Copper: toxicological relevance and mechanisms.

Copper (Cu) is a vital mineral essential for many biological processes. The vast majority of all Cu in healthy humans is associated with enzyme prosthetic groups or bound to proteins. Cu homeostasis is tightly regulated through a complex system of Cu transporters and chaperone proteins. Excess or toxicity of Cu, which is associated with the pathogenesis of hepatic disorder, neurodegenerative changes and other disease conditions, can occur when Cu homeostasis is disrupted. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced cellular toxicity. Recently, altered cellular events, including lipid metabolism, gene expression, alpha-synuclein aggregation, activation of acidic sphingomyelinase and release of ceramide, and temporal and spatial distribution of Cu in hepatocytes, as well as Cu-protein interaction in the nerve system, have been suggested to play a role in Cu toxicity. However, whether these changes are independent of, or secondary to, an altered cellular redox state of Cu remain to be elucidated.

A single nutrition counseling session with a registered dietitian improves short-term clinical outcomes for rural Kentucky patients with chronic diseases.

Relying on data derived from medical records of past visits to a physician, patients' charts were examined to evaluate the effectiveness of a single nutrition counseling session provided by the same registered dietitian in improving outcome measures for patients with type 2 diabetes mellitus or cardiovascular disease. This was a retrospective study of 175 patients' charts from which laboratory data were extracted before and at 3 months after seeing the dietitian. Records were categorized into two groups based on whether the patient had attended or not attended a single nutrition counseling session. At 3 months, the group that received the nutrition counseling had statistically significant improvements in blood values and body mass index compared with the group that did not receive nutrition counseling. This study further confirms the value of a single nutrition counseling session as an effective approach to treating type 2 diabetes and cardiovascular disease.

Nutrition and Other Protective Behaviors Motivated by Environmental Health Risk Awareness.

BACKGROUND: Research findings have suggested that exposure to environmental pollutants contributes to increased health risks, which may be modulated by certain nutrition and other protective health behaviors. Nutrition professionals play an important role in effectively disseminating this information and in devising specific community-based nutrition education programs for audiences located in areas with environmental health issues. OBJECTIVE: To assess awareness of environmental health problems and motivation to adopt protective health behaviors for use in planning nutrition education programs for communities exposed to environmental pollutants. METHOD: Data were collected from a modified, validated Environmental Health Engagement Profile (EHEP) survey instrument administered to adults (n=774) participating in community events in Kentucky based on location relative to hazardous waste sites. RESULTS: The modified EHEP survey instrument showed good internal consistency reliability, and demographic characteristics were evaluated. Correlation analyses revealed significant positive correlations in all groups, separately and combined, between awareness of environmental pollution in an individual's surroundings and the extent of concern that pollutants cause adverse health effects (P < 0.01) and between concern that pollutants cause adverse health effects and taking personal actions to protect against such environmental insults (P < 0.01). The groups having the highest level of awareness posed by pollution are those residing near federally designated hazardous waste sites. CONCLUSION: These results suggest that determining and expanding an audience's knowledge and perceptions of environmental health risks will enhance effective nutrition education program planning.

Copper toxicity, oxidative stress, and antioxidant nutrients.

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Although normally bound to proteins, Cu may be released and become free to catalyze the formation of highly reactive hydroxyl radicals. Data obtained from in vitro and cell culture studies are largely supportive of Cu's capacity to initiate oxidative damage and interfere with important cellular events. Oxidative damage has been linked to chronic Cu-overload and/or exposure to excess Cu caused by accidents, occupational hazards, and environmental contamination. Additionally, Cu-induced oxidative damage has been implicated in disorders associated with abnormal Cu metabolism and neurodegenerative changes. Interestingly, a deficiency in dietary Cu also increases cellular susceptibility to oxidative damage. A number of nutrients have been shown to interact with Cu and alter its cellular effects. Vitamin E is generally protective against Cu-induced oxidative damage. While most in vitro or cell culture studies show that ascorbic acid aggravates Cu-induced oxidative damage, results obtained from available animal studies suggest that the compound is protective. High intakes of ascorbic acid and zinc may provide protection against Cu toxicity by preventing excess Cu uptake. Zinc also removes Cu from its binding site, where it may cause free radical formation. Beta-carotene, alpha-lipoic acid and polyphenols have also been shown to attenuate Cu-induced oxidative damage. Further studies are needed to better understand the cellular effects of this essential, but potentially toxic, trace mineral and its functional interaction with other nutrients.

