolated from Lewis lung cancer tissues and LAK cells from spleen of tumor-bearing mouse were irradiated with different low doses of X-rays and were cultured after irradiation. Results: Low dose ionizing radiation improved the amplification volume of LAK/TIL cells, decreased the cell death ratio in amplification process, and increased the toxicity of LAK/TIL cells, Conclusions: Low dose ionizing radiation can result in amplification of biologically activated lymphocytes, and decreases the death ratio of the cells in amplification process

  4. Combining Operations Management and Information Systems Curricula: Assessing Alumni Preparations for the Workforce

    Science.gov (United States)

    Silva, David; McFadden, Kathleen L.

    2005-01-01

    The purpose of this study is to explore how well a curriculum that combines operations management and information systems uniquely prepares students for the workforce. To address our research questions, a Web-based survey was developed. We sent our survey to 203 alumni that graduated from the Department of Operations Management and Information…

  5. Sample preparation for combined chemical analysis and bioassay application in water quality assessment

    NARCIS (Netherlands)

    Kolkman, A.; Schriks, M.; Brand, W; Bäuerlein, P.S.; van der Kooi, M.M.E.; van Doorn, R.H.; Emke, E.; Reus, A.; van der Linden, S.; de Voogt, P.; Heringa, M.B.

    2013-01-01

    The combination of in vitro bioassays and chemical screening can provide a powerful toolbox to determine biologically relevant compounds in water extracts. In this study, a sample preparation method is evaluated for the suitability for both chemical analysis and in vitro bioassays. A set of 39

  6. Total Risk Management for Low Dose Radiation Exposures

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Sterc, D.

    2012-01-01

    Our civilization is witnessing about century of nuclear age mixed with enormous promises and cataclysmic threats. Nuclear energy seems to encapsulate both potential for pure good and evil or at least we humans are able to perceive that. These images are continuously with us and they are both helping and distracting from making best of nuclear potentials for civilization. Today with nuclear use significantly present and with huge potential to further improve our life with energy and medical use it is of enormous importance to try to have calmed, rational, and objective view on potential risks and certain benefits. Because all use of nuclear energy proved that their immediate risks are negligible (i.e., Three Mile Island and Fukushima) or much smaller than from the other alternatives (i.e., Chernobyl) it seems that the most important issue is the amount of risk from the long term effects to people from exposure to small doses of radiation. A similar issue is present in the increased use of modern computational tomography and other radiation sources use in medicine for examination and therapy. Finally, extreme natural exposures are third such potential risk sources. Definition of low doses varies depending on the way of delivery (i.e., single, multiple or continuous exposures), and for this paper usual dose of 100 mSv is selected as yearly upper amount. There are three very different scientifically supported views on the potential risks from the low doses exposure. The most conservative theory is that all radiation is harmful, and even small increments from background levels (i.e., 2-3 mSv) present additional risk. This view is called linear no threshold theory (LNT) and it is accepted as a regulatory conservative simple approach which guarantees safety. Risk is derived from the extrapolation of the measured effects of high levels of radiation. Opposite theory to LNT is hormesis which assumes that in fact small doses of radiation are helpful and they are improving our

  7. High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123 for Extraskeletal Ewing's Sarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomoya Sakabe

    2011-01-01

    Full Text Available Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123 contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment.

  8. Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Jahns, Jutta [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Anderegg, Ulf; Saalbach, Anja [Department for Dermatology, Venerology and Allergology, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Rosin, Britt; Patties, Ina; Glasow, Annegret [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany); Kamprad, Manja [Institute for Clinical Immunology and Transfusion Medicine, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Scholz, Markus [Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstr. 16-18, 04103 Leipzig (Germany); Hildebrandt, Guido, E-mail: Guido.Hildebrandt@uni-rostock.de [Department of Radiotherapy and Radiation Oncology, University of Rostock, Suedring 75, 18059 Rostock (Germany); Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig (Germany)

    2011-05-10

    Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

  9. 3D conditional generative adversarial networks for high-quality PET image estimation at low dose.

    Science.gov (United States)

    Wang, Yan; Yu, Biting; Wang, Lei; Zu, Chen; Lalush, David S; Lin, Weili; Wu, Xi; Zhou, Jiliu; Shen, Dinggang; Zhou, Luping

    2018-07-01

    Positron emission tomography (PET) is a widely used imaging modality, providing insight into both the biochemical and physiological processes of human body. Usually, a full dose radioactive tracer is required to obtain high-quality PET images for clinical needs. This inevitably raises concerns about potential health hazards. On the other hand, dose reduction may cause the increased noise in the reconstructed PET images, which impacts the image quality to a certain extent. In this paper, in order to reduce the radiation exposure while maintaining the high quality of PET images, we propose a novel method based on 3D conditional generative adversarial networks (3D c-GANs) to estimate the high-quality full-dose PET images from low-dose ones. Generative adversarial networks (GANs) include a generator network and a discriminator network which are trained simultaneously with the goal of one beating the other. Similar to GANs, in the proposed 3D c-GANs, we condition the model on an input low-dose PET image and generate a corresponding output full-dose PET image. Specifically, to render the same underlying information between the low-dose and full-dose PET images, a 3D U-net-like deep architecture which can combine hierarchical features by using skip connection is designed as the generator network to synthesize the full-dose image. In order to guarantee the synthesized PET image to be close to the real one, we take into account of the estimation error loss in addition to the discriminator feedback to train the generator network. Furthermore, a concatenated 3D c-GANs based progressive refinement scheme is also proposed to further improve the quality of estimated images. Validation was done on a real human brain dataset including both the normal subjects and the subjects diagnosed as mild cognitive impairment (MCI). Experimental results show that our proposed 3D c-GANs method outperforms the benchmark methods and achieves much better performance than the state

  10. Low dose coronary CT angiography with 256-slice helical CT

    International Nuclear Information System (INIS)

    Zhang Xiaodong; Tang Binghang; Li Fangyun

    2011-01-01

    of 573) in B, 96.1% (548 of 570) in C, and 85.7% (505/589) in D, with no significant difference for A vs C (Z= -1.351, P>0.05) and with significant differences for B vs D (Z=-2.236, P<0.05). Linear correlation analysis indicated a significant degradation of image quality with the increase of heart rate using SAS mode (Spearman correlation, r=0.577, P<0.01). ROC analysis established an upper HR threshold of 78 bpm for obtaining diagnostic image quality using SAS mode (AUC = 0.827, P<0.05). The average radiation dose in group A [(2.6±0.5) mSv] reduced 75% comparing with that in group C [(10.6±2.3) mSv], and the average radiation dose in group B [(4.0±0.7) mSv] reduced 69% comparing with that in group D [(13.0±1.4) mSv]. Conclusion: Using SAS mode to perform low-dose CCTA with 256-slice helical CT could keep the image quality and reduce radiation dose significantly. Our preliminary experience suggests a good promise of this technique which could be applied to a wider group of patients such as with higher heart rates. (authors)

  11. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  12. [Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

    Science.gov (United States)

    Kojima, Shuji

    2006-10-01

    We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

  13. Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients.

    Science.gov (United States)

    Dusilová-Sulková, Sylvie; Šafránek, Roman; Vávrová, Jaroslava; Horáček, Jiří; Pavlíková, Ladislava; Palička, Vladimír

    2015-01-01

    Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (pvitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels

  14. Ultra-low dose CT attenuation correction for PET/CT

    International Nuclear Information System (INIS)

    Xia Ting; Kinahan, Paul E; Alessio, Adam M; De Man, Bruno; Manjeshwar, Ravindra; Asma, Evren

    2012-01-01

    A challenge for positron emission tomography/computed tomography (PET/CT) quantitation is patient respiratory motion, which can cause an underestimation of lesion activity uptake and an overestimation of lesion volume. Several respiratory motion correction methods benefit from longer duration CT scans that are phase matched with PET scans. However, even with the currently available, lowest dose CT techniques, extended duration cine CT scans impart a substantially high radiation dose. This study evaluates methods designed to reduce CT radiation dose in PET/CT scanning. We investigated selected combinations of dose reduced acquisition and noise suppression methods that take advantage of the reduced requirement of CT for PET attenuation correction (AC). These include reducing CT tube current, optimizing CT tube voltage, adding filtration, CT sinogram smoothing and clipping. We explored the impact of these methods on PET quantitation via simulations on different digital phantoms. CT tube current can be reduced much lower for AC than that in low dose CT protocols. Spectra that are higher energy and narrower are generally more dose efficient with respect to PET image quality. Sinogram smoothing could be used to compensate for the increased noise and artifacts at radiation dose reduced CT images, which allows for a further reduction of CT dose with no penalty for PET image quantitation. When CT is not used for diagnostic and anatomical localization purposes, we showed that ultra-low dose CT for PET/CT is feasible. The significant dose reduction strategies proposed here could enable respiratory motion compensation methods that require extended duration CT scans and reduce radiation exposure in general for all PET/CT imaging. (paper)

  15. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells

    International Nuclear Information System (INIS)

    Weng, Yu-I; Hsu, Pei-Yin; Liyanarachchi, Sandya; Liu, Joseph; Deatherage, Daniel E.; Huang Yiwen; Zuo Tao; Rodriguez, Benjamin; Lin, Ching-Hung; Cheng, Ann-Lii; Huang, Tim H.-M.

    2010-01-01

    Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ERα signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ERα was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ERα-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ERα-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells.

  16. Ultra-low dose CT attenuation correction for PET/CT

    Science.gov (United States)

    Xia, Ting; Alessio, Adam M.; De Man, Bruno; Manjeshwar, Ravindra; Asma, Evren; Kinahan, Paul E.

