RESUMO
AIM: To determine cumulative scan frequencies and estimate lens dose for paediatric computed tomography (CT) head examinations in the context of potential cataract risk. MATERIALS AND METHODS: The cumulative number of head-region CT examinations among a cohort of 410,997 children and young adults who underwent CT in the UK between 1985 and 2014 was calculated. Images from a sample of these head examinations (n=668) were reviewed to determine the level of eye inclusion. Lens dose per scan was estimated using the computer program, NCICT V1.0, for different levels of eye inclusion and exposure settings typical of past and present clinical practice. RESULTS: In total 284,878 patients underwent 448,108 head-region CT examinations. The majority of patients (72%) had a single recorded head-region examination. A small subset (â¼1%, n=2,494) underwent ≥10 examinations, while 0.1% (n=387) underwent ≥20. The lens was included within the imaged region for 57% of reviewed routine head examinations. In many cases, this appeared to be intentional, i.e. protocol driven. In others, there appeared to have been an attempt to exclude the eyes through gantry angulation. Estimated lens doses were 20-75 mGy (mean: 47 mGy) where the eye was fully included within the examination range and 2-7 mGy (mean: 3.1 mGy) where the lens was fully excluded. Potential cumulative lens doses ranged from â¼3 mGy to â¼4,700 mGy, with 2,335 patients potentially receiving >500 mGy. CONCLUSION: The majority of young people will receive cumulative lens doses well below 500 mGy, meaning the risk of cataract induction is likely to be very small.
Assuntos
Cabeça/diagnóstico por imagem , Cristalino/efeitos da radiação , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Adolescente , Catarata/etiologia , Catarata/prevenção & controle , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Posicionamento do Paciente , Exposição à Radiação/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Germline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas. OBJECTIVES: To search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations. METHODS: A retrospective case-note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In-depth investigation was carried out for patients with pulmonary tumours. RESULTS: Four patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre-emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse. CONCLUSIONS: Pulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.
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Portador Sadio/patologia , Enzima Desubiquitinante CYLD/genética , Dispneia/etiologia , Neoplasias Pulmonares/secundário , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Portador Sadio/diagnóstico por imagem , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/diagnóstico por imagem , Síndromes Neoplásicas Hereditárias/genética , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/genéticaRESUMO
In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident.
Assuntos
Cromossomos Humanos/genética , Cromossomos Humanos/efeitos da radiação , Comportamento Cooperativo , Internet , Liberação Nociva de Radioativos , Radiometria/métodos , Triagem , Aberrações Cromossômicas/efeitos da radiação , Humanos , Doses de Radiação , Fatores de TempoRESUMO
Mass casualty scenarios of radiation exposure require high throughput biological dosimetry techniques for population triage in order to rapidly identify individuals who require clinical treatment. The manual dicentric assay is a highly suitable technique, but it is also very time consuming and requires well trained scorers. In the framework of the MULTIBIODOSE EU FP7 project, semi-automated dicentric scoring has been established in six European biodosimetry laboratories. Whole blood was irradiated with a Co-60 gamma source resulting in 8 different doses between 0 and 4.5Gy and then shipped to the six participating laboratories. To investigate two different scoring strategies, cell cultures were set up with short term (2-3h) or long term (24h) colcemid treatment. Three classifiers for automatic dicentric detection were applied, two of which were developed specifically for these two different culture techniques. The automation procedure included metaphase finding, capture of cells at high resolution and detection of dicentric candidates. The automatically detected dicentric candidates were then evaluated by a trained human scorer, which led to the term 'semi-automated' being applied to the analysis. The six participating laboratories established at least one semi-automated calibration curve each, using the appropriate classifier for their colcemid treatment time. There was no significant difference between the calibration curves established, regardless of the classifier used. The ratio of false positive to true positive dicentric candidates was dose dependent. The total staff effort required for analysing 150 metaphases using the semi-automated approach was 2 min as opposed to 60 min for manual scoring of 50 metaphases. Semi-automated dicentric scoring is a useful tool in a large scale radiation accident as it enables high throughput screening of samples for fast triage of potentially exposed individuals. Furthermore, the results from the participating laboratories were comparable which supports networking between laboratories for this assay.
