RESUMEN
Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10â¯Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.
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Diferenciación Celular , Células Madre Mesenquimatosas , Osteogénesis , Receptor Notch1 , Sumoilación , Animales , Osteogénesis/efectos de la radiación , Ratones , Sumoilación/efectos de la radiación , Receptor Notch1/metabolismo , Receptor Notch1/genética , Células Madre Mesenquimatosas/efectos de la radiación , Diferenciación Celular/efectos de la radiación , Transducción de Señal/efectos de la radiación , Masculino , Fémur/efectos de la radiación , Relación Dosis-Respuesta en la RadiaciónRESUMEN
Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups.
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Terapia por Luz de Baja Intensidad , Células Madre Mesenquimatosas , Animales , Ratas , Terapia por Luz de Baja Intensidad/métodos , Medios de Cultivo Condicionados , Femenino , Ratas Sprague-Dawley , Fémur/efectos de la radiación , Fémur/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Osteoporosis/radioterapia , Osteoporosis/terapia , Ovariectomía , Andamios del Tejido , Osteogénesis/efectos de la radiación , Regeneración Ósea/efectos de la radiaciónRESUMEN
Poor vascularization was demonstrated as a factor inhibiting bone regeneration in patients receiving radiotherapy. Various copper-containing materials have been reported to increase angiogenesis, therefore might improve bone formation. In this study, a Ti6Al4V-1.5Cu alloy was prepared using selective laser melting (SLM) technology. The immunomodulatory and pro-angiogenic effects of the Ti6Al4V-1.5Cu alloys were examined. In vitro, Ti6Al4V-1.5Cu stimulated vascular formation by restraining inflammatory factors and provoking angiogenic factors in non-irradiated and irradiated macrophages. In vivo, the angiogenic effects of the Ti6Al4V-1.5Cu alloy were confirmed using an irradiated rat femur defect model. Moreover, we found that the biological effects of the Ti6Al4V-1.5Cu alloy were partially due to the release of copper ions and associated with PI3K-Akt signaling pathway. In conclusion, this study indicated the potential of the Ti6Al4V-1.5Cu alloy to promote angiogenesis by releasing copper ions and inhibiting inflammation in normal and irradiated tissues.
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Cobre , Fémur , Neovascularización Fisiológica , Titanio , Aleaciones , Animales , Cobre/farmacología , Fémur/irrigación sanguínea , Fémur/efectos de los fármacos , Fémur/efectos de la radiación , Iones , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Neovascularización Fisiológica/efectos de los fármacos , Fosfatidilinositol 3-Quinasas , Ratas , Titanio/farmacologíaRESUMEN
BACKGROUND: Gamma irradiation, which minimizes the risk of infectious disease transmission when human bone allograft is used, has been found to negatively affect its biomechanical properties. However, in those studies, the deep-freezing temperature during irradiation was not necessarily maintained during transportation and sterilization, which may have affected the findings. Prior reports have also suggested that controlled deep freezing may mitigate the detrimental effects of irradiation on the mechanical properties of bone allograft. QUESTION/PURPOSE: Does a controlled deep-freezing temperature during irradiation help preserve the compressive mechanical properties of human femoral cortical bone allografts? METHODS: Cortical bone cube samples, each measuring 64 mm3, were cut from the mid-diaphyseal midshaft of five fresh-frozen cadaver femurs (four male donors, mean [range] age at procurement 42 years [42 to 43]) and were allocated via block randomization into one of three experimental groups (with equal numbers of samples from each donor allocated into each group). Each experimental group consisted of 20 bone cube samples. Samples irradiated in dry ice were subjected to irradiation doses ranging from 26.7 kGy to 27.1 kGy (mean 26.9 kGy) at a deep-freezing temperature below -40°C (the recommended long-term storage temperature for allografts). Samples irradiated in gel ice underwent irradiation doses ranging from 26.2 kGy and 26.4 kGy (mean 26.3 kGy) in a freezing temperature range between -40°C and 0°C. Acting as controls, samples in a third group were not subjected to gamma irradiation. The mechanical properties (0.2% offset yield stress, ultimate compression stress, toughness, and the Young modulus) of samples from each group were subsequently evaluated via axial compression loading to failure along the long axis of the bone. The investigators were blinded to sample group during compression testing. RESULTS: The mean ultimate compression stress (84 ± 27 MPa versus 119 ± 31 MPa, mean difference 35 [95% CI 9 to 60]; p = 0.005) and toughness (3622 ± 1720 kJ/m3 versus 5854 ± 2900 kJ/m3, mean difference 2232 [95% CI 70 to 4394]; p = 