Phase I and phase II xenobiotic reactions and metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in aggregating liver cell cultures.

Aggregating fetal liver cell cultures were tested for their ability to metabolize xenobiotics using ethoxycoumarin-O-deethylase (ECOD), as marker of phase I metabolism, and glutathione S-transferase (GST), as marker for phase II reactions. Significant basal activities, stable over 14 days in culture were measured for both ECOD and GST activities. The prototype cytochrome P450 inducers, 3-methylcholanthrene (3-MC) and phenobarbital (PB), increased ECOD and GST activities reaching an optimum 7 days after culturing, followed by a decline in activity. This decline was partially prevented by 1% dimethyl sulfoxide (DMSO) added chronically to the culture medium. DMSO was also found to induce ECOD activity and to a lesser extent GST activity. Furthermore, it potentiated in a dose-dependent manner the induction of ECOD by PB. The food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is metabolically transformed through a number of pathways in vivo. It was therefore used to examine the metabolic capacity in fetal and adult liver cell aggregates. Metabolism of MeIQx was mainly through N2-conjugation, resulting in formation of the N2-glucuronide and sulfamate conjugates for non-induced fetal liver cells. These metabolites were also found in large amounts in non-induced adult liver cells. Low levels of cytochrome P450-mediated ring-hydroxylated metabolites were detected in both non-induced fetal and adult liver cells. After induction with arochlor (PCB) or 3-MC, the major pathway was ring-hydroxylation (cytochrome P450 dependent), followed by conjugation to beta-glucuronic or sulfuric acid. The presence of the glucuronide conjugate of N-hydroxy-MeIQx, a mutagenic metabolite, suggested an induction of P450 CYP1A2. The metabolism of MeIQx by liver cell aggregates is very similar to that observed in vivo and suggests that aggregating liver cell cultures are a useful model for in vitro metabolic studies in toxicology.

Department for Social Development, Belfast City Centre Northside Urban Village, Draft Regeneration Framework. Health Impact Assessment Report

IPH conducted a rapid HIA appraisal in response to the consultation on DSD Draft Regeneration Framework. The Department for Social Development (DSD) has developed a Draft Regeneration Framework for the North West Quarter Part 2 area of Belfast City Centre, to be known as the Northside Urban Village. The Framework, which outlines the vision for the redevelopment of an inner city area of Belfast was released for public consultation in April 2008. In responding to this consultation, the Institute of Public Health in Ireland (IPH) conducted a Health Impact Assessment (HIA) in order to assess how the proposed Framework might impact on the health of those living in or close to the area as well as the wider Belfast population. The key recommendations which resulted from this process have been presented to the Department. This paper presents an overview of the HIA conducted.

IPH response to DSD Urban Regeneration and Community Development Policy Framework Consultation

The Urban Regeneration and Community Development Policy Framework for Northern Ireland sets out for DSD and its partners, clear priorities for urban regeneration and community development programmes, both before and after the operational responsibility for these is transferred to councils under the reform of local government. Four policy objectives have been developed, which will focus on the underlying structural problems in urban areas and also help strengthen community development throughout Northern Ireland. The policy objectives are as follows: Policy Objective 1 – To tackle area-based deprivation: Policy Objective 2 – To strengthen the competitiveness of our towns and cities: Policy Objective 3 – To improve linkages between areas of need and areas of opportunity: and Policy Objective 4 –To develop more cohesive and engaged communities. Key points from IPH response Urban regeneration and community development provide a basis for addressing the social determinants of health and reducing inequalities in health. This policy framework presents an opportunity for coherence and complementarity with ‘Fit and Well - Changing Lives’ as part of government’s overall approach to tackling health inequalities. It is now well established that a focus on early years’ interventions and family support services yields significant returns, so prioritising action in these areas is essential. Defined action plans on child poverty are essential if this policy framework is to make a real and lasting difference in deprived urban areas. Development of the environmental infrastructure to improve health in deprived areas should be supported by well-planned monitoring and evaluation. Linking the policy framework to economic development and local community plans will enhance effectiveness in the areas of education, job creation, commercial investment and access to services, which in turn are critical for the economic growth and stability of urban communities. Community profile data and health intelligence (as available through IPH Health Well) could usefully inform central and local government in terms of resource allocation and targeted service delivery.

