Cytotoxicity and genotoxicity of nanosized and microsized titanium dioxide and iron oxide particles in Syrian hamster embryo cells

Potential differences in the toxicological properties of nanosized and non-nanosized particles have been notably pointed out for titanium dioxide (TiO(2)) particles, which are currently widely produced and used in many industrial areas. Nanoparticles of the iron oxides magnetite (Fe(3)O(4)) and hematite (Fe(2)O(3)) also have many industrial applications but their toxicological properties are less documented than those of TiO(2). In the present study, the in vitro cytotoxicity and genotoxicity of commercially available nanosized and microsized anatase TiO(2), rutile TiO(2), Fe(3)O(4), and Fe(2)O(3) particles were compared in Syrian hamster embryo (SHE) cells. Samples were characterized for chemical composition, primary particle size, crystal phase, shape, and specific surface area. In acellular assays, TiO(2) and iron oxide particles were able to generate reactive oxygen species (ROS). At the same mass dose, all nanoparticles produced higher levels of ROS than their microsized counterparts. Measurement of particle size in the SHE culture medium showed that primary nanoparticles and microparticles are present in the form of micrometric agglomerates of highly poly-dispersed size. Uptake of primary particles and agglomerates by SHE exposed for 24 h was observed for all samples. TiO(2) samples were found to be more cytotoxic than iron oxide samples. Concerning primary size effects, anatase TiO(2), rutile TiO(2), and Fe(2)O(3) nanoparticles induced higher cytotoxicity than their microsized counterparts after 72 h of exposure. Over this treatment time, anatase TiO(2) and Fe(2)O(3) nanoparticles also produced more intracellular ROS compared to the microsized particles. However, similar levels of DNA damage were observed in the comet assay after 24 h of exposure to anatase nanoparticles and microparticles. Rutile microparticles were found to induce more DNA damage than the nanosized particles. However, no significant increase in DNA damage was detected from nanosized and microsized iron oxides. None of the samples tested showed significant induction of micronuclei formation after 24 h of exposure. In agreement with previous size-comparison studies, we suggest that in vitro cytotoxicity and genotoxicity induced by metal oxide nanoparticles are not always higher than those induced by their bulk counterparts.     

Seasonality of the dietary dimension of household food security in urban Burkina Faso

Food insecurity is affecting an increasing number of urban poor in the developing world. Yet seasonal characteristics of food intakes have rarely been studied in West African cities. The objective of the present study was to assess the seasonality of the dietary dimension of household food security in Ouagadougou (Burkina Faso). In 2007, two sets of data were collected during the lean and post-harvest seasons, respectively, on a representative sample of 1056 households. At each season, two non-consecutive 24 h recalls were performed at the household level. Food prices were also recorded. Household food security was assessed by the household's mean adequacy ratio (MAR) for energy and eleven micronutrients. Changes in the MAR according to the season were analysed by mixed multivariate linear regression. Results showed that intakes of energy and of ten micronutrients were significantly lower during the lean season than during the post-harvest season, leading to a lower MAR in the lean season (49·61 v. 53·57, P < 0·0001). This was related to less frequent consumption and consumption of smaller amounts of vegetables and of foods prepared at home. Food security relied heavily on food expenses (P < 0·0001) and on the price of meat/fish (P = 0·026). Households with economically dependent adults (P = 0·021) and larger households (P < 0·0001) were the most vulnerable, whereas education (P = 0·030), social network (P = 0·054) and urban origin other than Ouagadougou (P = 0·040) played a positive role in food security. To achieve food security in Ouagadougou, access to micronutrient-dense foods needs to be ensured in all seasons.     

The 2008 food price crisis negatively affected household food security and dietary diversity in urban burkina faso

Although the 2008 food price crisis presumably plunged millions of households into poverty and food insecurity, the real impact of the crisis has rarely been documented using field data. Our objective was to assess the consequences of this crisis for household food insecurity and dietary diversity in urban Burkina Faso. Two cross-sectional surveys were conducted among randomly selected households in Ouagadougou in July 2007 (n = 3017) and July 2008 (n = 3002). At each round, food insecurity assessed by the Household Food Insecurity Access Scale (HFIAS), the Dietary Diversity Score of an index-member of the household (IDDS = number of food groups consumed in the last 24 h), and food expenditure were collected. Food prices of the 17 most frequently consumed food items were recorded throughout the study area. Food prices at local markets increased considerably between 2007 and 2008, especially those of fish (113%), cereals (53%), and vegetable oil (44%), increasing the household monthly food expenditure by 18%. Thirty-three percent of households were food secure in 2007 and 22% in 2008 (P = 0.02). Individuals consumed fewer fruits and vegetables, dairy products, and meat/poultry in 2008 than in 2007 (mean IDDS = 5.7 ± 1.7 food groups in 2007 vs. 5.2 ± 1.5 in 2008; P < 0.0001). Differences in IDDS and HFIAS between the 2 y were even more marked after adjustment for confounding factors and food expenditure. Food security and dietary diversity significantly decreased between 2007 and 2008, whereas food prices increased. Households increased their food expenditure, but this was not sufficient to compensate the effects of the crisis.     