0.009) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than in those irradiated at deep-freezing temperatures (below -40°C). The mean 0.2% offset yield stress (73 ± 28 MPa versus 109 ± 38 MPa, mean difference 36 [95% CI 11 to 60]; p = 0.002) and ultimate compression stress (84 ± 27 MPa versus 128 ± 40 MPa, mean difference 44 [95% CI 17 to 69]; p < 0.001) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than the nonirradiated control group samples. The mean 0.2% offset yield stress (73 ± 28 MPa versus 101 ± 28 MPa, mean difference 28 [95% CI 3 to 52]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to those irradiated at deep-freezing temperature. The mean toughness (3622 ± 1720 kJ/m3 versus 6231 ± 3410 kJ/m3, mean difference 2609 [95% CI 447 to 4771]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to the non-irradiated control group samples. The mean 0.2% offset yield stress, ultimate compression stress, and toughness of samples irradiated in deep-freezing temperatures (below -40°C) were not different with the numbers available to the non-irradiated control group samples. The Young modulus was not different with the numbers available among the three groups. CONCLUSION: In this study, maintenance of a deep-freezing temperature below -40°C, using dry ice as a cooling agent, consistently mitigated the adverse effects of irradiation on the monotonic-compression mechanical properties of human cortical bone tissue. Preserving the mechanical properties of a cortical allograft, when irradiated in a deep-freezing temperature, may have resulted from attenuation of the deleterious, indirect effects of gamma radiation on its collagen architecture in a frozen state. Immobilization of water molecules in this state prevents radiolysis and the subsequent generation of free radicals. This hypothesis was supported by an apparent loss of the protective effect when a range of higher freezing temperatures was used during irradiation. CLINICAL RELEVANCE: Deep-freezing temperatures below -40°C during gamma irradiation may be a promising approach to better retain the native mechanical properties of cortical bone allografts. A further study of the effect of deep-freezing during gamma radiation sterilization on sterility and other important biomechanical properties of cortical bone (such as, tensile strength, fracture toughness, and fatigue) is needed to confirm these findings.
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Aloinjertos , Fuerza Compresiva/efectos de la radiación , Hueso Cortical/efectos de la radiación , Fémur/efectos de la radiación , Congelación , Rayos gamma , Esterilización/métodos , Adulto , Cadáver , Humanos , Masculino , Estrés MecánicoRESUMEN
Current models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain 'A' male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1ß, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1ß levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.
Asunto(s)
Síndrome de Radiación Aguda/etiología , Modelos Animales de Enfermedad , Enfermedades Hematológicas/etiología , Exposición a la Radiación/efectos adversos , Síndrome de Radiación Aguda/genética , Síndrome de Radiación Aguda/metabolismo , Animales , Radioisótopos de Cobalto/efectos adversos , Radioisótopos de Cobalto/química , Citocinas/genética , Citocinas/metabolismo , Fémur/metabolismo , Fémur/efectos de la radiación , Rayos gamma/efectos adversos , Enfermedades Hematológicas/genética , Enfermedades Hematológicas/metabolismo , Humanos , Masculino , RatonesRESUMEN
We assessed the combined impacts of human demineralized bone matrix (hDBM) scaffold, adipose-derived stem cells (hADS), and photobiomodulation (PBM) on bone repair of a critical size femoral defect (CSFD) in 72 rats. The rats were divided into six groups: control (group 1); ADS (group 2 - ADS transplanted into hDBM); PBM (group 3 - PBM-treated CSFDs); ADS + PBM in vivo (group 4 - ADS transplanted into hDBM and the CSFDs were treated with PBM in vivo); ADS + PBM in vitro (group 5 - ADS were treated with PBM in vitro, then seeded into hDBM); and ADS + PBM in vitro+in vivo (group 6 - PBM-treated ADS were seeded into hDBM, and the CSFDs were treated with PBM in vivo. At the anabolic phase (2 weeks after surgery), bone strength parameters of the groups 5, 6, and 4 were statistically greater than the control, ADS, and PBM in vivo groups (all, p = 0.000). Computed tomography (CT) scans during the catabolic phase (6 weeks after surgery) of bone healing revealed that the Hounsfield unit (HU) of CSFD in the groups 2 (p = 0.000) and 5 (p = 0.019) groups were statistically greater than the control group. The groups 5, 4, and 6 had significantly increased bone strength parameters compared with the PBM in vivo, control, and ADS groups (all, p = 0.000). The group 5 was statistically better than the groups 4, and 6 (both, p = 0.000). In vitro preconditioned of hADS with PBM significantly increased bone repair in a rat model of CSFD in vivo.
