RESUMO
This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.
Assuntos
Apoptose , Catarata , Proteína Forkhead Box M1 , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Raios Ultravioleta , Proteínas de Sinalização YAP , Apoptose/efeitos da radiação , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Raios Ultravioleta/efeitos adversos , Humanos , Animais , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Camundongos , Catarata/etiologia , Catarata/metabolismo , Catarata/patologia , Proteínas de Sinalização YAP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Cristalino/metabolismo , Cristalino/efeitos da radiação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Espécies Reativas de Oxigênio/metabolismo , Masculino , Transdução de Sinais , Camundongos Endogâmicos C57BLRESUMO
Cataracts are the world's number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment.
Assuntos
Catarata , Células Epiteliais , Cristalino , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Sirtuína 1 , Animais , Humanos , Ratos , Western Blotting , Luz Azul/efeitos adversos , Catarata/metabolismo , Catarata/patologia , Catarata/etiologia , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Cristalino/efeitos da radiação , Cristalino/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Piroptose/fisiologia , Piroptose/efeitos da radiação , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Sirtuína 1/metabolismoRESUMO
PURPOSES: The aim of this study is to investigate the time evolution of active caspase 3 within first 120 h in the rat lens after in vivo exposure to subthreshold dose of UVR-B. METHODS: Twenty three six-week-old female albino Sprague-Dawley rats were exposed to subthreshold dose (1 kJ/m2) of UVR-B unilaterally and sacrificed at 24, 41, 70 and 120 h after exposure. Lenses were enucleated and active caspase 3 was detected by Western Blot. The time evolution of active caspase 3 was then plotted as a function of relative mean difference in active caspase 3 between exposed and nonexposed lenses. RESULTS: There is expression of active caspase 3 in both exposed and nonexposed lenses but there is no difference in relative mean difference in active caspase 3 between exposed and nonexposed lenses in all four postexposure groups. CONCLUSIONS: Exposure to subthreshold dose of UVR-B does not induce apoptosis in the rat lens in vivo within first 120 h though there is a non-significant increase of active caspase 3 at 120 h. Increase in sample size might reduce the variation level in expression of active caspase 3 in the rat lenses.
Assuntos
Caspase 3 , Cristalino , Raios Ultravioleta , Animais , Feminino , Ratos , Apoptose , Western Blotting , Caspase 3/metabolismo , Caspase 3/efeitos da radiação , Cristalino/metabolismo , Cristalino/efeitos da radiação , Ratos Sprague-DawleyRESUMO
BACKGROUND: Adaptive collimation reduces the dose deposited outside the imaged volume along the z-axis. An increase in the dose deposited outside the imaged volume (to the lens and thyroid) in the z-axis direction is a concern in paediatric computed tomography (CT). OBJECTIVE: To compare the dose deposited outside the imaged volume (to the lens and thyroid) between 40-mm and 80-mm collimation during thoracic paediatric helical CT. MATERIALS AND METHODS: We used anthropomorphic phantoms of newborns and 5-year-olds with 40-mm and 80-mm collimation during helical CT. We compared the measured dose deposited outside the imaged volume using optically stimulated luminescence dosimeters (OSLD) at the surfaces of the lens and thyroid and the image noise between the 40-mm and 80-mm collimations. RESULTS: There were significant differences in the dose deposited outside the imaged volume (to the lens and thyroid) between the 40-mm and 80-mm collimations for both phantoms (P < 0.01). CONCLUSION: Compared with that observed for 80-mm collimation in helical CT scans of the paediatric thorax, the dose deposited outside the imaged volume (to the lens and thyroid) was significantly lower in newborns and 5-year-olds with 40-mm collimation.
