RESUMO
ABSTRACT: During a nuclear/radiological incident or an accident involving internal intakes with radioactive cobalt or strontium, the recommended treatments, consisting of the administration of diethylenetriaminepentaacetic acid for 60 Co and calcium gluconate for 90 Sr, are of low specificity, and their effectiveness can be enhanced. In this manuscript, a liposomal formulation was developed to deliver potential chelating agents to the main retention organs of both radionuclides. A bisphosphonate, etidronate, has been selected as a possible candidate due to its satisfying decorporation activity for uranium, bone tropism, and potential affinity with cobalt. Pre-clinical studies have been carried out on rats using radionuclide contamination and treatment administration by the intravenous route. The effectiveness of free or liposomal etidronate was evaluated, with an administration at 30 min, 48 h post-contamination with 60 Co. Regarding 85 Sr, a more extended experiment with etidronate liposomes was performed over 6 d. The results were compared to those performed with reference treatments, diethylenetriaminepentaacetic acid for cobalt and calcium gluconate for strontium. Unexpected results were found for the reference treatments that were significantly less effective than previously reported or showed no effectiveness. Free etidronate revealed no significant efficacy after 48 h, but the liposomal form suggested an interaction with radionuclides, not sufficient to change the biokinetics. This study emphasizes the need for early treatment administration and further research to provide a more effective medical countermeasure.
RESUMO
Between 2009 and 2013, a large cross-sectional study on the health consequences of the Chernobyl nuclear accident was performed in the contaminated and uncontaminated territories of the Bryansk Oblast (Russian Federation). The objective of this work was to confirm or refute a possible association between childhood cardiac arrhythmia and a chronic exposure to caesium-137. As part of this study, a large number of electrocardiographic and cardiac ultrasound parameters were collected from 18,152 children aged 2-18 years including 12,512 healthy ones not contaminated with caesium-137. It seemed therefore relevant for us to share in a second publication these medical data based on healthy and uncontaminated children with the scientific community because of the large quantities and the limited availability of such kind of data. In the present study, relating to electrocardiographic parameters, the measurements performed fully reflect the expected evolution of the paediatric electrocardiogram between 5 and 18 years of age. Thus, the median values were generally quite close to those available in the literature. In contrast, differences in the 2nd and 98th percentiles were notable and could be explained in particular by the type of equipment used, the number of subjects included in the study and racial disparities. As for echocardiographic parameters, the evolution of the measured values in age groups is consistent with what was expected considering factors such as growth. In comparison with other scientific studies that have investigated these echocardiographic parameters, some differences by age groups have been identified. The ethnic factor truly appears to be a relevant feature to consider. In view of the results, it appeared essential to the authors to approach the methodological conditions of the scientific studies already published on the topic to be truly comparable and thus to provide a reliable answer on a topic for which real expectations in terms of medical care are required.
Assuntos
Arritmias Cardíacas/diagnóstico , Radioisótopos de Césio/efeitos adversos , Ecocardiografia/normas , Eletrocardiografia/normas , Exposição à Radiação/efeitos adversos , Adolescente , Arritmias Cardíacas/etiologia , Acidente Nuclear de Chernobyl , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Valores de Referência , Federação RussaRESUMO
OBJECTIVE: To investigate childhood cardiac arrhythmia and chronic exposure to caesium-137 (137Cs) resulting from the Chernobyl accident. DESIGN: Prospective cross-sectional study using exposed/unexposed design conducted in the Bryansk region from May 2009 to May 2013 on children selected on the basis of 137Cs soil deposition: control territories ([137Cs]<37 kBq per square metre, where children were considered as unexposed) and contaminated territories ([137Cs]>555 kBq per square metre, where children were considered as exposed). SETTING: Russian territories affected by the Chernobyl fallout (Bryansk region). PARTICIPANTS: This cross-sectional study included 18 152 children aged 2-18 years and living in the Bryansk region (Russia). MAIN OUTCOME MEASURES: All children received three medical examinations (ECG, echocardiography and 137Cs whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. RESULTS: Cardiac arrhythmia was diagnosed in 1172 children living in contaminated territories and 1354 children living in control territories. The crude prevalence estimated to 13.3% in contaminated territories was significantly lower than in control territories with 15.2% over the period 2009-2013 (P<0.001). Considering 137Cs whole-body burden as exposure, cardiac arrhythmia was found in 449 contaminated children and 2077 uncontaminated children, corresponding to an estimated crude prevalence of 14.5% and 14.2%, respectively, which does not differ significantly (P=0.74). Also, we investigated the association between territory, exposure to 137Cs and cardiac arrhythmia: the adjusted OR was not significant (0.90 with 95% CI 0.81 to 1.00; P=0.06) for the territory. For 137Cs whole-body burden, the ORs close to 1 did not reach statistical significance (P for trend=0.97). CONCLUSION: This study does not observe an association between cardiac arrhythmia and 137Cs deposition levels in the Bryansk region exposed to Chernobyl fallout. The suspected increase of cardiac arrhythmia in children exposed to Chernobyl fallout is not confirmed.
