Flaxseed (FS) is a rich source of lignans and n-3 polyunsaturated fatty acids (PUFA), compounds that may help preserve normal bone cell function during aging. Understanding the effect of FS alone or combined with lower doses of estrogen therapy on bone and other estrogen-responsive tissues (e.g. uterus) is of particular interest to postmenopausal women who combine dietary bioactives (e.g. FS) with pharmacological agents (e.g. estrogen monotherapy) to attenuate postmenopausal bone loss. The overall objective of my research was to determine the effects and mechanisms of FS, alone or combined with lower doses of estrogen therapy, on bone and uterus health by measuring a comprehensive set of outcomes in the ovariectomized rat model of postmenopausal osteoporosis. The results demonstrated that FS enhances the protective effect of low-dose estrogen therapy (LD) on vertebral bone mineral density (BMD), three-dimensional microarchitecture and strength in ovariectomized rats. Moreover, FS exerts a stronger effect on bone outcomes when combined with LD than when combined with ultra-low-dose estrogen therapy (ULD). These studies also showed that FS feeding results in higher lignans and n-3 PUFAs in vertebrae, tibias and femurs. Histological analyses at the lumbar vertebra (LV) showed that there were no differences in TRAP-5β, CTX, or OPG/RANKL ratio between the FS+LD and LD groups. FS+LD did however result in lower protein expression of osteocalcin, a marker of bone formation and overall bone turnover, and higher expression of OPG compared to the negative control (NEG), while LD did not. While these findings suggest that FS+LD results in greater attenuation of deterioration of bone tissue compared to LD due to a reduction in bone turnover, significant differences between FS+LD and LD were not observed. Elucidating these specific mechanisms of action require further investigation. In the uterus, FS+LD did not induce greater cell proliferation or differences in qualitative indices of uterine morphology compared to LD. These findings suggest that there may be no increase in the risk of endometrial hyperplasia and carcinoma with FS+LD compared to LD. These findings may lead to the development of strategies that combine food bioactives and current pharmacological agents to more effectively normalize bone turnover during aging.

The RS 2400 irradiator has been looked to as a replacement for discontinued gamma irradiators. The RS 2400 has a cylindrical, rather than point, x-ray source, which yields higher dose rates. The irradiator unit allows the user to set the current, voltage, and time for which the sample is to be irradiated, but gives no conversion between these values and the dose delivered. Working with Mississippi State University’s Experimental Seafood Processing Laboratory (ESPL), the purpose of this research was to characterize the dose delivered by the RS 2400 for typical operating conditions. The RS 2400 exposure rate increases, as expected, as the current and voltage are increased. The x-ray beam is uniform within 10% at the surface of the x-ray tube over a wide range of voltages, with the exception of the leftmost 5 cm of the tube, where structural supports are located. At the maximum operating parameters (150 kV and 45 mA), the beam has a first half value layer (HVL1) of 13.66 mm aluminum, a homogeneity coefficient of 0.47, and equivalent photon energy (hveq) of 88.5 keV. This suggests a broad energy x-ray beam. The maximum deliverable dose rate to tissue at the surface of the x-ray tube is 65 Gy min-1 ± 3.1%, but it is unlikely that any sample will ever be irradiated this close to the x-ray tube. The standard sample canisters are 7.62 cm in diameter and the maximum deliverable dose rate to tissue at the canister location (with no canister present) is 37 Gy min-1 ± 3.1%. This is similar to the 45 Gy min-1 value that Rad Source Technologies, Inc. gives for the irradiator. Irradiation of live oysters is of primary interest to the ESPL. For irradiation, oysters will most likely be placed in the 10.2 cm diameter plastic canisters since the 7.62 cm diameter canisters are not wide enough to hold larger oysters. The oyster shells and increased distance from the x-ray source reduce the maximum deliverable dose rate to 14.1 Gy min-1 ± 6.5% for thin-shelled oysters and 12.3 Gy min-1 ± 6.2% for thick-shelled oysters.

