Maternal Blood Lead Levels and the Risk of Pregnancy-Induced Hypertension: The EDEN Cohort Study

International audienceBACKGROUND: Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure. OBJECTIVE: We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy. METHODS: One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l' Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation. RESULTS: PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean +/- SD, 2.2 +/- 1.4 mug/dL) than in normotensive patients (1.9 +/- 1.2 mug/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1-9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation. CONCLUSIONS: These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH

Effets d'une exposition environnementale au plomb, cadmium et manganèse sur la tension artérielle gravidique et la croissance fœtale

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Effect of maternal manganese blood levels on erythrocyte calcium-pump activity in newborns

Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se. POPULATION AND METHODS: 248 mother-newborn pairs were recruited at Robert Debre University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed. RESULTS: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model. CONCLUSION: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns

Environmental boron exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in a newborn population.

Following boron intake, multiple effects have been observed in animal experiments. However, human data is lacking, and no data is available on the ability of boron to accumulate in fetal tissues. Positive responses in animal species suggest that developmental toxicity may be an area of concern in humans, following exposure to boron. Two hypotheses have seemed to account for the multiple effects described in scientific findings. One hypothesis is that boron is a negative regulator that influences a number of metabolic pathways by competitively inhibiting some key enzyme reactions. The other hypothesis is that boron has a role in ionic membrane transport regulations. To better understand boron potential toxicity, the present study examined the relationship between boron exposure and some key enzymes, well-known for their affinity for mineral elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two fundamental enzymes having a role in ionic membrane transport regulations (Ca-pump and Na(+)K(+)-ATPase). We investigated the potential effects of an environmental boron exposure on the activity of these enzymes in an urban population of 197 "normal" newborns. Environmental boron exposure was assessed in placental tissue. Because of the well-known inhibiting effect of lead on these enzymes, cord blood and placental lead were also analyzed. After adjustment for potential confounders, including lead, placental boron levels were negatively significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase activities did not seem to be affected by the level of boron exposure. Given boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest that such a mechanism would explain the inhibiting effect of boron on ALA-D

Biomarkers of selenium status in the Amazonian context : blood, urine and sequential hair segments

Selenium (Se) is an essential element and deficit or excess of dietary Se is associated with health disorders. Relatively elevated Se levels have been reported in the Brazilian Amazon, where there are also important annual variations in the availability of different foods. The present study was conducted among six riparian communities of the Tapajo´ s River to evaluate seasonal variations in blood and sequential hair cm Se concentrations, and to examine the relationships between Se in blood and hair, and blood and urine. Two cross-sectional studies were conducted, at the descending water (DWS, n¼259) and the rising water (RWS, n¼137) seasons, with repeated measures for a subgroup (n¼112). Blood Se (B-Se), hair Se (H-Se) and urine Se (U-Se) were determined. Match-paired analyses were used for seasonal comparisons and the method of best fit was used to describe the relationships between biomarkers. B-Se levels presented a very large range (142–2447 mg/l) with no overall seasonal variation (median 284 and 292 mg/l, respectively). Sequential analysis of 13 cm hair strands showed significant variations over time: Se concentrations at the DWS were significantly lower compared with the rising water season (medians: 0.7 and 0.9 mg/g; ranges: 0.2–4.3 mg/g and 0.2–5.4 mg/g, respectively). At both seasons, the relationships between B-Se and H-Se were linear and highly significant (r2¼67.9 and 63.6, respectively), while the relationship between B-Se and U-Se was best described by a sigmoid curve. Gender, age, education and smoking did not influence Se status or biomarker relationships. Variations in H-Se suggest that there may be seasonal availability of Se sources in local food. For populations presenting a large range and/or elevated Se exposure, sequential analyses of H-Se may provide a good reflection of variations in Se status

Diphenyl quinolines and isoquinolines: Synthesis and primary biological evaluation

The synthesis of a series of 35 substituted 3,4-diphenyl quinolines and isoquinolines is described. The majority of these molecules differ from all other triphenylethylene based antiestrogens by a different spatial location of the aminoalkyl side chain. The binding affinity of the most representative molecules (8, 9, 19, 20, 21, 23 and 25), including analogues 8 and 21 without the side chain, for the estrogen receptor α (ER)(≠) was determined. The ability of these molecules to induce the progesterone receptor was also studied. Antiproliferative activity was evaluated on MCF-7 human breast cancer cells, while intrinsic cytotoxic/cytostatic properties resulting from interaction with other targets than ER were assayed on L1210 murine leukemia cells. Introduction of an aminoalkylamino side chain at carbon 2 confers strong cytotoxic properties to diphenylquinolines 9 and 10 as well as pure antiestrogenic activities. However, cytotoxicity is so high with respect to antiestrogenicity that the latter was clearly observable only in one case (9b). The structure of compound 9b was determined by X-ray crystallography. Molecular modeling of its docking within the hormone-binding domain of the receptor was subsequently undertaken. According to our results, the design of molecules with the side chain bound to the ethylene part of the triphenyl ethylene skeleton might generate compounds of potential pharmacological interest. Copyright (C) 2000 Elsevier Science Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe