Light-dark rhythms during incubation of broiler chicken embryos and their effects on embryonic and post hatch leg bone development.

There are indications that lighting schedules applied during incubation can affect leg health at hatching and during rearing. The current experiment studied effects of lighting schedule: continuous light (24L), 12 hours of light, followed by 12 hours of darkness (12L:12D), or continuous darkness (24D) throughout incubation of broiler chicken eggs on the development and strength of leg bones, and the role of selected hormones in bone development. In the tibiatarsus and femur, growth and ossification during incubation and size and microstructure at day (D)0, D21, and D35 post hatching were measured. Plasma melatonin, growth hormone, and IGF-I were determined perinatally. Incidence of tibial dyschondroplasia, a leg pathology resulting from poor ossification at the bone's epiphyseal plates, was determined at slaughter on D35. 24L resulted in lower embryonic ossification at embryonic day (E)13 and E14, and lower femur length, and lower tibiatarsus weight, length, cortical area, second moment of area around the minor axis, and mean cortical thickness at hatching on D0 compared to 12L:12D especially. Results were long term, with lower femur weight and tibiatarsus length, cortical and medullary area of the tibiatarsus, and second moment of area around the minor axis, and a higher incidence of tibial dyschondroplasia for 24L. Growth hormone at D0 was higher for 24D than for 12L:12D, with 24L intermediate, but plasma melatonin and IGF-I did not differ between treatments, and the role of plasma melatonin, IGF-I, and growth hormone in this process was therefore not clear. To conclude, in the current experiment, 24L during incubation of chicken eggs had a detrimental effect on embryonic leg bone development and later life leg bone strength compared to 24D and 12L:12D, while the light-dark rhythm of 12L:12D may have a stimulating effect on leg health.

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

γ-Irradiation sterilized bone strengthened and toughened by ribose pre-treatment.

OBJECTIVE: This study tested the hypothesis that a ribose-based pre-treatment would protect the strength, ductility and toughness of γ-irradiation sterilized cortical bone. METHODS: Experiment 1: The effects of ribose pre-treatment (1.8M in PBS at 60°C for 24h) prior to 33 kGy of irradiation on strength, ductility and toughness (beams in three-point bending) and fracture toughness (J-integral at instability in single edge notched (bending)) were tested against matched non-irradiated and irradiated controls from bovine tibiae. Experiment 2: Three-point bending tests were conducted using beams from human femora (males, 59-67 years). Bone collagen thermal stability and network connectivity were examined using hydrothermal isometric tension testing. RESULTS: Ribose pre-treatment protected the strength, ductility and toughness of irradiation sterilized bovine and human specimens to differing degrees. Their ultimate strength was not detectably different from non-irradiated control levels; toughness in bovine and human specimens was protected by 57 and 76%, respectively. Untreated human bone was less affected by irradiation and ribose pre-treatment was more effective in human bone than bovine bone. CONCLUSIONS: This paper presents the first proof-of-principle that irradiation-sterilized bone with improved mechanical properties can be produced through the application of a ribose pre-irradiation treatment, which provides a more stable and connected collagen network than found in conventionally irradiated controls.

Critical appraisal of volumetric-modulated arc therapy compared with electrons for the radiotherapy of cutaneous Kaposi's sarcoma of lower extremities with bone sparing.