This study was conducted to study absorption of glucosamine and chondroitin sulfate and to measure any changes in blood concentration of these compounds following feeding them to horses in different amounts. Six mature mares were used in a replicated 3x3 Latin square designed experiment. The experiment consisted of three 15-day periods, which included 10 days of diet adaptation followed by a 5-day sampling period. Blood was drawn on one day during each sampling period. Horses were fed a control diet (40% hay, 60% concentrate) balanced to meet NRC (1989) requirements for maintenance of mature horses. In one experimental diet, 2.0 g chondroitin sulfate and 5.5 g glucosamine were added to the basal ration at each feeding. In the other experimental diet, 3.5 g chondroitin sulfate and 8.5 g glucosamine were added to the basal ration at each feeding. Following total collections, blood was centrifuged and plasma was harvested and data analyzed for the presence of each compound. Analyses for plasma glucosamine were performed in the Protein and Chemistry Lab at Texas A&M University using HPLC. Chondroitin sulfate in the plasma was analyzed using a color reagent, dimethylmethylene blue, followed by UV spectrophotometry. There were no significant differences (P<0.05) in the concentration of chondroitin sulfate or glucosamine concentrations in plasma when comparing the three different diets. This leads to a conclusion that these compounds were not absorbed through the intestinal wall into the bloodstream in the same form as they were fed. This poses a question as to whether or not oral forms of these compounds are absorbed and are able to migrate to joints through the blood to improve joint function. With the significant economic impact that products containing chondroitin sulfate and glucosamine are making in the animal nutrition industry, more research is needed to further elucidate actual efficacy of these compounds in diet supplements for horses.

No description available.

Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model. [The original version of this article, along with updated information and services is located on the World Wide Web at: http://dx.doi.org/10.1016/j.bbalip.2009.08.001]

No description available.

When astronauts travel in space, their primary health hazards are high-energy cosmic radiations from galactic cosmic rays (GCR). Most galactic cosmic rays have energies between 100 MeV and 10 GeV. For occupants inside of a space shuttle, the structural material is efficient to absorb most of the cosmic-ray energy and reduce the interior dose rate to below 1.2 mGy per day. However, the biological effects of prolonged exposure to low-dose radiation are not well understood. The purpose of this research was to examine the feasibility of constructing a low-dose irradiation facility to simulate the uniform radiation field that exists in space. In this research, we used a pre-manufactured incubator, specifically the Thermo Scientific Forma Series II Water Jacketed CO2 Incubator, to act as shielding and simulate the exterior of the space shuttle. To achieve the desired dose rate (< 1 mGy/h) inside the incubator volume, the computer code MCNPX was used to determine required source activity and distance between the shielding and source. Once the activity and distance were calculated, an experiment was carried out to confirm the simulation results. The confirmation used survey meters and thermoluminescence dosimeters (TLDs) to map the radiation field within the incubator.

The research in this thesis was undertaken because information on the relationship between scan parameters and image quality for the MARS spectral CT was lacking. However, the MARS spectral CT is expected to extend into clinical use in the future, so it is absolutely crucial that we know how the quality of the images that it produces is effected by different can parameters. This will allow us to make further improvements to the machine, and ultimately help clinicians to visualise important information in patients which are not revealed by other imaging modalities. This thesis provides information on how the image quality is affected by different scan parameters on the MARS spectral CT using a Medipix3 silicon quad detector. In particular, it explores how different numbers of projections, exposure time products (mAs), and peak tube voltages (kVp) with different threshold energies (kV) effect the image noise, image resolution and image uniformity, respectively. This provides a set of guidelines for future work using the MARS scanner to obtain images of optimal quality. This thesis also determines that the new image reconstruction software mART developed by Niels de Ruiter, is a suitable replacement for the reconstruction software OctopusCT that is currently being used by the MARS team. Using mART reduces the scan times and dose delivered by the MARS spectral CT.

