The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.

DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1ß secretion, but increasing cellular ROS and mitochondrial O2•-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-ß1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1ß secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1ß secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1ß secretion process, as the NLRP3 activation, deserves further study.

Differential Expression of AhR in Peripheral Mononuclear Cells in Response to Exposure to Polycyclic Aromatic Hydrocarbons in Mexican Women.

The exposure to air pollutants causes significant damage to health, and inefficient cooking and heating practices produce high levels of household air pollution, including a wide range of health-damaging pollutants such as fine particles, carbon monoxide and PAHs. The exposure to PAHs has been associated with the development of neoplastic processes, asthma, genotoxicity, altered neurodevelopment and inflammation. The effects on the induction of proinflammatory cytokines are attributed to the activation of AhR. However, the molecular mechanisms by which the PAHs produce proinflammatory effects are unknown. This study was performed on a group of 41 Mexican women from two rural communities who had stoves inside their houses, used wood as biomass fuel, and, thus, were vulnerable. According to the urinary 1-OHP concentration, the samples were stratified into two groups for determination of the levels of TNF-α, AhR, CYP1B1, miR-125b and miR-155 expression. Our results showed that the CYP1B1, TNF-α, miR-125b and miR-155 expression levels were not statistically different between women with the lowest and highest levels of 1-OHP. Interestingly, high levels of PAHs promoted augmented expression of AhR, which is a protein involved in the modulation of inflammatory pathways in vivo, suggesting that cell signaling of AhR may be implicated in several pathogenesis processes.

Low concentrations of lead disturb phenotypical markers of the inflammatory and the anti-inflammatory profile of bone marrow-derived macrophages from BALB/c mice.

Lead (Pb) is a ubiquitous toxic metal that decreases resistance to infections, in which the macrophages have an essential role. Pb adverse effects on nitric oxide (NO-) production and variable effects on inflammatory cytokines in activated macrophages have been reported, but no effects have been reported in anti-inflammatory macrophages. We studied Pb (0.03-6 µg/dL equivalent to 0.014-2.89 µM) effects on the function of bone marrow-derived macrophages (BMDM) induced to either inflammatory or anti-inflammatory phenotypes, with LPS + IFNγ or IL-4+IL-13, respectively, and whether these effects are related. Pb did not induce cytotoxicity at any concentration in both macrophage phenotypes. In inflammatory BMDM, Pb (6 µg/dL) inhibited NO- production without affecting inducible nitric oxide synthase (iNOS) levels or basal arginase activity. At 3 and 6 µg/dL, Pb enhanced the major histocompatibility complex class II (MHC II) membrane expression but did not modify CD86 expression, TNFα, or IL-1ß production and secretion. In anti-inflammatory BMDM, Pb did not alter arginase activity, but at 3 and 6 µg/dL, increased TGF-ß1 and mannose receptor expression. Results showed that environmentally relevant concentrations of Pb alter functional outcomes or phenotypic markers of anti-inflammatory for the first time. The Pb effects on the inflammatory macrophages are not dependent on negative feedback resulting from the Pb effect on the anti-inflammatory phenotype. The Pb affected only some molecules or specific pathways related to both phenotypes. These effects could be related to Pb effects on immune defense against intracellular pathogens and allergy susceptibility.

Role of aromatase activation on sodium arsenite-induced proliferation, migration, and invasion of MDA-MB-231 and MDA-MB-453 breast cancer cell lines.