    2012-01-01

    A challenge for PET/CT quantitation is patient respiratory motion, which can cause an underestimation of lesion activity uptake and an overestimation of lesion volume. Several respiratory motion correction methods benefit from longer duration CT scans that are phase matched with PET scans. However, even with the currently-available, lowest dose CT techniques, extended duration CINE CT scans impart a substantially high radiation dose. This study evaluates methods designed to reduce CT radiation dose in PET/CT scanning. Methods We investigated selected combinations of dose reduced acquisition and noise suppression methods that take advantage of the reduced requirement of CT for PET attenuation correction (AC). These include reducing CT tube current, optimizing CT tube voltage, adding filtration, CT sinogram smoothing and clipping. We explored the impact of these methods on PET quantitation via simulations on different digital phantoms. Results CT tube current can be reduced much lower for AC than that in low dose CT protocols. Spectra that are higher energy and narrower are generally more dose efficient with respect to PET image quality. Sinogram smoothing could be used to compensate for the increased noise and artifacts at radiation dose reduced CT images, which allows for a further reduction of CT dose with no penalty for PET image quantitation. Conclusion When CT is not used for diagnostic and anatomical localization purposes, we showed that ultra-low dose CT for PET/CT is feasible. The significant dose reduction strategies proposed here could enable respiratory motion compensation methods that require extended duration CT scans and reduce radiation exposure in general for all PET/CT imaging. PMID:22156174

  17. China National Lung Cancer Screening Guideline with Low-dose Computed 
Tomography (2018 version

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2018-02-01

    . Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.

  18. [China National Lung Cancer Screening Guideline with Low-dose Computed 
Tomography (2018 version)].

    Science.gov (United States)

    Zhou, Qinghua; Fan, Yaguang; Wang, Ying; Qiao, Youlin; Wang, Guiqi; Huang, Yunchao; Wang, Xinyun; Wu, Ning; Zhang, Guozheng; Zheng, Xiangpeng; Bu, Hong; Li, Yin; Wei, Sen; Chen, Liang'an; Hu, Chengping; Shi, Yuankai; Sun, Yan

    2018-02-20

    Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice. The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is

  19. Revisiting Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Cameron, E-mail: cameronh@stanford.edu [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Young, James; Navi, Daniel [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Riaz, Nadeem [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States); Lingala, Bharathi; Kim, Youn [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Hoppe, Richard [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States)

    2011-11-15

    Purpose: Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile. Methods and Materials: One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded. Results: Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose. Conclusions: OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose ({>=} 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

  20. Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

    International Nuclear Information System (INIS)

    Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young

    2017-01-01

    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.

  1. 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.

  2. The biological effects of low doses of radiation: medical, biological and ecological aspects

    International Nuclear Information System (INIS)

    Gun-Aajav, T.; Ajnai, L.; Manlaijav, G.

    2007-01-01

    Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

  3. Modeling low-dose-rate effects in irradiated bipolar-base oxides

    International Nuclear Information System (INIS)

    Graves, R.J.; Cirba, C.R.; Schrimpf, R.D.; Milanowski, R.J.; Saigne, F.; Michez, A.; Fleetwood, D.M.; Witczak, S.C.

    1997-02-01

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in BJTs. Simulations show that space charge limited transport is partially responsible for the low-dose-rate enhancement

  4. Low-dose radiation induces drosophila innate immunity through toll pathway activation

    International Nuclear Information System (INIS)

    Seong, Ki Moon; Kim, Cha Soon; Lee, Byung-Sub; Nam, Seon Young; Yang, Kwang Hee; Kim, Ji-Young; Jin, Young-Woo; Park, Joong-Jean; Min, Kyung-Jin

    2012-01-01

    Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and N-terminal kinase (JNK). These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. (author)

  5. 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.

  6. Role of Immunomodulators in Tumor Regression in Mice Exposed to Fractionated Low Dose of Gamma Radiation

    International Nuclear Information System (INIS)

    Rokaya Elsayed Maaroaf Elsayed

    2015-01-01

    Immunotherapy is one of the most promising approaches of cancer treatment. The present study was designed to examine the role of irradiated tumor cell lysate vaccine, IFNα-2b and low dose of gamma irradiation as immunomodulators either alone or combined in tumor regression. Ehrlich ascite carcinoma (EAC) cells and 9 groups of female mice were used. Mice were immunized intramuscularly by tumor cell lysate vaccine one time/week for 3 weeks in the right thigh of mice. After two weeks from last immunization, all mice were challenged with normal viable EAC cells at count of 2.5 ×10 6 /mouse in the opposite left thigh for Ehrlich carcinoma (EC) production. Mice were subcutaneously injected with 10.000 units of IFNα-2b 3 times/week for 4 weeks and others were exposed to fractionated dose of γ- radiation (0.5 Gy/day x 4, day after day). Tumor size, serum tumor markers (TNF-α and CEA), tumor DNA fragmentation and Caspase-3 were evaluated. Oxidative stress (MDA and NO) markers and antioxidants (GSH, GPX and SOD) were determined in spleen and tumor tissues. Histopathological examinations, apoptosis and necrosis in spleen and tumor tissues were also examined. The results revealed significant inhibition in tumor size throughout the observation period either for treatments with vaccine or IFNα-2b either alone or combined with γ-irradiation. DNA fragmentation and Caspase-3 enzyme activities were significantly elevated in immunized mice as compared with EC group along with diminished tumor size while, tumor markers were significantly decreased. MDA and NO were significantly increased in tumor tissue.while, tumor GSH content, GPX and SOD activities were significantly decreased. Combined treatments of female mice bearing EC with IFN-α-2b, tumor cell lysate vaccine and low dose of γ-radiation cause a highly significant decrease in serum TNF-α and CEA levels, increase in Cas-3 activity, no DNA fragmentation, significant increase in MDA, decrease in SOD activity and decreased

  7. Assessment of low-dose radiotoxicity in microorganisms and higher organisms

    International Nuclear Information System (INIS)

    Obeid, Muhammad Hassan

    2016-01-01

    This work was dedicated to quantify and distinguish the radio- and chemitoxic effects of environmentally relevant low doses of uranium on the metabolism of microorganisms and multicellular organisms by a modern and highly sensitive microcalorimetry. In such low-dose regime, lethality is low or absent. Therefore, quantitative assays based on survival curves cannot be employed, particularly for multicellular organisms. Even in the case of microbial growth, where individual cells may be killed by particle radiation, classical toxicity assessments based on colony counting are not only extremely time-consuming but also highly error-prone. Therefore, measuring the metabolic activity of the organism under such kinds of conditions would give an extremely valuable quantitative measure of viability that is based on life cell monitoring, rather than determining lethality at higher doses and extrapolating it to the low dose regime. The basic concept is simple as it relies on the metabolic heat produced by an organism during development, growth or replication as an inevitable byproduct of all biochemical processes. A metabolic effect in this concept is defined as a change in heat production over time in the presence of a stressor, such as a heavy metal. This approach appeared to be particular versatile for the low dose regime. Thus, the thesis attempted in this case to measure the enthalpy production of a bacterial population as a whole to derive novel toxicity concepts. In the following chapters, an introduction about the properties of ionizing radiation will be briefly presented, in addition to a review about the isothermal calorimetry and its application in studying the bacterial growth. Later in chapter 2, the effect of uranium on the metabolic activity of three different bacterial strains isolated form a uranium mining waste pile together with a reference strain that is genetically related to them will be investigated. Due to the lack of published dedicated calibration

  8. Assessment of low-dose radiotoxicity in microorganisms and higher organisms

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, Muhammad Hassan

    2016-01-11

    This work was dedicated to quantify and distinguish the radio- and chemitoxic effects of environmentally relevant low doses of uranium on the metabolism of microorganisms and multicellular organisms by a modern and highly sensitive microcalorimetry. In such low-dose regime, lethality is low or absent. Therefore, quantitative assays based on survival curves cannot be employed, particularly for multicellular organisms. Even in the case of microbial growth, where individual cells may be killed by particle radiation, classical toxicity assessments based on colony counting are not only extremely time-consuming but also highly error-prone. Therefore, measuring the metabolic activity of the organism under such kinds of conditions would give an extremely valuable quantitative measure of viability that is based on life cell monitoring, rather than determining lethality at higher doses and extrapolating it to the low dose regime. The basic concept is simple as it relies on the metabolic heat produced by an organism during development, growth or replication as an inevitable byproduct of all biochemical processes. A metabolic effect in this concept is defined as a change in heat production over time in the presence of a stressor, such as a heavy metal. This approach appeared to be particular versatile for the low dose regime. Thus, the thesis attempted in this case to measure the enthalpy production of a bacterial population as a whole to derive novel toxicity concepts. In the following chapters, an introduction about the properties of ionizing radiation will be briefly presented, in addition to a review about the isothermal calorimetry and its application in studying the bacterial growth. Later in chapter 2, the effect of uranium on the metabolic activity of three different bacterial strains isolated form a uranium mining waste pile together with a reference strain that is genetically related to them will be investigated. Due to the lack of published dedicated calibration

  9. Study of interaction of low doses of ionizing radiation with selected pesticides on Artemia franciscana

    Directory of Open Access Journals (Sweden)

    Michaela Špalková

    2015-01-01

    Full Text Available The aim of our study was to observe the effect of low doses of ionizing radiation, azoxystrobin and glyphosate separately as well as in their mutual combinations on the lethality of Artemia franciscana. Increasing intensity of agricultural production leads to continual exposure of animals to pesticide residues. Animals could be exposed to these negative factors in case of possible nuclear accident. A total of 1000 nauplia, randomly placed in 20 groups (1 control and 19 experimental groups, were irradiated with gamma rays (0, 20, 30, 40 or 50 Gy and were kept in solution of standardized sea water and standardized sea water with addition of pesticides (azoxystrobin at a concentration of 0.0001 g·l-1 and glyphosate at a concentration of 0.5 g·l-1 individually or in combination. A significant increase of lethality was observed after 48, 72 and 96 h of exposure to only azoxystrobin, but also in the group exposed to the combined effect of azoxystrobin and glyphosate at all time intervals. On the other hand, a significant decrease of lethality was observed in those groups exposed to ionizing radiation even at the dose of 30 Gy at all time intervals compared to non-irradiated groups. These results confirm the toxicity of azoxystrobin to aquatic organisms; non-toxicity of glyphosate to crustaceans and support the theory of radiation hormesis at the level of 30 Gy radiation dose.