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Tejido Adiposo/citología , Fémur/patología , Fémur/efectos de la radiación , Terapia por Luz de Baja Intensidad , Células Madre/citología , Células Madre/efectos de la radiación , Cicatrización de Heridas/efectos de la radiación , Animales , Biomarcadores/metabolismo , Fenómenos Biomecánicos , Matriz Ósea/efectos de la radiación , Matriz Ósea/ultraestructura , Supervivencia Celular/efectos de la radiación , Módulo de Elasticidad , Humanos , Masculino , Ratas WistarRESUMEN
Gamma radiation sterilization is the method used by the majority of tissue banks to reduce disease transmission from infected donors to recipients through bone allografts. However, many studies have reported that gamma radiation impairs the structural and mechanical properties of bone via formation of free radicals, the effect of which could be reduced using free radical scavengers. The aim of this study is to examine the radioprotective role of hydroxytyrosol (HT) and alpha lipoic acid (ALA) on the mechanical properties of gamma-sterilized cortical bone of bovine femur, using three-point bending and microhardness tests. Specimens of bovine femurs were soaked in ALA and HT for 3 and 7 days, respectively, before being exposed to 35-kGy gamma radiation. In unirradiated samples, both HT and ALA pre-treatment improved the cortical bone bending plastic properties (maximum bending stress, maximum bending strain, and toughness) without affecting microhardness. Irradiation resulted in a drastic reduction of the plastic properties and an increased microhardness. ALA treatment before irradiation alleviated the aforementioned reductions in maximum bending stress, maximum bending strain, and toughness. In addition, under ALA treatment, the microhardness was not increased after irradiation. For HT treatment, similar effects were found. In conclusion, the results indicate that HT and ALA can be used before irradiation to enhance the mechanical properties of gamma-sterilized bone allografts.
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Antioxidantes/farmacología , Fémur/efectos de los fármacos , Fémur/efectos de la radiación , Rayos gamma , Alcohol Feniletílico/análogos & derivados , Protectores contra Radiación/farmacología , Ácido Tióctico/farmacología , Animales , Fenómenos Biomecánicos , Trasplante Óseo , Bovinos , Dureza , Alcohol Feniletílico/farmacología , Esterilización/métodos , Estrés MecánicoRESUMEN
Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.
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Campos Electromagnéticos , Fémur/fisiopatología , Fémur/efectos de la radiación , Heparina/farmacología , Osteoporosis/inducido químicamente , Osteoporosis/fisiopatología , Animales , Fémur/metabolismo , Fémur/patología , Masculino , Osteoporosis/metabolismo , Osteoporosis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Erythroid precursors from the femoral bone marrow of Wistar rats were characterized after 30-day hindlimb suspension, fractionated γ-radiation, and their combination. After hindlimb suspension, the total content of myeloid CFU decreased; activity of erythroid differon also considerably suppressed, which manifested in a decrease in the number of erythroid burst-forming units and area of colonies formed by erythrocyte precursors. After irradiation and combined exposure to these two factors, no significant differences from the control were revealed; optical density of formed colonies slightly increased in all experimental groups. Thus, suppression of the erythroid lineage was most pronounced during hindlimb unloading. The combined effect of radiation and hindlimb suspension produced no appreciable negative effect on erythropoiesis in rat bone marrow.