Assuntos
Aberrações Cromossômicas/efeitos da radiação , Cromossomos Humanos/efeitos da radiação , Raios gama/efeitos adversos , Laboratórios/normas , Linfócitos/efeitos da radiação , Monitoramento de Radiação/métodos , Liberação Nociva de Radioativos/prevenção & controle , Automação , Radioisótopos de Cobalto , Relação Dose-Resposta à Radiação , Europa (Continente) , HumanosRESUMO
Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.
Assuntos
Bioensaio , Coleta de Amostras Sanguíneas , Estudos Retrospectivos , Citocinese , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
Lens epithelial cell proliferation and differentiation are naturally well regulated and controlled, a characteristic essential for lens structure, symmetry and function. The effect of ionizing radiation on lens epithelial cell proliferation has been demonstrated in previous studies at high acute doses, but the effect of dose and dose rate on proliferation has not yet been considered. In this work, mice received single acute doses of 0.5, 1 and 2 Gy of radiation, at dose rates of 0.063 and 0.3 Gy/min. Eye lenses were isolated postirradiation at 30 min up until 14 days and flat-mounted. Then, cell proliferation rates were determined using biomarker Ki67. As expected, radiation increased cell proliferation 2 and 24 h postirradiation transiently (undetectable 14 days postirradiation) and was dose dependent (changes were very significant at 2 Gy; P = 0.008). A dose-rate effect did not reach significance in this study (P = 0.054). However, dose rate and lens epithelial cell region showed significant interactions (P < 0.001). These observations further our mechanistic understanding of how the lens responds to radiation.
Assuntos
Cristalino/efeitos da radiação , Animais , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Células Epiteliais , Feminino , Humanos , Camundongos Endogâmicos C57BL , Doses de Radiação , Exposição à Radiação , Radiação IonizanteRESUMO
Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (<2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis. Recently we have reported an inverse dose-rate effect, as well as the low-dose response, of DNA damage and repair in lens epithelial cells (LECs). Here, we present further initial findings from two mutated strains (Ercc2+/- and Ptch1+/-) of mice, both reportedly susceptible to radiation-induced cataract, and their DNA damage and repair response to low-dose and low-dose-rate gamma rays. Our results support the hypothesis that the lens epithelium responds differently to radiation than other tissues, with reported radiation susceptibility to DNA damage not necessarily translating to the LECs. Genetic predisposition and strain(s) of mice have a significant role in radiation-induced cataract susceptibility.
Assuntos
Catarata/etiologia , Dano ao DNA/efeitos da radiação , Cristalino/efeitos dos fármacos , Animais , Células Epiteliais , Raios gama , Humanos , Camundongos , Receptor Patched-1/metabolismo , Exposição à Radiação , Proteína Grupo D do Xeroderma Pigmentoso/metabolismoRESUMO
Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy 60Co gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min-1. Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken postirradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time postirradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (<1 Gy) dose, multiple dose rate, sex and strain effects in lens opacification, and clearly demonstrates the importance of these experimental factors in radiobiological investigations on the lens. The results provide insight into the effects of ionizing radiation on the lens as well as the need for further work in this area to underpin appropriate radiation protection legislation and guidance.