Assuntos
Cristalino , Imagens de Fantasmas , Doses de Radiação , Radiografia Torácica , Glândula Tireoide , Humanos , Glândula Tireoide/diagnóstico por imagem , Recém-Nascido , Cristalino/diagnóstico por imagem , Cristalino/efeitos da radiação , Radiografia Torácica/métodos , Radiografia Torácica/instrumentação , Pré-Escolar , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada Espiral/métodosRESUMO
BACKGROUND: Reports comparing field lens doses between helical scans with a 40-mm detector width and axial scans with a 160-mm detector width using different computed tomography (CT) scanners are currently scarce. OBJECTIVE: To compare scatter doses for lenses between a helical scan with a 40-mm detector width and an axial scan with a 160-mm detector width when using different CT scanners in the context of pediatric chest examinations. MATERIALS AND METHODS: Two different CT machines were used: Revolution CT (GE Healthcare, Waukesha, WI) with a 256-row, 0.625-mm multidetector; and Aquilion ONE GENESIS Edition (Canon Medical Systems, Otawara, Japan) with a 320-row, 0.5-mm multidetector. Three pediatric anthropomorphic phantoms were used, with optically stimulated luminescence dosimeters (OSLDs) placed on the left and right lenses. The scatter dose values measured by the OSLDs were compared between a helical scan with a 40-mm detector width and an axial scan with a 160-mm detector width during pediatric chest CT examinations. RESULTS: Median equivalent doses for the helical and axial scans were 0.12 and 0.12 mSv/mGy for the newborn, 0.17 and 0.16 mSv/mGy for the 1-year-old, and 0.18 and 0.15 mSv/mGy for the 5-year-old, respectively, when using the Revolution CT. With the Revolution CT, no significant differences were observed in the scatter doses between helical and axial scans in the newborn and 1-year-old phantoms. However, the lens scatter dose for the helical scan was approximately 20-35% higher than that for the axial scan in the 5-year-old phantom (P<0.01). The median equivalent doses of eye lenses for the helical and axial scans were 0.12 and 0.07 mSv/mGy for the newborn, 0.07 and 0.05 mSv/mGy for the 1-year-old, and 0.14 and 0.12 mSv/mGy for the 5-year-old, respectively, when using the Aquilion ONE. With the Aquilion ONE, lens scatter doses for the helical scan were approximately 70%, 40%, and 30% higher in the newborn, 1-year-old, and 5-year-old phantoms, respectively, than those for the axial scan (P<0.01). CONCLUSIONS: When using the Aquilion ONE, lens scatter doses for the helical scan were significantly higher in all three phantoms than those for the axial scan. In contrast, when using the Revolution CT, the lens scatter dose for the helical scan was significantly higher in the 5-year-old phantom than that for the axial scan. These results suggest that although scattered doses may vary with respect to the CT scanner and body size, they are generally lower in the case of axial scans.
Assuntos
Cristalino , Doses de Radiação , Espalhamento de Radiação , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Cristalino/diagnóstico por imagem , Cristalino/efeitos da radiação , Tomografia Computadorizada Espiral/métodos , Tomografia Computadorizada por Raios X/métodos , Imagens de Fantasmas , Radiometria , Exposição à Radiação , Recém-Nascido , Lactente , Pré-EscolarRESUMO
Vision badge is an eye lens dosimeter to measureHp(3). This study aimed to evaluate the basic characteristics of the Vision badge and its performance as an eye lens dosimeter for endoscopists by phantom study. Energy dependence was evaluated by changing the tube voltage to 50 kV (effective energy of 27.9 keV), 80 kV (32.2 keV), and 120 kV (38.7 keV). Dose linearity was evaluated by changing the number of irradiation to 1, 5, and 40 times, which corresponded to 0.53, 5.32, and 21.4 mGy. Batch uniformity was evaluated by calculating the coefficient of variation ofHp(3) obtained from 10 Vision badges. Angular dependence was evaluated at 0° (perpendicular to the incident direction of x-rays), 30°, 60°, 75°, and 90°. The Vision badge and optically stimulated luminescence (OSL) dosimeter were attached to the inside of the radioprotective glasses, worn on the endoscopist phantom, and theHp(3) obtained from both dosimeters were compared. TheHp(3) obtained from the Vision badge with 38.7 keV was 3.8% higher than that with 27.9 keV. The Vision badge showed excellent linearity (R2= 1.00) with the air kerma up to 21.4 mGy. The coefficient of variation of theHp(3) for 10 Vision badges was 3.47%. The relative dose of the Vision badge decreased as the angle increased up to 75°, but increased at 90°. TheHp(3) obtained by the OSL dosimeter and the Vision badge were decreased as the endoscopist phantom was turned away from the patient phantom. TheHp(3) that was obtained by the Vision badge was 35.5%-55.0% less than that obtained by the nanoDot. In conclusion, the Vision badge showed specific angular dependence due to its shape, but satisfactory basic properties were exhibited for all characteristics. In phantom study, the Vision badge showed generally similar trends with the OSL dosimeter.
