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A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfillment of the requirements for the degree of MSc (Dent) / A comparison of radiation doses to selected vital organs in the maxillo-facial region at three different settings on the Galileos cone-beam computed tomography (CBCT) machine in the Wits Dental Hospital, was conducted with the courtesy of the Department of Medical Physics of the Charlotte Maxeke Johannesburg Academic Hospital. The study made use of the RANDO phantom and TLD- 100 detector chips, which provided detailed mapping of the dose distribution from the Galileos CBCT machine. Sixty-two Sanford® lithium fluoride dosimeters- (TLD- 100) were irradiated using a calibrated known x-ray source after having undergone a recommended annealing cycle. The data showed great consistency in the results. Association between the different imaging modalities was further investigated using Kruskal-Wallis equality-of-populations rank test and Chi-squared test. A p-value of <0.05 was considered statistically significant. Since there do not appear to be major differences between the radiation doses for the different settings of the Galileos CBCT machine, the author recommends the use of the combined setting at all times for optimum image quality.

Degree of Master of Science in Dentistry by coursework and dissertation A research report submitted to the Faculty of Health Sciences, University of the Health Sciences. University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Dentistry Johannesburg, 2014 / Introduction: Dental Cone beam CT has encountered great success in diagnostics and treatment planning in dentistry. However, it makes use of ionizing radiation. Lots of concern on the effects of x-rays on vital organs of the head and neck region has been raised. Clarity on the amount of radiation received on these specific organs will be a contribution to a better use of the emergent technology. Aim: The aim of this study is to determine the potential dose of radiation received on the eye and thyroid and to quantify the amount of potential scatter on the gonads during CBCT examinations. Material and Methods: Calibrated Lithium- Fluoride thermoluminescent dosimeters were inserted inside an anthropomorphic phantom, on sites of the eye, thyroid and the gonads. After its submission to a CBCT examination, using the high and standard resolution for a similar scanning protocol, the dose of radiation received on each organ was calculated according to the ICRP guidelines. Results: An equivalent dose of 0.059 mGy was calculated for the eye. Compared to the threshold dose of 0.5 Gy fixed by the ICRP 2007, this can be considered as relatively low. The thyroid with an effective dose of 23.5 μSv represented 20% of the full body effective dose existing in literature. The gonads absorbed an effective dose of 0.05 μSv, which was considered as negligible. Conclusion: The doses calculated were considered as relatively low. However, dentists must be aware of risks of cumulative exposure. Therefore adherence to the ALARA principle and consideration of clinical indication for CBCT remain a priority.

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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]

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 7 uppsatser.

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Genotoxic effects such as mutations and chromosome abnormalities can augment the risk of adverse health effects such as cancer and heritable genetic diseases; chemicals in commerce must be screened for genotoxic activity. To this end, Toxys B.V. developed the in vitro ToxTracker® assay, which detects (geno)toxicity by monitoring the activity of six reporter genes in cultured mES cells (murine embryonic stem cells), i.e., Rtkn, Bscl2, Btg2, Srxn1, Blvrb and Ddit3. The reporters respond to genotoxic stress, oxidative stress, and endoplasmic reticulum stress characterized by protein unfolding; reporter induction is monitored using flow cytometry. The ToxTracker® assay generates large amounts of multivariate concentration-response data; this study employed innovative quantitative methods to scrutinize ToxTracker® assay results. The work (i) defined a fold-change threshold for identification of a significant positive response, (ii) used two analytical approaches to define endpoint-specific Benchmark Response (BMR) values, (iii) used the BMD (Benchmark Dose) combined-covariate approach for potency ranking of assay validation compounds, and (iv) used PCA (Principal Component Analysis) to investigate functional and statistical relationships between the reporters. The results revealed fold-change cut-offs of 1.5 and 1.7 for identification of weak and strong positive responses, respectively. 1.5-fold is consistent with the value advocated by Toxys B.V.; 1.7-fold is more conservative than the Toxys-advocated 2-fold value. Potency ranking of the validation compounds permitted comparative identification of the most potent inducers of each reporter. The most potent compounds consistently included clastogens used for cancer chemotherapy. BMR values determined using the Zeller et al. (2017) approach ranged from 2.2% for Blvrb and Rtkn, to 7.0% for Ddit3, with an average of 3.9% across all the reporters. The Slob (2016) approach yielded values that ranged from 30% for Ddit3, to 52% for Rtkn, with an average of 43%. The PCA results indicated the Rtkn, Bscl2 and Btg2 reporters are functionally redundant; collectively indicative of genotoxic stress. The Blvrb and Ddit3 reporters are orthogonal indicators of oxidative stress and protein unfolding, respectively; they are essential for toxicological profiling using the ToxTracker® assay. PCA axis scores reflect the toxicological MOA (Mode of Action) of the tested compounds; hitherto unknown MOAs can be inferred using PCA axis-plot proximity to well-studied compounds. Like most in vitro (geno)toxicity assessment assays, ToxTracker® employs a material known as S9 to simulate mammalian hepatic metabolism. S9 is prepared from the livers of rats exposed to an inducer of microsomal CYP (Cytochrome P450) isozymes; the most common CYP inducer is the PCB (polychlorinated biphenyl) mixture known as Aroclor-1254. Due to restrictions in the availability of Aroclor-1254, this study also evaluated the utility of Phenobarbital (PB)/β-Naphthoflavone (BNF)-induced S9, a proposed substitute for Aroclor-induced S9. The results indicate that, despite differences in enzymatic profiles, a 24-hr protocol using 0.40% v/v PB/BNF-induced S9 yields results that are comparable to those obtained using 0.25% v/v Aroclor-induced S9. This study constitutes a significant step towards augmenting the utility of the ToxTracker® assay; it provides a foundation for eventual adoption of high-throughput reporter assays for routine regulatory screening of new and existing chemicals.

The severity and number of people affected by cancer is a worldwide problem with millions of people affected annually. The search for treatment and cures of cancer continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, most from plants located in tropical regions. However, this study reports that extracts of Atriplex confertifolia, a native North American plant, has significant bioactivity against human breast cancer cell lines MCF-7, 435, and 231, and HeLa cells (cervical cancer cells). The bioactivity of A. confertifolia extracts of these cells lines was compared to an FDA-approved cancer drug and an industry-standard leukocyte control cell line. Active portions of the extracts were found primarily in the polar fractions of the plant. A dose-response curve of the extracts clearly showed significant cell death similar to the FDA-approved drug. The plant extracts did not inhibit the viability of the leukocyte cell line. Cancer cell death was followed as a function of time and concentration. Cell death appears to be a result of apoptosis.