OBJECTIVE: To evaluate the use of volumetric-modulated arc therapy [VMAT, RapidArc® (RA); Varian Medical Systems, Palo Alto, CA] for the treatment of cutaneous Kaposi's sarcoma (KS) of lower extremities with adequate target coverage and high bone sparing, and to compare VMAT with electron beam therapy. METHODS: 10 patients were planned with either RA or electron beams. The dose was prescribed to 30 Gy, 10 fractions, to mean the planning target volume (PTV), and significant maximum dose to bone was limited to 30 Gy. Plans were designed for 6-MV photon beams for RA and 6 MeV for electrons. Dose distributions were computed with AcurosXB® (Varian Medical Systems) for photons and with a Monte Carlo algorithm for electrons. RESULTS: V(90%) was 97.3±1.2 for RA plans and 78.2±2.6 for electrons; similarly, V(107%) was 2.5±2.2 and 37.7±3.4, respectively. RA met coverage criteria. Concerning bone sparing, D(2%) was 29.6±1.1 for RA and 31.0±2.4 for electrons. Although acceptable for bone involvement, pronounced target coverage violations were obtained for electron plans. Monitor units were similar for electrons and RA, although for the latter they increased when superior bone sparing was imposed. Delivery times were 12.1±4.0 min for electrons and 4.8±1.3 min for the most modulated RA plans. CONCLUSION: High plan quality was shown for KS in the lower extremities using VMAT, and this might simplify their management in comparison with the more conventional usage of electrons, particularly in institutes with limited staff resources and heavy workloads. ADVANCES IN KNOWLEDGE: VMAT is also dosimetrically extremely advantageous in a typology of treatments where electron beam therapy is mainly considered to be effective owing to the limited penetration of the beams.

Monte Carlo simulation of in vivo measurement of the most suitable knee position for the optimal measurement of activity.

A new computational model has been developed using the Monte Carlo (MC) technique to simulate in vivo measurements with the objective of understanding the most precise measurement location with respect to quantifying the activity of Am in the bones. To benchmark the model, in vivo measurements were performed on the U.S. Transuranium and Uranium Registries (USTUR) case 0846 leg. Front and lateral measurements of the knee of the USTUR case 0846 leg in a bent position and the same measurements with the leg in a straight position using a HP(Ge) detector were completed. Experimental results concluded that the front measurement of the knee in a bent leg position gave the highest count rate, which is an indication of optimal detection efficiency. Therefore, this geometry and knee-detector position were considered as the most appropriate position for knee monitoring. A computational model using MCNPX version 2.6.0 was used to simulate the experimental measurements by using a leg voxel phantom. The mean value and standard deviation (SD) of peak efficiency due to an isotropic 59.5-keV photon from Am were calculated in four different counting geometries. An extra sum of squares F-test was performed on the mean values of the simulated detection efficiencies. The p-value obtained from this statistical test indicates that the differences among the mean values for different counting geometries were significant. These results suggest that the front measurement of a knee in a bent leg position is the optimal counting geometry for in vivo measurement of Am deposited in the bones. The computational model was validated through comparison of the measured and simulated detection efficiencies. It was observed that there is no difference at the 0.1 significant levels between the simulated and measured detection efficiencies in assessment of Am within the bones.

Detection of irradiated frog (Limnonectes macrodon) leg bones by multifrequency EPR spectroscopy.

The free radicals of irradiated frog Limnonectes macrodon leg bones tissue were studied by electron paramagnetic resonance in both X and Q bands. The kinetic behaviour, the activation energy as well as the thermal stability of the radiation-induced radicals in bone tissue were investigated by means of both isothermal and isochronal annealing. Unirradiated bone tissue displayed the presence of Mn(2+) ions at both frequencies, while a week EPR singlet was evidenced only at 34 GHz. When irradiated with (60)Co gamma ray, the EPR spectra completely changed their patterns and intensity, the overall spectra provin, at both frequencies, to be typical axial ones. The 100°C isothermal annealing studies attested the existence of two different free radical species, significantly more labile than in the case of mammal bone tissues. At the same time, the Arrhenius plot of 15 kGy irradiated bones evidenced two different kinetic regimes with two different activation energies.

Skeletal dosimetry for external exposures to photons based on microCT images of spongiosa: consideration of voxel resolution, cluster size, and medullary bone surfaces.