Assuntos
Cristalino , Dosímetros de Radiação , Humanos , Radiografia , Raios X , Imagens de Fantasmas , Cristalino/efeitos da radiaçãoRESUMO
The purpose of this study is to evaluate the occupational doses (eye lens, extremities and whole body) in paediatric cardiac interventional and diagnostic catheterization procedures performed in a paediatric reference hospital located in Recife, Pernambuco. For eye lens dosimetry, the results show that the left eye receives a higher dose than the right eye, and there is a small difference between the doses received during diagnostic (D) and therapeutic (T) procedures. The extrapolated annual values for the most exposed eye are close to the annual limit. For doses to the hands, it was observed that in a significant number of procedures (37 out of 45 therapeutic procedures, or 82%) at least one hand of the physician was exposed to the primary beam. During diagnostic procedures, the physician's hand was in the radiation field in 11 of the 17 catheterization procedures (65%). This resulted in a 10-fold increase in dose to the hands. The results underscore the need for optimization of radiation safety and continued efforts to engage staff in a radiation safety culture.
Assuntos
Exposição Ocupacional , Doses de Radiação , Humanos , Exposição Ocupacional/análise , Criança , Cateterismo Cardíaco , Proteção Radiológica , Cristalino/efeitos da radiação , Radiografia Intervencionista , Exposição à Radiação/análiseRESUMO
According to International Commission of Radiological Protection, the equivalent dose limit for the eye lens for occupational exposure is recommended to be 20 mSv yr-1, averaged over 5 years, with no single year above 50 mSv. Some studies reported the measurement of assistant's lens exposure in diagnostic computed tomography (CT) examinations, but further investigation is still required in the association between the lens dose for assistants and various dose parameters. Therefore, we measured the assistant's lens exposure using small optically stimulated luminescence dosimeters. The type of occupation, type of assistance, total scan time, total mAs, total scan length, and dose-length product (DLP) were recorded and analyzed in association with air kerma at the lens position. The assistance was classified into four types: 'assisted ventilation,' 'head holding,' 'body holding,' and 'raising patient's arm.' The air kerma of lens position was not significantly different for each assistance type (p< 0.05, Kruskal-Wallis test). Further, the lens doses for assistants correlated with DLP, but with various strengths of correlation with the assistance type and were influenced by the distance from the CT gantry. In conclusion, lens dose during assistance and DLP demonstrated the strongest correlation. 'Raising patient's arm' and 'head holding' exhibited stronger correlations, which required less table movement during the CT scan than 'assisted ventilation' and 'body holding'.
Assuntos
Cristalino , Exposição Ocupacional , Doses de Radiação , Tomografia Computadorizada por Raios X , Cristalino/efeitos da radiação , Humanos , Exposição Ocupacional/análise , Proteção Radiológica , Exposição à Radiação/análiseRESUMO
ABSTRACT: Radioactive materials and ionizing radiation have both medical value and disease risks, necessitating radiation dose measurement and risk reduction strategies. The International Commission on Radiological Protection (ICRP) lowered the lens of the eye exposure limit, leading to Japan's revised "Ionizing Radiation Ordinance." However, the effects on radiation exposure in medical settings and compliance feasibility remain unclear. To examine the impact of the revision to the "Ionizing Radiation Ordinance" and use it for measures to reduce exposure to radiation, a comprehensive analysis was conducted on data collected from Nagasaki University Hospital, Hiroshima University Hospital, and Fukushima Medical University Hospital in 2018, 2020, and April to September 2021. This included information on age, sex, occupation, department, and monthly radiation doses of workers, aiming to assess the impact of the revision to the "Ionizing Radiation Ordinance" on radiation exposure before and after its enforcement. Out of 9,076 cases studied, 7,963 (87.7%) had radiation doses below the measurable limit throughout the year. Only 292 cases (3.2%) exceeded 1 mSv y -1 , with 9 doctors and 2 radiological technologists surpassing 5 mSv y -1 . Radiological technologists showed significantly higher doses compared to doctors, dentists, and nurses (p < 0.01), while male subjects had significantly higher exposure doses than females (p < 0.01). No significant changes in radiation exposure were observed before and after the revision of the Ionizing Radiation Ordinance; however, variations in radiation exposure control were noted, particularly among nurses and radiological technologists, suggesting the impact of the revision and the need for tailored countermeasures to reduce radiation dose in each group.