Métabolisme énergétique des personnes âgées [Energy metabolism in the elderly].

The energy metabolism in elderly subjects is discussed on the basis of previous analyses of the influence of age on the three components of energy expenditure in man: basal metabolic rate, thermogenesis and physical activity. All three components are diminished in elderly people. We conclude that the modifications of body composition, in particular the age-related loss of lean body mass, result in decreased basal metabolic rate and probably also a blunted diet-induced thermogenesis. Moreover we emphasize that the decrease in physical activity observed in elderly people is the most likely causal factor.

Oxidative and nonoxidative glucose metabolism following graded doses of oral glucose in man.

The oxidative and nonoxidative glucose metabolism represent the two major mechanisms of the utilization of a glucose load. Eight normal subjects were administered oral loads of 50, 100 and 150 g glucose and gas exchange measurements were performed for eight hours by means of computerized continuous indirect calorimetry. The glycemic peaks were almost identical with all three doses with a rise to between 141 and 147 mg/dl at 60 min. The fall back to basal level was reached later with the high than with the low glucose doses. The glucose oxidation rate rose to values between 223 and 253 mg/min after the three glucose doses, but while falling immediately after the peak at 120 min following the 50 g load, the glucose oxidation rate remained at its maximum rate until 210 min for the 100 g glucose load and plateaued up to 270 min for the 150 g glucose dose. The oxidation rates then fell gradually to reach basal levels at 270, 330 and 420 min according to the increasing size of the load. Altogether 55 +/- 3 g glucose were oxidized during the 8 hours following the 50 g glucose load, 75 +/- 3 g after the 100 g load and 80 +/- 5 g after the 150 g load. The nonoxidative glucose disposal, which corresponds essentially to glucose storage, varied according to the size of the glucose load, with uptakes of 20 +/- 1, 60 +/- 1 and 110 +/- 1 g glucose 180 min after the 50, 100 and 150 g glucose loads respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

IPH Submission: Belfast City Centre Northside Urban Village Regeneration Framework - June 2008

IPH welcome the opportunity to comment on the Department for Social Development, Draft Regeneration Framework for the North West Quarter Part 2 area of Belfast City Centre, the ‘Northside Urban Village’. The Framework outlines the vision for the redevelopment of an inner city area of Belfast.    It is recognized that a number of social, economic and environmental factors influence health. Urban regeneration has major implications for health as it includes not only physical redevelopment but also issues such as education, employment, environmental conditions, housing, welfare and healthcare.   Urban regeneration can also help to address health inequalities at a local level, as the areas where regeneration is undertaken are usually marked by poor economic and social conditions. The North West Quarter Part 2 area of Belfast is a historic part of the city. The identified area is one of the most socio-economically deprived areas of not only Belfast but Northern Ireland. The area is characterised by the large number of people who receive income and housing benefits, have low levels of educational qualifications, high rates of long-term illnesses and it is also an area of high long-term unemployment.

Submission to the Department of Environment, Heritage and Local Government: Sustainable Residential Development in Urban Areas

The Institute of Public Health in Ireland is an all-island body which aims to improve health in Ireland by working to combat health inequalities and influence public policies in favour of health. The Institute promotes co-operation in research, training, information and policy in order to contribute to policies which tackle inequalities in health.   Over the past ten years the Institute has worked closely with the Department of Health and Children and the Department of Health, Social Services and Public Safety in Northern Ireland to build capacity for public health across the island of Ireland.   The Institute takes the view that health is determined by policies, plans and programmes in many sectors outside the health sector as well as being dependent on access to and availability of first class health services. The importance of other sectors is encapsulated in a social determinants of health perspective which recognises that health is largely shaped and influenced by the physical, social, economic and cultural environments in which people live, work and play. Figure 1 illustrates these multi-dimensional impacts on health and also serves to highlight the clear and inextricable links between health and sustainable development. Factors that impact on long-term sustainability will thus also impact on health.

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.