Fruit and vegetable intake, as reflected by serum carotenoid concentrations, predicts reduced probability of polychlorinated biphenyl-associated risk for type 2 diabetes: National Health and Nutrition Examination Survey 2003-2004.

Type 2 diabetes has been shown to occur in response to environmental and genetic influences, among them nutrition; food intake patterns; sedentary lifestyle; body mass index; and exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs). Nutrition is essential in the prevention and management of type 2 diabetes and has been shown to modulate the toxicity of PCBs. Serum carotenoid concentrations, considered a reliable biomarker of fruit and vegetable intake, are associated with the reduced probability of chronic diseases, such as type 2 diabetes and cardiovascular disease. Our hypothesis is that fruit and vegetable intake, reflected by serum carotenoid concentrations, is associated with the reduced probability of developing type 2 diabetes in US adults with elevated serum concentrations of PCBs 118, 126, and 153. This cross-sectional study used the Center for Disease Control and Prevention database, National Health and Nutrition Examination Survey 2003-2004, in logistic regression analyses. Overall prevalence of type 2 diabetes was approximately 11.6% depending on the specific PCB. All 3 PCBs were positively associated with the probability of type 2 diabetes. For participants at higher PCB percentiles (eg, 75th and 90th) for PCB 118 and 126, increasing serum carotenoid concentrations were associated with a smaller probability of type 2 diabetes. Fruit and vegetable intake, as reflected by serum carotenoid concentrations, predicted notably reduced probability of dioxin-like PCB-associated risk for type 2 diabetes.

Yogurt protects against growth retardation in weanling rats fed diets high in phytic acid.

The purpose of this study was to determine the effects of adding yogurt to animal diets that were high in phytic acid (PA) and adequate in zinc (38 microg Zn/g). The PA:Zn molar ratio was 60:1. Zinc status was determined by documenting growth and measuring the zinc concentration in bone (tibia) and plasma. For 25 days, six groups (n=6) of Sprague-Dawley weanling rats were fed one of six AIN-76 diets. Half of the diets contained PA. Four of the diets contained yogurt with either active or heat-treated (inactive) cultures added at 25% of the diet. The diets were as follows: (a) AIN, (b) AIN with active yogurt, (c) AIN and inactive yogurt, (d) AIN with PA, (e) AIN with PA plus active yogurt and (f) AIN with PA plus inactive yogurt. Body weight, weight gain and zinc concentration in bone and plasma were measured, and food efficiency ratio was calculated. Rats fed diets with PA and yogurt had normal growth compared to the control group. Growth retardation was evident in the group fed the diet with PA and no yogurt. This group had significantly lower body weight compared to all other groups (P<.05). Rats fed diets with PA, with or without yogurt, had significantly lower zinc concentration in bone and plasma (P<.05). Adding yogurt to diets high in PA resulted in normal growth in weanling rats; however, zinc concentration in bone and plasma was still suboptimal.

The assessment of physical activity and nutrition in home schooled versus public schooled children.

The purpose of this study was to descriptively compare the physical activity and dietary intake of public school (PSC) versus home schooled children (HSC). Potential parental and home influences were also examined. Thirty six matched pairs of public school-home school children aged 7-11 years participated in this study. Each participant wore an activity monitor and recorded their dietary intake concurrently for seven consecutive days. PSC had significantly more total and weekday steps, and spent more time in moderate-to-vigorous physical activity compared with HSC. There were no differences in dietary intake between the two groups. These results suggest differences in physical activity between PSC and HSC and encourage further study of public and home school environments, in relation to the obesity epidemic.

Decreased food intake rather than zinc deficiency is associated with changes in plasma leptin, metabolic rate, and activity levels in zinc deficient rats( small star, filled).

