Arsenic alters monocyte superoxide anion and nitric oxide production in environmentally exposed children.

Arsenic (As) exposure has been associated with alterations in the immune system, studies in experimental models and adults have shown that these effects involve macrophage function; however, limited information is available on what type of effects could be induced in children. The aim of this study was to evaluate effects of As exposure, through the association of inorganic As (iAs) and its metabolites [monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] with basal levels of nitric oxide (NO(-)) and superoxide anion (O(2)(-)), in peripheral blood mononuclear cells (PBMC) and monocytes, and NO(-) and O(2)(-) produced by activated monocytes. Hence, a cross-sectional study was conducted in 87 children (6-10 years old) who had been environmentally exposed to As through drinking water. Levels of urinary As species (iAs, MMA and DMA) were determined by hydride generation atomic absorption spectrometry, total As (tAs) represents the sum of iAs and its species; tAs urine levels ranged from 12.3 to 1411 microg/g creatinine. Using multiple linear regression models, iAs presented a positive and statistical association with basal NO(-) in PBMC (beta=0.0048, p=0.049) and monocytes (beta=0.0044, p=0.044), while basal O(2)(-) had a significant positive association with DMA (beta=0.0025, p=0.046). In activated monocytes, O(2)(-) showed a statistical and positive association with iAs (beta=0.0108, p=0.023), MMA (beta=0.0066, p=0.022), DMA (beta=0.0018, p=0.015), and tAs (beta=0.0013, p=0.015). We conclude that As exposure in the studied children was positively associated with basal levels of NO(-) and O(2)(-) in PBMC and monocytes, suggesting that As induces oxidative stress in circulating blood cells. Additionally, this study showed a positive association of O(2)(-) production with iAs and its metabolites in stimulated monocytes, supporting previous data that suggests that these cells, and particularly the O(2)(-) activation pathway, are relevant targets for As toxicity.

Inner Scar Umbilicus: New Horizons for Vertical Abdominoplasty.

BACKGROUND: It is reasonable that deflated tissue in massive weight loss patients may demand not only lifting but also some extent of central body tightening, by the fleur-de-lis procedure. Although achieving nice contouring results, poor visible scars, including umbilical complications, have restricted the indications for the anterior vertical approach. The purpose of this article is to present the authors' experience with the inner scar umbilical reconstruction, reflecting overall results in vertical abdominoplasties. METHODS: Massive weight loss patients who underwent fleur-de-lis abdominoplasties with the inner scar umbilicus were reviewed retrospectively. The original stalk was resected along with the surgical specimen, and two marked parallel skin flaps were kept and sutured against each other into the deep medial fascia, to reconstruct the umbilical base. Additional sutures were made to approximate fat tissue immediately under and above it, enhancing a deepening effect. Conventional upper and lower vertical closure helped to establish the tridimensional shape of the new navel. RESULTS: One hundred ten consecutive patients were studied, and 52 (47 percent) presented small inflammatory exudate arising from the inner suture, which resolved with conservative dry dressings. No further umbilical complications such as infection, necrosis, dehiscence, widening, or stenosis were reported, and all patients showed natural and scarless new navels with nice shapes and correct position. CONCLUSIONS: The inner scar umbilicus is a simple, safe, and reproducible technique, presenting low complication rates with sustainable and natural results. High-quality navel reconstruction favors the indication of vertical abdominoplasties, especially for post-bariatric surgery body contouring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic.

Exposure of several human populations to arsenic has been associated with a high incidence of detrimental dermatological and carcinogenic effects. To date, studies examining the immunotoxic effects of arsenic in humans, and specifically in children, are lacking. Therefore, we evaluated several parameters of immunological status in a group of children exposed to arsenic through their drinking water. Peripheral blood mononuclear cells (PBMCs) of 90 children (6 to 10 years old) were collected. Proportions of lymphocyte subpopulations, PBMC mitogenic proliferative response, and urinary arsenic levels were evaluated. Increased urine arsenic levels were associated with a reduced proliferative response to phytohemaglutinin (PHA) stimulation (P=0.005), CD4 subpopulation proportion (P=0.092), CD4/CD8 ratio (P=0.056), and IL-2 secretion levels (P=0.003). Increased arsenic exposure was also associated with an increase in GM-CSF secretion by mononucleated cells (P=0.000). We did not observe changes in CD8, B, or NK cell proportions, nor did we observe changes in the secretion of IL-4, IL-10, or IFN-gamma by PHA-activated PBMCs. These data indicate that arsenic exposure could alter the activation processes of T cells, such that an immunosuppression status that favors opportunistic infections and carcinogenesis is produced together with increased GM-CSF secretion that may be associated with chronic inflammation.

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.

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.