Cardiovascular effects of lead and mercury and their mixtures in rats

Cardiovascular diseases are the major cause of death worldwide. It is a group of diseases, which affect the heart, the vasculature and the brain. Lifestyle and metabolic risk factors are major contributors to cardiovascular ill-health. In addition to these risk factors, a growing number of scientific studies show that some environmental pollutants, e.g. lead and mercury, can adversely affect cardiovascular health. Despite the increasing amount of knowledge from human and animal studies, cardiovascular effects of lead, mercury species or their mixtures are not well understood. It is also unknown if safe exposure thresholds for these metals exist or the underlying mechanisms of action for the elicitation of cardiovascular toxicity. The first set of studies had the objectives to elucidate the range of effects of single exposure to lead, inorganic mercury or methylmercury on the cardiovascular system. Therefore, male Wistar rats were exposed to a broad range of doses of lead, inorganic mercury or methylmercury for four weeks through the drinking water. Cardiovascular health of the rats was assessed by measuring the blood pressure and the cardiac electrical activity after four weeks of exposure, while the heart function and blood flow in the carotid artery was measured at baseline and at the end of the exposure duration. The study showed that all three metals differ in their effects on the cardiovascular system. Lead showed bi-phasic dose-response curves for several cardiovascular end-points. No cardiovascular effects were observed for inorganic mercury, while methylmercury showed linear dose-response curves. Based on these results, safe levels of exposure for lead and methylmercury were derived. The second study applied the same experimental design as the previous study in order to investigate the cardiovascular effects of combined exposures to lead, inorganic mercury and methylmercury. The mixture ratios were based on reference and exposure values published in the scientific literature. The adverse cardiovascular effects, which were observed for single exposures were reversed for the mixtures indicating antagonism. In contrast to single exposures, mixtures negatively affected the electrical activity of the heart (synergism), which could lead to arrhythmias and heart failure. The third set of studies focused on the exploration of oxidative stress, kidney function and damage, and global DNA methylation as potential mechanisms of action for the development of elevated blood pressure. Results for lead showed an increase in oxidative stress but not mercury. While only lead was associated with kidney damage, only inorganic mercury was related to altered global DNA methylation. Methylmercury appears to elevate blood pressure through a not investigated mechanism. Therefore, oxidative stress and kidney damage seem to be associated with elevated blood pressure but not global DNA methylation. Overall, the research presented in this thesis shows that lead, inorganic mercury and methylmercury and their mixtures have the ability to adversely affect the cardiovascular system. However, each metal affected the cardiovascular system differently and surprisingly, mixtures showed antagonism or synergism depending on the examined end-point, which was reflected in the results of the mechanistic study. As health problems of the cardiovascular system, e.g. hypertension, occur mainly in the adult population and in particular the elderly, cardiovascular effects should be considered as an important end-point for this age group in addition to neurodevelopmental effects in children

an In Vitro Study

The poor healing potential of tendons is still a clinical problem, and the use of Platelet Rich Plasma (PRP) was hypothesized to stimulate healing. As the efficacy of PRPs remains unproven, platelet lysate (PL) could be an alternative with its main advantages of storage and characterization before use. Five different blood products were prepared from 16 male donors: human serum, two PRPs (Arthrex, (PRP-ACP); RegenLab (PRP-BCT)), platelet concentrate (apheresis, PC), and PL (freezing-thawing destruction of PC). Additionally, ten commercial allogenic PLs (AlloPL) from pooled donors were tested. The highest concentration of most growth factors was found in AlloPL, whereas the release of growth factors lasted longer in the other products. PRP-ACP, PRP- BCT, and PC significantly increased cell viability of human tenocyte-like cells, whereas PC and AlloPL increased Col1A1 expression and PRP-BCT increased Col3A1 expression. MMP-1, IL-1β, and HGF expression was significantly increased and Scleraxis expression decreased by most blood products. COX1 expression significantly decreased by PC and AlloPL. No clear positive effects on tendon cell biology could be shown, which might partially explain the weak outcome results in clinical practice. Pooled PL seemed to have the most beneficial effects and might be the future in using blood products for tendon tissue regeneration

Application of the TTC concept to unknown substances found in analysis of foods

Unknown substances, not previously observed, are frequently detected in foods by quality control laboratories. In many cases, the assessment of these 'new' substances requires additional chemical analysis for their identification prior to assessing risk. This identification procedure can be time-consuming, expensive and in some instances difficult. Furthermore, in many cases, no toxicological information will be available for the substance. Therefore, there is a need to develop pragmatic tools for the assessment of the potential toxicity of substances with unknown identity to avoid delays in their risk assessment. Hence, the 'ILSI Europe expert group on the application of the threshold of toxicological concern (TTC) to unexpected peaks found in food' was established to explore whether the TTC concept may enable a more pragmatic risk assessment of unknown substances that were not previously detected in food. A step-wise approach is introduced that uses expert judgement on the source of the food, information on the analytical techniques, the dietary consumption of food sources containing the unknown substance and quantitative information of the unknown substance to assess the safety to the consumer using the TTC. By following this step-wise approach, it may be possible to apply a TTC threshold of 90. µg/day for an unknown substance in food. © 2011 Elsevier Ltd

Intake of selected nutrients from foods, from fortification and from supplements in various European countries