This study investigated the hypothesis that the reduced food intake and poor weight gain in zinc deficient rats is due to: increased plasma leptin concentration, increased physical activity and/or increased metabolic rate. Weanling rats were assigned to three groups: controls fed ad libitum (C), zinc deficient (ZD), and pair-fed controls (PF), and tested in a metabolic chamber and activity monitor at baseline and weekly for four weeks. At the end of the study, all groups were compared for differences in plasma leptin concentrations. ZD and PF animals had markedly reduced food intake and weight gain. ZD had reduced stereotypic and locomotor activity compared to PF animals and both groups demonstrated an abolished peri-nocturnal activity spike and were much less active than controls. This was associated with a reduced total metabolic rate by day 30: ZD (0.73 +/- 0.07 kcal/hr, p = 0.0001) and PF (0.83 +/- 0.06 kcal/hr, p = 0.0001) groups vs. controls (1.82 +/- 0.09 kcal/hr). Plasma leptin concentrations in ZD (1.55 +/- 0.06 &mgr;g/L) were lower than controls (2.01 +/- 0.18 &mgr;g/L, p < 0.03), but neither ZD nor controls were statistically different from PF (1.68 +/- 0.05 &mgr;g/L). Both low leptin concentrations and low metabolic rates in the ZD and PF rats were associated with decreased food intake rather than zinc deficiency. The reduced food intake and poor weight gain observed in zinc deficient rats could not be explained by elevated leptin concentrations, hypermetabolism, or increased activity. Low serum leptin concentrations, hypometabolism, and decreased activity are more likely the result of the anorexia of zinc deficiency.

Anti-TNF-alpha antibody normalizes serum leptin in IL-2 deficient mice.

OBJECTIVE: A recent study reports that the interleukin-2 deficient (IL-2(-/-)) mouse model of autoimmune and inflammatory bowel disease (IBD) with elevated pro-inflammatory cytokine production has elevated leptin concentrations during food deprivation. The objective of this study was to examine whether increased tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, contributes to the abnormally elevated leptin in IL-2(-/-) mice. METHODS: Eight week old, IL-2(-/-) and wild-type control (IL-2(+/+)), male mice were fed regular laboratory mouse food for two weeks. At the end of the study, blood was collected in the fed state, IL-2(-/-) and IL-2(+/+) mice were injected with either anti-TNF-alpha monoclonal antibody or normal saline, and blood was collected in the starved state. RESULTS: The IL-2(-/-) mice consumed less food and lost weight. Administration of anti-TNF-alpha antibody markedly reduced serum leptin concentrations in IL-2(-/-) and control mice after food deprivation. Serum leptin in the IL-2(-/-) mice not receiving anti-TNF-alpha antibody increased significantly in the starved state. Serum concentrations of TNF-alpha were higher in IL-2(-/-) mice compared to controls in both the fed and starved state. CONCLUSIONS: These results suggest that elevated TNF-alpha may be one mechanism for the sustained elevated leptin observed in IL-2(-/-) mice during food deprivation.

The leptin defense against wasting is abolished in the IL-2-deficient mouse model of inflammatory bowel disease.

Anorexia is a major complication of inflammatory bowel disease (IBD). We postulated that chronic intestinal inflammation with increased proinflammatory cytokines elevates serum leptin concentration, thereby contributing to anorexia. This hypothesis was studied in interleukin-2-deficient (IL-2(-/-)) mice, a model of IBD with elevated proinflammatory cytokine production. IL-2(-/-), wild-type pair-fed and wild-type control male mice (8 wk old) were fed regular laboratory mouse food for 2 wk. The IL-2(-/-) and pair-fed groups consumed less food and lost weight. Serum leptin concentrations in the IL-2(-/-) mice in the fed state were lower than controls, but not different from pair-fed mice, and paradoxically increased in the starved state to levels significantly higher than both starved control and pair-fed groups. This result did not change when serum leptin was adjusted for amount of body fat. These data show abnormal leptin responses in IL-2(-/-) mice with increased leptin concentrations disproportionate to fat mass and prevention of the normal decline in leptin with food restriction.