Recent Developments in Low-Level Lead Exposure and Intellectual Impairment in Children

In the last decade children’s blood lead levels have fallen significantly in a number of countries, and current mean levels in developed countries are in the region of 3 μg/dL. Despite this reduction, childhood lead poisoning continues to be a major public health problem for certain at-risk groups of children, and concerns remain over the effects of lead on intellectual development in infants and children. The evidence for lowered cognitive ability in children exposed to lead has come largely from prospective epidemiologic studies. The current World Health Organization/Centers for Disease Control and Prevention blood level of concern reflects this and stands at 10 μg/dL. However, a recent study on a cohort of children whose lifetime peak blood levels were consistently < 10 μg/dL has extended the association of blood lead and intellectual impairment to lower levels of lead exposure and suggests there is no safety margin at existing exposures. Because of the importance of this finding, we reviewed this study in detail along with other recent developments in the field of low-level lead exposure and children’s cognitive development. We conclude that these findings are important scientifically, and efforts should continue to reduce childhood exposure. However, from a public health perspective, exposure to lead should be seen within the many other risk factors impacting on normal childhood development, in particular the influence of the learning environment itself. Current lead exposure accounts for a very small amount of variance in cognitive ability (1–4%), whereas social and parenting factors account for 40% or more

No association between the aluminium content of trabecular bone and bone density, mass or size of the proximal femur in elderly men and women

BACKGROUND: Aluminium is considered a bone toxic metal since poisoning can lead to aluminium-induced bone disease in patients with chronic renal failure. Healthy subjects with normal renal function retain 4% of the aluminium consumed. They might thus also accumulate aluminium and eventually be at risk of long-term low-grade aluminium intoxication that can affect bone health. METHODS: We therefore examined 62 patients with femoral neck fractures or osteoarthritis of the hip (age range 38–93), with the aim of examining whether aluminium in bone is associated with bone-mineral density (BMD), content (BMC) or width of the femoral neck measured by dual-energy X-ray absorptiometry (DXA). During operations bone biopsies were taken from the trabecular bone of the proximal femur. The samples were measured for their content of aluminium using a mass spectrometer. RESULTS: No significant association between the aluminium content in bone and femoral neck BMD, BMC or width could be found after multivariate adjustment. CONCLUSION: Our results indicate that the accumulated aluminium content in bone during life does not substantially influence the extent of osteoporosis

Longitudinal evaluation the pulmonary function of the pre and postoperative periods in the coronary artery bypass graft surgery of patients treated with a physiotherapy protocol

<p>Abstract</p> <p>Background</p> <p>The treatment of coronary artery disease (CAD) seeks to reduce or prevent its complications and decrease morbidity and mortality. For certain subgroups of patients, coronary artery bypass graft surgery (CABG) may accomplish these goals. The objective of this study was to assess the pulmonary function in the CABG postoperative period of patients treated with a physiotherapy protocol.</p> <p>Methods</p> <p>Forty-two volunteers with an average age of 63 ± 2 years were included and separated into three groups: healthy volunteers (n = 09), patients with CAD (n = 9) and patients who underwent CABG (n = 20). Patients from the CABG group received preoperative and postoperative evaluations on days 3, 6, 15 and 30. Patients from the CAD group had evaluations on days 1 and 30 of the study, and the healthy volunteers were evaluated on day 1. Pulmonary function was evaluated by measuring forced vital capacity (FVC), maximum expiratory pressure (MEP) and Maximum inspiratory pressure (MIP).</p> <p>Results</p> <p>After CABG, there was a significant decrease in pulmonary function (p < 0.05), which was the worst on postoperative day 3 and returned to the preoperative baseline on postoperative day 30.</p> <p>Conclusion</p> <p>Pulmonary function decreased after CABG. Pulmonary function was the worst on postoperative day 3 and began to improve on postoperative day 15. Pulmonary function returned to the preoperative baseline on postoperative day 30.</p

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

A Study of Nuclear Transcription Factor-Kappa B in Childhood Autism

BACKGROUND: Several children with autism show regression in language and social development while maintaining normal motor milestones. A clear period of normal development followed by regression and subsequent improvement with treatment, suggests a multifactorial etiology. The role of inflammation in autism is now a major area of study. Viral and bacterial infections, hypoxia, or medication could affect both foetus and infant. These stressors could upregulate transcription factors like nuclear factor kappa B (NF-κB), a master switch for many genes including some implicated in autism like tumor necrosis factor (TNF). On this hypothesis, it was proposed to determine NF-κB in children with autism. METHODS: Peripheral blood samples of 67 children with autism and 29 control children were evaluated for NF-κB using electrophoretic mobility shift assay (EMSA). A phosphor imaging technique was used to quantify values. The fold increase over the control sample was calculated and statistical analysis was carried out using SPSS 15. RESULTS: We have noted significant increase in NF-κB DNA binding activity in peripheral blood samples of children with autism. When the fold increase of NF-κB in cases (n = 67) was compared with that of controls (n = 29), there was a significant difference (3.14 vs. 1.40, respectively; p<0.02). CONCLUSION: This finding has immense value in understanding many of the known biochemical changes reported in autism. As NF-κB is a response to stressors of several kinds and a master switch for many genes, autism may then arise at least in part from an NF-κB pathway gone awry

Arbovirus-Derived piRNAs Exhibit a Ping-Pong Signature in Mosquito Cells

The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved in antiviral defense remains unclear. Here, we report in cells derived from the two main vectors for arboviruses, Aedes albopictus and Aedes aegypti, the production of viral small RNAs that exhibit the hallmarks of ping-pong derived piwi-associated RNAs (piRNAs) after infection with positive or negative sense RNA viruses. Furthermore, these cells produce endogenous piRNAs that mapped to transposable elements. Our results show that these mosquito cells can initiate de novo piRNA production and recapitulate the ping-pong dependent piRNA pathway upon viral infection. The mechanism of viral-piRNA production is discussed

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

Local iron homeostasis in the breast ductal carcinoma microenvironment

Abstract BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context.info:eu-repo/semantics/publishedVersio