Assuntos
Cristalino , Exposição Ocupacional , Exposição à Radiação , Feminino , Humanos , Masculino , Japão , Cristalino/efeitos da radiação , Exposição à Radiação/efeitos adversos , Pessoal de Saúde , Radiação Ionizante , Exposição Ocupacional/análise , Doses de RadiaçãoRESUMO
In India, the prevailing approach to eye lens dosimetry is the placement of an existing dosemeter on the forehead region after slight modification serves as a dedicated Eye Lens Dosemeter. A methodology for estimating the eye lens dose in terms of the Hp(3) has been previously explored employing an algorithm based on the response characteristics of this dosemeter using ISO slab phantom. It was observed that the performance of the dosemeter in terms of Hp(3) using previous algorithm showed under response at higher angles of incidence and photon beams of energy < 200 keV. Further, study was conducted to modify the algorithm following the latest ISO recommendations. This involved generation of data from the response of existing dosemeter on a cylindrical phantom. The results of this study revealed better performance of the newly established algorithm in estimating eye lens dose in terms of Hp(3) when compared to the earlier algorithm.
Assuntos
Algoritmos , Cristalino , Imagens de Fantasmas , Dosimetria Termoluminescente , Humanos , Calibragem , Cristalino/efeitos da radiação , Dosimetria Termoluminescente/instrumentação , Dosimetria Termoluminescente/métodos , Doses de Radiação , Fótons , Cabeça/efeitos da radiação , Índia , Proteção Radiológica/normas , Proteção Radiológica/instrumentaçãoRESUMO
OBJECTIVES: To establish conversion coefficients (CCs), between mean absorbed dose to the brain and eye lens of the cardiologist and the air kerma-area product, PKA, for a set of projections in cardiac interventional procedures. Furthermore, by taking clinical data into account, a method to estimate the doses per procedure, or annual dose, is presented. METHODS: Thermoluminescence dosimeters were used together with anthropomorphic phantoms, simulating a cardiologist performing an interventional cardiac procedure, to estimate the CCs for the brain and eye lens dose for nine standard projections, and change in patient size and x-ray spectrum. Additionally, a single CC has been estimated, accounting for each projections fraction of use in the clinic and associated PKA using clinical data from the dose monitoring system in our hospital. RESULTS: The maximum CCs for the eye lens and segment of the brain, is 5.47 µGy/Gycm2 (left eye lens) and 1.71 µGy/Gycm2 (left brain segment). The corresponding weighted CCs: are 3.39 µGy/Gycm2 and 0.89 µGy/Gycm2, respectively. CONCLUSIONS: Conversion coefficients have been established under actual scatter conditions, showing higher doses on the left side of the operator. Using modern interventional x-ray equipment, interventional cardiac procedures will not cause high radiation dose levels to the operator when a ceiling mounted shield is used, otherwise there is a risk that the threshold dose values for cataract will be reached. ADVANCE IN KNOWLEDGE: In addition to the CCs for the different projections, methods for deriving a single CC per cardiac interventional procedure and dose per year were introduced.
