Cd, Pb and Zn oral bioaccessibility of urban soils contaminated in the past by atmospheric emissions from two lead and zinc smelters.

Ingestion of dust or soil particles could pose a potential health risk due to long-term metal trace element (MTE) exposure. Twenty-seven urban topsoil samples (kitchen garden and lawn) were collected and analyzed for Cd, Pb and Zn using the unified Bioaccessibility Research Group of Europe (BARGE) method (UBM) test to estimate the human bioaccessibility of these elements. The quantities of Cd, Pb and Zn extracted from soils indicated, on average, 68, 62 and 47% bioaccessibility, respectively, in the gastric phase and 31, 32 and 23% bioaccessibility, respectively, in the gastro-intestinal phase. Significant positive correlations were observed between concentrations extracted with UBM and total MTE contents. Stepwise multiple regression analysis showed that human bioaccessibility was also affected by some physico-chemical soil parameters (i.e. total nitrogen, carbonates, clay contents and pH). The unified test presents some valuable data for risk assessment. Indeed, the incorporation of oral bioaccessible concentrations into risk estimations could give more realistic information for health risk assessment.

Contamination of woody habitat soils around a former lead smelter in the North of France.

The contamination of the topsoil of 262 woody habitats around a former lead smelter in the North of France was assessed. In this urbanized and industrialized area, these kinds of habitats comprise of hedges, groves, small woods, anthropogenic creations and one large forest. Except for the latter, which is 3 km away, these woody habitat soils often present a high anthropization degree (a significant amount of pebbles and stones related to human activities) with a high metal contamination. In the studied woody habitat topsoils, Cd, Pb and Zn concentrations largely exceeded those of agricultural topsoils located in the same environmental context. Therefore, atmospheric emissions from the smelter are not the only cause of the high contamination of the woody habitat soils. This last one is related to the nature and the contamination level of deposit in relation with human activities (rubbles, slag, soils, etc). With regard to the results obtained with chemical extractions, the mobility of Cd, Pb and Zn in these soils is also greater than in agricultural soils. In the forest, pollutant solubility is increased by soil acidic pH. The variability of the physico-chemical parameters and the high metal contamination of the topsoils are the main characteristics of the woody habitats located around the former smelter. Although never taken into account during risk assessment, the disturbance of these environmental components could have important biogeochemical impacts (nutrients and metal cycles). Moreover, any modification of the soils' use could potentially cause mobilization and transfer of the pollutants to the biosphere. Six years after the closure of the smelter, and as social and economic pressures considerably increase in this area, the study of these peculiar ecosystems is necessary to understand and predict the bioavailability, transfer, bioaccumulation and effects of pollutants in food chains.

Type 1 multiple endocrine neoplasia (MEN1): contribution of genetic analysis to the screening and follow-up of a large French kindred.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal genetic disorder, the clinical phenotype of which includes tumours of the parathyroids and/or anterior pituitary and/or endocrine pancreas. The genetic defect has been mapped to the chromosome 11q13 and the MEN1 gene has been recently identified, thus allowing genetic screening in affected kindreds. The aim of this study was to establish the usefulness of genetic screening in the follow-up of a large MEN1 kindred. PATIENTS: We describe a large kindred of 91 members, of whom 56 had clinical, biochemical and genetic screening. Twenty eight of them have been tested annually for the last 5 years. RESULTS: Although the precise mutation is still undetermined in this kindred, genotypic determination confirmed linkage with the MEN1 gene in affected members and excluded 28 members from annual testing. By drawing our attention to susceptible subjects, genetic screening improved the evaluation of age-related penetrance of the disease in the 3 generations from this kindred. For instance, annual screening showed conversion from unaffected to affected phenotype in 4 subjects aged 14, 14, 15, and 17 years. Moreover, genetics helped us to evaluate the specificity of clinical or biochemical markers, and thus to discard useless investigations. So far however, the genetics have not helped to explain the phenotypic heterogeneity and particularly low incidence of pancreatic tumours in this kindred. CONCLUSION: Genetic screening is very useful in detecting high risk individuals for MEN 1, since it avoids time-consuming and expensive investigations in non-affected subjects. By providing better understanding of the age-related penetrance of this syndrome, it improves the efficiency of screening. Genetic studies allow differentiation between clinical and biochemical features that are useful in follow-up and other confusing or unhelpful parameters.

Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.

[Gonadotropic adenomas]. / Adénomes gonadotropes.

Since the advent of immunohistochemical and cell culture techniques, the role of gonadotroph adenomas in hypophyseal disorders appears more important than formerly. A large part of "nonfunctional" adenomas in fact correspond to gonadotroph adenomas in vitro. These adenomas raise many clinical and biological questions since their presentation is not univocal. In addition, diagnosis of these adenomas is important since their spontaneous development leads to neuro-opthalmological complications, which presently are still too often the revealing manifestations of these adenomas.