2 resultados para target organ

em CORA - Cork Open Research Archive - University College Cork - Ireland


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Introduction The objectives of this thesis are to: (1) examine how ambulatory blood pressure monitoring (ABPM) refines office blood pressure (BP) measurement; (2) determine if absolute ambulatory BP or dipping status is better associated with target organ damage (TOD); (3) explore the association of isolated nocturnal hypertension (INH) with TOD; and (4) investigate the association of night-time BP with ultrasound markers of cardiovascular damage. Methods Data from the Mitchelstown Cohort Study was analysed to deliver objectives 1 and 2. Objective 3 was addressed by a systematic review and analysis of data from the Mitchelstown Study. A sample of participants from the Mitchelstown Study underwent an echocardiogram for speckle tracking analysis and carotid ultrasound to achieve objective 4. Results ABPM reclassifies hypertension status in approximately a quarter of individuals, with white coat and masked hypertension prevalence rates of 11% and 13% respectively. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level. In multi-variable models the odds ratio (OR) for LVH was 1.4 (95% CI 1.1 -1.8) and for albumin:creatinine ratio ≥ 1.1 mg/mmol was 1.5 (95% CI 1.2 – 1.8) for each 10 mmHg rise in night-time systolic BP. The evidence for the association of INH with TOD is inconclusive. Night-time systolic BP is significantly associated with global longitudinal strain (GLS) (beta coefficient 0.85 for every 10 mmHg rise, 95% CI 0.3 – 1.4) and carotid plaques (OR 1.9 for every 10 mmHg rise, 95% CI 1.1 – 3.2) in univariable analysis. The findings persist for GLS in sex and age adjusted models but not in multivariable models. Discussion Hypertension cannot be effectively managed without using ABPM. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level, and therefore, may be a better therapeutic target in future studies.

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Anthropogenic pollutant chemicals pose a major threat to aquatic organisms. There is a need for more research on emerging categories of environmental chemicals such as nanomaterials, endocrine disruptors and pharmaceuticals. Proteomics offers options and advantages for early warning of alterations in environmental quality by detecting sub-lethal changes in sentinel species such as the mussel, Mytilus edulis. This thesis aimed to compare the potential of traditional biomarkers (such as enzyme activity measurement) and newer redox proteomic approaches. Environmental proteomics, especially a redox proteomics toolbox, may be a novel way to study pollutant effects on organisms which can also yield information on risks to human health. In particular, it can probe subtle biochemical changes at sub-lethal concentrations and thus offer novel insights to toxicity mechanisms. In the first instance, the present research involved a field-study in three stations in Cork Harbour, Ireland (Haulbowline, Ringaskiddy and Douglas) compared to an outharbour control site in Bantry Bay, Ireland. Then, further research was carried out to detect effects of anthropogenic pollution on selected chemicals. Diclofenac is an example of veterinary and human pharmaceuticals, an emerging category of chemical pollutants, with potential to cause serious toxicity to non-target organisms. A second chemical used for this study was copper which is a key source of contamination in marine ecosystems. Thirdly, bisphenol A is a major anthropogenic chemical mainly used in polycarbonate plastics manufacturing that is widespread in the environment. It is also suspected to be an endocrine disruptor. Effects on the gill, the principal feeding organ of mussels, were investigated in particular. Effects on digestive gland were also investigated to compare different outcomes from each tissue. Across the three anthropogenic chemicals studied (diclofenac, copper and bisphenol A), only diclofenac exposure did not show any significant difference towards glutathione transferase (GST) responses. Meanwhile, copper and bisphenol A significantly increased GST in gill. Glutathione reductase (GR) enzyme analysis revealed that all three chemicals have significant responses in gill. Catalase activity showed significant differences in digestive gland exposed to diclofenac and gills exposed to bisphenol A. This study focused then on application of redox proteomics; the study of the oxidative modification of proteins, to M. edulis. Thiol proteins were labelled with 5-iodoacetamidofluorescein prior to one-dimensional and two-dimensional electrophoresis. This clearly revealed some similarities on a portion of the redox proteome across chemical exposures indicating where toxicity mechanism may be common and where effects are unique to a single treatment. This thesis documents that proteomics is a robust tool to provide valuable insights into possible mechanisms of toxicity of anthropogenic contaminants in M. edulis. It is concluded that future research should focus on gill tissue, on protein thiols and on key individual proteins discovered in this study such as calreticulin and arginine kinase which have not previously been considered as biomarkers in aquatic toxicology prior to this study.