Assuntos
Encéfalo , Cardiologistas , Cristalino , Exposição Ocupacional , Imagens de Fantasmas , Doses de Radiação , Humanos , Cristalino/efeitos da radiação , Encéfalo/efeitos da radiação , Encéfalo/diagnóstico por imagem , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Dosimetria Termoluminescente , Cardiologia , Radiografia Intervencionista/métodosRESUMO
BACKGROUND: Since 2011, the International Commission on Radiological Protection (ICRP) has recommended an annual eye lens dose limit of 20 mSv for radiation workers, averaged over 5 years, with no year exceeding 50 mSv. However, limited research has been conducted on dose rate conversion coefficients (DCCs) for direct contamination of the eye. PURPOSE: This study aimed to accurately determine DCCs for the eye lens and cornea for ocular contamination with radionuclides used in nuclear medicine. METHODS: DCCs for 37 radionuclides used in nuclear medicine were determined using two different methods. Method 1 involved conducting Monte Carlo (MC) simulations of an ICRU cylinder to determine the absorbed dose at a depth of 3 mm resulting from a point source. The accuracy of this simulation approach was validated by experimental thermoluminescent dosimeter (TLD) measurements for 18F, 68Ga, 99mTc, and 177Lu. In method 2, average DCCs were calculated for the eye lens (complete and radiosensitive parts) and the cornea for both a point source and thin surface contamination centered on the cornea using MC simulations on the adult mesh-type reference computational phantom of the eye from the ICRP (MRCP). RESULTS: DCCs determined from TLD measurements showed excellent agreement (deviations: +1.4%, +4.7%, -3.1%, and -2.5% for 18F, 68Ga, 99mTc, and 177Lu, respectively) compared to MC simulations of the experimental set-up. For the 37 radionuclides, DCCs of the complete eye-lens for a point source ranged from 2.53 × 10-7 to 4.15 × 10-2 mGy MBq-1 s-1 for the adult MRCPs, being substantially smaller compared to DCCs determined via MC simulations of a ICRU cylinder. In general, point source and surface contamination showed comparable DCCs for the eye lens. Radionuclides emitting low-energy beta radiation or conversion electrons (e.g., 177Lu, 99mTc) showed low DCCs as the radiation does not penetrate to the depth of the eye lens, while radionuclides emitting high-energy beta radiation (e.g., 90Y) showed high DCCs. Overall, DCCs for the radiosensitive part of the eye lens were larger (up to a factor of 3) compared to the complete eye lens. DCCs for the cornea were larger than for the eye lens with a factor that strongly depended on the emitted radiation type. Especially alpha emitters (e.g., 211At, 223Ra) showed high DCCs for the cornea because of the short range of alpha radiation, leading to local maxima in the cornea and not reaching the eye lens. CONCLUSION: DCCs at a depth of 3 mm in an ICRU cylinder and adult MRCP DCCs for both the complete and sensitive parts of the eye lens and cornea were determined for 37 radionuclides having applications in nuclear medicine. These DCCs are highly useful in radiation safety assessments and radiation dose calculations in ocular contamination incidents.
Assuntos
Método de Monte Carlo , Medicina Nuclear , Doses de Radiação , Humanos , Cristalino/efeitos da radiação , Olho/efeitos da radiação , Olho/diagnóstico por imagem , Córnea/efeitos da radiação , Córnea/diagnóstico por imagem , Imagens de Fantasmas , Dosimetria Termoluminescente , RadioisótoposRESUMO
We quantified the level of backscatter radiation generated from physicians' heads using a phantom. We also evaluated the shielding rate of the protective eyewear and optimal placement of the eye-dedicated dosimeter (skin surface or behind the Pb-eyewear). We performed diagnostic X-rays of two head phantoms: Styrofoam (negligible backscatter radiation) and anthropomorphic (included backscatter radiation). Radiophotoluminescence glass dosimeters were used to measure the eye-lens dose, with or without 0.07-mm Pb-equivalent protective eyewear. We used tube voltages of 50, 65 and 80 kV because the scattered radiation has a lower mean energy than the primary X-ray beam. The backscatter radiation accounted for 17.3-22.3% of the eye-lens dose, with the percentage increasing with increasing tube voltage. Furthermore, the shielding rate of the protective eyewear was overestimated, and the eye-lens dose was underestimated when the eye-dedicated dosimeter was placed behind the protective eyewear. We quantified the backscatter radiation generated from physicians' heads. To account for the effect of backscatter radiation, an anthropomorphic, rather than Styrofoam, phantom should be used. Close contact of the dosimeter with the skin surface is essential for accurate evaluation of backscatter radiation from physician's own heads. To assess the eye-lens dose accurately, the dosimeter should be placed near the eye. If the dosimeter is placed behind the lens of the protective eyewear, we recommend using a backscatter radiation calibration factor of 1.2-1.3.