  10. 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, Annamaria; 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; 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, 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; Sing Leung, Po; 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; Abd Hamid, Roslida; 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

    2015-06-01

    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. © The Author 2015. Published by Oxford University Press.

  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. A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea

    Directory of Open Access Journals (Sweden)

    Renan B. Domingues

    2009-12-01

    Full Text Available Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a propranolol, at a dose of 40 mg per day, (b nortriptyline, at a dose of 20 mg per day, and (c the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a popranolol, na dose de 40 mg por dia, (b nortriptilina, na dose de 20 mg por dia e (c combinação destas duas drogas nestas dosagens. Os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. O período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. Os

  13. Gynecological brachytherapy - from low-dose-rate to high-tech. Gynaekologische Brachytherapie - von Low-dose-rate zu High-tech

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, T. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Christen, N. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Alheit, H.D. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany))

    1993-03-01

    The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects - scored after EORT/RTOG criteria - showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiolgical point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid reppopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors. (orig.)

  14. DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy

    International Nuclear Information System (INIS)

    Grishina, Olga; Schmoor, Claudia; Döhner, Konstanze; Hackanson, Björn; Lubrich, Beate; May, Annette M.; Cieslik, Caroline; Müller, Michael J.; Lübbert, Michael

    2015-01-01

    Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of decitabine (DAC) in the European Union (EU) in 2012 for the treatment of patients with AML ≥65 years marks the potential for hypomethylating agents in elderly AML. Nevertheless the situation is dissatisfactory and the quest for novel treatment approaches, including combination epigenetic therapy is actively ongoing. The given randomized trial should be helpful in investigating the question whether combinations of DAC with the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and/or all-trans retinoic acid (ATRA), which in vitro show a very promising synergism, are superior to the DAC monotherapy. The accompanying translational research project will contribute to find surrogate molecular end points for drug efficacy and better tailor epigenetic therapy. An additional aim of the study is to investigate the prognostic value of geriatric assessments for elderly AML patients treated non-intensively. DECIDER is a prospective, randomized, observer blind, parallel group, multicenter, Phase II study with a 2x2 factorial design. The primary endpoint is objective best overall response (complete remission (CR) and partial remission (PR)). The target population is AML patients aged 60 years or older and unfit for standard induction chemotherapy. Patients are randomized to one of the four treatment groups: DAC alone or in combination with VPA or ATRA or with both add-on drugs. One interim safety analysis was planned and carried out with the objective to stop early one or more of the treatment arms in case of an unacceptable death rate. This analysis showed that in all treatment arms the critical stopping rule was not reached. No important safety issues were observed. The Data Monitoring Committee (DMC) recommended continuing the study as planned. The first patient was included in December 2011. A total of 189 out of 200 planned patients were randomized

  15. Irradiation preservation study on Beijing roast duck by low dose

    Energy Technology Data Exchange (ETDEWEB)

    Weiguo, Wang; Yongbao, Gu; Fengmei, Li [Beijing Normal Univ., BJ (China). Inst. of Low Energy Nuclear Physics; and others

    1989-02-01

    The irradiation technique combined with freezing has been used to control the microorganism in Beijing Roast Duck. Cobal-60 was chosen as {gamma}-ray source. The absorbed dose was 2 kGy on an average. After irrdiation, the microbe counts have reached the tolerable. Compared with untreated ducks, the irradiated ones showed no remarkable change in nutrition, chemistry, vitamin etc. It has been proved through test that the irradiated frozen Beijing Roast Duck is wholesome.

  16. Irradiation preservation study on Beijing roast duck by low dose

    International Nuclear Information System (INIS)

    Wang Weiguo; Gu Yongbao; Li Fengmei

    1989-01-01

    The irradiation technique combined with freezing has been used to control the microorganism in Beijing Roast Duck. Cobal-60 was chosen as γ-ray source. The absorbed dose was 2 kGy on an average. After irrdiation, the microbe counts have reached the tolerable. Compared with untreated ducks, the irradiated ones showed no remarkable change in nutrition, chemistry, vitamin etc. It has been proved through test that the irradiated frozen Beijing Roast Duck is wholesome

  17. Sample preparation method for the combined extraction of ethyl glucuronide and drugs of abuse in hair.

    Science.gov (United States)

    Meier, Ulf; Briellmann, Thomas; Scheurer, Eva; Dussy, Franz

    2018-04-01

    Often in hair analysis, a small hair sample is available while the analysis of a multitude of structurally diverse substances with different concentration ranges is demanded. The analysis of the different substances often requires different sample preparation methods, increasing the amount of required hair sample. When segmental hair analysis is necessary, the amount of hair sample needed is further increased. Therefore, the required sample amount for a full analysis can quickly exceed what is available. To combat this problem, a method for the combined hair sample preparation using a single extraction procedure for analysis of ethyl glucuronide with liquid chromatography-multistage fragmentation mass spectrometry/multiple reaction monitoring (LC-MS 3 /MRM) and common drugs of abuse with LC-MRM was developed. The combined sample preparation is achieved by separating ethyl glucuronide from the drugs of abuse into separate extracts by fractionation in the solid-phase extraction step during sample clean-up. A full validation for all substances for the parameters selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, and recovery was successfully completed. The following drugs of abuse were included in the method: Amphetamine; methamphetamine; 3,4-methylenedioxy-N-methylamphetamine (MDMA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxy-N-ethylamphetamine (MDE); morphine; 6-monoacetylmorphine; codeine; acetylcodeine; cocaine; benzoylecgonine; norcocaine; cocaethylene; methadone; 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and methylphenidate. In conclusion, as only 1 sample preparation is needed with 1 aliquot of hair, the presented sample preparation allows an optimal analysis of both ethyl glucuronide and of the drugs of abuse, even when the sample amount is a limiting factor. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

    Science.gov (United States)

    Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

    2009-08-01

    The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

  19. Monte Carlo investigation of the low-dose envelope from scanned proton pencil beams

    International Nuclear Information System (INIS)

    Sawakuchi, Gabriel O; Titt, Uwe; Mirkovic, Dragan; Ciangaru, George; Zhu, X Ronald; Sahoo, Narayan; Gillin, Michael T; Mohan, Radhe

    2010-01-01

    Scanned proton pencil beams carry a low-dose envelope that extends several centimeters from the individual beam's central axis. Thus, the total delivered dose depends on the size of the target volume and the corresponding number and intensity of beams necessary to cover the target volume uniformly. This dependence must be considered in dose calculation algorithms used by treatment planning systems. In this work, we investigated the sources of particles contributing to the low-dose envelope using the Monte Carlo technique. We used a validated model of our institution's scanning beam line to determine the contributions to the low-dose envelope from secondary particles created in a water phantom and particles scattered in beam line components. Our results suggested that, for high-energy beams, secondary particles produced by nuclear interactions in the water phantom are the major contributors to the low-dose envelope. For low-energy beams, the low-dose envelope is dominated by particles undergoing multiple Coulomb scattering in the beam line components and water phantom. Clearly, in the latter situation, the low-dose envelope depends directly on beam line design features. Finally, we investigated the dosimetric consequences of the low-dose envelope. Our results showed that if not modeled properly the low-dose envelope may cause clinically relevant dose disturbance in the target volume. This work suggested that this low-dose envelope is beam line specific for low-energy beams, should be thoroughly experimentally characterized and validated during commissioning of the treatment planning system, and therefore is of great concern for accurate delivery of proton scanning beam doses.

