Biomedical subjects

E O'Brien

Publications and source records attributed to E O'Brien.

At least 19 recordsLinked to original sources

PubMed2006

Effects of repeated ochratoxin exposure on renal cells in vitro.

In the present study an in vitro model of subchronic repeated exposure to OTA and OTB was employed to generate ochratoxin-derived subpopulations of human and porcine proximal tubular cells (HKC, IHKE, PKC, LLC-PK1). These cell subpopulations were subsequently used to investigate effects on cell proliferation rates, expression of marker proteins (cytokeratins, vimentin) and the acute cytotoxicity of OTA and OTB (MTT reduction, neutral red uptake, cell number). The hypothesis was tested whether repeated exposure at moderate concentrations of these toxins could provide for a reduced sensitivity of selected cell subpopulations to subsequent toxin exposure. Despite the observed increased cell population doubling times and the reduced sensitivity toward OTA and OTB exposure of some cell types, with the exception of the primary human epithelial cells, no overt changes in the expression of cytokeratin and vimentin could be determined. The presented data, however suggest that repeated exposure of renal epithelial cells to ochratoxins A or B will provide for a subpopulation of cells with reduced ochratoxin-sensitivity and alterations in growth characteristics.

Animals↗

PubMed2006

The impact on coronary artery disease of common polymorphisms known to modulate responses to pathogens.

There are two distinct models to explain how genetic variants contributing to cardiovascular disease may have arisen. Firstly, variants may result from random, initially neutral, mutations whose effects are largely revealed in post-reproductive individuals in industrialized societies. Alternatively, the introduced variants may confer an adaptive advantage in certain circumstances. Resistance to pathogens is one of the strongest selection pressures on human proteins. To determine whether this evolutionary pressure has made a large contribution to heart disease we tested whether seventeen polymorphisms in fourteen innate-immunity genes, with documented evidence of modulating response to pathogens, had an impact on heart disease. Genotyping was performed in 1,598 CAD subjects (ACS or stable angina) and 332 controls. The TLR4 399Ile allele had the greatest impact on ACS risk (uncorrected p = 0.006); however there was no evidence overall that the resistance alleles cumulatively influenced the risk of ACS compared to controls or stable angina patients (p = 0.12, and p = 0.40, respectively). We did note a significant interaction between age at onset of disease and combined resistance allele carriership when the ACS and non-thrombotic, stable angina groups were compared (p = 0.04, 16 d.f.). This suggests that innate immunity factors could have a greater impact on thrombus formation among younger CAD patients.

Acute Disease↗

PubMed2005

In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells.

Hundreds of mycotoxins are known to date and many of them are of great interest with regard to human and animal health since they are detected frequently in plant-derived products. Various mycotoxins may occur simultaneously, depending on the environmental and substrate conditions. Considering this coincident production, it is very likely, that humans and animals are always exposed to mixtures rather than to individual compounds. Therefore, future risk assessments should consider mixture toxicity data. This is particularly true for ochratoxin A (OTA), ochratoxin B (OTB), citrinin (CIT) and occasionally for patulin (PAT) as they are all produced by a number of Penicillium and Aspergillus species. Therefore, these four toxins were chosen to study the interactive effects in vitro, using the well-established porcine renal cell line LLC-PK1 and the MTT reduction test as a cytotoxicity endpoint. By application of a step-wise approach to test combination toxicity, using various full factorial as well as a central composite experimental designs, the interactive (synergistic) cytotoxic effects of the these four toxins were assessed. The results obtained in this study confirm a potential for interactive (synergistic) effects of CIT and OTA and possibly other mycotoxins in cells of renal origin.

Algorithms↗

PubMed2005

Factors associated with the wastage and achievements in competition of event horses registered in the United Kingdom.