Assuntos
Dispositivos de Proteção dos Olhos , Cristalino , Exposição Ocupacional , Imagens de Fantasmas , Doses de Radiação , Espalhamento de Radiação , Humanos , Cristalino/efeitos da radiação , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/análise , Radiometria , Proteção Radiológica , Dosímetros de Radiação , Relação Dose-Resposta à RadiaçãoRESUMO
Health effects of space radiation are a serious concern for astronauts on long-duration missions. The lens of the eye is one of the most radiosensitive tissues in the body and, therefore, ocular health risks for astronauts is a significant concern. Studies in humans and animals indicate that ionizing radiation exposure to the eye produces characteristic lens changes, termed "radiation cataract," that can affect visual function. Animal models of radiation cataractogenesis have previously utilized inbred mouse or rat strains. These studies were essential for determining morphological changes and dose-response relationships between radiation exposure and cataract. However, the relevance of these studies to human radiosensitivity is limited by the narrow phenotypic range of genetically homogeneous animal models. To model radiation cataract in genetically diverse populations, longitudinal cataract phenotyping was nested within a lifetime carcinogenesis study in male and female heterogeneous stock (HS/Npt) mice exposed to 0.4 Gy HZE ions (n = 609) or 3.0 Gy γ-rays (n = 602) and in unirradiated controls (n = 603). Cataractous change was quantified in each eye for up to 2 years using Merriam-Focht grading criteria by dilated slit lamp examination. Virtual Optomotry™ measurement of visual acuity and contrast sensitivity was utilized to assess visual function in a subgroup of mice. Prevalence and severity of posterior lens opacifications were 2.6-fold higher in HZE ion and 2.3-fold higher in γ-ray irradiated mice compared to unirradiated controls. Male mice were at greater risk for spontaneous and radiation associated cataracts. Risk for cataractogenesis was associated with family structure, demonstrating that HS/Npt mice are well-suited to evaluate genetic determinants of ocular radiosensitivity. Last, mice were extensively evaluated for cataract and tumor formation, which revealed an overlap between individual susceptibility to both cancer and cataract.
Assuntos
Catarata , Cristalino , Lesões por Radiação , Camundongos , Ratos , Masculino , Feminino , Humanos , Animais , Catarata/etiologia , Catarata/epidemiologia , Catarata/patologia , Lesões por Radiação/epidemiologia , Cristalino/patologia , Cristalino/efeitos da radiação , Raios gama/efeitos adversos , Íons , Relação Dose-Resposta à RadiaçãoRESUMO
The knowledge on responses of human lens epithelial cells (HLECs) to ionizing radiation exposure is important to understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLECs following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of γ-H2AX foci as a marker for DNA double-strand breaks (DSBs) and cell survival in HLECs after exposure to photon beams at various dose rates (i.e., 150 kVp X-rays at 1.82, 0.1, and 0.033 Gy/min, and 137Cs γ-rays at 0.00461 Gy/min (27.7 cGy/h) and 0.00081 Gy/min (4.9 cGy/h)), compared to those in human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSBs and cell survival using a biophysical model. The study revealed that HLECs have a lower DSB repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. In contrast, the experimental residual γ-H2AX foci showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.
Assuntos
Sobrevivência Celular , Quebras de DNA de Cadeia Dupla , Relação Dose-Resposta à Radiação , Células Epiteliais , Histonas , Cristalino , Humanos , Células Epiteliais/efeitos da radiação , Células Epiteliais/metabolismo , Cristalino/efeitos da radiação , Cristalino/citologia , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Histonas/metabolismo , Sobrevivência Celular/efeitos da radiação , Radiação Ionizante , Linhagem Celular , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Fibroblastos/metabolismo , Raios X , Raios gama/efeitos adversosRESUMO
The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.