  20. Low Dose Sarin Leads To Murine Cardiac Dysfunction

    Science.gov (United States)

    2010-03-01

    hypoxia resulting from bronco -constriction also affects the cardiovascular system by reinforcing sympathetic tone, while ACh induced epinephrine...3000 4000 5000 6000 7000 8000 Septum LV Wall Total LV Ca rd io m yo cy te Si ze (P ix el s/ nu cl ei ) Control 0.4 LD50 0.5 LD50 * pɘ.05 vs... el s/ nu cl ei ) Control Sarin (Combined Groups) * pɘ.05 vs. control ** pɘ.01 vs. control † pɘ.001 vs. control 59 Results of Collagen

  1. Low-dose exposure to Veratrum album in children causes mild effects--a case series.

    Science.gov (United States)

    Rauber-Lüthy, Christine; Halbsguth, Ulrike; Kupferschmidt, Hugo; König, Naoko; Mégevand, Chloé; Zihlmann, Karin; Ceschi, Alessandro

    2010-03-01

    White or false hellebore (Veratrum album) has a toxicological relevance because of the potential for misidentification of this plant as yellow gentian (Gentiana lutea). We report a retrospective case series of 11 children (8-12 years) with accidental intake of V. album at a youth camp where they had collected herbs for preparing fresh herb tea. Two children (18%) remained asymptomatic. Nine (82%) developed mild gastrointestinal symptoms, six (55%) presented neurological symptoms, and three (27%) showed bradycardia. All children recovered completely within 10 h of ingestion. The plant was identified at the emergency department; however, detection of veratridine and cevadine by means of high-performance liquid chromatography-Mass spectrometry from the blood of the child with the most severe symptoms was negative (limit 0.01 ng/mL). Veratrum species contain more than 200 different alkaloids, which are the principal toxins and are responsible for most clinical symptoms. There are likely multiple mechanisms of toxicity and some of them are only partially understood. The opening of voltage-gated sodium channels is probably one of the most relevant pathophysiological mechanisms. Veratrum album intoxication in children demonstrated the same clinical course as observed in adults. Accidental ingestion of a low dose of the plant had a favorable outcome with supportive care.

  2. Effect of continuous low-dose γ-irradiation on rat Sertoli cell function

    International Nuclear Information System (INIS)

    Kamtchouing, P.; Papadopoulos, V.; Drosdowsky, M.A.; Carreau, S.; Pinon-Lataillade, G.; Maas, J.; Guillaumin, J.M.; Bardos, P.; Perreau, C.; Hochereau de Reviers, M.T.

    1988-01-01

    Continuous low-dose γ-irradiation of mature rats induced a progressive degeneration of the germ cells. Blood FSH increased by 127, 176 and 214%, respectively, after 55, 70 and 85 days of treatment when compared to FSH levels in control rats (8.50 ± 0.60 ng/ml); conversely, serum LH and testosterone levels were unchanged. The Sertoli cell function was affected by the treatment from 70 days on, as attested by androgen binding protein (ABP) and transferrin secretions which diminished 35-40%. Serum ABP levels were not altered, whatever the duration of irradiation, even though epididymal ABP contents (as well as concentrations) diminished 34-60% when compared to those of the controls. Moreover, in purified Leydig cells, LH-stimulated intracellular cAMP levels, which were decreased by seminiferous tubule medium (STM) from control rats, were enhanced in presence of STM from treated animals. Testosterone output was stimulated 9-fold in presence of oLH and further increased (46-76%) from stages XIV-V by STM prepared from control and irradiated rats, respectively. After 85 days the STM effects on both cAMP and testosterone syntheses were zero. These results demonstrate a probable alteration of Sertoli cell function after irradiation, but also a role of the germ cells in the regulation of the synthesis of ABP, transferrin and Sertoli cell paracrine factors

  3. The use of combined radiation methods for decreasing the bacterial dissemination of enzyme preparations

    International Nuclear Information System (INIS)

    Samojlenko, I.I.; Fedotov, N.S.; Tumanyan, M.A.; Korolev, N.I.

    1984-01-01

    A study was made on possibility of using ionizing radiation in combination with alternative magnetic field (AMF) and heating for decreasing the bacterial dissemination of proteolytic enzymes. Papain, trypsin, chymotrypsin and amylorysin (the preparation possessing proteolytic and amylolytic activities) were subjected to gamma irradiation at 10-25 kGy dose range, the effect of AMF with 750 oe and heating at 50 deg during 60 min. Model tests conducted with the use of Escherichia Coli cells and Bacillus anthracoides spores showed that survival rate of bacteria irradiated in protective medium was lower in the case of combined magnetoradiation and thermoradiation effect. The use of 10 kGy dose of ionizing radiation in combination with treatment in alternative magnetic field or with heating provided the required decrease of dissemination of irradiated enzyme samples with complete conservation of proteolytic activity by them

  4. Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis

    NARCIS (Netherlands)

    Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

    2018-01-01

    Objective: To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing

  5. Direct action of low doses of radiation of neurons

    International Nuclear Information System (INIS)

    Peimer, S.I.; Dudkin, A.O.; Sverdlov, A.G.

    1986-01-01

    The authors experiment with new technology of surviving mammalian brain sections for the detection of the direct action of ionizing radiation on the functioning neurons of mammals. The authors selected the rat hippocampus as the object of investigation. Sections of the hippocampus were prepared according to standard procedure, 0.3 mm thick, and incubated for several hours under the following conditions: temperature 35.5 0 C, rate of perfusion 2-3 ml/min, rate of delivery of a mixture of oxygen (95%), and carbon monoxide (5%), in the perfusion solution 35 ml/min. Composition of solution (mM): NaCl 124, KCl 5, CACl 2 2.4, MgSO 4 1.3, NaHCO 3 26, glucose 10; pH 7.4. In an individual series of experiments, calcium was not added to the solution, but an excess of magnesium ions was introduced up to 2.6 mM. Extracellular takeoffs were performed with glass microelectrodes. For irradiation, the authors used sources of x-rays and gamma radiation. In the 5-DI x-ray apparatus, the working voltage and current on the tube were 50 quanta and 8 mA, respectively; there were no filters. Gamma irradiation was performed using ampuls with the radionuclide cesium-137 (IGI-C-3 type), which can be delivered on a holder directly to the section for 1 min

  6. Enhanced low dose rate radiation effect test on typical bipolar devices

    International Nuclear Information System (INIS)

    Liu Minbo; Chen Wei; Yao Zhibin; He Baoping; Huang Shaoyan; Sheng Jiangkun; Xiao Zhigang; Wang Zujun

    2014-01-01

    Two types of bipolar transistors and nine types bipolar integrated circuit were selected in the irradiation experiment at different "6"0Co γ dose rate. The base current of bipolar transistor and input bias current of amplifier and comparator was measured, low dose enhance factor of test device was obtained. The results show that bipolar device have enhanced low dose rate sensitivity, enhancement factor of bipolar integrated circuit was bigger than that of transistor, and enhanced low dose rate sensitivity greatly varied with different structure and process of bipolar device. (authors)

  7. Low-dose radiation attenuates chemical mutagenesis in vivo. Cross adaptation

    International Nuclear Information System (INIS)

    Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

    2009-01-01

    The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea. (author)

  8. Better management of wheat allergy using a very low-dose food challenge: A retrospective study.

    Science.gov (United States)

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

    2016-01-01

    Low-dose reactive wheat-allergic children are at a high risk of a positive oral food challenge (OFC). The present study aimed to evaluate whether the results of a very low-dose (VL) OFC would contribute to better wheat allergy management in this population. We retrospectively reviewed wheat-allergic subjects who underwent a VL OFC with 2 g of udon noodles (equivalent to 53 mg of wheat protein) and had a previous allergic reaction to management of some low-dose reactive wheat-allergic children from complete avoidance to partial wheat intake. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  9. 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.

  10. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  11. Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

    International Nuclear Information System (INIS)

    Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

    2007-01-01

    To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

  12. Proceedings of the 8. LOWRAD: International conference on the effects of low doses and very low doses of ionizing radiation on human health and biotopes

    International Nuclear Information System (INIS)

    2009-01-01

    Theoretical and experimental papers are presented in these proceedings covering the following subjects: radiation protection, dosimetry, radiation dosimetry, cells, technetium, plutonium, uranium, thorium, low dose irradiation, radiation doses, cesium, radiation chemistry, nuclear medicine, safety and occupational exposure, neoplasm, cytology and radioisotopes

  13. A systematic review of Bisphenol A "low dose" studies in the context of human exposure: a case for establishing standards for reporting "low-dose" effects of chemicals.

    Science.gov (United States)

    Teeguarden, Justin G; Hanson-Drury, Sesha

    2013-12-01

    Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed industrialized societies. Structural features similar to estrogen confer the ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in the group of environmental pollutants called endocrine disruptors. References by scientists, the media, political entities, and non-governmental organizations to many toxicity studies as "low dose" has led to the belief that exposure levels in these studies are similar to humans, implying that BPA is toxic to humans at current exposures. Through systematic, objective comparison of our current, and a previous compilation of the "low-dose" literature to multiple estimates of human external and internal exposure levels, we found that the "low-dose" moniker describes exposures covering 8-12 orders of magnitude, the majority (91-99% of exposures) being greater than the upper bound of human exposure in the general infant, child and adult U.S. Population. "low dose" is therefore a descriptor without specific meaning regarding human exposure. Where human exposure data are available, for BPA and other environmental chemicals, reference to toxicity study exposures by direct comparison to human exposure would be more informative, more objective, and less susceptible to misunderstanding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Effects of low-dose fractionated external irradiation on metabolic and structural characteristics of rat thyroid

    Energy Technology Data Exchange (ETDEWEB)

    Nadolnik, L.; Niatsetskaya, Z. [Institute of Biochemistry, National Academy of Sciences of Belarus, Grodno (Belarus)