Assuntos
Catarata/etiologia , Animais , Feminino , Patrimônio Genético , Humanos , Cristalino/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Exposição Ocupacional , Receptor Patched-1/metabolismo , Doses de Radiação , Exposição à Radiação , Radiação Ionizante , Proteína Grupo D do Xeroderma Pigmentoso/metabolismoAssuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/terapia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/terapia , Biópsia , Broncoscopia , Ablação por Cateter , Árvores de Decisões , Humanos , Imageamento por Ressonância Magnética , Imagem Multimodal , Pneumonectomia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Reino UnidoRESUMO
INTRODUCTION: Chest wall sarcomas are rare. Resection and reconstruction pose significant anatomical and functional challenges. We present our experience of managing these tumours as plastic surgeons working within a specialist sarcoma MDT. METHODS: All cases of chest wall sarcoma in which a plastic surgeon took part were analysed (2003-2016). Tumours of the breast, abdomen and groin were excluded. Demographics, surgical details and outcomes were analysed. RESULTS: Forty-seven patients were identified. Median age at presentation was 61 years (range 7-91). Thirty-three were male and 14 were female. Chondrosarcoma (nâ¯=â¯16) was the most frequently occurring tumour, followed by myxofibrosarcoma (nâ¯=â¯6), leiomyosarcoma (nâ¯=â¯5) and unclassified sarcomas (nâ¯=â¯5). The majority of tumours were of high (nâ¯=â¯16) or intermediate grade (nâ¯=â¯17) histologically. Wide local excision was carried out in all cases. Twenty-two cases required a mesh and cement reconstruction of the chest wall. Soft tissue reconstruction involved pedicled LD flap +-skin graft (nâ¯=â¯17), direct closure (nâ¯=â¯13), pedicled VRAM (nâ¯=â¯7), free ALT flap (nâ¯=â¯6), and others (nâ¯=â¯4). Clear resection margins were achieved in 32 patients (68%). Fourteen patients underwent adjuvant radiotherapy and four adjuvant chemotherapy. Nine patients (19%) developed a local recurrence, and the median duration from resection to recurrence was 17 months (range 3-72). Nine patients (19%) developed metastasis. Eleven patients died (23.4%), and the median duration of survival 30 months (range 3-92). Thirty-six patients remain well, with a median duration of follow up 57.5 months (range 6-141). Estimated 5 year disease specific survival is 74.2%. CONCLUSION: Plastic surgeons have a vital role in the management of chest wall sarcomas. We present a reconstructive algorithm, which has enabled us to achieve good oncological and functional outcomes and a low complication profile .
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Sarcoma/cirurgia , Neoplasias Torácicas/cirurgia , Parede Torácica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Procedimentos de Cirurgia PlásticaRESUMO
A novel chemical sensor has been developed in which the polymer ethylene-vinyl acetate is used as a controlled-release system to deliver reagents to the sensing region of an optical fiber for a homogeneous competitive immunoassay based on fluorescence energy transfer. A competition reaction is used to enable continuous measurements of the solution antigen concentration. More generally, the technique allows irreversible indicating chemistries to be used in the construction of chemical sensors that can measure continuously for long periods. Although the sensor configuration has not been optimized in all respects, data are presented for a model system in which a fluorescein-labeled antibody and Texas Red-labeled immunoglobulin G (IgG) are used.
Assuntos
Antígenos/análise , Imunoglobulina G , Especificidade de Anticorpos , Técnicas Biossensoriais , Imunofluorescência/instrumentação , Corantes Fluorescentes , XantenosRESUMO
OBJECTIVES: We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT. METHODS: Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n = 26). RESULTS: Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9-17.4%) at 1 month and 10% (26/259; 6.7-14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1-14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs). CONCLUSIONS: Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/normal. Trial registration ISRCTN58038795.
Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/isolamento & purificação , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Adolescente , Infecções por Chlamydia/epidemiologia , Programas de Triagem Diagnóstica , Etnicidade , Estudos de Viabilidade , Feminino , Humanos , Londres/epidemiologia , Masculino , Prevalência , Fatores de Risco , Comportamento Sexual , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Estudantes , Inquéritos e Questionários , Tempo para o Tratamento , Adulto JovemRESUMO
Morgagni hernias are uncommon congenital diaphragmatic deficiencies that may remain asymptomatic till adulthood. We report a case of Morgagni hernia presenting with subacute bowel obstruction in a bilateral lung transplant recipient. This diaphragmatic deficiency was not evident during bilateral lung transplantation surgery via clamshell incision. To our knowledge this is the first report of a congenital defect evident after lung transplantation.
