A Critical Review of Biomarkers Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and Future Needs

Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 μg/dL (0.48 μmol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 μg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth

In vitro effect of levonorgestrel on sperm fertilizing capacity and mouse embryo development

The objectives of this study were to assess the expression Of alpha-D-mannose binding sites in human spermatozoa, human sperm-oocyte interaction and the development of early stages of mouse embryo in the presence of levonorgestrel (LNG). Semen samples were obtained from 16 normozoospermic men. Spermatozoa were separated by Percoll gradient and incubated overnight for capacitation. The kinetic analysis of the expression of alpha-D-mannose binding sites was determined at 0, 4 and 22 h and in 22 h-capacitated spermatozoa that had been exposed to 1, 10 or 100 ng/mL of LNG or to a control medium for 30 min. Sperm binding sites for alpha-D-mannose were detected using commercial alpha-D-mannosylated bovine serum albumin conjugated with fluorescein isothiocyanate. To evaluate sperm-oocyte interaction, each oocyte was placed in a 100-mu L droplet containing one of the three doses of LNG or control medium and inseminated with 1.0X10(5) Motile spermatozoa/mL, after which the number of bound spermatozoa was evaluated. A total of 157 two-cell embryos recovered from eight mice was pooled and assigned randomly to treatment (1, 10 or 100 ng/mL of LNG) or control groups. There was a significant increase in the expression of specific alpha-D-mannose binding sites (Patterns II and III) during the incubation of spermatozoa under capacitating conditions. In the presence of LNG, results showed that there was no significant difference in the expression of specific alpha-D-mannose binding sites (Patterns II and III) at any LNG concentration tested compared with those spermatozoa in control medium. None of the LNG concentrations were capable of modifying the number of spermatozoa tightly bound to the human zona pellucida. There was no association between the presence or absence of LNG or the different doses of LNG evaluated and mouse embryo development. In conclusion, the hypothesis that in vitro exposure to LNG could interfere with sperm function and could contribute to the mechanism of action of this form of contraception was not confirmed but cannot be ruled out by the results of this study. (C) 2005 Elsevier Inc. All rights reserved.721717

Iron from haemoglobin and haemin modulates nucleotide hydrolysis inTrichomonas vaginalis

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5’-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5’-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron