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BACKGROUND: We used the Monte Carlo code "CELLDOSE" to assess the dose received by specific target cells from electron emissions in a complex environment. (131)I in a simulated thyroid was used as a model. METHODS: Thyroid follicles were represented by 170 microm diameter spherical units made of a lumen of 150 microm diameter containing colloidal matter and a peripheral layer of 10 microm thick thyroid cells. Neighbouring follicles are 4 microm apart. (131)I was assumed to be homogeneously distributed in the lumen and absent in cells. We firstly assessed electron dose distribution in a single follicle. Then, we expanded the simulation by progressively adding neighbouring layers of follicles, so to reassess the electron dose to this single follicle implemented with the contribution of the added layers. RESULTS: Electron dose gradient around a point source showed that the (131)I electron dose is close to zero after 2,100 microm. Therefore, we studied all contributions to the central follicle deriving from follicles within 12 orders of neighbourhood (15,624 follicles surrounding the central follicle). The dose to colloid of the single follicle was twice as high as the dose to thyroid cells. Even when all neighbours were taken into account, the dose in the central follicle remained heterogeneous. For a 1-Gy average dose to tissue, the dose to colloidal matter was 1.168 Gy, the dose to thyroid cells was 0.982 Gy, and the dose to the inter-follicular tissue was 0.895 Gy. Analysis of the different contributions to thyroid cell dose showed that 17.3% of the dose derived from the colloidal matter of their own follicle, while the remaining 82.7% was delivered by the surrounding follicles. On the basis of these data, it is shown that when different follicles contain different concentrations of (131)I, the impact in terms of cell dose heterogeneity can be important. CONCLUSION: By means of (131)I in the thyroid as a theoretical model, we showed how a Monte Carlo code can be used to map electron dose deposit and build up the dose to target cells in a complex multi-source environment. This approach can be of considerable interest for comparing different radiopharmaceuticals as therapy agents in oncology.
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Electrones , Método de Montecarlo , Dosis de Radiación , Glándula Tiroides/citología , Glándula Tiroides/efectos de la radiación , Radioisótopos de Yodo , Modelos BiológicosRESUMEN
The large increase in the incidence of thyroid cancer among children who were mainly less than five years old at the time of the Chernobyl accident is still a major preoccupation for endocrinologists and nuclear physicians. Epidemiological studies have focused solely on iodine 131. However, past knowledge on thyroid irradiation (medical use of iodine 131, radioactive fallout on Marshall islands and the Nevada, and Hanford site releases) as well as number of recent works (about low-dose irradiation), raise question on the role of other factors. It is here shown that post-Chernobyl thyroid irradiation is complex and that all factors (iodine 131, but also short lived isotopes of iodine and external irradiation) should be considered. Finally, one need to think about some of the present medical uses of iodine 131, and especially to the treatment of hyperthyroidism in young subjects.
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Accidente Nuclear de Chernóbil , Radioisótopos de Yodo/toxicidad , Neoplasias Inducidas por Radiación/etiología , Neoplasias de la Tiroides/etiología , Preescolar , Humanos , Lactante , Recién Nacido , Radioisótopos de Yodo/efectos adversos , Japón/epidemiología , Micronesia/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Nevada/epidemiología , Gases Nobles/toxicidad , Ceniza Radiactiva/efectos adversos , Liberación de Radiactividad Peligrosa , Radioterapia/efectos adversos , Neoplasias de la Tiroides/epidemiología , Ucrania/epidemiología , Washingtón/epidemiologíaRESUMEN
The spatiotemporal distribution of cellular uptake site of radiotoxics is essential data for microdosimetric studies. As early as 1950, the heterogeneity of iodine incorporation within the thyroid has been shown using autoradiography. The objective of this study is to describe the kinetic cellular distribution of newly organified iodine in the thyroid of newborn rats using secondary ion mass microscopy (NanoSIMS50). Ionic images obtained at high mass resolution and with a lateral resolution of about 50 nm show that the early distribution of iodine is heterogeneous from one follicle to another, from one thyrocyte to another inside the same follicle, and that this distribution varies as a function of time. The obtained kinetic profile will allow us to refine the studies concerning the aetiopathology of thyroid cancers of the Chernobyl children.
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Animales Recién Nacidos/metabolismo , Radioisótopos de Yodo/farmacocinética , Espectrometría de Masa de Ion Secundario , Glándula Tiroides/metabolismo , Animales , Coloides , Yodo/análisis , Radioisótopos de Yodo/toxicidad , Cinética , Ratas , Ratas Wistar , Glándula Tiroides/química , Glándula Tiroides/citología , Distribución TisularRESUMEN
The most significant impact of the Chernobyl accident is the increased incidence of thyroid cancer among children who were exposed to short-lived radioiodines and 131-iodine. In order to accurately estimate the radiation dose provided by these radioiodines, it is necessary to know where iodine is incorporated. To do that, the distribution at the cellular level of newly organified iodine in the immature rat thyroid was performed using secondary ion mass microscopy (NanoSIMS50). Actual dosimetric models take only into account the averaged energy and range of beta particles of the radio-elements and may, therefore, imperfectly describe the real distribution of dose deposit at the microscopic level around the point sources. Our approach is radically different since based on a track-structure Monte Carlo code allowing following-up of electrons down to low energies (~ 10eV) what permits a nanometric description of the irradiation physics. The numerical simulations were then performed by modelling the complete disintegrations of the short-lived iodine isotopes as well as of 131I in new born rat thyroids in order to take into account accurate histological and biological data for the thyroid gland.
O impacto mais significante do acidente de Chernobyl é o crescimento da incidência de câncer de tireóide em crianças que foram expostas a radioiodos de vida curta e ao Iodo-131. Na estimativa precisa da dose de radiação fornecida por esses radioiodos, é necessário conhecer onde o iodo está incorporado. Para obtermos esse resultado, a distribuição em nível celular de iodo recentemente organificado na tireóde de ratos imaturos foi realizada usando microscopia de massa iônica secundária (NanoSIMS50). Modelos dosimétricos atuais consideram apenas a energia média das partículas beta dos radioelementos e pode, imperfeitamente descrever a distribuição real de dose ao nível microscópico em torno dos pontos pesquisados. Nossa abordagem é radicalmente diferente desde que é baseada na simulação de Monte Carlo permitindo acompanhar os elétrons de energias menoress (~ 10eV) o que permite uma descrição nanométrica da física da radiação. As simulações numéricas foram então realizadas pelo modelo de desintegração completa de isotopos do iodo de vida curta assim como do Iodo-131 em tireóide de ratos recém nascidos na tentativa de obter resultados biológicos e histológicos de maior precisão para a glândula tireóide.
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OBJECTIVES: In patients with anorexia nervosa (AN), weight gain is lower than that expected from the energy content of the meals. Thus we investigated the thermic effect of food (TEF) in relation to subjective feelings and plasma hormone levels in a group of AN patients. METHODS: TEF, feelings (14 items), and plasma release of beta-endorphin, ACTH, cortisol, dopamine, and catecholamines were evaluated in 15 AN patients (body mass index, 13.6 +/- 1.2 kg.m(-2)) and in 15 healthy women after three gastric loads (0, 300, 700 kcal) infused by a nasogastric tube in a blind design. RESULTS: In AN, the blind loads induced an energy-dependent increase in TEF (P < 0.001), which was higher than that observed in healthy women (P < 0.001). Only in AN, a load-dependent decline in the high basal plasma level of beta-endorphin (P < 0.01), an increase in plasma ACTH (P < 0.02) after the two caloric loads, and an increase in cortisol, norepinephrine, and dopamine levels after the 700-kcal load only (P < 0.05) were noted. A calorie-dependent (P < 0.001) increase in nausea, abdominal discomfort, and fear of being fat ratings and a decrease in liking to eat (P < 0.001) and body image were observed in AN patients (P < 0.05). TEF correlated with ratings on satiation, nausea, uncomfortable abdominal swelling, body image, and fear of being fat (for all, P < 0.01). CONCLUSION: In AN women, blindly infused loads induced a dose-dependent increase in TEF, which correlated with the increase in plasma cortisol, ACTH, and catecholamines as in unpleasant sensations, fear of being fat, and anxiety as well as a decline in elevated basal beta-endorphin. These results could explain the difficulty for AN patients in gaining weight.