Assuntos
Catarata , Suplementos Nutricionais , Fator 2 Relacionado a NF-E2 , Raios Ultravioleta , Vitis , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X , Animais , Camundongos , Antocianinas/farmacologia , Catarata/prevenção & controle , Catarata/metabolismo , Catarata/etiologia , Glutationa/metabolismo , Cristalino/metabolismo , Cristalino/efeitos da radiação , Cristalino/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Vitis/química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
El número y la complejidad de los procedimientos de diagnóstico e intervencionismo cardiovascular han incrementado de manera significativa, hecho que genera mayor exposición a dosis bajas de radiación ionizante debido a la radiación dispersa por el paciente. El cristalino es una de las estructuras más sensibles a la radiación y las cataratas son la enfermedad ocular más estudiada y frecuente en el personal de la salud ocupacionalmente expuesto a dosis bajas de radiación. La formación de cataratas es un proceso multifactorial y la exposición a la radiación ionizante se ha asociado a opacidades subcapsulares posteriores, que es la forma más común de lesión, seguida por las cataratas corticales. Existen varios estudios que han evaluado los efectos de la exposición ocupacional por radiación ionizante en el cristalino en cardiólogos intervencionistas, comparándolos con controles no expuestos. Concluyen que hay mayor prevalencia de opacidades subcapsulares posteriores en el personal expuesto a radiación ionizante, especialmente en los cardiólogos intervencionistas (por trabajar muy cerca del generador de rayos X), las cuales están relacionadas con la duración de la práctica del intervencionismo cardíaco y disminuyen con el uso regular de los lentes plomados. Lo llamativo de muchos estudios es el bajo uso por parte de los cardiólogos intervencionistas de los elementos de protección radiológica, especialmente gafas y mampara plomada, las cuales han demostrado efectividad en la reducción de la radiación ionizante recibida por el personal de la sala de cateterismo cardiaco.
As the number and complexity of diagnostic and cardiovascular intervention procedures has increased significantly, this has led to a greater exposure to low doses of ionising radiation due to the radiation dispersal by the patient. The crystalline lens is one of the structures most sensitive to radiation, and cataracts are the most studied eye disease, and are common in health staff occupationally exposed to low radiation doses. The formation of cataracts is a process involving many factors, and exposure to ionising radiation has been associated with posterior sub-capsular opacities, the most common form of the injury, followed by cortical cataracts. There are several studies that have evaluated the effects of occupational exposure due to ionising radiation in the crystalline lens in interventionist cardiologists, and comparing them with non-exposed controls. They conclude that there is a higher prevalence of posterior sub-capsular opacities in personnel exposed to ionising radiation, especially in interventionist cardiologists (due to working very near the X-ray generator). These are associated with the duration of the practice of cardiac interventions, and decrease with the regular use of leaded glasses. The low use of radiation protection wear by interventionist cardiologists is highlighted in many studies, especially glasses and a leaded screen, which have shown to be effective in the reduction in the ionising radiation by the staff in the cardiac catheterisation room.
Assuntos
Humanos , Radiação Ionizante , Proteção Radiológica , Catarata/etiologia , Traumatismos Oculares/etiologia , Cristalino/efeitos da radiação , Relação Dose-Resposta à Radiação , Doenças ProfissionaisRESUMO
Abstract Background: Posterior subcapsular cataract is a tissue reaction commonly found among professionals exposed to ionizing radiation. Objective: To assess the prevalence of cataract in professionals working in hemodynamics in Brazil. Methods: Professionals exposed to ionizing radiation (group 1, G1) underwent slit lamp examination with a biomicroscope for lens examination and compared with non-exposed subjects (group 2, G2). Ophthalmologic findings were described and classified by opacity degree and localization using the Lens Opacities Classification System III. Both groups answered a questionnaire on work and health conditions to investigate the presence of risk factors for cataract. The level of significance was set at 5% (p < 0.05). Results: A total of 112 volunteers of G1, mean age of 44.95 (±10.23) years, and 88 volunteers of G2, mean age of 48.07 (±12.18) years were evaluated; 75.2% of G1 and 85.2% of G2 were physicians. Statistical analysis between G1 and G2 showed a prevalence of posterior subcapsular cataract of 13% and 2% in G1 and G2, respectively (0.0081). Considering physicians only, 38% of G1 and 15% of G2 had cataract, with the prevalence of posterior subcapsular cataract of 13% and 3%, respectively (p = 0.0176). Among non-physicians, no difference was found in the prevalence of cataract (by types). Conclusions: Cataract was more prevalent in professionals exposed to ionizing radiation, with posterior subcapsular cataract the most frequent finding.