Teleost fish larvae adapt to dietary arachidonic acid supply through modulation of the expression of lipid metabolism and stress response genes

Dietary fatty acid supply can affect stress response in fish during early development. Although knowledge on the mechanisms involved in fatty acid regulation of stress tolerance is scarce, it has often been hypothesised that eicosanoid profiles can influence cortisol production. Genomic cortisol actions are mediated by cytosolic receptors which may respond to cellular fatty acid signalling. An experiment was designed to test the effects of feeding gilthead sea-bream larvae with four microdiets, containing graded arachidonic acid (ARA) levels (0·4, 0·8, 1·5 and 3·0 %), on the expression of genes involved in stress response (steroidogenic acute regulatory protein, glucocorticoid receptor and phosphoenolpyruvate carboxykinase), lipid and, particularly, eicosanoid metabolism (hormone-sensitive lipase, PPARα, phospholipase A2, cyclo-oxygenase-2 and 5-lipoxygenase), as determined by real-time quantitative PCR. Fish fatty acid phenotypes reflected dietary fatty acid profiles. Growth performance, survival after acute stress and similar whole-body basal cortisol levels suggested that sea-bream larvae could tolerate a wide range of dietary ARA levels. Transcription of all genes analysed was significantly reduced at dietary ARA levels above 0·4 %. Nonetheless, despite practical suppression of phospholipase A2 transcription, higher leukotriene B4 levels were detected in larvae fed 3·0 % ARA, whereas a similar trend was observed regarding PGE2 production. The present study demonstrates that adaptation to a wide range of dietary ARA levels in gilthead sea-bream larvae involves the modulation of the expression of genes related to eicosanoid synthesis, lipid metabolism and stress response. The roles of ARA, other polyunsaturates and eicosanoids as signals in this process are discussed.

Insights into neuronal cell metabolism using NMR spectroscopy: uridyl diphosphate N-acetyl-glucosamine as a unique metabolic marker.

Making the switch: Compounds 1 and 2 are used as metabolic markers for NMR detection. When neuronal cells switch to a glycolytic state, an uneven distribution of (13) C in the N-acetyl group results, thus giving a mixture of the metabolites 1 and 2. It is therefore possible to monitor flux through different metabolic pathways, such as glycolysis, the tricarboxylic acid cycle, and the hexosamine biosynthetic pathway, using a single molecule.

Enteropathogens associated with diarrheal disease in infants of poor urban areas of Porto Velho, Rondônia: a preliminary study

One hundred and thirty cases of diarrhea and 43 age-matched controls, 0 to 5 years old, were studied in a pediatric outpatient unit from a poor peri urban area of Porto Velho, Rondônia. Eighty percent of diarrheal cases were observed in the groups under 2 years of age. Rotavirus (19.2%) was the most frequent enteropathogen associated with diarrhea, followed by Shigella flexneri (6.15%) and S. sonnei (1.5%) and Salmonella sp. (6.9%). Four cases of E. coli enterotoxigenic infections (3.1%), E. coli enteropathogenic (EPEC)(2.3%) one case of E. coli enteroinvasive infection (0.8%) and one case of Yersinia enterocolitica (0.8%) were also identified. Mixed infections were frequent, associating rotavirus, EPEC and Salmonella sp. with Entamoeba histolytica and Giardia lamblia.

Epidemiological Aspects of Head Lice in Children Attending Day Care Centres, Urban and Rural Schools in Uberlândia, Central Brazil

From November 1996 to March 2000, a total of 884 children between 0 and 15 years, from 11 institutions including day care centres, public urban and public rural schools in Uberlândia, State of Minas Gerais, central Brazil, were examined for head louse infestation. Children's sex, race, age and some hairs characteristics were shown to be associated to parasite infestation. A prevalence rate of 35% was found and the highest rates were observed in black, female children, with long, dark, wavy hairs. Hairs density and thickness did not seem to influence significantly the distribution of this pediculosis in Uberlândia's schoolchildren. Differences observed between the prevalence rates of head lice in children from the urban institutions suggest there is a greater epidemiological heterogeneity in this group when compared to the rural schoolchildren.