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Células de la Médula Ósea/efectos de la radiación , Médula Ósea/efectos de la radiación , Células Precursoras Eritroides/efectos de la radiación , Rayos gamma , Hematopoyesis/efectos de la radiación , Suspensión Trasera , Animales , Células de la Médula Ósea/citología , Linaje de la Célula/fisiología , Linaje de la Célula/efectos de la radiación , Células Precursoras Eritroides/citología , Fémur/citología , Fémur/efectos de la radiación , Hematopoyesis/fisiología , Masculino , Ratas , Ratas Wistar , Irradiación Corporal TotalRESUMEN
RATIONALE: Whole-bone proteomic analyses rely on lengthy sample preparation including demineralization and digestion to break bone down into peptides to recover using mass spectrometry. However, microwave-assisted acid hydrolysis, a technique used in proteomic analyses of other soft tissues and cells, will combine both demineralization and digestion and only take minutes. METHODS: To test microwave-assisted hydrolysis on whole moose bone, we microwaved five concentrations of acetic and formic acids (15%, 12.5%, 10%, 7.5% and 5%) for three times (10, 20 and 30 min) at 140°C using an ETHOS UP high performance microwave digestion system. Peptides were injected and separated using Thermo BioBasic C18 columns and detected with an LTQ Orbitrap Velos mass spectrometer. We searched the raw data on PEAKS 8.5 against the white-tailed deer database. RESULTS: Formic acid hydrolysis led to the most complete digestion, and therefore the highest number of peptide spectrum matches, more protein groups and better sequence coverage for collagenous proteins. However, for the formic acid samples there is a tradeoff with digestion completeness and a higher incidence of in vitro modifications (i.e. formylation) that are not induced using acetic acid. Acetic acid has greater cleavage specificity and higher sequence coverage for non-collagenous proteins. CONCLUSIONS: Depending on the goals of analysis, there are benefits and drawbacks to using both acetic acid and formic acid. Overall, microwave-assisted acid hydrolysis was successful in demineralizing and digesting bone fragments to considerably speed up the preparation for bottom-up proteomics analysis.
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Ácido Acético/química , Fémur/química , Formiatos/química , Proteómica/métodos , Animales , Ciervos , Fémur/efectos de la radiación , Hidrólisis , Espectrometría de Masas , Microondas , Paleontología , Péptidos/químicaRESUMEN
Radiation therapy and estrogen deficiency can damage healthy bone and lead to an increased fracture risk. The goal of this study is to develop a mouse model for radiation therapy using a fractionated biologically equivalent dose for cervical cancer treatment in both pre- and postmenopausal women. Thirty-two female C57BL/6 mice 13 weeks of age were divided into four groups: Sham + non-irradiated (SHAM + NR), Sham + irradiated (SHAM + IRR), ovariectomy + non-irradiated (OVX + NR) and ovariectomy + irradiated (OVX + IRR). The irradiated mice received a 6 Gy dose of X-rays to the hindlimbs at Day 2, Day 4 and Day 7 (18 Gy total). Tissues were collected at Day 35. DEXA, microCT analysis and FEA were used to quantify structural and functional changes at the proximal tibia, midshaft femur, proximal femur and L1 vertebra. There was a significant (p < 0.05) decline in proximal tibia trabecular BV/TV from (1) IRR compared to NR mice within Sham (- 46%) and OVX (- 41%); (2) OVX versus Sham within NR mice (- 36%) and IRR mice (- 30%). With homogenous material properties applied to the proximal tibia mesh using FEA, there was (1) an increase in whole bone (trabecular + cortical) structural stiffness from IRR compared to NR mice within Sham (+ 10%) and OVX (+ 15%); (2) a decrease in stiffness from OVX versus Sham within NR mice (- 18%) and IRR mice (- 14%). Fractionated irradiation and ovariectomy both had a negative effect on skeletal microarchitecture. Ovariectomy had a systemic effect, while skeletal radiation damage was largely specific to trabecular bone within the X-ray field.
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Huesos/fisiología , Estradiol/deficiencia , Traumatismos Experimentales por Radiación , Animales , Densidad Ósea/efectos de los fármacos , Densidad Ósea/efectos de la radiación , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Huesos/efectos de la radiación , Modelos Animales de Enfermedad , Estradiol/sangre , Estradiol/farmacología , Femenino , Fémur/efectos de los fármacos , Fémur/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Ovariectomía , Traumatismos Experimentales por Radiación/complicaciones , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/fisiopatología , Radiografía , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Tibia/efectos de los fármacos , Tibia/efectos de la radiación , Microtomografía por Rayos XRESUMEN
A moderate radiation dose, in vivo µCT scanning protocol was developed and validated for long-term monitoring of multiple skeletal sites (femur, tibia, vertebra) in mice. A customized, 3D printed mouse holder was designed and utilized to minimize error associated with animal repositioning, resulting in good to excellent reproducibility in most cortical and trabecular bone microarchitecture and density parameters except for connectivity density. Repeated in vivo µCT scans of mice were performed at the right distal femur and the 4th lumbar vertebra every 3 weeks until euthanized at 9 weeks after the baseline scan. Comparing to the non-radiated counterparts, no radiation effect was found on trabecular bone volume fraction, osteoblast and osteoblast number/surface, or bone formation rate at any skeletal site. However, trabecular number, thickness, and separation, and structure model index were sensitive to ionizing radiation associated with the µCT scans, resulting in subtle but significant changes over multiple scans. Although the extent of radiation damage on most trabecular bone microarchitecture measures are comparable or far less than the age-related changes during the monitoring period, additional considerations need to be taken to minimize the confounding radiation factors when designing experiments using in vivo µCT imaging for long-term monitoring of mouse bone.
