Peter J. Aggett

Copper and Human Health: Biochemistry, Genetics, and Strategies for Modeling Dose-response Relationships

Copper (Cu) and its alloys are used extensively in domestic and industrial applications. Cu is also an essential element in mammalian nutrition. Since both copper deficiency and copper excess produce adverse health effects, the dose-response curve is U-shaped, although the precise form has not yet been well characterized. Many animal and human studies were conducted on copper to provide a rich database from which data suitable for modeling the dose-response relationship for copper may be extracted. Possible dose-response modeling strategies are considered in this review, including those based on the benchmark dose and categorical regression. The usefulness of biologically based dose-response modeling techniques in understanding copper toxicity was difficult to assess at this time since the mechanisms underlying copper-induced toxicity have yet to be fully elucidated. A dose-response modeling strategy for copper toxicity was proposed associated with both deficiency and excess. This modeling strategy was applied to multiple studies of copper-induced toxicity, standardized with respect to severity of adverse health outcomes and selected on the basis of criteria reflecting the quality and relevance of individual studies. The use of a comprehensive database on copper-induced toxicity is essential for dose-response modeling since there is insufficient information in any single study to adequately characterize copper dose-response relationships. The dose-response modeling strategy envisioned here is designed to determine whether the existing toxicity data for copper excess or deficiency may be effectively utilized in defining the limits of the homeostatic range in humans and other species. By considering alternative techniques for determining a point of departure and low-dose extrapolation (including categorical regression, the benchmark dose, and identification of observed no-effect levels) this strategy will identify which techniques are most suitable for this purpose. This analysis also serves to identify areas in which additional data are needed to better define the characteristics of dose-response relationships for copper-induced toxicity in relation to excess or deficiency.

Innovation in infant formula development:: A reassessment of ribonucleotides in 2002

Nucleotides play a significant role in many physiologic functions, ranging from the encoding of genetic information to signal transduction. Accumulating evidence from recent animal and clinical studies supports the original notion that nucleotides are semi-essential dietary nutrients. The development of a new technique, total potentially available nucleosides, to accurately quantify the nucleotide content in various biological fluids has allowed investigators to properly assess the importance of nucleotide function and availability in various conditions. Data from animal studies indicate that exogenous nucleotides produce beneficial gastrointestinal and immunologic effects, especially during times of rapid growth, when nucleotide availability may be low. Infant studies confirm these findings and are presented in this review. Regulatory agencies are currently using this information collectively to support the rationale for the supplementation of infant formulas with higher amounts of nucleotides.

TRACE ELEMENTS OF THE MICROPREMIE

The current limited understanding of the ontogeny and mechanisms of the metabolism of iron, zinc, copper, selenium, iodine, and manganese in the micropremie are reviewed. The effects of early delivery on these processes are considered, as are the suggested amounts of these trace elements required for micropremies.

The Process for the Assessment of Scientific Support for Claims on Food

The concerted action “The process for the assessment of the scientific support for claims on foods”, PASSCLAIM, proposed criteria that could provide an international yardstick for the harmonised transparent assessment of evidence submitted to support a claim for a food or food component. The evidence would be systematically appraised against specific criteria: namely, (1) a characterisation of the food or food component to which the claimed effect is attributed; (2) human data, primarily from intervention studies that represent the target populations for the claim; (3) a dose response relationship; (4) evidence allowing for confounders such as lifestyle, consumption patterns, background diet and food matrix etc.; (5) an appropriate duration for the study; (6) a measure of compliance; (7) adequate statistical power to test the hypothesis. Validated and quality assured markers of intermediate or final outcomes could be used when ideal endpoints are not easily accessible for measurement as long as their relationship to the development of the principal outcome relevant to the claim is well characterised and substantiated. The overall coherence and totality of published and unpublished evidence should be considered in the process. Assessments for substantiation claims need expert judgement, weighting of the strength of the claim, and intelligent use of the criteria applied on an individual basis with respect both to gaps in the knowledge and to any need for new knowledge and data.

Validation of an Instrument to Measure Quality of Life inBritish Children With Inflammatory Bowel Disease

Objective: To validate IMPACT-III (UK), a health-related quality of life (HRQoL) instrument, in British children with inflammatory bowel disease (IBD). Patients and Methods: One hundred six children and parents were invited to participate. IMPACT-III (UK) was validated by inspection by health professionals and children to assess face and content validity, factor analysis to determine optimum domain structure, use of Cronbach alpha coefficients to test internal reliability, ANOVA to assess discriminant validity, correlation with the Child Health Questionnaire to assess concurrent validity, and use of intraclass correlation coefficients to assess test-retest reliability. The independent samples t test was used to measure differences between sexes and age groups, and between paper and computerised versions of IMPACT-III (UK). Results: IMPACT-III (UK) had good face and content validity. The most robust factor solution was a 5-domain structure: body image, embarrassment, energy, IBD symptoms, and worries/concerns about IBD, all of which demonstrated good internal reliability (&agr;u200a=u200a0.74–0.88). Discriminant validity was demonstrated by significant (*Pu200a<u200a0.05, **Pu200a<u200a0.01) differences in HRQoL scores between the severe, moderate, and inactive/mild symptom severity groups for the embarrassment scale (63.7* vs 81.0 vs 81.2), IBD symptom scale (45.0** vs 64.2* vs 80.6), and the energy scale (46.4* vs 62.1* vs 77.7). Concurrent validity of IMPACT-III (UK) with comparable domains of the Child Health Questionnaire was confirmed. Test-retest reliability was confirmed with good intraclass correlation coefficients of 0.66 to 0.84. Paper and computer versions of IMPACT-III (UK) collected comparable scores, and there were no differences between the sexes and age groups. Conclusions: IMPACT-III (UK) appears to be a useful tool to measure HRQoL in British children with IBD.

Educational recommendations for processed foods for infant feeding.

There is relatively little systematic evidence on which to base any informed advice about the introduction of foods other than breast milk or breast milk substitutes. Arguably once solids have become the major component of a young child’s diet there is even less evidence about optimum feeding [1]. Typically diversification of an infant’s diet has been very much influenced by parental belief and cultural practice. It is difficult in such circumstances to give firm evidence-based guidelines on feeding practice for young children, and on the foods involved, and even less easy to conceive defensible regulatory approaches to this issue, although there are, for example, some compositional guidelines for cereal-based weaning products. Even so, there is considerable interest in the potential for harm that can arise from inappropriate early childhood feeding and strategies to minimize this form the basis of most recognized educational needs in the issues of early childhood feeding. Here the principal message is that there is key knowledge based on the nutritional needs of young children and practice which should be widely disseminated as part of the societal responsibilities of all concerned in the food chain of young children. Once their diet has become diversified, regardless of whether or not processed foods are used, it is not realistic to regulate for ideal feeding practices. Ideal feeding practices should be seen as a key component of the inter-professional and interagency governance of public health nutrition. This principle, in itself, indicates the nature of the educational needs and the research that in turn is needed to enable these to be met. Hernell O, Schmitz J (eds): Feeding during Late Infancy and Early Childhood: Impact on Health. Nestlé Nutr Workshop Ser Pediatr Program, vol 56, pp 207–217, Nestec Ltd., Vevey/S. Karger AG, Basel,