    2006-07-01

    Full text of publication follows: The problem of thyroid radiosensitivity to the effect of low dose external ionizing irradiation presently seems to be the least studied, and the experimental findings - the most contradictory. The aim of the work was to study the effects of long-term low-dose fractionated irradiation on the iodide metabolism and structure of the thyroid. Female Wistar rats weighing 140-160 g were irradiated 20 times (5 times a week, for 4 weeks) using a 60 Co installation. The single absorbed doses were 0.1, 0.25 and 0.5 Gy and the total ones - 2.0, 5.0 and 10.0 Gy, respectively. The animals were decapitated after 1 day, 4 and 24 weeks following the last irradiation. The thyroid tissue was used to assay for thyro-peroxidase (T.P.O.) activity as well as total, protein -bound and free iodide concentrations. Microscopic and morphometric examination of histologic thyroid preparations was carried out. Blood was assayed for thyroxin (T4) and triiodothyronine (T3) concentrations. After a day following the irradiation, the thyroid showed a pronounced increase in the concentration of total iodide (30.0-54.4%) as well in that of free (32.1-60.8%) and protein-bound ones (24.4-37.4%). The most pronounced iodide concentration elevation was noted in the 0.1 -Gy animals, with thyroid T.P.O. activity being raised by 48.0%. Only the 0.5 Gy-group had 1.4-1.5-fold reduced thyroid hormone levels. Four weeks after the irradiation, studied parameters of irradiated rats were brought back to the control values, except for the 0.5 Gy-group. However, after 24-weeks, the 0.5-and 0.25- irradiated rats experienced a 12-20% thyroid weight elevation in comparison with the control. The thyroid of these animals demonstrated reduced contents of total and free iodide as well as T.P.O. activity by 24.5 and 34.8%. The 0.1 Gy-group had a 1.7-fold increased T.P.O. activity. The concentration of the thyroid hormones was maintained diminished only in the 0.5 Gy -irradiated group. However

  15. Use of hyaluronic acid preparations in the combination therapy of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yu. A. Olyunin

    2016-01-01

    Full Text Available The current recommendations for the pharmacotherapy of osteoarthritis (OA primarily focus on analgesics and main concern is with the use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs. Intraarticular injections of first of all hyaluronic acid (HA preparations that have proven to be effective in clinical practice are a promising treatment for OA. By taking into account the favorable safety profile of HA preparations, it may be suggested that these injections may be an acceptable alternative to NSAIDs or successfully used in combination with the latter. There have been recently the recommendations for the administration of HA preparations in OA treatment, which characterize the current practice of HA use for OA and had been prepared by a group of experts from 5 European countries. The experts consider that there is today rather solid evidence to demonstrate the efficacy of HA in mild and moderately severe knee OA; moreover, its effect is clinically significant in such patients. In the authors’ view, topical HA therapy should be a compulsory component of treatment for knee OA, since the alternative possibilities of therapy for this disease are limited. Although the optimal effect of HA is observed when it is applied in the early stage of OA, this treatment may be also useful in its late stage. HA should be regarded as an adjunct method that must be applied if surgery cannot be performed in these patients.

  16. Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

    Science.gov (United States)

    Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

    2017-05-01

    Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

  17. Priori mask guided image reconstruction (p-MGIR) for ultra-low dose cone-beam computed tomography

    Science.gov (United States)

    Park, Justin C.; Zhang, Hao; Chen, Yunmei; Fan, Qiyong; Kahler, Darren L.; Liu, Chihray; Lu, Bo

    2015-11-01

    Recently, the compressed sensing (CS) based iterative reconstruction method has received attention because of its ability to reconstruct cone beam computed tomography (CBCT) images with good quality using sparsely sampled or noisy projections, thus enabling dose reduction. However, some challenges remain. In particular, there is always a tradeoff between image resolution and noise/streak artifact reduction based on the amount of regularization weighting that is applied uniformly across the CBCT volume. The purpose of this study is to develop a novel low-dose CBCT reconstruction algorithm framework called priori mask guided image reconstruction (p-MGIR) that allows reconstruction of high-quality low-dose CBCT images while preserving the image resolution. In p-MGIR, the unknown CBCT volume was mathematically modeled as a combination of two regions: (1) where anatomical structures are complex, and (2) where intensities are relatively uniform. The priori mask, which is the key concept of the p-MGIR algorithm, was defined as the matrix that distinguishes between the two separate CBCT regions where the resolution needs to be preserved and where streak or noise needs to be suppressed. We then alternately updated each part of image by solving two sub-minimization problems iteratively, where one minimization was focused on preserving the edge information of the first part while the other concentrated on the removal of noise/artifacts from the latter part. To evaluate the performance of the p-MGIR algorithm, a numerical head-and-neck phantom, a Catphan 600 physical phantom, and a clinical head-and-neck cancer case were used for analysis. The results were compared with the standard Feldkamp-Davis-Kress as well as conventional CS-based algorithms. Examination of the p-MGIR algorithm showed that high-quality low-dose CBCT images can be reconstructed without compromising the image resolution. For both phantom and the patient cases, the p-MGIR is able to achieve a clinically

  18. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  19. The reduction of image noise and streak artifact in the thoracic inlet during low dose and ultra-low dose thoracic CT

    International Nuclear Information System (INIS)

    Paul, N S; Prezelj, E; Burey, P; Menezes, R J; Blobel, J; Ursani, A; Kashani, H; Siewerdsen, J H

    2010-01-01

    Increased pixel noise and streak artifact reduce CT image quality and limit the potential for radiation dose reduction during CT of the thoracic inlet. We propose to quantify the pixel noise of mediastinal structures in the thoracic inlet, during low-dose (LDCT) and ultralow-dose (uLDCT) thoracic CT, and assess the utility of new software (quantum denoising system and BOOST3D) in addressing these limitations. Twelve patients had LDCT (120 kV, 25 mAs) and uLDCT (120 kV, 10 mAs) images reconstructed initially using standard mediastinal and lung filters followed by the quantum denoising system (QDS) to reduce pixel noise and BOOST3D (B3D) software to correct photon starvation noise as follows: group 1 no QDS, no B3D; group 2 B3D alone; group 3 QDS alone and group 4 both QDS and B3D. Nine regions of interest (ROIs) were replicated on mediastinal anatomy in the thoracic inlet, for each patient resulting in 3456 data points to calculate pixel noise and attenuation. QDS reduced pixel noise by 18.4% (lung images) and 15.8% (mediastinal images) at 25 mAs. B3D reduced pixel noise by ∼8% in the posterior thorax and in combination there was a 35.5% reduction in effective radiation dose (E) for LDCT (1.63-1.05 mSv) in lung images and 32.2% (1.55-1.05 mSv) in mediastinal images. The same combination produced 20.7% reduction (0.53-0.42 mSv) in E for uLDCT, for lung images and 17.3% (0.51-0.42) for mediastinal images. This quantitative analysis of image quality confirms the utility of dedicated processing software in targeting image noise and streak artifact in thoracic LDCT and uLDCT images taken in the thoracic inlet. This processing software potentiates substantial reductions in radiation dose during thoracic LDCT and uLDCT.

  20. Sperm parameters in rats after low-dose irradiation of sex cells in male parents during two cycles of gametogenesis

    International Nuclear Information System (INIS)

    Karpenko, N.O.; Chub, N.N.; Brizgalova, G.A.

    2001-01-01

    Chronic combined (internal and external) irradiation in low doses (absorbed doses 0.4 - 3.6 cGy) during two cycles of gametogenesis results in defective stimulation of spermatogenesis in male rats and provokes genotoxic action. The offspring from fathers with 0.7 and 3.6 cGy irradiation have decreased viability and oligozoospermia in mature age. The offsprings from the father with 3.6 cGy have increased sensitivity to weak irradiation and react by increases oligozoospermia. The data are accord with the idea about more pronounced genetic radioresistance of premeiosis cells during gametogenesis

  1. Detection of carcinogenicity of low-dose radiation

    International Nuclear Information System (INIS)

    Yokoro, Kenjiro; Sumi, Chiyo; Hamada, Katsutomo

    1978-01-01

    Induction of mammary tumors in female, W/Fu strain rats which were irradiated using an experimental atomic pile--KUR was described. Thermal neutron of 0.025 eV on an average transmitted through a heavy water equipment was emitted into a uranium converter which consists of enriched uranium to atomic fission. This produces fission neutron of 2 MeV on an average, prompt γ-ray, and γ-ray which is emitted from atomic fission products. When a dose of 4.8 rem (2.4 + 2.4), 8.9 rem (4.8 + 4.1), or 19.5 rem (12.5 + 7.5) in the total of fission neutron and γ-ray was irradiated to rats, benign fibroadenoma occurred in one (4.8 rem) of 48 rats after 230 days of latency. When irradiation of the same amount of neutron and γ-ray was given to rats and, in addition, prolactin was given, breast tumor which consisted mainly of adeno carcinoma occurred in 17 of the 48 rats (about 35%). Combination of irradiation (even the least dose, 4.8 rem) and prolactin had a carcinogenetic effect. (Ueda, J.)