Arsenic is an endocrine disruptor that promotes breast cancer (BCa) development. Estrogen synthesis, through aromatase activation, is essential for BCa promotion and progression through activating the G-coupled estrogen receptor 1 (GPER1), regulating rapid nongenomic effects involved in cell proliferation and migration of BCa cells. Herein, was studied the role of aromatase activation and the GPER1 pathway on sodium arsenite-induced promotion and progression of MDA-MB-231 and MDA-MB-453 BCa cell lines. Our results demonstrated that 0.1 µM of sodium arsenite induces cell proliferation, migration, invasion, and stimulates aromatase activity of BCa cell lines MDA-MB-231, MDA-MB-453, MCF-7, but not in a nontumorigenic breast epithelial cell line (MCF-12A). Using letrozole (an aromatase inhibitor) and G-15 (a GPER1-selective antagonist), we demonstrated that sodium arsenite-induced proliferation and migration is mediated by induction of aromatase enzyme and, at least in part, by GPER1 activation in MDA-MB-231 and MDA-MB-453 cells. Sodium arsenite induced phosphorylation of Src that participated in sodium arsenite-induced aromatase activity, and -cell proliferation of MDA-MB-231 cell line. Overall, data suggests that sodium arsenite induces a positive-feedback loop, resulting in the promotion and progression of BCa cells, through induction of aromatase activity, E2 production, GPER1 stimulation, and Src activation.

CYP1A1, GSTT1, IL-6 and IL-8 transcription and IL-6 secretion on umbilical endothelial cells from hypertensive pregnant women: Preliminary results.

The impact of pregnancy hypertension in the offspring endothelia remains unknown. We evaluated the transcriptional expression of four genes that participate in the process of endothelial dysfunction using umbilical vein endothelial cell cultures (HUVEC) from healthy pregnant women (PW) and those with hypertensive disorders (HD). The cytochrome P450 1A1 (CYP1A1), gluthathione S-transferase subtype T1 (GSTT1), interleukin 6 (IL-6) and 8 (IL-8) mRNA and IL-6 protein levels were assessed. IL-6 and IL-8 transcripts were significantly reduced in HUVEC obtained from HD women. Our results suggest that a hypertensive environment in utero modifies the transcriptional expression of key inflammatory molecules in the newborn.

Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively. CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

MeHg affects the activation of FAK, Src, Rac1 and Cdc42, critical proteins for cell movement in PDGF-stimulated SH-SY5Y neuroblastoma cells.

Methylmercury (MeHg) is an environmental neurotoxicant that inhibits neuronal migration. This process requires several cyclic steps involving the formation of membrane protrusions (lamellipodia and filopodia) and focal adhesion turnover. FAK and Src are critical proteins that regulate both processes. The FAK-Src complex promotes the activation of Rac1 and Cdc42, two GTPases involved in the remodeling of the actin cytoskeletal network. Here, we studied the effect of MeHg (1, 10, 100, 500 and 1000nM) on cell migration, the formation of cell protrusions, focal adhesion location and the activation of FAK, Src, Rac1 and Cdc42 using the SH-SY5Y neuroblastoma cell line stimulated with PDGF-BB (PDGF). The data show that MeHg (1-500nM) inhibited PDGF-stimulated cell migration. In PDGF-stimulated cells, MeHg (100-1000nM) decreased protrusions and increased the size of the p-FAKY397 clusters. MeHg also inhibited PDGF-induced FAK and Src activation and, at 100nM, MeHg inhibited the activation of Rac1 and Cdc42. Altogether, the findings show that low concentrations of MeHg inhibit SH-SY5Y cell migration by disrupting the activation and disassembly of FAK. This negatively affects the activation of Src, Rac1 and Cdc42, all of which are critical proteins for the regulation of cell movement. These effects could be related to the MeHg-mediated inhibition of PDGF-induced formation of lamellipodia and filopodia, focal adhesion disassembly and PDGF-induced movement.

Exposure to p,p'-DDE Induces Morphological Changes and Activation of the PKCα-p38-C/EBPß Pathway in Human Promyelocytic HL-60 Cells.