Resumo Fundamento: A catarata subcapsular posterior é uma reação tecidual encontrada com frequência nos profissionais expostos à radiação ionizante. Objetivo: Avaliar a prevalência de catarata nos profissionais que atuam na área de hemodinâmica no Brasil. Métodos: Profissionais expostos à radiação ionizante (grupo 1, G1) foram submetidos ao exame biomicroscópico com lâmpada de fenda para avaliação do cristalino, e comparados aos não expostos (grupo 2, G2). Os achados foram descritos e classificados quanto ao grau de opacidade e localização por meio do Lens opacities classification system III. Ambos os grupos responderam questionário sobre condições de trabalho e de saúde para afastar fatores de risco para catarata, e foram comparados quanto aos achados. Foi utilizado um nível de significância de 5% (p < 0,05). Resultados: Foram avaliados 112 voluntários (G1) com média de idade 44,95 (±10,23) anos e 88 voluntários (G2) com média de 48,07 (±12,18) anos. Desses, 75,2% (G1) e 85,2% (G2) eram médicos. A análise estatística entre os grupos G1 e G2 mostrou uma prevalência da catarata no grupo G1 de 33% comparada ao G2 de 16% (p = 0,0058), sendo a catarata subcapsular posterior presente em 13% no G1 e 2% no G2 (p = 0,0081). Considerando apenas os médicos, 38% no G1 e 15% no G2 (p = 0,0011) apresentaram catarata, sendo a subcapsular posterior 13% e 3% (p = 0,0176), respectivamente. No grupo dos profissionais não médicos, não houve diferença estatisticamente significativa na prevalência dos achados oftalmológicos. Conclusões: A catarata esteve mais presente no grupo de profissionais expostos à radiação ionizante, sendo que a catarata subcapsular posterior foi o dano tecidual mais encontrado.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Catarata/epidemiologia , Exposição à Radiação/efeitos adversos , Cardiologistas/estatística & dados numéricos , Cristalino/efeitos da radiação , Doenças Profissionais/epidemiologia , Radiação Ionizante , Catarata/etiologia , Brasil/epidemiologia , Prevalência , Fatores de Risco , Exposição Ocupacional/efeitos adversos , Estatísticas não Paramétricas , Exposição à Radiação/estatística & dados numéricos , Dispositivos de Proteção dos Olhos/estatística & dados numéricos , Hemodinâmica , Doenças Profissionais/etiologiaRESUMO
O presente trabalho visa quantificar a radiação que incide em órgãos considerados críticos (tireóide, gônadas, cristalinos e pele), durante a tomada de radiografias intra-bucais pelas técnicas periapical da bissetriz e oclusal. Como dosímetros foram utilizados os termoluminescentes de fluoreto de lítio - 700. Os autores constataram que as maiores dosagens nos órgãos críticos foram: 0,101 rad para a tireóide na incidência oclusal inferior; 0,007 rad para as gônadas em ambas as técnicas; 0,268 rad no cristalino para a tomada periapical para molares superiores e 0,415 rad para a pele, em média
Assuntos
Humanos , Masculino , Criança , Glândula Tireoide/efeitos da radiação , Cristalino/efeitos da radiação , Efeitos da Radiação , Radiografia Dentária/efeitos adversos , Pele/efeitos da radiação , Dentição MistaRESUMO
Dada a grande importância do exame radiográfico como complemento no diagnóstico, e sabendo dos efeitos biológicos dos raios X, muitos estudos têm sido realizados para a determinaçäo das doses de radiaçäo que atingem o organismo humano. Neste trabalho nos preocupamos com algumas técnicas extra-bucais como as de Waters, Granger e Shuller e as doses que atingem as gônadas, glândula tireóide e o cristalino na aplicaçäo de cada uma dessas técnicas. Estabeleceu-se comparaçöes sobre os métodos utilizados (filmes dosimétricos e dosímetros termoluminescentes de fluoreto de lítio - Lif 700), os tipos morfológicos estudados com a finalidade de encontrar meios para diminuir os índices de radiaçäo (fatores elétricos, filtraçäo e filmes) nos órgäos críticos citados