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Anorexia Nerviosa/fisiopatología , Anorexia Nerviosa/psicología , Regulación de la Temperatura Corporal/fisiología , Ingestión de Alimentos/fisiología , Ayuno/fisiología , Hormonas/sangre , Desnutrición/fisiopatología , Adolescente , Adulto , Afecto/fisiología , Composición Corporal/fisiología , Índice de Masa Corporal , Método Doble Ciego , Ingestión de Energía/fisiología , Metabolismo Energético/fisiología , Femenino , Humanos , Náusea/etiología , Náusea/psicología , Sensación/fisiologíaRESUMEN
BACKGROUND: Biological dosimetry, which determines the dose of acquired radiation by measuring radiation-induced variation of biological parameters, can help assess radiation damage in an individual. Evaluation of radiation exposure requires setting up reference curves for each type of radiation. AIM: To evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. METHODS: Dicentrics, rings, excess fragments, complete reciprocal translocations and incomplete reciprocal translocations were scored in peripheral blood lymphocytes from patients exposed to a 99mTc bone scintigraphy. A specific relationship between the radiation dose delivered by 99mTc and the frequency of stable and unstable chromosomal aberrations was established in vitro to estimate whole-body dose. Chromosome analysis using fluorescence plus Giemsa and fluorescence in-situ hybridization was undertaken on six patients before and after a 99mTc bone scintigraphy. Dicentrics, rings, excess fragments, and translocations were scored in blood lymphocytes after in vitro 99mTc external irradiation in order to construct dose calibration curves. RESULTS: Analysis of the in-vitro data shows that the number of both unstable and stable aberrations has a quadratic linear relationship to the dose. Our in-vivo irradiation studies showed that activities of 99mTc-hexamethylene diphosphonate (99mTc-HDP) used for bone investigations do not induce any additional unstable chromosome aberrations and translocations. The frequencies obtained did not differ significantly from background values. CONCLUSIONS: 99mTc can produce unstable and stable chromosomal aberrations in vitro. 99mTc-HDP administration does not induce supplementary chromosomal aberrations. The dose-response curves will allow a more accurate evaluation of the risk related to in-vivo administration of 99mTc labelled radiopharmaceuticals, and they can be used to assess the safe upper limit of injected activity in humans.
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Aberraciones Cromosómicas/efectos de la radiación , Cromosomas Humanos/genética , Cromosomas Humanos/efectos de la radiación , Traumatismos por Radiación/etiología , Traumatismos por Radiación/genética , Medición de Riesgo/métodos , Tecnecio/efectos adversos , Adulto , Relación Dosis-Respuesta en la Radiación , Humanos , Dosis de Radiación , Radiofármacos/efectos adversos , Factores de RiesgoRESUMEN
Previous studies suggest that brain opioid activity decreases aggression in animal models. The main objective of the current study was to examine the possible genetic relationship between intermale aggression and brain levels of enkephalins, endorphins, and dynorphins in 11 inbred strains of mice. Pursuit, rattling, and attack behaviors were observed in a dyadic encounter with a standard opponent. It appeared that, as expected, enkephalins and endorphins were always negatively correlated with aggression scores. The findings indicate that brain Met5-enkephalin levels were significantly and highly positively correlated with attack latency. Brain adrenocorticotrophic hormone (ACTH) and beta-endorphin levels were significantly and negatively correlated with the number of rattlings, which is consistent with the hypothesis that rattling is a stress-related behavior. In contrast with Met5-enkephalin, ACTH and beta-endorphin, the correlations between dynorphin A and aggression scores were nonsignificant and very low. These preliminary results suggest that common genetic sources of variation contribute to differences between the 11 inbred strains in both endogenous opioidergic systems and intermale aggression. Further studies are required to confirm the genetic relationship between offensive aggression and brain enkephalins and endorphins and to better understand the mechanisms underlying the role of endogenous opioids in offensive aggression with regard to opioid receptor activity.