Dichlorodiphenyldichloroethylene (p,p'-DDE), the most persistent metabolite of dichlorodiphenyltrichloroethane (DDT), is still present in the human population. Both are present in the bone marrow of patients with bone marrow disorders, but thus far there are no studies that assess the capability of p,p'-DDE to affect myeloid cells. The aim of this study was to determine the effect of p,p'-DDE on promyelocytic cell differentiation and intracellular pathways related to this event. p,p'-DDE induced morphological changes compatible with promyelocytic differentiation in a concentration-dependent manner. The p,p'-DDE effect on [Ca2+]i, C/EBPß protein levels, PKCα and p38 activation, and the role of oxidative stress or PLA2 was assayed. Exposure to 1.9 µg/mL of p,p'-DDE increased [Ca2+]i, PKCα, p38, and C/EBPß protein levels; the increase of nuclear C/EBPß protein was dependent on p38. PKCα phosphorylation was dependent on PLA2 and p,p'-DDE-induced oxidative stress. p38 phosphorylation induced by p,p'-DDE was dependent on PLA2, PKC activation, and oxidative stress. These effects of p,p'-DDE at concentrations found in human bone marrow may induce alterations in immature myeloid cells and could affect their cellular homeostasis. In order to establish the risk from exposure to p,p'-DDE on the development of bone marrow disorders in humans, these effects deserve further study.

Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats.

Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 µg/kg/day MeHg, (3) 500 µg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.

A permethrin/allethrin mixture induces genotoxicity and cytotoxicity in human peripheral blood lymphocytes.

Two pyrethroids, permethrin and allethrin, are often combined for large-scale use in public health programs to control vector-borne diseases. In this study, the genotoxic potential of a commercial formulation of permethrin and allethrin was examined using cultured human peripheral blood lymphocytes (PBL). Genotoxicity was evaluated using the cytokinesis-block micronucleus cytome (CBMN cyt) assay by measuring the frequency of micronuclei (MN), nuclear division index (NDI), formation of nucleoplasmic bridges (NPB) and nuclear buds (NBUD), as well as apoptotic and necrotic cells. Human PBL were treated with different concentrations of a permethrin/allethrin mixture (1/0.01, 5/0.07, and 10/0.14 µg/ml) for 24 or 36 h. The highest concentration (10/0.14 µg/ml) of permethrin/allethrin mixture significantly increased MN frequency and percent apoptotic cells after incubations for 24 or 36 h. The NDI was markedly decreased in response to treatment with 5/0.07 or 10/0.14 µg/ml permethrin/allethrin for both 24 and 36 h. Exposure to the permethrin/allethrin mixture did not significantly alter formation of NBUD, NPB, or percent necrotic cells. The MN frequency was significantly correlated with the number of apoptotic and necrotic cells but inversely correlated with NDI. Data demonstrated that a mixture of permethrin and allethrin induced concentration- and time-dependent cytotoxic and genotoxic damage to human PBL in vitro.

Association of vWA and TPOX polymorphisms with venous thrombosis in Mexican mestizos.

OBJECTIVE: Venous thromboembolism (VTE) is a multifactorial disorder and, worldwide, the most important cause of morbidity and mortality. Genetic factors play a critical role in its aetiology. Microsatellites are the most important source of human genetic variation having more phenotypic effect than many single nucleotide polymorphisms. Hence, we evaluate a possible relationship between VTE and the genetic variants in von Willebrand factor, human alpha fibrinogen, and human thyroid peroxidase microsatellites to identify possible diagnostic markers. METHODS: Genotypes were obtained from 177 patients with VTE and 531 nonrelated individuals using validated genotyping methods. The allelic frequencies were compared; Bayesian methods were used to correct population stratification to avoid spurious associations. RESULTS: The vWA-18, TPOX-9, and TPOX-12 alleles were significantly associated with VTE. Moreover, subjects bearing the combination vWA-18/TPOX-12 loci exhibited doubled risk for VTE (95% CI = 1.02-3.64), whereas the combination vWA-18/TPOX-9 showed an OR = 10 (95% CI = 4.93-21.49). CONCLUSIONS: The vWA and TPOX microsatellites are good candidate biomarkers in venous thromboembolism diseases and could help to elucidate their origins. Additionally, these polymorphisms could become useful markers for genetic studies of VTE in the Mexican population; however, further studies should be done owing that this data only show preliminary evidence.

Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of Mexico.

This study aims to portray the complex diversity of the Mexican Mestizo population, which represents 98.8% of the entire population of Mexico. We compiled extended haplotype data of the Y chromosome from populations in the Central Valley of Mexico (CVM), which we compared with other Mestizo and parental (Amerindian, European, and African) populations. A complex ancestral relationship was found in the CVM population, suggesting cosmopolitan origins. Nevertheless, the most preeminent lineages point toward a European ancestry, where the R1b lineage was most frequent. In addition, important frequencies of Amerindian lineages were also found in the Mestizo sample studied. Interestingly, the Amerindian ancestry showed a remarkable substructure, which was represented by the two main founding lineages: QL54 (× M3) and M3. However, even within each lineage a high diversity was found despite the small number of sample bearers of these lineages. Further, we detected important genetic differences between the CVM populations and the Mexican Mestizo populations from the north and south. This result points to the fact that Mestizo populations present different ancestral proportions, which are related to the demographic events that gave origin to each population. Finally, we provide additional forensic statistical parameters that are useful in the interpretation of genetic analysis where autosomal loci are limited. Our findings illustrate the complex genetic background of the Mexican Mestizo population and reinforce the need to encompass more geographic regions to generate more robust data for forensic applications.

Maternal C677T MTHFR polymorphism and environmental factors are associated with cleft lip and palate in a Mexican population.

INTRODUCTION: Nonsyndromic cleft lip and cleft palate (CL/P) is associated with environmental, nutritional, and genetic factors. Maternal polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with CL/P. OBJECTIVES: To determine the relationship between the risk of having a child with CL/P and maternal C677T and A1298C MTHFR polymorphisms, the intake of folate supplements, and exposure to environmental factors during the first trimester of pregnancy, a case-control study of Mexican mothers (88 case mothers and 116 control mothers) was conducted. METHODS: A questionnaire was used to assess exposure to environmental factors. The C677T and A1298C polymorphisms were identified by polymerase chain reaction with restriction fragment length polymorphism. RESULTS: Mothers with the 677CT or 677TT genotype had a higher risk of having a child with CL/P than mothers with the 677CC genotype (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.7). An increased risk of having a child with CL/P was associated with the lack of folate supplementation during the first trimester of pregnancy (OR, 3.8; 95% CI, 1.9-7.6), and this risk was greater in the mothers with the 677TT or 677CT genotype than mothers who reported taking folate supplements and had the 677CC genotype (OR, 11.2; 95% CI, 3.3-37.5). Pesticide exposure was associated with CL/P. There was no significant association between either the A1298C variant or tobacco exposure and the risk of CL/P. CONCLUSION: These results suggest that gene-environment interactions play an important role in the development of CL/P.

TLR4 is a target of environmentally relevant concentration of lead.

Lead (Pb) alters the susceptibility to different pathogens suggesting that macrophage-mediated defense mechanisms, through activation of toll-like receptors (TLRs), may be affected by Pb. The aim of this study was to test whether activation of TLR4 is a targeted molecule to the effect of environmentally relevant Pb concentrations (0.05, 0.5 and 5µg/dL). The function of macrophages activated through TLR4 was evaluated using as TLR4 ligand lipopolysaccharides (LPSs) from two different pathogens: Escherichia coli and Salmonella typhimurium. Pb induced proliferation, increased the NO(-) baseline, IL-1ß and IL-6 secretion. Interestingly, Pb exposure induced differential effects on cells stimulated with the two LPS used: in macrophages stimulated with LPS from E. coli, Pb caused an early decrease in proliferation, increase NO(-) production, and decrease IL-6 and TNF-α secretion; in macrophages stimulated with LPS from S. typhimurium, Pb decreased proliferation after 36h, induced a biphasic effect on NO(-) production, and enhance the secretion of IL-1ß, IL-6 and TNF-α. Results suggest that TLR4 is a target for the Pb effect, which up to 5.0µg/dL affect immune competence against pathogens, dependent on the bacterial species. This effect may be attributable to structural differences that determine LPS affinity for TLR4.