In radionuclide therapy it is still common to administer standard activities or to scale administered activity with blunt parameters such as body weight or surface area. This is not ideal because, due to considerable variation in kinetics, large safety margins have to be applied to avoid radiation damage to healthy organs, which causes under-treatment of many patients. To base the administered activity on individual dosimetry, as in other therapy modalities using ionizing radiation, will essentially solve this problem. However, dosimetry in radionuclide therapy is resource-demanding and debilitating for the patient because it involves a number of measurements to determine the kinetics of the therapy radionuclide and needs to be optimized for clinical feasibility. First, the ability to measure radioactivity distributions of radionuclides for therapy was investigated. SPECT measurements of 177Lu, which was later used clinically, showed good spatial resolution and a reasonable quantitative accuracy. A new method to calculate absorbed dose to solid risk organs and tumours was developed and applied in the clinic. Kinetic data were obtained by repeated SPECT measurements. Radiation concentration determined in small volumes of interest could then be multiplied by a constant to obtain absorbed dose because it was shown that cross-fire was negligible in organs with high activity concentration. The new dosimetry method, compared to other methods, was found to give better results with less effort. In addition, a method to calculate absorbed dose to bone marrow was developed and clinically implemented. In 200 patients, individual kinetics and absorbed dose were studied and variations were found to be large. Kidney was the dose-limiting organ in almost all patients (98.5%). Keeping the kidney dose &lt; 23Gy, about half of the patients could receive 5, or up to 10 treatments instead of the stipulated 4.

The BEAMnrc and DOSXYZnrc codes from EGSnrc Monte Carlo (MC) system are considered to be the gold standards for simulating radiotherapy linear accelerators and resulting dose depositions (Rogers, Faddegon et al. 1995). The aim of this project was to setup the EGSnrc system for the simulation of the linear accelerator (linac) head and a Scanning Liquid Ionisation Chamber (SLIC) Electronic Portal Imaging Device (EPID) for calculations of transmitted dose in the EPID. The project was divided into two parts. The head of a 6 MV Varian 600C/D photon linac was first simulated by BEAMnrc. The modelling parameters such as the electron beam energy and the Full Width at Half Maximum (FWHM) of the electron spatial distribution were adjusted until the absorbed dose profiles and the Percentage Depth Dose (PDD) curves, in general agreed better than the measured profiles and PDDs by 2%. The X-ray beam obtained from the modelled linac head was used for the simulation of the transmitted dose in the EPID in the second part of the project. The EPID was simulated by DOSXYZnrc based on the information obtained from Spezi and Lewis 2002 (Spezi and Lewis 2002), who also modelled the Varian SLIC EPID (MK2 Portal Vision system, Varian Inc., Palo Alto, CA, USA). The comparisons between the measured and the simulated transmitted doses were carried out for three different phantom setups consisting of an open field, homogeneous water equivalent phantom and a humanoid phantom (RANDO). These phantom setups were designed so that the accuracy of the MC method for simulating absorbed dose in air, homogeneous and inhomogeneous phantoms could be assessed. In addition, the simulated transmitted dose in an EPID was also compared with values obtained from the Pinnacle treatment planning system (v6.2b, Phillips Medical Systems). In the process of selecting the electron beam energy and FWHM, it was confirmed (Sheikh-Bagheri and Rogers 2002; Keall, Siebers et al. 2003) that the variation of the electron beam FWHM and energy influenced the beam profiles strongly. The PDD was influenced by the electron beam energy less strongly. The increase in the energy led to the increase in the depth of maximum dose. However, the effect could not be observed until the energy change of 0.2 MeV was made. Based on the analysis of the results, it was found that the combination of FWHM and energy of 1.3 mm and 5.7 MeV provided the best match between the measured and MC simulated beam profiles and PDDs. It can be concluded that an accuracy of 1.5% can be achieved in the simulation of the linac head using Monte Carlo method. In the comparison between the Monte Carlo and the measured transmitted dose maps, agreements of 2% were found for both the open field and homogeneous water equivalent phantom setups. The same agreements were also found for the comparison between Monte Carlo and Pinnacle transmitted dose maps for these setups. In the setup where the humanoid phantom RANDO was introduced in between the radiation field and the EPID, a general agreement of about 5% found for the comparison between Monte Carlo and measured transmitted dose maps. Pinnacle and measured transmitted dose map was also compared for this setup and the same agreement was found. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352973 / Thesis (M.Sc.) - University of Adelaide, School of Chemistry and Physics, 2009