Skeletal dosimetry based on microCT images of trabecular bone has recently been introduced to calculate the red bone marrow (RBM) and the bone surface cell (BSC) equivalent doses in human phantoms for external exposure to photons. In order to use the microCT images for skeletal dosimetry, spongiosa voxels in the skeletons were replaced at run time by so-called micromatrices, which have exactly the size of a spongiosa voxel and contain segmented trabecular bone and marrow micro-voxels. A cluster (=parallelepiped) of 2 x 2 x 2 = 8 micromatrices was used systematically and periodically throughout the spongiosa volume during the radiation transport calculation. Systematic means that when a particle leaves a spongiosa voxel to enter into a neighboring spongiosa voxel, then the next micromatrix in the cluster will be used. Periodical means that if the particle travels through more than two spongiosa voxels in a row, then the cluster will be repeated. Based on the bone samples available at the time, clusters of up to 3 x 3 x 3 = 27 micromatrices were studied. While for a given trabecular bone volume fraction the whole-body RBM equivalent dose showed converging results for cluster sizes between 8 and 27 micromatrices, this was not the case for the BSC equivalent dose. The BSC equivalent dose seemed to be very sensitive to the number, form, and thickness of the trabeculae. In addition, the cluster size and/or the microvoxel resolution were considered to be possible causes for the differences observed. In order to resolve this problem, this study used a bone sample large enough to extract clusters containing up to 8 x 8 x 8 = 512 micro-matrices and which was scanned with two different voxel resolutions. Taking into account a recent proposal, this investigation also calculated the BSC equivalent dose on medullary surfaces of cortical bone in the arm and leg bones. The results showed (1) that different voxel resolutions have no effect on the RBM equivalent dose but do influence the BSC equivalent dose due to voxel effects by up to 5% for incident photon energies up to 200 keV, (2) that the whole-body BSC equivalent dose calculated with a cluster with 2 x 2 x 2 = 8 micromatrices is consistent with results received with clusters of up to 8 x 8 x 8 = 512 micromatrices, and (3) that for external whole-body exposure the inclusion of the BSC on medullary surfaces of cortical bone has a negligible effect on the whole-body BSC equivalent dose.

Novel radioprotectant drugs for sparing radiation-induced damage to the physis.

PURPOSE: To determine if pentoxifylline, interleukin 1alpha, selenium and misoprostol can minimize damage to physeal longitudinal growth during single radiation dose exposure in an animal model. MATERIALS AND METHODS: Eighty-seven weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left limb serving as an internal control. Pentoxifylline was injected 30 min before exposure, sodium selenite and interleukin 1alpha 24 h before exposure and misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks, animals were sacrificed, the hind limb lengths were measured and detailed histomorphometric analysis was performed. RESULTS: Statistically significant reductions (p < or = 0.03) in mean limb length discrepancy compared with irradiation alone were seen following administration of pentoxifylline (50 mg kg(-1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6 weeks despite treatment, but length discrepancy reduction was highly correlated with the appearance of regenerative clones. CONCLUSIONS: Each drug reduced the amount of anticipated growth arrest in the animal model and some compared favourably in magnitude with that previously demonstrated for the established radioprotectant drug amifostine. Restoration of growth appears related to appearance of regenerative clones.

[Radiation therapy in treatment of the sclerotic form of pathological rearrangement of bone tissue of the lower extremities]. / Primenenie luchevoi terapii pri lechenii skleroticheskoi formy patologicheskoi perestroiki kostnoi tkani nizhnikh konechnostei.

An analysis was done of treatment of 77 servicemen with a sclerotic form of pathological rearrangement of bones of the inferior limbs. Used in the above subjects was oteoscintillography that promoted the accuracy of diagnosis and allowed the study of the time-related course of the process in bones, which measure permitted correcting the therapeutic regimen designed to deal with the pathology under consideration. The complex of conservative treatment was supplemented by a course of gamma-radiation therapy in a cumulative dose of 1.6 Gy, which measure has been shown to yield better results as compared with the control group of patients.

Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma.

AIMS: To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment. METHODS: We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed. RESULTS: Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4 (1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy. CONCLUSIONS: GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.