Mexican mestizo population sub-structure: effects on genetic and forensic statistical parameters.

Since Mexican mestizos are an admixed population, it is necessary to determine the effects that the substructure of the population has on genetic and forensic parameters. With this aim, a study was performed with 15 STR loci (CODIS plus D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for genetic population stratification, the results show that the Mexican mestizo population is substructured into three subgroups, which are in HW and linkage equilibrium. The combination of the 15 loci in the whole population has high forensic efficiency with the capacity to genetically discriminate one individual in one quintillion (1/10(18)). Our data potentially validates the use of these 15 STR loci to establish forensic identity and parentage testing for legal purposes, and offers a powerful tool for genetic variation analysis. However, given that the population is stratified, we highly recommend applying a correction with the inbreeding coefficient in calculations of paternity and forensic studies to avoid erroneous assumptions.

Immunization with A91 peptide or copolymer-1 reduces the production of nitric oxide and inducible nitric oxide synthase gene expression after spinal cord injury.

Immunization with neurally derived peptides (INDP) boosts the action of an autoreactive immune response that has been shown to induce neuroprotection in several neurodegenerative diseases, especially after spinal cord (SC) injury. This strategy provides an environment that promotes neuronal survival and tissue preservation. The mechanisms by which this autoreactive response exerts its protective effects is not totally understood at the moment. A recent study showed that INDP reduces lipid peroxidation. Lipid peroxidation is a neurodegenerative phenomenon caused by the increased production of reactive nitrogen species such as nitric oxide (NO). It is possible that INDP could be interfering with NO production. To test this hypothesis, we examined the effect of INDP on the amount of NO produced by glial cells when cocultured with autoreactive T cells. We also evaluated the amount of NO and the expression of the inducible form of nitric oxide synthase (iNOS) at the injury site of SC-injured animals. The neural-derived peptides A91 and Cop-1 were used to immunize mice and rats with SC injury. In vitro studies showed that INDP significantly reduces the production of NO by glial cells. This observation was substantiated by in vivo experiments demonstrating that INDP decreases the amount of NO and iNOS gene expression at the site of injury. The present study provides substantial evidence on the inhibitory effect of INDP on NO production, helpingour understanding of the mechanisms through which protective autoimmunity promotes neuroprotection.

Environmental exposure to lead and mercury in Mexican children: a real health problem.

Exposure to lead (Pb) and mercury (Hg) remains a world public health problem, particularly for young children in developing countries. In Mexico, the main sources of exposure to Pb and Hg are wastes from human activities that increase the natural sources of these metals. Pb and Hg are highly toxic during development and maturation periods of the central nervous system (CNS); these effects are associated with the risk for neurodegenerative diseases. Mexico has numerous exposure sources to Pb and Hg; nevertheless, information on exposure in children is limited, particularly for Hg. Therefore, we conducted a review of the studies performed in children exposed to Pb and Hg. Data presented support that an important proportion of Mexican children have Pb levels above values associated with dangerous effects. On the other hand, studies on Hg-exposure are scarce, so we need more studies to estimate the magnitude of the problem and to determine exposure levels in Mexican children. Available data support the urgent need for coordinated actions among researchers, and health and environmental government authorities to implement education and nutritional campaigns, as well as to decrease exposure and effects of Pb and Hg. In addition, there must be a priority for the implementation of educational campaigns directed to the general population, but with emphasis in parents, education staff and health care providers to decrease both the risk of exposure of children to Pb and Hg and the effects of the exposure to these metals.