  2. Use of BEIR V and UNSCEAR 1988 in radiation risk assessment: Lifetime total cancer mortality risk estimates at low doses and low dose rates for low-LET radiation

    International Nuclear Information System (INIS)

    1992-12-01

    In November 1986, the Department of Defense (DoD) asked the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) to develop a coordinated Federal position on risk assessment for low levels of ionizing radiation. Since Federal risk assessment activities are based primarily on the scientific data and analyses in authoritative review documents prepared by groups like the National Academy of Sciences' Committee on the Biological Effects of Ionizing Radiation (BEIR), the National Council on Radiation Protection and Measurements (NCRP) and the United Nations' Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), DoD proposed that the CIRRPC Science Panel undertake the task of providing coordinated interagency positions on the use of information in the reports of such groups. The practice has been for individual Federal agencies to interpret and decide independently how to use the information provided in such reports. As a result of its deliberations, the Subpanel recommends two nominal risk estimates for lifetime total cancer mortality following whole-body exposure to low levels of low-LET ionizing radiation, one for the general population and one for the working-age population (see Section II). The recommended risk estimates reflect the general agreement of information in BEIR V and UNSCEAR 1988 for total cancer mortality. The Subpanel's risk estimates and associated statements are intended to meet the needs of the Federal agencies for: (a) values that are current; (b) values that are relevant to the low-dose and low dose-rate ionizing radiation exposures principally encountered in carrying out Federal responsibilities; (c) a statement of the change in the estimates of lifetime total cancer mortality relative to estimates in previous authoritative review documents; and (d) a practical statement on the scientific uncertainty associated with applying the lifetime total cancer mortality values at very low doses

  3. Synergistic Effects of Ad-Libitum Low-Dose Fructose Drinking and Low-Dose Streptozotocin Treatment in Wistar Rats: A Mild Model of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Asie Sadeghi

    2017-07-01

    Full Text Available To develop a convenient animal model of T2D by pretreatment with low-dose 10% w/v fructose (FRC solution followed by the injection of low doses of streptozotocin (STZ in Wistar rats. For this 8-week experimental study; rats were first fed a standard chow ad-libitum diet and either tap water (n=40 or 10% w/v FRC solution (n=40 for 4 weeks. Next, rats in each category were randomly allocated to 4 subgroups (n=10 each of low-dose STZ (25,35, and 45 mg/kg. The final mean fasting blood sugar (FBG of FRC+STZ45 (197±55.87 mg/dl were significantly higher than that of the STZ45 (P=0.015 and FRC (P=0.019 groups. FRC+STZ45 showed the highest insulin resistance demonstrated by insulin tolerance test [area under the curve (AUC of insulin tolerance test; P<0.05]. AUC was not significantly different between the STZ45 and non-STZ groups and between FRC and non-FRC fed groups. Furthermore, FBG levels did not differ between FRC and non-FRC groups. Body weight measurement showed that the FRC+STZ45 group had the lowest body weight compared to all other groups. Our data provide the evidence that FRC and STZ45 synergistically could induce hyperglycemia and insulin resistance in Wistar rats. Here we presented a feasible model for initial forms of T2D by employing pretreatment with low-dose FRC solution and treatment with low-dose STZ.

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

    International Nuclear Information System (INIS)

    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

  5. Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Xiao Dong

    1999-01-01

    The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

  6. Treatment of symptomatic splenomegaly with low doses of radiotherapy: Retrospective analysis and review of the literature

    Directory of Open Access Journals (Sweden)

    Carolina de la Pinta

    2017-09-01

    Conclusion: Low doses of radiation therapy for treatment of symptomatic splenomegaly were effective, with a low rate of side effects. Splenic pain and abdominal discomfort completely improved and cytopenias rised to secure levels.

  7. 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.

  8. Indications for suboptimal low-dose direct oral anticoagulants for non-valvular atrial fibrillation patients

    Directory of Open Access Journals (Sweden)

    Masahiko Umei, MD

    2017-10-01

    Conclusions: With good adherence, the clinical course associated with DOACs is comparatively good. In the future, suboptimal low-dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding.

  9. 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.)

  10. 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...

  11. 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.

  12. Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis.

    Science.gov (United States)

    Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

    2018-02-01

    To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment. Not applicable. Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment. We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model. The primary outcome was ongoing pregnancy rate (PR) per woman randomized. We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62-1.57, I 2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk

  13. Effects of low dose radiation on repair processes in human lymphocytes

    International Nuclear Information System (INIS)

    Tuschl, H.; Altmann, H.; Kovac, R.; Topaloglou, A.; Egg, D.; Guenther, R.

    1978-10-01

    DNA excision repair was investigated in lymphocytes of persons occupationally exposed to low dose radiation of 222 Rn. Autoradiographic studies of unscheduled DNA synthesis and measurement of 3 H-thymidine incorporation by repair replication into double stranded and single-strand containing DNA fractions obtained by BND cellulose chromatography seem to indicate a stimulatory effect of repeated low dose radiation on repair enzymes. (author)

  14. Low dose radiation exposure and atherosclerosis in ApoE{sup -/-} mice

    Energy Technology Data Exchange (ETDEWEB)

    Mitchel, R.E.J. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Hasu, M. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada); Bugden, M.; Wyatt, H. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Little, M. [Imperial Coll., Faculty of Medicine, St. Marys Campus, London (United Kingdom); Hildebrandt, G. [Univ. Hospital, Dept. of Radiotherapy, Rostock (Germany); Priest, N.D. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Whitman, S.C. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada)

    2010-07-01

    The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

  15. Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

    Science.gov (United States)

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

  16. Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation

    OpenAIRE

    Liu, Shu-Zheng

    2006-01-01

    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 p...

  17. Responses of epithelial cells to low and very low doses of low let radiation

    International Nuclear Information System (INIS)

    Mothersill, Carmel; Seymour, Colin

    2003-01-01

    Recent advances in our knowledge of the biological effects of low doses of ionizing radiation have shown unexpected phenomena. These vary in the endpoint used to detect them and in the dose range examined but all occur as high-frequency events in cell populations. They include: 1. a 'bystander effect' which can be demonstrated at low doses as a transferable.factor(s) causing radiobiological effects in unexposed cells, 2. an assortment of delayed effects' occurring in progeny of cells exposed to low doses, 3. Low-dose Hypersensitivity (HRS) and Increased radioresistance (IRR) which can collectively be demonstrated as a change in the dose-effect relationship, occurring around 0.5-1 Gy of low LET radiation and 4. adaptive responses where cells exposed to very low doses followed by higher doses, exhibit an induced relatively resistant response to the second dose. In all cases, the effect of very low doses is greater than would be predicted by extrapolation of high dose data and is inconsistent with conventional DNA break/repair-based radiobiology. In practical risk assessment terms, the relative importance of the effects are high at low doses where they dominate the response, and small at high doses. This paper reviews these assorted phenomena and in particular seeks to explore whether related or distinct mechanisms underlie these various effects Understanding the mechanistic basis of these phenomena may suggest new approaches to controlling death or survival sectoring at low radiation doses. The key question is whether these low dose phenomena necessitate a new approach to risk assessment. (author)

  18. The genetic effects induced by an irradiation in low doses at Drosophila melanogaster

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Taskaev, A.I.; Moskalev, A.A.; Shaposhnikov, M.V.

    2006-01-01

    The review generalizes the results obtained in researches of genetic radiation effects for Drosophila melanogaster from contamination regions near the Chernobylsk NPP. The results of laboratory investigations of low dose irradiation effects on genotype variability and lifetime of Drosophila are presented too. It supposed that the main effect of low dose irradiation is caused by the induced genetic instability against the background of which the realization of different-directed radiobiological reactions is possible [ru

  19. 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.

  20. Low dose radiation exposure and atherosclerosis in ApoE-/- mice

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M.; Hildebrandt, G.; Priest, N.D.; Whitman, S.C.

    2010-01-01

    The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

  1. 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.

  2. Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

    Science.gov (United States)

    Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

    2015-04-01

    Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

  3. Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

    Directory of Open Access Journals (Sweden)

    Keqiang Chen

    2015-04-01

    Full Text Available Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP. This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

  4. The risk of low doses of ionising radiation and the linear no threshold relationship debate

    International Nuclear Information System (INIS)

    Tubiana, M.; Masse, R.; Vathaire, F. de; Averbeck, D.; Aurengo, A.

    2007-01-01

    The ICRP and the B.E.I.R. VII reports recommend a linear no threshold (L.N.T.) relationship for the estimation of cancer excess risk induced by ionising radiations (IR), but the 2005 report of Medicine and Science French Academies concludes that it leads to overestimate of risk for low and very low doses. The bases of L.N.T. are challenged by recent biological and animal experimental studies which show that the defence against IR involves the cell microenvironment and the immunologic system. The defence mechanisms against low doses are different and comparatively more effective than for high doses. Cell death is predominant against low doses. DNA repairing is activated against high doses, in order to preserve tissue functions. These mechanisms provide for multicellular organisms an effective and low cost defence system. The differences between low and high doses defence mechanisms are obvious for alpha emitters which show several greys threshold effects. These differences result in an impairment of epidemiological studies which, for statistical power purpose, amalgamate high and low doses exposure data, since it would imply that cancer IR induction and defence mechanisms are similar in both cases. Low IR dose risk estimates should rely on specific epidemiological studies restricted to low dose exposures and taking precisely into account potential confounding factors. The preliminary synthesis of cohort studies for which low dose data (< 100 mSv) were available show no significant risk excess, neither for solid cancer nor for leukemias. (authors)

  5. ATM phosphorylation in HepG2 cells following continuous low dose-rate irradiation

    International Nuclear Information System (INIS)

    Mei Quelin; Du Duanming; Chen Zaizhong; Liu Pengcheng; Yang Jianyong; Li Yanhao

    2008-01-01

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells following a continuous low dose-rate irradiation. Methods: Cells were persistently exposed to low dose-rate (8.28 cGy/h) irradiation. Indirect immunofluorescence and Western blot were used to detect the expression of ATM phosphorylated proteins. Colony forming assay was used to observe the effect of a low dose-rate irradiation on HepG2 cell survival. Results: After 30 min of low dose-rate irradiation, the phosphorylation of ATM occurred. After 6 h persistent irradiation, the expression of ATM phosphorylated protein reached the peak value, then gradually decreased. After ATM phosphorylation was inhibited with Wortmannin, the surviving fraction of HepG2 cells was lower than that of the irradiation alone group at each time point (P<0.05). Conclusions: Continuous low dose-rate irradiation attenuated ATM phosphorylation, suggesting that continuous low dose-rate irradiation has a potential effect for increasing the radiosensitivity of HepG2 cells. (authors)

  6. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    International Nuclear Information System (INIS)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang; Wu Lijun

    2007-01-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of γ-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process ( G -methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy α-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose α-particle irradiation and nitric oxide generated by irradiation was also very important in this process

  7. Low doses of gamma radiation in the management of postharvest Lasiodiplodia theobromae in mangos

    Directory of Open Access Journals (Sweden)

    Alice Maria Gonçalves Santos

    2015-09-01

    Full Text Available The postharvest life of mango is limited by the development of pathogens, especially fungi that cause rot, among which stands out the Lasiodiplodia theobromae. Several control methods have been employed to minimize the damages caused by this fungus, chemical control can leave residues to man and nature; physical control by the use of gamma radiation in combination with modified atmosphere and cold storage. The use of gamma radiation helps to reduce the severity of the pathogen assist in the ripening process of fruits, even at low doses (0.25, 0.35 and 0.45 kGy chemical properties such as pH, soluble solids, acid ascorbic, titratable acidity and also the quality parameters of the pulp showed no damage that are ideal for trade and consumption of mangoes. This treatment can be extended for use in the management of diseases such as natural infections for penducular rot complex that has as one of L. theobroma pathogens involved.

