Soil Properties on the Bioavailability and Toxicity of Metals to Eisenia Andrei

Environmental Scienc

Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils

BACKGROUND: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. However, it is unclear whether human microbiota display similar As metabolism, especially when present in a contaminated matrix. OBJECTIVES: We evaluated the metabolic potency of in vitro cultured human colon microbiota toward inorganic As (iAs) and As-contaminated soils. METHODS: A colon microbial community was cultured in a dynamic model of the human gut. These colon microbiota were incubated with iAs and with As-contaminated urban soils. We determined As speciation analysis using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. RESULTS: We found a high degree of methylation for colon digests both of iAs (10 mu g methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 mu g/g biomass/hr). Besides the formation of monomethylarsonic acid (MMA(V)), we detected the highly toxic monomethylarsonous acid (MMA(III)). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTA(V)). MMMTA(V), the toxicokinetic properties of which are not well known, was in many cases a major metabolite. CONCLUSIONS: Presystemic As metabolism is a significant process in the human body. Toxicokinetic studies aiming to completely elucidate the As metabolic pathway would therefore benefit from incorporating the metabolic potency of human gut microbiota. This will result in more accurate risk characterization associated with As exposures

Relative Bioavailability and Bioaccessibility and Speciation of Arsenic in Contaminated Soils

Background: Assessment of soil arsenic (As) bioavailability may profoundly affect the extent of remediation required at contaminated sites by improving human exposure estimates. Because small adjustments in soil As bioavailability estimates can significantly alter risk assessments and remediation goals, convenient, rapid, reliable, and inexpensive tools are needed to determine soil As bioavailability

CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes

Interleukin-1 has opposing effects on connective tissue growth factor and tenascin-C expression in human cardiac fibroblasts.

Cardiac fibroblasts (CF) play a central role in the repair and remodeling of the heart following injury and are important regulators of inflammation and extracellular matrix (ECM) turnover. ECM-regulatory matricellular proteins are synthesized by several myocardial cell types including CF. We investigated the effects of pro-inflammatory cytokines on matricellular protein expression in cultured human CF. cDNA array analysis of matricellular proteins revealed that interleukin-1α (IL-1α, 10ng/ml, 6h) down-regulated connective tissue growth factor (CTGF/CCN2) mRNA by 80% and up-regulated tenascin-C (TNC) mRNA levels by 10-fold in human CF, without affecting expression of thrombospondins 1-3, osteonectin or osteopontin. Western blotting confirmed these changes at the protein level. In contrast, tumor necrosis factor α (TNFα) did not modulate CCN2 expression and had only a modest stimulatory effect on TNC levels. Signaling pathway inhibitor studies suggested an important role for the p38 MAPK pathway in suppressing CCN2 expression in response to IL-1α. In contrast, multiple signaling pathways (p38, JNK, PI3K/Akt and NFκB) contributed to IL-1α-induced TNC expression. In conclusion, IL-1α reduced CCN2 expression and increased TNC expression in human CF. These observations are of potential value for understanding how inflammation and ECM regulation are linked at the level of the CF

A Systematic Analysis of Audiological Servicesin EHDI

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that examined 12 areas within state EHDI programs. For audiological evaluation and services, 299 items were listed by 49 coordinators, and themes were identified within each SWOT category. A threats, opportunities, weaknesses, and strengths, or TOWS, analysis yielded 12 recommendations that focused on similar themes. Out of these 12 recommendations, 3 distinct strategies emerged: 1) states need to address data management needs; 2) professional educational opportunities in pediatric audiology should be enhanced; and 3) funding opportunities for audiological services should be expanded. Addressed appropriately, these recommendations can substantially strengthen audiological services needed by state EHDI programs

Professional Development: Are We Meeting the Needs of State EHDI Programs?

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that consisted of 12 evaluative areas of EHDI programs. For the professional development area, 47 coordinators responded with a total of 223 items, and themes were identified in each SWOT category. A threats, opportunities, weaknesses, and strengths, or TOWS, analysis yielded 12 recommendations that focused on similar themes. Out of these 32 recommendations, 3 distinct strategies emerged: 1) target personnel shortages through collaborative relationships and partnerships by providing a range of professional development activities that target medical, clinical, and educational professionals who deliver direct services to young children with hearing loss and their families; 2) establish policies and procedures to eliminate barriers to training; and 3) publicize all training opportunities to foster greater participation. Addressed successfully, these recommendations can strengthen professional development in state EHDI programs

Integrating the Medical Home into the EHDI Process: EHDI Coordinators Perspectives

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that examined 12 areas within state EHDI programs. Related to how the medical home is integrated into the EHDI process, 273 items were listed by 48 coordinators, and themes were identified ivithin each SWOT category. A threats, opportunities, weaknesses, and strengths, or TOWS, analysis yielded 12 recommendations that focused on similar themes. Out of these 12 recommendations, 3 distinct strategies emerged. Specifically, states should: 1) utilize chapter champions to expand educational outreach to other health care providers, primary care physicians, medical homes, and residency training programs; 2) recruit several chapter champions to represent different areas within medicine as well as across the state; and 3) improve data management systems to allow for easier reporting and to alert the medical home/primary care provider about newborn hearing test results. Addressed appropriately, these recommendations can significantly strengthen medical home integration in state EHDI programs