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Fémur/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Tibia/diagnóstico por imagen , Microtomografía por Rayos X , Animales , Femenino , Fémur/efectos de la radiación , Vértebras Lumbares/efectos de la radiación , Ratones Endogámicos C57BL , Reproducibilidad de los Resultados , Tibia/efectos de la radiaciónRESUMEN
PURPOSE: To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo-based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. METHODS AND MATERIALS: Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. RESULTS: In comparison to segmentation scheme 4, TG-43-based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. CONCLUSIONS: Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging-based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.
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Braquiterapia/métodos , Radioisótopos de Iridio/administración & dosificación , Órganos en Riesgo/efectos de la radiación , Radioisótopos/administración & dosificación , Neoplasias del Recto/radioterapia , Radioisótopos de Selenio/administración & dosificación , Iterbio/administración & dosificación , Braquiterapia/instrumentación , Fémur/efectos de la radiación , Humanos , Método de Montecarlo , Órganos en Riesgo/diagnóstico por imagen , Huesos Pélvicos/efectos de la radiación , Dosificación Radioterapéutica , Recto/efectos de la radiación , Tomografía Computarizada por Rayos X , Vejiga Urinaria/efectos de la radiaciónRESUMEN
Structural bone allografts are often sterilized with γ-irradiation to decrease infection risk, which unfortunately degrades the bone collagen connectivity, making the bone weak and brittle. In previous studies, we successfully protected the quasi-static mechanical properties of human cortical bone by pre-treating with ribose, prior to irradiation. This study focused on the quasi-static and fatigue tensile properties of ribose treated irradiated sterilized bone allografts. Seventy-five samples were cut from the mid-shaft diaphysis of human femurs into standardized dog-bone shape geometries for quasi-static and fatigue tensile testing. Specimens were prepared in sets of three adjacent specimens. Each set was made of a normal (N), irradiated (I) and ribose pre-treated + irradiation (R) group. The R group was incubated in a 1.2 M ribose solution before γ-irradiation. The quasi-static tensile and decalcified tests were conducted to failure under displacement control. The fatigue samples were tested under cyclic loading (10 Hz, peak stress of 45MP, minimum-to-maximum stress ratio of 0.1) until failure or reaching 10 million cycles. Ribose pre-treatment significantly improved significantly the mechanical properties of irradiation sterilized human bone in the quasi-static tensile and decalcified tests. The fatigue life of the irradiated group was impaired by 99% in comparison to the normal control. Surprisingly, the R-group has significantly superior properties over the I-group and N-group (p < 0.01, p < 0.05) (> 100%). This study shows that incubating human cortical bone in a ribose solution prior to irradiation can indeed improve the fatigue life of irradiation-sterilized cortical bone allografts.
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Fémur/efectos de los fármacos , Fémur/efectos de la radiación , Rayos gamma/efectos adversos , Ribosa/farmacología , Resistencia a la Tracción/efectos de los fármacos , Resistencia a la Tracción/efectos de la radiación , Adolescente , Adulto , Anciano , Aloinjertos/efectos de la radiación , Diáfisis/efectos de los fármacos , Diáfisis/efectos de la radiación , Femenino , Fémur/trasplante , Humanos , Masculino , Persona de Mediana Edad , Estrés Mecánico , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: The increased use of cell phones has raised many questions as to whether their use is safe for patients with dental implants. This study aimed to assess the consequences of cell phone-emitted radiation on bone-to-implant osseointegration during the healing phase. MATERIALS AND METHODS: Twelve rabbits were grouped into three groups of four. Group 1 (control) was not exposed to electromagnetic radiation; group 2 (test) was exposed for 8 hours/day in speech mode and 16 hours/day in standby mode; and group 3 (test) was exposed for 24 hours continuously in standby mode for 3 months. Forty-eight implants were placed in tibia and femur bone of rabbits, and after 90 days the rabbits were sacrificed and bone surrounding the implant was retrieved. Histopathologic evaluations of the specimens were done using transmitted light microscope. The differences among the three groups were statistically analyzed with analysis of variance (ANOVA) and pairwise comparisons via Fisher's exact test. RESULTS: Significantly less bone-to-implant contact and bone area surrounding implant threads were found in the test groups compared to the control group. There was a significant difference in regular bone formation (P < .001) among the three groups. CONCLUSION: Implants exposed to cell phone radiation showed more inflammatory reaction when compared to the nonexposed implants, thus indicating that cellular phone overuse could affect the maturation of bone and thus delay osseointegration.