Assuntos
Arritmias Cardíacas/epidemiologia , Acidente Nuclear de Chernobyl , Exposição Ambiental/efeitos adversos , Exposição à Radiação/efeitos adversos , Radiação Ionizante , Cinza Radioativa/efeitos adversos , Adolescente , Arritmias Cardíacas/etiologia , Radioisótopos de Césio/análise , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Estudos Prospectivos , Federação Russa/epidemiologia , Solo/químicaRESUMO
This study aimed to compare the cell stress effects of low and high uranium concentrations and relate them to its localization, precipitate formation, and exposure time. The time-course analysis shows that uranium appears in cell nuclei as a soluble form within 5 min of exposure, and quickly induces expression of antioxidant and DNA repair genes. On the other hand, precipitate formations began at the very beginning of exposure at the 300-µM concentration, but took longer to appear at lower concentrations. Adaptive response might occur at low concentrations but are overwhelmed at high concentrations, especially when uranium precipitates are abundant.
Assuntos
Núcleo Celular/efeitos da radiação , Estresse Fisiológico/efeitos da radiação , Urânio/toxicidade , Apoptose/efeitos da radiação , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Células Hep G2 , Humanos , Estresse Oxidativo/efeitos da radiação , Urânio/farmacocinéticaRESUMO
An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds.
Assuntos
Calixarenos/química , Quelantes/química , Descontaminação/métodos , Pele/química , Urânio/química , Urânio/isolamento & purificação , Animais , Calixarenos/metabolismo , Calixarenos/farmacologia , Quelantes/metabolismo , Quelantes/farmacologia , Química Farmacêutica , Emulsões , Óleos/química , Permeabilidade , Pele/efeitos dos fármacos , Pele/metabolismo , Suínos , Viscosidade , Água/químicaRESUMO
Cutaneous contamination by radionuclides is a major concern in the nuclear industry. In case of skin exposure to uranium, no efficient emergency treatment is available to remove the actinide from the skin. For this purpose, we developed a nanoemulsion containing calixarene molecules displaying good chelating properties towards uranium. In this paper, we describe the ability of this formulation to trap uranium and limit its transfer from the cutaneous contaminated site into the blood. Uranium percutaneous diffusion kinetics was assessed with Franz cells over 24 h through intact and excoriated pig ear skin biopsies, after or without application of the nanoemulsion. Uranium distribution in the skin layers was analysed by SIMS microscopy. The results showed that prompt application of the calixarene nanoemulsion allows a 94% and 98% reduction of the amount of uranium diffused respectively through intact and excoriated skin. The formulation is still efficient in case of delayed application up to 30 minutes since the 24 h-uranium transfer through excoriated skin is reduced by 71%. Besides, no accumulation of uranium or uranium-calixarene chelate was observed in the different skin layers. In conclusion, this study demonstrated the efficiency of the calixarene nanoemulsion, which can be regarded as a promising treatment for uranium cutaneous contamination.