The aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for... Show moreThe aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for cancer hazard assessment of chemicals, to reduce the use of in vivo experiments. The scope of this thesis was twofold. First, an improved in vitro approach to assess genotoxicity was developed, with the intention to reduce the number of misleading positive test results. The emphasis was on characterization of the cell system, primary hepatocytes derived from transgenic mice. Results showed that this cell system will be of added value in genotoxicity testing. In the second part of this thesis, the focus was on the development of a ‘trancriptomics’-based approach to detect modes of action of non-genotoxic carcinogens. It has been demonstrated that the described comparison approach is promising in recognizing gene expression patterns, which can be related to modes of action. In addition, the approach is also suitable to detect toxicity of chemicals in general. In conclusion, through the development of in vitro approaches, as described within this thesis, an important contribution in the improvement of testing strategies for cancer hazard assessment of chemicals has been delivered. Show less
This thesis reviews the available coral studies in the Persian Gulf at a large scale, discusses the environmental challenges for corals in the context of climate change, and expands our... Show more This thesis reviews the available coral studies in the Persian Gulf at a large scale, discusses the environmental challenges for corals in the context of climate change, and expands our knowledge of coral biodiversity and biogeography of the region, highlights the remaining gaps in our knowledge and goes on to provide recommendations for further research. This is of special importance given recent international interest in the region as a harbinger of coral adaptation to climate change as the impacts to the global environment, human society and the economy unfold. Show less
We have developed an integrated PK/PD model that adequately captures the disposition kinetics of benazeprilat, as well as the time-varying changes of systemic renin-angiotensin aldosterone (RAA)... Show moreWe have developed an integrated PK/PD model that adequately captures the disposition kinetics of benazeprilat, as well as the time-varying changes of systemic renin-angiotensin aldosterone (RAA) biomarkers without, and with ACE inhibition therapy. This mechanistic representation provides a quantitative framework for better understanding the effect of ACE inhibition on the RAAS in dogs, but also in humans. Our data show that benazepril influences the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a profound but temporary decrease in angiotensin II (AII) and aldosterone (ALD), while increasing RA for about 24 hours. Based on recent literature in human heart failure (HF) patients (G_der et al., 2007), the reduction of AII and ALD may be one of the drivers of increased survival and improved quality of life in benazepril-treated dogs. To support and consolidate this hypothesis, additional efforts should be directed towards collection of circulating RAA peptides in spontaneous cases of canine HF. If such a link can be established, profiling of these peptides could support the determination of the severity of heart failure, complement clinical and echocardiographic findings, and be used for therapeutic drug monitoring purposes. Show less