Asunto(s)
Prótesis Anclada al Hueso , Teléfono Celular , Implantes Dentales , Oseointegración/efectos de la radiación , Ondas de Radio/efectos adversos , Análisis de Varianza , Animales , Implantación Dental Endoósea , Radiación Electromagnética , Fémur/efectos de la radiación , Conejos , Exposición a la Radiación/efectos adversos , Tibia/efectos de la radiación , Cicatrización de Heridas/efectos de la radiaciónRESUMEN
AIMS: The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children. PATIENTS AND METHODS: A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child. RESULTS: Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave 'negligible' risk in 26 children and 'minimal' risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom. CONCLUSION: The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241-245.
Asunto(s)
Deformidades Congénitas de las Extremidades Inferiores/diagnóstico por imagen , Neoplasias Inducidas por Radiación/epidemiología , Dosis de Radiación , Exposición a la Radiación/efectos adversos , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Relación Dosis-Respuesta en la Radiación , Femenino , Fémur/anomalías , Fémur/diagnóstico por imagen , Fémur/efectos de la radiación , Fémur/cirugía , Pie/diagnóstico por imagen , Pie/efectos de la radiación , Pie/cirugía , Humanos , Deformidades Congénitas de las Extremidades Inferiores/cirugía , Masculino , Neoplasias Inducidas por Radiación/etiología , Medición de Riesgo , Factores de Riesgo , Tibia/anomalías , Tibia/diagnóstico por imagen , Tibia/efectos de la radiación , Tibia/cirugíaRESUMEN
The aim of this study was to evaluate the effects of low-level laser therapy using the gallium arsenide laser (λ = 830 nm) on the articular cartilage (AC) organization from knee joint in an experimental model of microcrystalline arthritis in adult male Wistar rats. Seventy-two animals were divided into three groups: A (control), B (induced arthritis), and C (induced arthritis + laser therapy). The arthritis was induced in the right knee using 2 mg of Na4P2O7 in 0.5 mL of saline solution. The treatments were daily applied in the patellar region of the right knee after 48 h of induction. On the 7th, 14th, and 21st days of treatment, the animals were euthanized and their right knees were removed and processed for structural and biochemical analysis of the AC. The chondrocytes positively labeled for the TUNEL reaction were lower in C than in B on the 14th and 21st days. The content of glycosaminoglycans and hydroxyproline in A and C was higher than B on the 21st day. The amount of tibial TNF-α in B and C was lower than in A. The amount of tibial BMP-7 in B and C was higher than in A. The femoral MMP-13 was lower in B and C than for A. The tibial TGF-ß for C was higher than the others. The femoral ADAMT-S4 content of A and C presented similar and inferior data to B on the 21st day. The AsGa-830 nm therapy preserved the content of glycosaminoglycans, reduced the cellular changes and the inflammatory process compared to the untreated group.
Asunto(s)
Artritis Experimental/radioterapia , Cartílago Articular/patología , Cartílago Articular/efectos de la radiación , Terapia por Luz de Baja Intensidad , Proteína ADAMTS4/metabolismo , Animales , Apoptosis/efectos de la radiación , Artritis Experimental/patología , Proteína Morfogenética Ósea 7/metabolismo , Cartílago Articular/ultraestructura , Condrocitos/patología , Condrocitos/efectos de la radiación , Modelos Animales de Enfermedad , Fémur/patología , Fémur/efectos de la radiación , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Ratas Wistar , Tibia/patología , Tibia/efectos de la radiación , Tibia/ultraestructura , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
This study investigated the level of magnetic energy around implants possessing a static magnetic field (SMF) and assessed the in vivo influence of SMF on bone regeneration. Implants possessing a sintered neodymium magnet internally were placed in a rabbit femur. An implant without SMF was placed as control. After 12 weeks of healing in vivo, the bone samples were subjected to histologic/histomorphometric evaluation. The bone-to-implant contact for the test group and the control group were 32.4 ± 13.6% and 17.1 ± 4.5%, respectively, and the differences were statistically significant (P < .05). The results suggested that the SMF promoted new bone apposition.