Assuntos
Hérnia Diafragmática/diagnóstico , Obstrução Intestinal/diagnóstico , Transplante de Pulmão/efeitos adversos , Fibrose Pulmonar/cirurgia , Seguimentos , Hérnia Diafragmática/diagnóstico por imagem , Humanos , Obstrução Intestinal/complicações , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Ruptura EspontâneaRESUMO
Many offshore oil and gas production facilities are nearing the end of their operational life, with decommissioning now becoming a global challenge. The compatibility of decommissioning operations to marine protected areas (MPAs) creates further challenges. The recently-developed DAPSI(W)R(M) problem structuring framework (covering Drivers, Activities, Pressures, State changes, Impacts (on Welfare) and Responses (as Measures)) was applied here to interrogate the complexity of decommissioning oil and gas infrastructure within MPAs, with outputs feeding into the development of a novel database tool for Screening Potential Impacts of Decommissioning Activities (SPIDA). In meeting the current requirements of the marine regulatory regime, SPIDA provides a more streamlined, evidence-based process which can be applied by industry, statutory nature conservation bodies and regulators for identifying and evaluating evidence that supports the implications of decommissioning alternatives on the condition of MPAs. SPIDA has been developed to be adapted for other activities and sectors, including offshore renewables.
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Conservação dos Recursos Hídricos/métodos , Bases de Dados Factuais , Campos de Petróleo e Gás , Animais , Técnicas de Apoio para a Decisão , Ecossistema , Meio AmbienteRESUMO
PURPOSE: Epidemiological evidence regarding the radiosensitivity of the lens of the eye and radiation cataract development has led to changes in the EU Basic Safety Standards for protection of the lens against ionizing radiation. However, mechanistic details of lens radiation response pathways and their significance for cataractogenesis remain unclear. Radiation-induced DNA damage and the potential impairment of repair pathways within the lens epithelium, a cell monolayer that covers the anterior hemisphere of the lens, are likely to be involved. MATERIALS AND METHODS: In this work, the lens epithelium has been analyzed for its DNA double-strand break (DSB) repair response to ionizing radiation. The responses of epithelial cells located at the anterior pole (central region) have been compared to at the very periphery of the monolayer (germinative and transitional zones). Described here are the different responses in the two regions and across four strains (C57BL/6, 129S2, BALB/c and CBA/Ca) over a low dose (0-25 mGy) in-vivo whole body X-irradiation range up to 24 hours post exposure. RESULTS: DNA damage and repair as visualized through 53BP1 staining was present across the lens epithelium, although repair kinetics appeared non-uniform. Epithelial cells in the central region have significantly more 53BP1 foci. The sensitivities of different mouse strains have also been compared. CONCLUSIONS: 129S2 and BALB/c showed higher levels of DNA damage, with BALB/c showing significantly less inter-individual variability and appearing to be a more robust model for future DNA damage and repair studies. As a result of this study, BALB/c was identified as a suitable radiosensitive lens strain to detect and quantify early low dose ionizing radiation DNA damage effects in the mouse eye lens specifically, as an indicator of cataract formation.
Assuntos
Dano ao DNA , Cristalino/metabolismo , Cristalino/efeitos da radiação , Animais , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Epitélio/metabolismo , Epitélio/efeitos da radiação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Tolerância a Radiação/genética , Especificidade da Espécie , Fatores de TempoRESUMO
In many European shelters, dogs may spend many years confined. A poor environment and inappropriate management may lead to a low quality of life. The absence of harmonised European regulatory frameworks defining the minimum requirements for shelter facilities makes the definition of welfare standards for kennelled dogs challenging. Here, a new protocol was developed and tested to help identify the main welfare issues for shelter dogs. Twenty-six indicators were identified including management, resource and animal based measures. Accuracy and interobserver reliability were checked between four assessors. The protocol was applied in 29 shelters (n=1308 dogs) in six European countries. Overall prevalence of poor health conditions was below 10%. Test-retest reliability and validity of the protocol were investigated with encouraging results. A logistic regression was carried out to assess the potential of the protocol as a tool to identify welfare hazards in shelter environments. Inappropriate space allowance, for example, was found to be a risk factor potentially affecting the animal's cleanliness, skin condition and body condition. The protocol was designed to be concise and easy to implement. Systematic data collection could help identify welfare problems that are likely to arise in certain shelter designs and thus determine improvement in animal care standards.
