Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health

Cadmium (Cd) was recently identified as a risk factor for osteoporosis. Skeletal damage may be the critical effect of low-level long-term exposure to Cd in the general population exposed via food, but the mechanisms behind this are not clearly understood.We investigated the effects of dietary Cd exposure on metals involved in bone turnover. Female rats received a Cd-supplemented diet (0, 10, 50, or 200 CdCl2 mg/kg diet) for 13 weeks. Cd and essential metals stored in the liver were measured by ICP-MS multianalysis. Mineral content of the livers was modified according to Cd level : iron, magnesium and selenium decreased while copper, zinc and manganese increased with increasing Cd levels. Iron was the most strikingly affected metal, falling to one-fifth of control values at high dietary Cd exposure. In this dosage group, selenium decreased to 36% of mean control concentrations while zinc increased to 168%. This mineral imbalance, especially depleted iron stores, can contribute, at least in part, to the Cd-associated risk of osteoporosis. The association between iron metabolism and Cd exposure should be investigated in humans, as Cd and low iron stores could act synergistically as risk factors for osteoporosis

HPLC assay of zearalenone and reduced metabolites in S9 fractions of duck liver

HPLC analysis of zearalenone (ZEA), zearalenols (-ZOL and ß-ZOL) and zearalanols (-ZAL and ß-ZAL) was developed, in order to obtain a sensitive and reproducible method to quantify ZEA and its reduced metabolites in subcellular fractions of animal livers (S9 samples). Optimal in vitro metabolism was observed by incubating 5 mg S9 proteins with 0.016 μmol. ZEA. Acetonitrile and diethylether/chloroform mixture were compared for extraction, as well as different mobile phases and two detection modes in HPLC analysis. Extracted samples were eluted with water/acetonitrile (55:45, v/v) at a flow-rate of 1.0 ml/min-1, resulting in well separated peaks between ZEA and the metabolites. The limits of detection ranged from 0.5 to 2 ng/mg S9 proteins using UV, and from 0.04 to 4 ng/mg S9 proteins, using fluorescence detection. Fluorescence showed a ten-fold higher sensitivity than UV detection for ZEA and -ZOL. Repeatability (10 assays) was 2.7% to 6.99% for zearalenols. Day-by-day coefficients of variation for zearalenone and zeranols with UV detection were 3.3 to 8.5 %, and 2.5 to 4.3 %, respectively. This analysis applied to S9 samples from ducks after 30 min of ZEA incubation allowed to demonstrate that -ZOL is the main reduced metabolite in the duck. The present method is particularly adapted for studying in vitro metabolism of ZEA and inter-species variations

Variations in zearalenone activation in avian food species

Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites identified in vitro and in vivo: alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL). The efficiency to produce alpha-reduced metabolites appears of particular interest in risk assessment as alpha-reduced metabolites constitute activated forms whereas beta-reduced metabolites are less oestrogenic than ZEA. In this study ZEA activation was compared in avian food species. ZEA and its reduced metabolites were quantified in subcellular fractions of six avian species and rat livers. The α-ZOL/β-ZOL ratio in rats was 19. The various avian food species cannot be considered to be equivalent in terms of ZEA reduction (P<0.001). Quails represented high “beta reducers”, with α-ZOL/β-ZOL ratio less than two. Weak “beta reducers” included on one part ducks and chickens showing α-ZOL/β-ZOL ratio greater than 3 and up to 5.6 and on a second part geese, showing a lower production of α-ZOL than other poultry. Comparisons of enzyme kinetics in ducks and in quails show that these variations can be explained by the action of various isoforms of dehydrogenases. These results are relevant to food safety, in the context of frequently inevitable contamination of animal feed

Strong vs. Weak Coupling Duality and Coupling Dependence of the Kondo Temperature in the Two-Channel Kondo Model

We perform numerical renormalization group (NRG) as well as analytical calculations for the two-channel Kondo model to obtain the dependence of the Kondo temperature $T_K$ on the dimensionless (bare) spin exchange coupling $g$ over the complete parameter range from $g\ll 1$ to $g\gg 1$. We show that there exists a duality between the regimes of small and large coupling. It is unique for the two-channel model and enables a mapping between the strong and the weak coupling cases via the identification $g\leftrightarrow 3/(2g)$, implying an exponential dependence of $T_K$ on $1/g$ and $g$, respectively, in the two regimes. This agrees quantitatively with our NRG calculations where we extract $T_K(g)$ over the complete parameter range and obtain a non-monotonous $T_K(g)$ dependence, strongly peaked at the 2CK fixed point coupling $g^*$. These results may be relevant for resolving the long-standing puzzle within the 2CK interpretation of certain random defect systems, why no broad distribution of $T_K$ is observed in those systems.Comment: 6 pages, 3 figures; PRB published version, shortened, nomenclature clarifie