Patient perspectives on improving oral health-care practices among people living with HIV/AIDS

This qualitative study explored the impact on oral health-care knowledge, attitudes, and practices among 39 people living with HIV/AIDS (PLWHA) participating in a national initiative aimed at increasing access to oral health care. Personal values and childhood dental experiences, beliefs about the importance of oral health in relation to HIV health, and concerns for appearance and self-esteem were found to be determinants of oral health knowledge and practice. Program participation resulted in better hygiene practices, improved self-esteem and appearance, relief of pain, and better physical and emotional health. In-depth exploration of the causes for these changes revealed a desire to continue with dental care due to the dental staff and environmental setting, and a desire to maintain overall HIV health, including oral health. Our findings emphasize the importance of addressing both personal values and contextual factors in providing oral health-care services to PLWHA.     

Analysis of multiple exposures in the case-crossover design via sparse conditional likelihood

We adapt the least absolute shrinkage and selection operator (lasso) and other sparse methods (elastic net and bootstrapped versions of lasso) to the conditional logistic regression model and provide a full R implementation. These variable selection procedures are applied in the context of case‐crossover studies. We study the performances of conventional and sparse modelling strategies by simulations, then empirically compare results of these methods on the analysis of the association between exposure to medicinal drugs and the risk of causing an injurious road traffic crash in elderly drivers. Controlling the false discovery rate of lasso‐type methods is still problematic, but this problem is also present in conventional methods. The sparse methods have the ability to provide a global analysis of dependencies, and we conclude that some of the variants compared here are valuable tools in the context of case‐crossover studies with a large number of variables. Copyright © 2012 John Wiley & Sons, Ltd.     

Serum erythropoietin in chronic lymphocytic leukaemia

Anaemia is a frequent complication of advanced chronic lymphocytic leukaemia (CLL) and several cytokines known to inhibit erythropoietin (Epo) formation are produced by CLL B cells. Therefore we measured serum Epo levels in 47 CLL patients to determine whether Epo was a significant factor in the development of their anaemia. Epo levels were increased compared to normal individuals and this elevation appeared adequate for the degree of anaemia. The slope of the regression of Epo versus haemoglobin (Hb) was similar to that of a reference group. Serum transferrin receptor (sTfR) levels were also appropriately elevated for the degree of anaemia and correlated with serum Epo. Advanced stage was not associated with reduction of Epo production but diminished erythropoietic activity was observed in several patients. The results indicate that anaemia in CLL is not characterized by inadequate Epo production.     

Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients

OBJECTIVE: To determine whether anti-endothelial cell autoantibodies (AECAs) from systemic lupus erythematosus (SLE) patients with the antiphospholipid syndrome are involved in the initial endothelial cell (EC) membrane perturbation effect that is postulated to provide a target for antiphospholipid antibody (aPL) binding and, hence, to trigger the thrombotic cascade. To identify the AECA antigenic target on ECs and to determine the mechanism whereby the EC membrane is disrupted. METHODS: AECAs from SLE patients were assayed for binding to ECs by flow cytometry. Positive AECAs were assayed by immunoblotting, and a consensus antigen was identified by mass spectrometry. This candidate antigen was tested in recombinant form for AECA recognition. AECAs were affinity-purified on this antigen and incubated with ECs to determine their physiologic effects. Anti-Hsp60 antibody titers were determined by enzyme-linked immunosorbent assay. The relationship of anti-Hsp60 status and lupus anticoagulant (LAC) status to thrombotic manifestations between disease onset and the last followup visit were analyzed. RESULTS: Most of the SLE sera (73%) possessed IgG that bound to the surface of ECs. These positive IgG shared reactivity against a 60-kd EC surface polypeptide that was identified as human Hsp60. The presence of Hsp60 at the EC surface was established using anti-Hsp60 antibodies from commercial sources or affinity-purified from SLE sera that bound ECs. Incubation of ECs with these anti-Hsp60 antibodies induced apoptosis in a time- and dose-dependent manner, as determined by Hoechst 33342 dye staining of condensed nuclei and by annexin V binding to surface phosphatidylserine. Anti-Hsp60 antibodies were not restricted to SLE patients, but were found in patients with other autoimmune diseases. However, anti-Hsp60 antibodies were significantly associated with an increased frequency of thrombosis when present in combination with LAC in the SLE patients. CONCLUSION: The presence of Hsp60 at the surface of ECs serves as a target for the anti-Hsp60 antibodies in SLE sera. These anti-Hsp60 antibodies bind to ECs and induce apoptosis, particularly phosphatidylserine exposure, thus providing a target for the binding of aPL and inducing the subsequent thrombotic cascade.     

A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity

Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5'-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor gamma2, caveolin-1, and mitochondrial markers in white adipose tissue. These studies strongly suggest that increasing endogenous adiponectin levels has direct effects on insulin sensitivity and may induce similar physiological responses as prolonged treatment with peroxisomal proliferator-activated receptor gamma agonists.     

Escherichia coli RNA-Polymerase Binding Sites on DNA Are Only 14 Base Pairs Long and Are Located between Sequences That Are Very Rich in A+T

E. coli DNA-dependent RNA-polymerase binding sites on DNAs of T5, T7, and lambda coliphages have been isolated according to three different methods in order to analyze the binding sites themselves as well as the nearest neighboring regions. It is shown that the binding sites are regions that are rather rich in G+C, are about 14 base pairs long and are located between DNA sequences highly enriched in A+T. The biological implications of this result are discussed.