Mercury, cadmium, and lead levels in human placenta: a systematic review

BACKGROUND: Placental tissue may furnish information on the exposure of both mother and fetus. Mercury (Hg), cadmium (Cd), and lead (Pb) are toxicants of interest in pregnancy because they are associated with alterations in child development. OBJECTIVES: The aim of this study was to summarize the available information regarding total Hg, Cd, and Pb levels in human placenta and possible related factors. METHODS: We performed a systematic search of PubMed/MEDLINE, EMBASE, Lilacs, OSH, and Web of Science for original papers on total Hg, Cd, or Pb levels in human placenta that were published in English or Spanish (1976-2011). Data on study design, population characteristics, collection and analysis of placenta specimens, and main results were extracted using a standardized form. RESULTS: We found a total of 79 papers (73 different studies). Hg, Cd, and Pb levels were reported in 24, 46, and 46 studies, respectively. Most studies included small convenience samples of healthy pregnant women. Studies were heterogeneous regarding populations selected, processing of specimens, and presentation of results. Hg concentrations > 50 ng/g were found in China (Shanghai), Japan, and the Faroe Islands. Cd levels ranged from 1.2 ng/g to 53 ng/g and were highest in the United States, Japan, and Eastern Europe. Pb showed the greatest variability, with levels ranging from 1.18 ng/g in China (Shanghai) to 500 ng/g in a polluted area of Poland. CONCLUSION: The use of the placenta as a biomarker to assess heavy metals exposure is not properly developed because of heterogeneity among the studies. International standardized protocols are needed to enhance comparability and increase the usefulness of this promising tissue in biomonitoring studies.We thank the librarians of the Móstoles Hospital and of the National Health Sciences Library (ISCIII).S

Prevalence of prenatal zinc deficiency and its association with socio-demographic, dietary and health care related factors in Rural Sidama, Southern Ethiopia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Several studies witnessed that prenatal zinc deficiency (ZD) predisposes to diverse pregnancy complications. However, scientific evidences on the determinants of prenatal ZD are scanty and inconclusive. The purpose of the present study was to assess the prevalence and determinants of prenatal ZD in Sidama zone, Southern Ethiopia.</p> <p>Methods</p> <p>A community based, cross-sectional study was conducted in Sidama zone in January and February 2011. Randomly selected 700 pregnant women were included in the study. Data on potential determinants of ZD were gathered using a structured questionnaire. Serum zinc concentration was measured using Atomic Absorption Spectrometry. Statistical analysis was done using logistic regression and linear regression.</p> <p>Results</p> <p>The mean serum zinc concentration was 52.4 (+/-9.9) μg/dl (95% CI: 51.6-53.1 μg/dl). About 53.0% (95% CI: 49.3-56.7%) of the subjects were zinc deficient. The majority of the explained variability of serum zinc was due to dietary factors like household food insecurity level, dietary diversity and consumption of animal source foods. The risk of ZD was 1.65 (95% CI: 1.02-2.67) times higher among women from maize staple diet category compared to <it>Enset </it>staple diet category. Compared to pregnant women aged 15-24 years, those aged 25-34 and 35-49 years had 1.57 (95% CI: 1.04-2.34) and 2.18 (95% CI: 1.25-3.63) times higher risk of ZD, respectively. Women devoid of self income had 1.74 (95% CI: 1.11-2.74) time increased risk than their counterparts. Maternal education was positively associated to zinc status. Grand multiparas were 1.74 (95% CI: 1.09-3.23) times more likely to be zinc deficient than nulliparas. Frequency of coffee intake was negatively association to serum zinc level. Positive association was noted between serum zinc and hemoglobin concentrations. Altitude, history of iron supplementation, maternal workload, physical access to health service, antenatal care and nutrition education were not associated to zinc status.</p> <p>Conclusion</p> <p>ZD is of public health concern in the area. The problem must be combated through a combination of short, medium and long-term strategies. This includes the use of household based phytate reduction food processing techniques, agricultural based approaches and livelihood promotion strategies.</p

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

VapC Toxins from Mycobacterium tuberculosis Are Ribonucleases that Differentially Inhibit Growth and Are Neutralized by Cognate VapB Antitoxins

The chromosome of Mycobacterium tuberculosis (Mtb) encodes forty seven toxin-antitoxin modules belonging to the VapBC family. The role of these modules in the physiology of Mtb and the function(s) served by their expansion are unknown. We investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis. Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic when expressed from a tetracycline-regulated promoter in M. smegmatis. The same genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c in M. smegmatis correlated with the level of protein expressed, suggesting that the VapC level must exceed a threshold for toxicity to be observed. In addition, the level of Rv2456 protein induced in M. smegmatis was markedly lower than Rv2549c, which may account for the lack of toxicity of this and other VapCs scored as ‘non-toxic’. The growth inhibitory effects of toxic VapCs were neutralized by expression of the cognate VapB as part of a vapBC operon or from a different chromosomal locus, while that of non-cognate antitoxins did not. These results demonstrated a specificity of interaction between VapCs and their cognate VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered the organisms more susceptible to growth inhibition following toxic VapC expression. However, toxicity of ‘non-toxic’ VapCs was not unveiled in deletion mutant strains, even when the mutation eliminated the corresponding cognate VapB, presumably due to insufficient levels of VapC protein. Together with the ribonuclease (RNase) activity demonstrated for Rv0065 and Rv0617 – VapC proteins with similarity to Rv0549c and Rv3320c, respectively – these results suggest that the VapBC family potentially provides an abundant source of RNase activity in Mtb, which may profoundly impact the physiology of the organism

Paternal effects on early embryogenesis

Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field