Asunto(s)
Fémur/crecimiento & desarrollo , Campos Magnéticos , Osteogénesis/efectos de la radiación , Animales , Implantación Dental Endoósea/métodos , Fémur/efectos de la radiación , Fémur/cirugía , ConejosRESUMEN
Radiation therapy leads to increased risk of late-onset fragility and bone fracture due to the loss of bone mass. On the other hand, iron overloading causes osteoporosis by enhancing bone resorption. It has been shown that total body irradiation increases iron level, but whether the systemic bone loss is related to the changes in iron level and hepcidin regulation following bone irradiation remains unknown. To investigate the potential link between them, we first created an animal model of radiation-induced systemic bone loss by targeting the mid-shaft femur with a single 2â¯Gy dose of X-rays. We found that mid-shaft femur focal irradiation led to structural deterioration in the distal region of the trabecular bone with increased osteoclasts surface and expressions of bone resorption markers in both irradiated and contralateral femurs relative to non-irradiated controls. Following irradiation, reduced hepcidin activity of the liver contributed to elevated iron levels in the serum and liver. By injecting hepcidin or deferoxamine (an iron chelator) to reduce iron level, deterioration of trabecular bone microarchitecture in irradiated mice was abrogated. The ability of iron chelation to inhibit radiation-induced osteoclast differentiation was observed in vitro as well. We further showed that ionizing radiation (IR) directly stimulated osteoclast differentiation and bone resorption in bone marrow cells isolated not from contralateral femurs but from directly irradiated femurs. These results suggest that increased iron levels after focal radiation is at least one of the main reasons for systemic bone loss. Furthermore, bone loss in directly irradiated bones is not only due to the elevated iron level, but also from increased osteoclast differentiation. In contrast, the bone loss in the contralateral femurs is mainly due to the elevated iron level induced by IR alone. These novel findings provide proof-of-principle evidence for the use of iron chelation or hepcidin as therapeutic treatments for IR-induced osteoporosis.
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Resorción Ósea/prevención & control , Fémur/efectos de la radiación , Hierro/metabolismo , Animales , Hueso Esponjoso/efectos de los fármacos , Hueso Esponjoso/patología , Hueso Esponjoso/efectos de la radiación , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/efectos de la radiación , Deferoxamina/farmacología , Fémur/efectos de los fármacos , Fémur/patología , Hepcidinas/farmacología , Masculino , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteoclastos/efectos de la radiación , Osteogénesis/efectos de los fármacos , Osteogénesis/efectos de la radiación , Radiación IonizanteRESUMEN
The application of pulsed electromagnetic fields (PEMFs) in the prevention and treatment of osteoporosis has long been an area of interest. However, the clinical application of PEMFs remains limited because of the poor understanding of the PEMF action mechanism. Here, we report that PEMFs promote bone formation by activating soluble adenylyl cyclase (sAC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) signaling pathways. First, it was found that 50 Hz 0.6 millitesla (mT) PEMFs promoted osteogenic differentiation of rat calvarial osteoblasts (ROBs), and that PEMFs activated cAMP-PKA-CREB signaling by increasing intracellular cAMP levels, facilitating phosphorylation of PKA and CREB, and inducing nuclear translocation of phosphorylated (p)-CREB. Blocking the signaling by adenylate cyclase (AC) and PKA inhibitors both abolished the osteogenic effect of PEMFs. Second, expression of sAC isoform was found to be increased significantly by PEMF treatment. Blocking sAC using sAC-specific inhibitor KH7 dramatically inhibited the osteogenic differentiation of ROBs. Finally, the peak bone mass of growing rats was significantly increased after 2 months of PEMF treatment with 90 min/day. The serum cAMP content, p-PKA, and p-CREB as well as the sAC protein expression levels were all increased significantly in femurs of treated rats. The current study indicated that PEMFs promote bone formation in vitro and in vivo by activating sAC-cAMP-PKA-CREB signaling pathway of osteoblasts directly or indirectly.