The aims of this study were to estimate the wastage of horses registered for eventing in Britain, to investigate the reasons for this wastage and to evaluate factors affecting the horses' achievement of grade I status (at least 61 points) while registered. An analysis of the database of the British Eventing register found that 33.7 per cent of horses registered for the first time in 1999 were not re-registered for eventing in subsequent years. By using multivariable logistic regression analysis, it was shown that horses that were kept at an event yard were more likely to be re-registered than those kept on other premises (odds ratio [or] 2.0, 95 per cent confidence interval [ci] 1.2 to 3.2), and those that took part in showjumping while registered were also more likely to be re-registered (or 1.5, 95 per cent ci 1.1 to 2.2). Horses that took part in unaffiliated eventing while registered were less likely to be re-registered the following year (or 0.7, 95 per cent ci 0.5 to 0.9), as were those that were not insured (or 0.7, 95 per cent ci 0.5 to 1.0) and those from outside the British Isles (or 0.6, 95 per cent ci 0.3 to 1.0). Veterinary problems were the most commonly cited explanation (35.1 per cent) why horses that remained in their original ownership were not re-registered with British Eventing the following year. Horses from Australia were more likely to achieve grade I status than horses from the British Isles (or 9.7, 95 per cent ci 7.1 to 13.2), as were horses from New Zealand (or 6.4, 95 per cent ci 5.0 to 8.2), the usa (or 5.2, 95 per cent ci 3.8 to 7.2) and France (or 2.8, 95 per cent ci 2.1 to 3.7), but horses from the Netherlands (or 0.5, 95 per cent ci 0.3 to 0.9) and Belgium (or 0.3, 95 per cent ci 0.1 to 0.9) were less likely to achieve grade I status. Mares were less likely to achieve grade I status than geldings (or 0.4, 95 per cent ci 0.4 to 0.5).

Animals↗

PubMed2005

Investigation of the teratogenic potential of ochratoxin A and B using the FETAX system.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin produced by certain Aspergillus and Penicillium species. It has been observed to be teratogenic in a number of animal models including rat, mouse, hamster, and chick, with reduced birth weight and craniofacial abnormalities being the most commonly observed malformations. Neither the potential of OTA to cause malformations in humans nor its teratogenic mode of action is known. The FETAX system is an embryotoxicity assay system, with a high correlation to animal models and epidemiological data. Analysis of OTA-mediated teratogenesis using this system could provide a useful tool for the generation of high numbers of samples for mechanistic studies. METHODS: Using the standard ASTM 96-hr exposure protocol, the effect of OTA and its structural analogue OTB on the development of Xenopus laevis embryos in vitro was assessed. The accumulation of both substances in Xenopus embryos was also examined using tritiated OTA and OTB. RESULTS: Both OTA and OTB caused craniofacial malformations, while OTA also caused reduced embryo growth. As expected, OTA was far more potent in inducing these effects than OTB. This could at least in part be due to greater levels of OTA being accumulated within the embryos. CONCLUSIONS: The ability of FETAX to differentiate between close structural analogues indicates the assay has great potential for the elucidation of the embryotoxic and teratogenic mechanisms of action. Hence, the model could provide a suitable system for the investigation of other known teratogens or for the pre-screening of new agents for teratogenic potential.

Abnormalities, Drug-Induced↗

PubMed2004

Determinants of white-coat hypertension.

BACKGROUND: The prevalence of white-coat hypertension (WCH) is considerable in patients referred with elevated office blood pressure. Failure to recognise this phenomenon can lead to the inappropriate use of antihypertensive medications. We undertook this study to determine the profile of patients with WCH. METHODS: Baseline clinic and daytime ambulatory blood pressures were available from 5716 patients referred over a 22-year period. Individuals were considered to have WCH if they had an elevated clinic blood pressure measurement greater than 140/90 mmHg and normal daytime mean ambulatory blood pressure. Mean age was 53.6 years and 53.2% were female. RESULTS: The overall prevalence of white-coat hypertension was 15.4%. A higher prevalence was seen amongst older adults, females, and non-smokers. CONCLUSION: Multivariate logistic regression analysis confirmed these characteristics as independent predictors of WCH.

Blood Pressure Determination↗

PubMed2002