  8. Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

    International Nuclear Information System (INIS)

    Miyamoto, Miyako; Sakamoto, Kiyohiko

    1987-01-01

    The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

  9. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

    Directory of Open Access Journals (Sweden)

    Ellebaek Eva

    2012-08-01

    Full Text Available Abstract Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL, in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625 including patients with metastatic melanoma, PS ≤1, age Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months, 2 patients had stable disease (4 and 5 months and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

  10. Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

    Science.gov (United States)

    Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Chen, Cheng; Zhou, Qiang; Yang, Liu

    2018-02-21

    The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone. This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score. The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p 0.05). The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

  11. Low-Dose Dextromethorphan, a NADPH Oxidase Inhibitor, Reduces Blood Pressure and Enhances Vascular Protection in Experimental Hypertension

    Science.gov (United States)

    Wu, Tao-Cheng; Chao, Chih-Yu; Lin, Shing-Jong; Chen, Jaw-Wen

    2012-01-01

    Background Vascular oxidative stress may be increased with age and aggravate endothelial dysfunction and vascular injury in hypertension. This study aimed to investigate the effects of dextromethorphan (DM), a NADPH oxidase inhibitor, either alone or in combination treatment, on blood pressure (BP) and vascular protection in aged spontaneous hypertensive rats (SHRs). Methodology/Principal Findings Eighteen-week-old WKY rats and SHRs were housed for 2 weeks. SHRs were randomly assigned to one of the 12 groups: untreated; DM monotherapy with 1, 5 or 25 mg/kg/day; amlodipine (AM, a calcium channel blocker) monotherapy with 1 or 5 mg/kg/day; and combination therapy of DM 1, 5 or 25 mg/kg/day with AM 1 or 5 mg/kg/day individually for 4 weeks. The in vitro effects of DM were also examined. In SHRs, AM monotherapy dose-dependently reduced arterial systolic BP. DM in various doses significantly and similarly reduced arterial systolic BP. Combination of DM with AM gave additive effects on BP reduction. DM, either alone or in combination with AM, improved aortic endothelial function indicated by ex vivo acetylcholine-induced relaxation. The combination of low-dose DM with AM gave most significant inhibition on aortic wall thickness in SHRs. Plasma total antioxidant status was significantly increased by all the therapies except for the combination of high-dose DM with high-dose AM. Serum nitrite and nitrate level was significantly reduced by AM but not by DM or the combination of DM with AM. Furthermore, in vitro treatment with DM reduced angiotensin II-induced reactive oxygen species and NADPH oxidase activation in human aortic endothelial cells. Conclusions/Significance Treatment of DM reduced BP and enhanced vascular protection probably by inhibiting vascular NADPH oxidase in aged hypertensive animals with or without AM treatment. It provides the potential rationale to a novel combination treatment with low-dose DM and AM in clinical hypertension. PMID:23049937

  12. Low-dose dextromethorphan, a NADPH oxidase inhibitor, reduces blood pressure and enhances vascular protection in experimental hypertension.

    Directory of Open Access Journals (Sweden)

    Tao-Cheng Wu

    Full Text Available BACKGROUND: Vascular oxidative stress may be increased with age and aggravate endothelial dysfunction and vascular injury in hypertension. This study aimed to investigate the effects of dextromethorphan (DM, a NADPH oxidase inhibitor, either alone or in combination treatment, on blood pressure (BP and vascular protection in aged spontaneous hypertensive rats (SHRs. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen-week-old WKY rats and SHRs were housed for 2 weeks. SHRs were randomly assigned to one of the 12 groups: untreated; DM monotherapy with 1, 5 or 25 mg/kg/day; amlodipine (AM, a calcium channel blocker monotherapy with 1 or 5 mg/kg/day; and combination therapy of DM 1, 5 or 25 mg/kg/day with AM 1 or 5 mg/kg/day individually for 4 weeks. The in vitro effects of DM were also examined. In SHRs, AM monotherapy dose-dependently reduced arterial systolic BP. DM in various doses significantly and similarly reduced arterial systolic BP. Combination of DM with AM gave additive effects on BP reduction. DM, either alone or in combination with AM, improved aortic endothelial function indicated by ex vivo acetylcholine-induced relaxation. The combination of low-dose DM with AM gave most significant inhibition on aortic wall thickness in SHRs. Plasma total antioxidant status was significantly increased by all the therapies except for the combination of high-dose DM with high-dose AM. Serum nitrite and nitrate level was significantly reduced by AM but not by DM or the combination of DM with AM. Furthermore, in vitro treatment with DM reduced angiotensin II-induced reactive oxygen species and NADPH oxidase activation in human aortic endothelial cells. CONCLUSIONS/SIGNIFICANCE: Treatment of DM reduced BP and enhanced vascular protection probably by inhibiting vascular NADPH oxidase in aged hypertensive animals with or without AM treatment. It provides the potential rationale to a novel combination treatment with low-dose DM and AM in clinical hypertension.

  13. Spectrotemporal CT data acquisition and reconstruction at low dose

    International Nuclear Information System (INIS)

    Clark, Darin P.; Badea, Cristian T.; Lee, Chang-Lung; Kirsch, David G.

    2015-01-01

    Purpose: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D + dual energy + time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. Methods: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction

  14. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

    Science.gov (United States)

    Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

    2016-10-01

    Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Complex mixtures: Relevance of combined exposure to substances at low dose levels

    NARCIS (Netherlands)

    Leeman, W.R.; Krul, L.; Houben, G.F.

    2013-01-01

    Upon analysis of chemically complex food matrices a forest of peaks is likely to be found. Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies. Recently, a safety assessment

  16. use of combined paracetamol and low dose ketamine in pain control

    African Journals Online (AJOL)

    Setting: The burns ward of Moi Teaching and Referral Hospital, a 750 bed capacity tertiary centre in Western ... Results: Of the Fifty nine patients who were recruited into the study, seventy percent of them were ... in a cylinder, self inflating bag for ventilation, face masks .... Behavioral Tool in Assessing Acute Pain in Critically.

  17. Experimental investigation of combined blastomogenic effect of chronic low-dose ionizing radiation and chemical carcinogen

    International Nuclear Information System (INIS)

    Poruba, G. M.

    2001-01-01

    Exposure of high-and low cancer lines of mice in the contaminated area of Cherikov district in Gomel Region (dose rate 380-400 mR/h) for 120 days caused intensification of urethane-induced carcinogenesis in the lung of the high-cancer mouse line and did not exert a modifying effect on urethane pulmonary carcinogenesis in low-cancer animals. The findings indicate to genetic determination of body sensitivity to a complex blastomogenic effect of the factors studied (authors)

  18. Low-dose extrapolation of radiation health risks: some implications of uncertainty for radiation protection at low doses.

    Science.gov (United States)

    Land, Charles E

    2009-11-01

    Ionizing radiation is a known and well-quantified human cancer risk factor, based on a remarkably consistent body of information from epidemiological studies of exposed populations. Typical examples of risk estimation include use of Japanese atomic bomb survivor data to estimate future risk from radiation-related cancer among American patients receiving multiple computed tomography scans, persons affected by radioactive fallout, or persons whose livelihoods involve some radiation exposure, such as x-ray technicians, interventional radiologists, or shipyard workers. Our estimates of radiation-related risk are uncertain, reflecting statistical variation and our imperfect understanding of crucial assumptions that must be made if we are to apply existing epidemiological data to particular situations. Fortunately, that uncertainty is also highly quantifiable, and can be presented concisely and transparently. Radiation protection is ultimately a political process that involves consent by stakeholders, a diverse group that includes people who might be expected to be risk-averse and concerned with plausible upper limits on risk (how bad could it be?), cost-averse and concerned with lower limits on risk (can you prove there is a nontrivial risk at current dose levels?), or combining both points of view. How radiation-related risk is viewed by individuals and population subgroups also depends very much on perception of related benefit, which might be (for example) medical, economic, altruistic, or nonexistent. The following presentation follows the lead of National Council on Radiation Protection and Measurements (NCRP) Commentary 14, NCRP Report 126, and later documents in treating radiation protection from the viewpoint of quantitative uncertainty analysis.

  19. 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....