Role of nitric oxide produced by iNOS through NF-κB pathway in migration of cerebellar granule neurons induced by Lipopolysaccharide.

Inflammatory stimulus during development increases the risk for adverse neurologic outcome. One possible mechanism is disrupting neuronal migration. Using lipopolysaccharide (LPS)-treatment to assess inflammatory stimulus on neuronal migration of cerebellar granule neurons, we previously found that LPS-activation increased the neuronal migration. The precise mechanisms behind these effects have not been investigated. Independently, it was shown that nitric oxide (NO(•-)) regulates neuronal migration during development, that NO(•-) is produced by inducible nitric oxide synthase (iNOS) in response to LPS through the activation of nuclear factor (NF)-κB, and that LPS induce the expression of genes under the transcriptional control of NF-κB in primary cultures from developing mouse cerebellum. To investigate the relationship between these events, we used this culture model to study the role of NO(•-) produced by iNOS through NF-κB signaling pathway, in the effect of LPS on neuron migration. LPS increased NO(•-) production, iNOS protein levels and NF-κB nuclear levels; concomitantly with NO(•-) production, LPS increased the neuronal migration as compared to non stimulated cultures. The necessary roles of the NO(•-) and iNOS were demonstrated by chelating of NO(•-) with hemoglobin and the inhibition of iNOS by 1400W. Each of these treatments reduced neuronal migration induced by LPS. The role of NF-κB was showed by using the inhibitor JSH-23, which decreased NO(•-) production and neuronal migration in LPS activated cultures. These results suggest that neuronal migration during development is susceptible to be modified by pro-inflammatory stimulus such as LPS through intracellular pathways associated with their receptors.

Biomonitoring of metal in children living in a mine tailings zone in Southern Mexico: A pilot study.

Accumulation of metals in soil represents a health risk for individuals living near mining areas, especially for children who have a higher susceptibility to metal related diseases. The Taxco mining district in Southern Mexico was one of the largest Mexican metal producers of silver and gold, among other metals. The aim of this pilot study was to evaluate metal exposure on children aged 6-11 years living in and around the Taxco mine tailings zone. Lead in blood (PbB) was measured by graphite furnace atomic absorption spectrophotometry (AAS). Urine arsenic (AsU) was measured by hydride generation AAS, urinary Hg (HgU) by flow injection cold vapor atomic absorption, and urinary concentration of other metals such as chromium (Cr), nickel (Ni), cadmium (Cd), barium (Ba), cobalt (Co), copper (Cu), zinc (Zn), manganese (Mn), molybdenum (Mo), strontium (Sr), and iron (Fe) were determined by inductively coupled plasma optical emission spectrometry. Fifty samples were analyzed for PbB, AsU, and HgU, and 35 samples for the other metals. The mean concentration+/-SD for each metal was: PbB, 9.4+/-3.3 microg/dL; NiU, 75.4+/-30.7 microg/L; BaU, 18.4+/-4.1 microg/L; MnU, 5.2+/-0.7 microg/L; CuU, 29.6+/-6.8 microg/L; AsU, 16.5+/-8.3 microg/L; HgU, 0.7+/-0.86 microg/L; CdU, 4.7+/-2.7 microg/L; CrU, 15.1+/-4.45 microg/L; CoU, 18.3+/-9.7 microg/L; SrU, 49.2+/-30.7 microg/L; ZnU, 628.4+/-438.9 microg/L; FeU, 30.5+/-17.7 microg/L; and MoU, 52.1+/-29.3 microg/L. Results of this exploratory study show that children residing in the mining area of Taxco were environmentally exposed to several metals and a high percentage of these children had levels of Ni, Ba, Mn, Cr, Co, Cd, As, Hg, and Pb above reference values. Thus, further studies are needed to assess the effects of simultaneous exposure to toxic metals in children residing in mining areas.