Background: Recent European Union regulation requires setting of maximum amount of micronutrients in dietary supplements or foods taking into account the tolerable upper intake levels (ULs) established by scientific risk assessment and population reference intakes. Objective: To collect and evaluate recently available data on intakes of selected vitamins and minerals from conventional foods, food supplements and fortified foods in adults and children. Intake of calcium, copper, iodine, iron, magnesium, phosphorus, selenium, zinc, folic acid, niacin and total vitamin A/retinol, B6, D and E was derived from nationally representative surveys in Denmark, Germany, Finland, Ireland, Italy, the Netherlands, Poland, Spain and the United Kingdom. Intake of high consumers, defined as the 95th percentile of each nutrient, was compared to the UL. Results: For most nutrients, adults and children generally consume considerably less than the UL with exceptions being retinol, zinc, iodine, copper and magnesium. The major contributor to intakes for all nutrients and in all countries is from foods in the base diet. The patterns of food supplements and voluntary fortification vary widely among countries with food supplements being responsible for the largest differences in total intakes. In the present study, for those countries with data on fortified foods, fortified foods do not significantly contribute to higher intakes for any nutrient. Total nutrient intake expressed as percentage of the UL is generally higher in children than in adults. Conclusion: The risk of excessive intakes is relatively low for the majority of nutrients with a few exceptions. Children are the most vulnerable group as they are more likely to exhibit high intakes relative to the UL. There is a need to develop improved methods for estimating intakes of micronutrients from fortified foods and food supplements in future dietary surveys

A Comprehensive Framework for Building Multilingual Domain Ontologies: Creating a Prototype Biosecurity Ontology

This paper presents our ongoing work in establishing a multilingual domain ontology for a biosecurity portal. As a prototypical approach, this project is embedded into the bigger context of the Agricultural Ontology Service (AOS) project of the Food and Agriculture Organization (FAO) of the UN. The AOS will act as a reference tool for ontology creation assistance and herewith enable the transfer of the agricultural domain towards the Semantic Web. The paper focuses on introducing a comprehensive, reusable framework for the process of semi-automatically supported ontology evolvement, which aims to be used in follow-up projects and can eventually be applied to any other domain. Within the multinational context of the FAO, multilingual aspects play a crucial role and therefore an extendable layered ontology modelling approach will be described within the framework. The paper will present the project milestones achieved so far: the creation of a core ontology, the semiautomatic extension of this ontology using a heuristic toolset, and the representation of the resulting ontology in a multilingual web portal. The reader will be provided with a practical example for the creation of a specific domain ontology, which can be applied to any possible domain. Future projects, including automatic text classification, and ontology facilitated search opportunities, will be addressed at the end of the paper

A comprehensive framework for building multilingual domain ontologies: Creating a prototype biosecurity ontology. DC-2002: Metadata for e-Communities: Supporting Diversity and Convergence

Abstract:This paper presents our ongoing work in establishing a multilingual domain ontology for the biosecurity portal. As a prototypical approach, this project is embedded into the bigger context of the Agricultural Ontology Service (AOS) project of the Food and Agriculture Organization (FAO) of the UN. The AOS will act as a reference tool for ontology creation assistance and herewith enable the transfer of the agricultural domain towards the Semantic Web. The paper focuses on introducing a comprehensive, reusable framework for the process of semi-automatically supported ontology evolvement, which aims to be used in follow-up projects and can eventually be applied to any other domain. Within the multinational context of the FAO, multilingual aspects play a crucial role and therefore an extendable layered ontology modelling approach will be described within the framework. The paper will present the project milestones achieved so far: the creation of a core ontology, the semiautomatic extension of this ontology using a heuristic toolset, and the representation of the resulting ontology in a multilingual web portal. The reader will be provided with a practical example for the creation of a specific domain ontology which can be applied to any possible domain. Future projects, including automatic text classification, and ontology facilitated search opportunities, will be addressed at the end of the paper. These Semantic Web application scenarios initiate the motivation for creating domain ontologies

Comparative Analysis of Different Platelet Lysates and Platelet Rich Preparations to Stimulate Tendon Cell Biology: An In Vitro Study

The poor healing potential of tendons is still a clinical problem, and the use of Platelet Rich Plasma (PRP) was hypothesized to stimulate healing. As the efficacy of PRPs remains unproven, platelet lysate (PL) could be an alternative with its main advantages of storage and characterization before use. Five different blood products were prepared from 16 male donors: human serum, two PRPs (Arthrex, (PRP-ACP); RegenLab (PRP-BCT)), platelet concentrate (apheresis, PC), and PL (freezing-thawing destruction of PC). Additionally, ten commercial allogenic PLs (AlloPL) from pooled donors were tested. The highest concentration of most growth factors was found in AlloPL, whereas the release of growth factors lasted longer in the other products. PRP-ACP, PRP-BCT, and PC significantly increased cell viability of human tenocyte-like cells, whereas PC and AlloPL increased Col1A1 expression and PRP-BCT increased Col3A1 expression. MMP-1, IL-1β, and HGF expression was significantly increased and Scleraxis expression decreased by most blood products. COX1 expression significantly decreased by PC and AlloPL. No clear positive effects on tendon cell biology could be shown, which might partially explain the weak outcome results in clinical practice. Pooled PL seemed to have the most beneficial effects and might be the future in using blood products for tendon tissue regeneration