  20. Dilute ferromagnetic semiconductors prepared by the combination of ion implantation with pulse laser melting

    International Nuclear Information System (INIS)

    Zhou, Shengqiang

    2015-01-01

    Combining semiconducting and ferromagnetic properties, dilute ferromagnetic semiconductors (DFS) have been under intensive investigation for more than two decades. Mn doped III–V compound semiconductors have been regarded as the prototype of DFS from both experimental and theoretic investigations. The magnetic properties of III–V:Mn can be controlled by manipulating free carriers via electrical gating, as for controlling the electrical properties in conventional semiconductors. However, the preparation of DFS presents a big challenge due to the low solubility of Mn in semiconductors. Ion implantation followed by pulsed laser melting (II-PLM) provides an alternative to the widely used low-temperature molecular beam epitaxy (LT-MBE) approach. Both ion implantation and pulsed-laser melting occur far enough from thermodynamic equilibrium conditions. Ion implantation introduces enough dopants and the subsequent laser pulse deposit energy in the near-surface region to drive a rapid liquid-phase epitaxial growth. Here, we review the experimental study on preparation of III–V:Mn using II-PLM. We start with a brief description about the development of DFS and the physics behind II-PLM. Then we show that ferromagnetic GaMnAs and InMnAs films can be prepared by II-PLM and they show the same characteristics of LT-MBE grown samples. Going beyond LT-MBE, II-PLM is successful to bring two new members, GaMnP and InMnP, into the family of III–V:Mn DFS. Both GaMnP and InMnP films show the signature of DFS and an insulating behavior. At the end, we summarize the work done for Ge:Mn and Si:Mn using II-PLM and present suggestions for future investigations. The remarkable advantage of II-PLM approach is its versatility. In general, II-PLM can be utilized to prepare supersaturated alloys with mismatched components. (topical review)

  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 total skin electron beam therapy for cutaneous lymphoma : Minimal risk of acute toxicities.

    Science.gov (United States)

    Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor

    2017-12-01

    Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T‑cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses.

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

    International Nuclear Information System (INIS)

    Xu, X.J.; Lou, F.L.; Zhang, M.M.; Pan, Z.M.; Zhang, L.

    2007-01-01

    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

  4. Incidental renal tumours on low-dose CT lung cancer screening exams.

    Science.gov (United States)

    Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

    2017-06-01

    Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

  5. Cancer and low dose responses in vivo: implications for radiation protection

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.

    2006-01-01

    Full text: Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be genetically cancer prone. Mice heterozygous for the Tp 53 gene are cancer prone, and their increased risk from high doses was not different from Tp 53 normal mice. However, in either Tp 53 normal or heterozygous mice, a single low dose of low LET radiation given at low dose rate protected against both spontaneous and radiation-induced cancer by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp 53 function) overall risk is reduced below that of unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish radiation weighting factors (Wr) used in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate

  6. Studies of health effects of low dose radiation and its application to medicare

    International Nuclear Information System (INIS)

    Yamaoka, Kiyonori; Ishida, Kenji; Iwasaki, Toshiyasu; Koana, Takao; Magae, Junji; Watanabe, Masami; Sakamoto, Kiyohiko

    2008-01-01

    The articles contain following 7 topics of low dose radiation effects. Studies of Health Effects of Low dose Radiation and Its Application to Medicare'', describes the indication of Rn therapy and investigations of its usefulness mechanism mainly in Misasa Spa, Okayama Pref. ''Challenges for the Paradigm Shift (CRIEPI Studies)'', introduces studies against the paradigm that radiation dose is linearly and proportionally hazardous. ''Studies of High Background Radiation Area (CRIEPI Studies)'', describes global HBRA studies on chromosome affection and effect of smoking in HBRA. ''Is the Radiation Effect on Man Proportional to Dose? (CRIEPI Studies)'', describes studies of immature sperm irradiated at low dose against Linear-Non-threshold Theory (LNT) hypothesis. ''Induction of Radiation Resistance by Low Dose Radiation and Assessment of Its Effect in Models of Human Diseases (CRIEPI Studies)'', explains the adoptive response in radiation effect, suppression of carcinogenesis and immune regulation by previous low dose radiation in the mouse, and improvement of diabetes in the db/db mouse. ''Modulation of Biological Effects of Low Dose Radiation: Adoptive Response, Bystander Effect, Genetic Instability and Radiation Hormesis'', summarizes findings of each item. ''Cancer Treatment with Low dose Radiation to the Whole Body'', describes basic studies in the mouse tumor in relation to suppression of carcinogenesis and metastasis, immune activation and treatment, and successful clinical studies in patients with ovary, colon cancers and malignant lymphoma where survival has been significantly improved: a base of recent European Organization for Research and Treatment of Cancer (EORTC) clinical trials. The mechanism is essentially based on immune activation of patients to cure the disease. (R.T.)

  7. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A.

    Science.gov (United States)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L; Linares, Victoria

    2016-01-18

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ((137)Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to (137)Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to (137)Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A

    International Nuclear Information System (INIS)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L.; Linares, Victoria

    2016-01-01

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ( 137 Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to 137 Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to 137 Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA.

  9. Panel discussion on health effects of low-dose ionizing radiation. Scientific findings and non-threshold hypothesis

    International Nuclear Information System (INIS)

    1995-06-01

    This is a record of a panel discussion in the IAEA Interregional Training Course. In current radiation work, protection measures are taken on the assumption that any amount of radiation, however small, entails a risk of deleterious effects. This so-called non-threshold assumption of radiation effects, on the one hand, creates public distrust of radiation use. However, because the health effects of low-dose ionizing radiation are difficult to verify, wide views ranging from the non-threshold hypothesis to one which sees small amounts of radiation as rather useful and necessary are presented. In this panel discussion, how the health effects of low-dose ionizing radiation should be considered from the standpoint of radiation protection was discussed. Panelists included such eminent scientists as Dr. Sugahara and Dr. Okada, who are deeply interested in this field and are playing leading parts in radiobiology research in Japan, and Dr. Stather, deputy Director of NRPB, UK, who, in UNSCEAR and ICRP, is actively participating in the international review of radiation effects and the preparation of reports on radiation protection recommendations. They agreed with each other that although it is reasonable, under the current scientific understanding, to follow the recommendation of ICRP, research in this area should be strongly promoted hereafter, for basing radiation protection on firm scientific grounds. Many participants actively asked about and discussed problems in their own field. (author)

  10. Estimates of Health Detriments and Tissue Weighting Factors for Hong Kong Populations from Low Dose, Low Dose Rate and Low LET Ionising Radiation Exposure

    International Nuclear Information System (INIS)

    Lee, S.K.

    1998-01-01

    The total health detriments and the tissue weighting factors for the Hong Kong populations from low dose, low dose rate and low LET ionising radiation exposure are obtained according to the methodology recommended in ICRP Publication 60. The probabilities of fatal cancers for the general (ages 0-90) and working (ages 20-64) populations due to lifetime exposure at low dose and low dose rate are 4.9 x 10 -2 Sv -1 and 3.6 x 10 -2 Sv -1 respectively, comparing with the ICRP 60 estimates of 5.0 x 10 -2 Sv -1 and 4.0 x 10 -2 Sv -1 . The corresponding total health detriments for the general and working populations are 6.9 x 10 -2 Sv -1 and 4.9 x 10 -2 Sv -1 respectively comparing with the ICRP 60 estimates of 7.3 x 10 -2 Sv -1 and 5.6 x 10 -2 Sv -1 . Tissue weighting factors for the general population are 0.01 (bone surface and skin), 0.02 (liver, oesophagus and thyroid), 0.04 (bladder and breast), 0.08 (remainder), 0.10 (stomach), 0.11 (bone marrow), 0.15 (colon), 0.19 (lung) and 0.21 (gonads) and for the working population are 0.01 (bone surface and skin), 0.03 (liver, oesophagus and thyroid), 0.04 (breast), 0.06 (remainder), 0.07 (bladder), 0.08 (colon), 0.14 (bone marrow and stomach), 0.16 (lung) and 0.20 (gonads). (author)

  11. Low-Dose Irradiation Enhances Gene Targeting in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Hatada, Seigo; Subramanian, Aparna; Mandefro, Berhan; Ren, Songyang; Kim, Ho Won; Tang, Jie; Funari, Vincent; Baloh, Robert H; Sareen, Dhruv; Arumugaswami, Vaithilingaraja; Svendsen, Clive N

    2015-09-01

    Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy. The simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells. ©AlphaMed Press.

  12. Effects of low dose radiation on kidney function and morphology of diabetic mice

    International Nuclear Information System (INIS)

    Zhang Chi; Li Xiaokun; Gong Shouliang; Meng Tao; Li Cai; Cai Lu

    2010-01-01

    Objective: To study the effect of low dose radiation (LDR) on the kidney function and morphology in C57BL/6J mice with diabetic nephropathy (DN) induced by streptozotocin (STZ) and illuminate the protective function of LDR on kidney damage caused by diabetes mellitus (DM). Methods: The healthy and right age C57BL/6J mice were divided into 4 groups including control, DM, LDR and DM/LDR. The mice in DM and DM/LDR groups were injected intraperitoneally with STZ to set up DM models. The mice in DM/LDR and LDR groups were irradiated with 25 mGy X-rays every other day for 4 weeks. The changes of blood glucose level, urine index level and the morphology of glomerular were detected at 2, 4, 8, 12, 16 weeks after radiation. Results: The blood glucose levels of mice in DM and DM/LDR groups after STZ-induced DM model preparation were higher than those in LDR and control groups (P<0.05). After treated with LDR for 2 weeks, the blood glucose level in DM/LDR group was sup