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Bem-Estar do Animal/organização & administração , Bem-Estar do Animal/normas , Abrigo para Animais/normas , Animais , Cães , Europa (Continente) , Estudos de Viabilidade , Abrigo para Animais/estatística & dados numéricos , Fatores de TempoRESUMO
The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices.
Assuntos
Oftalmopatias/etiologia , Cristalino/efeitos da radiação , Exposição Ocupacional , Oftalmologia , Optometria , Lesões por Radiação/etiologia , Animais , Oftalmopatias/patologia , Oftalmopatias/fisiopatologia , Humanos , Camundongos , Doses de Radiação , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Risco , Reino UnidoRESUMO
In the event of a mass casualty radiation incident, the gamma-H2AX foci assay could be a useful tool to estimate radiation doses received by individuals. The rapid processing time of blood samples of just a few hours and the potential for batch processing, enabling high throughput, make the assay ideal for early triage categorisation to separate the 'worried well' from the low and critically exposed by quantifying radiation-induced foci in peripheral blood lymphocytes. Within the RENEB framework, 8 European laboratories have taken part in the first European gamma-H2AX biodosimetry exercise, which consisted of a telescoring comparison of 200 circulated foci images taken from 8 samples, and a comparison of 10 fresh blood lymphocyte samples that were shipped overnight to participating labs 4 or 24 h post-exposure. Despite large variations between laboratories in the dose-response relationship for foci induction, the obtained results indicate that the network should be able to use the gamma-H2AX assay for rapidly identifying the most severely exposed individuals within a cohort who could then be prioritised for accurate chromosome dosimetry.
Assuntos
Bioensaio/métodos , Dano ao DNA/genética , Raios gama , Histonas/genética , Linfócitos/efeitos da radiação , Exposição à Radiação/análise , Células Cultivadas , Relação Dose-Resposta à Radiação , Europa (Continente) , Imunofluorescência , Humanos , Laboratórios , Linfócitos/fisiologia , Incidentes com Feridos em Massa , Doses de Radiação , Liberação Nociva de RadioativosRESUMO
Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.
Assuntos
Bioensaio/métodos , Planejamento em Desastres/organização & administração , Lesões por Radiação/prevenção & controle , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Liberação Nociva de Radioativos/prevenção & controle , Emergências , Europa (Continente) , Humanos , Exposição à Radiação/prevenção & controle , Gestão da Segurança/organização & administraçãoRESUMO
The widely used analgesic paracetamol (P) produces fulminant hepatocellular necrosis in humans when taken in overdose. The toxicity is mediated by drug oxidation and depletion of hepatic glutathione. We have, therefore, explored the effects of fluorine substitution on the hepatotoxicity of P in female CD1 mice. 3-Fluoro-4-hydroxyacetanilide (1FPO), 3,5-difluoro-4-hydroxyacetanilide (2FPO), 2,6-difluoro-4-hydroxyacetanilide (2FPN) and 2,3,5,6-tetrafluoro-4-hydroxyacetanilide (4FP) were synthesized, characterized and investigated for their potential to cause hepatotoxicity in the mouse. Introduction of fluorine into P increases the oxidation potential of the drug. The oxidation potentials of paracetamol and its fluorinated analogues were measured by cyclic voltametry and found to increase in the order P < 1FPO < 2FPO < 2FPN < 4FP. Serum transaminase (ALT) and hepatic glutathione were measured 24 and 6 hr, respectively, after administration of a single dose (2.65 mmol/kg) of each compound to female CD1 mice. There was significant elevation of ALT in mice given P, 1FPO and 2FPO, but not in those which received either 2FPN or 4FP. Hepatic glutathione was reduced significantly by administration of P and IFP, but not after administration of 2FPO, 2FPN or 4FP. Accordingly, glucuronide and sulphate conjugates, but not thioether metabolites, were detected in urine after administration of 14C-labelled 2FPO, 2FPN and 4FP. These data indicate that introduction of fluorine into the 2 and 6 positions increases the oxidation potential of paracetamol which in turn reduces the propensity of the molecule to undergo oxidative bioactivation, and thereby reduces the in vivo toxicity of the molecule.