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Agresión/fisiología , Encéfalo/metabolismo , Dinorfinas/metabolismo , Encefalina Metionina/metabolismo , betaendorfina/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Endogámicos DBA , Modelos Animales , Fragmentos de Péptidos/metabolismo , RadioinmunoensayoRESUMEN
OBJECTIVE: To localize magnetic resonance imaging (MRI) contrast agents injected intravenously into mouse livers. STUDY DESIGN: Parallel studies were performed on fluorescent europium and nonfluorescent, paramagnetic gadolinium and on a product combining nanoparticles of Fe and Texas Red to obtain combined information on the distribution of these molecules inside the liver. The distribution of different superparamagnetic iron oxides was also studied because the size of these new compounds is not always convenientfor microcirculation studies. RESULTS: Europium and Texas Red can be detected by confocal microscopy. Europium, iron and gadolinium can be detected by secondary ion mass spectrometry (SIMS) microscopy. Studies confirmed the complementarity of both microscopies. They also confirmed the possibility of using europium as a model of gadolinium to analyze thefate of MRI contrast agents. CONCLUSION: The methodology can be used on mice injected intravenously and analyzed by confocal and SIMS microscopy to localize MRI contrast agents inside cellular and tissue specimens of mice.
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Medios de Contraste/farmacocinética , Hígado/metabolismo , Imagen por Resonancia Magnética/métodos , Meglumina/análogos & derivados , Meglumina/farmacocinética , Compuestos Organometálicos/farmacocinética , Animales , Isótopos de Calcio/farmacocinética , Europio/farmacocinética , Femenino , Compuestos Férricos/farmacocinética , Colorantes Fluorescentes/farmacocinética , Isótopos de Hierro/farmacocinética , Isótopos/farmacocinética , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Microscopía Confocal , Isótopos de Potasio/farmacocinética , Sodio/farmacocinética , Espectrometría de Masa de Ion Secundario , Distribución Tisular , Xantenos/farmacocinéticaRESUMEN
In nuclear medicine, radiation absorbed dose estimates calculated by standard models at the whole body or organ are very low. At cellular level, however, the heterogeneity of radionuclide distributions of radiation dose patterns may be significant. We present here absorbed doses at cellular level and evaluate their possible impact on the usually assumed risk/benefit relationships in nuclear medicine studies. The absorbed dose values calculated are surprisingly high, and are difficult to interpret. In the present study, we show calculated doses at the cellular level and discuss possible biological consequences, for two radiopharmaceuticals labelled with technetium-99m: human serum albumin microspheres used for pulmonary scintigrapies and HMPAO used to labelled leukocytes
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The Chernobyl accident, which occurred 32 years after the accidental exposure of Marshall islanders, resulted in the exposure of neighbouring populations to a mixture of iodine isotopes and in an increased incidence of thyroid cancer. The highest thyroid doses were received by the youngest age groups. This review describes the existing evidence, and examines factors that may have increased the risk. It also stresses problems with contemporary thyroid measurements, and the lack of information on the sensitivity of the thyroid to short-lived iodine isotopes and iodine-131. Practical considerations for nuclear physicians, epidemiologists and thyroidologists are discussed in the light of this major accident.