Comment on "Fano Resonance for Anderson Impurity Systems"

In a recent Letter, Luo et al. (Phys. Rev. Lett. 92, 256602 (2004)) analyze the Fano line shapes obtained from scanning tunneling spectroscopy (STS) of transition metal impurities on a simple metal surface, in particular of the Ti/Au(111) and Ti/Ag(100) systems. As the key point of their analysis, they claim that there is not only a Fano interference effect between the impurity d-orbital and the conduction electron continuum, as derived in Ujsaghy et al. (Phys. Rev. Lett. 85, 2557 (2000)), but that the Kondo resonance in the d-electron spectral density has by itself a second Fano line shape, leading to the experimentally observed spectra. In the present note we point out that this analysis is conceptually incorrect. Therefore, the quantitative agreement of the fitted theoretical spectra with the experimental results is meaningless.Comment: 1 page, no figures. Accepted for publication in PRL; revised version uploaded on November 18th, 200

Reply to "Comment on 'Fano resonance for Anderson Impurity Systems' "

In a recent Comment, Kolf et al. (cond-mat/0503669) state that our analysis of the Fano resonance for Anderson impurity systems [Luo et al., Phys. Rev. Lett 92, 256602 (2004)] is incorrect. Here we want to point out that their comments are not based on firm physical results and their criticisms are unjustified and invalid.Comment: 1 page, 1 figure, to appear in PR

Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol: histopathological analysis

The digestive tract is a target for the mycotoxin deoxynivalenol (DON), a major cereals grain contaminant of public health concern in Europe and North America. Pig, the most sensitive species to DON toxicity, can be regarded as the most relevant animal model for studying the intestinal effects of DON. A pig jejunal explants culture was developed to assess short-term effects of DON. In a first step, jejunal explants from 9-13 week-old and from 4-5 week-old pigs were cultured in vitro for up to 8 hours. Explants from younger animals were better preserved after 8 hours, as assessed by morphological scores and by villi lengths. In a second step, dose-related alterations of the jejunal tissue were observed, including shortened and coalescent villi, lysis of enterocytes, oedema. After 4h of DON exposure of explants from 4-5 week-old pigs, a no-effect concentration level of 1 µM was estimated (corresponding to diet contaminated with 0.3 mg DON/kg) based on morphological scores, and of 0.2 µM based on villi lengths. In conclusion, our data indicate that pig intestinal explants represent a relevant and sensitive model to investigate the effects of food contaminants

Micromamíferos y metales pesados: biomonitorización del medio ambiente

Environmental biomonitoring constitutes one of the most important research lines recently developed in Ecotoxicology. This tool helps to evidence and characterize the effect of environmental contaminants on ecosystems, even before those environmental contaminants could be directly measured in the nature. At the present work, a review about recent research of adequate animal species which could be used to improve biomonitoring programs of heavy metal environmental contamination is shown

Nascent osteoblast matrix inhibits osteogenesis of human mesenchymal stem cells in vitro

Introduction\ud Adult mesenchymal stem cells (MSCs) are considered promising candidates for cell-based therapies. Their potential utility derives primarily from their immunomodulatory activity, multi-lineage differentiation potential, and likely progenitor cell function in wound healing and repair of connective tissues. However, in vitro, MSCs often senesce and spontaneously differentiate into osteoblasts after prolonged expansion, likely because of lack of regulatory microenvironmental signals. In vivo, osteoblasts that line the endosteal bone marrow surface are in close proximity to MSCs in the marrow stroma and thus may help to regulate MSC fate.\ud \ud Methods\ud We examined here how osteogenic differentiation of MSCs in vitro is affected by exposure to osteoblastic cells (OBCs). Human bone marrow MSCs were exposed to OBCs, derived by induced osteogenic differentiation of MSCs, either directly in contact co-cultures, or indirectly to OBC-conditioned medium or decellularized OBC extracellular matrix (ECM).\ud \ud Results\ud Our results showed that OBCs can act as negative regulators of MSC osteogenesis. mRNA expression profiling revealed that OBCs did not affect MSC osteogenesis in direct contact cultures or via secreted factors. However, seeding MSCs on decellularized OBC ECM significantly decreased expression of several osteogenic genes and maintained their fibroblastic morphologies. Proteomic analysis identified some of the candidate protein regulators of MSC osteogenesis.\ud \ud Conclusions\ud These findings provide the basis for future studies to elucidate the signaling mechanisms responsible for osteoblast matrix-mediated regulation of MSC osteogenesis and to better manipulate MSC fate in vitro to minimize their spontaneous differentiation