The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms.

Background: The modulation of energetic homeostasis by pollutants has recently emerged as a potential contributor to the onset of metabolic disorders. Diethylhexyl phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. Phthalates can activate the three peroxisome proliferatoractivated receptor (PPAR) isotypes on cellular models and induce peroxisome proliferation in rodents.Objectives: In this study, we aimed to evaluate the systemic and metabolic consequences of DEHP exposure that have remained so far unexplored and to characterize the underlying molecular mechanisms of action.Methods: As a proof of concept and mechanism, genetically engineered mouse models of PPARs were exposed to high doses of DEHP, followed by metabolic and molecular analyses.Results: DEHP-treated mice were protected from diet-induced obesity via PPARalpha-dependent activation of hepatic fatty acid catabolism, whereas the activity of neither PPARbeta nor PPARgamma was affected. However, the lean phenotype observed in response to DEHP in wild-type mice was surprisingly abolished in PPARalpha-humanized mice. These species differences are associated with a different pattern of coregulator recruitment.Conclusion: These results demonstrate that DEHP exerts species-specific metabolic actions that rely to a large extent on PPARalpha signaling and highlight the metabolic importance of the species-specific activation of PPARalpha by xenobiotic compounds. Editor's SummaryDiethylhexyl phthalate (DEHP) is an industrial plasticizer used in cosmetics, medical devices, food packaging, and other applications. Evidence that DEHP metabolites can activate peroxisome proliferatoractivated receptors (PPARs) involved in fatty acid oxidation (PPARalpha and PPARbeta) and adiposite function and insulin resistance (PPARgamma) has raised concerns about potential effects of DEHP on metabolic homeostasis. In rodents, PPARalpha activation also induces hepatic peroxisome proliferation, but this response to PPARalpha activation is not observed in humans. Feige et al. (p. 234) evaluated systemic and metabolic consequences of high-dose oral DEHP in combination with a high-fat diet in wild-type mice and genetically engineered mouse PPAR models. The authors report that mice exposed to DEHP gained less weight than controls, without modifying their feeding behavior; they also exhibited lower triglyceride levels, smaller adipocytes, and improved glucose tolerance compared with controls. These effects, which were observed in mice fed both high-fat and standard diets, appeared to be mediated by PPARalpha-dependent activation of hepatic fatty acid catabolism without apparent involvement of PPARbeta or PPARgamma. However, mouse models that expressed human (versus mouse) PPARalpha tended to gain more weight on a high-fat diet than their DHEP-unexposed counterparts. The authors conclude that findings support species-specific metabolic effects of DEHP mediated by PPARalpha activation.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.

Vaccination against schistosomiasis and fascioliasis with the new recombinant antigen Sm14: potential basis of a multi-valent anti-helminth vaccine?

Molecular cloning of components of protective antigenic preparations have suggested that related parasite fatty acid binding proteins could form the basis of the well documented protective, immune cross reactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed the cross protective potential of parasite fatty acid binding proteins and suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni of veterinary and human importance respectively.

A one-year monitoring of nicotine use in sport: frontier between potential performance enhancement and addiction issues.

Tobacco consumption is a global epidemic responsible for a vast burden of disease. With pharmacological properties sought-after by consumers and responsible for addiction issues, nicotine is the main reason of this phenomenon. Accordingly, smokeless tobacco products are of growing popularity in sport owing to potential performance enhancing properties and absence of adverse effects on the respiratory system. Nevertheless, nicotine does not appear on the 2011 World Anti-Doping Agency (WADA) Prohibited List or Monitoring Program by lack of a comprehensive large-scale prevalence survey. Thus, this work describes a one-year monitoring study on urine specimens from professional athletes of different disciplines covering 2010 and 2011. A method for the detection and quantification of nicotine, its major metabolites (cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide) and minor tobacco alkaloids (anabasine, anatabine and nornicotine) was developed, relying on ultra-high pressure liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-TQ-MS/MS). A simple and fast dilute-and-shoot sample treatment was performed, followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) data acquisition. After method validation, assessing the prevalence of nicotine consumption in sport involved analysis of 2185 urine samples, accounting for 43 different sports. Concentrations distribution of major nicotine metabolites, minor nicotine metabolites and tobacco alkaloids ranged from 10 (LLOQ) to 32,223, 6670 and 538 ng/mL, respectively. Compounds of interest were detected in trace levels in 23.0% of urine specimens, with concentration levels corresponding to an exposure within the last three days for 18.3% of samples. Likewise, hypothesizing conservative concentration limits for active nicotine consumption prior and/or during sport practice (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide, cotinine-N-oxide, anabasine, anatabine and nornicotine) revealed a prevalence of 15.3% amongst athletes. While this number may appear lower than the worldwide smoking prevalence of around 25%, focusing the study on selected sports highlighted more alarming findings. Indeed, active nicotine consumption in ice hockey, skiing, biathlon, bobsleigh, skating, football, basketball, volleyball, rugby, American football, wrestling and gymnastics was found to range between 19.0 and 55.6%. Therefore, considering the adverse effects of smoking on the respiratory tract and numerous health threats detrimental to sport practice at top level, likelihood of smokeless tobacco consumption for performance enhancement is greatly supported.

Effects of three organophosphorus insecticides in the reproductive potential of Culex quinquefasciatus

A Culex quinquefasciatus Say 1823 strain with resistant genes to organophosphates was tested in the laboratory to know the reproductive potential after exposure, as larvae, at the LC30 and LC70 (mg/l) of three organophosphorus insecticides: malathion, chlorpyrifos and methyl-pirimiphos. Data showed that fecundity was decreased significantly by malathion at LC30 = 0.0025 and LC70 = 0.0075, whereas fertility has a no significant decrement by chlorpyrifos and methyl-pirimiphos at the LC70 (0.000016, 0.00043). The sexual index was affected by chlorpyrifos and methyl-pirimiphos showing a greater number of adult females.

Oxidative potential of a panel of carbonaceous and metallic nanoparticles

Characterisation of nanoparticles (NP) based on size distribution, surface area, reactivity, and aggregation status of nanoparticles (NP) are of prime importance because they are usually closely related to toxicity. To date, most of the toxicity studies are quite time and money consuming. In the present study we report the oxidative properties of a panel of various NP (four Carbonaceous, nine Metal oxides, and one Metal as showed in Table 1) assessed with an acellular reactivity test measuring dithiothreitol (DTT) consumption (Sauvain et al. 2008). Such a test allows determining the ability of NP to catalyse the transfer of electrons from DTT to oxygen. DTT is used as a reductant species. NP were diluted and sonicated in Tween 80® to a final concentration of 50 g/mL. Printex 90 was diluted 5 times before doing the DTT assay because of its expected higher activity. Suspensions were characterised for NP size distribution by Nanoparticle Tracking Analysis (Nanosight©). Fresh solutions were incubated with DTT (100 μM). Aliquots were taken every 5 min and the remaining DTT was determined by reacting it with DTNB. The reaction rate was determined for NP suspensions and blank in parallel. The mean Brownian size distribution of NP agglomerates in suspension is presented in Table 1. D values correspond to 10th, and 50th percentiles of the particle diameters. All the NP agglomerated in Tween 80 with a D50 size corresponding to at least twice their primary size, except for Al2O3 (300 nm). The DTT test showed Printex 90 sample to be the most reactive one, followed by Diesel EPA and Nanotubes. Most of the metallic NP was nonresponding toward this test, except for NiO and Ag which reacted positively and ZnO which presented the most negative reactivity (see Figure 1). This last observation suggests that electron transfer between DTT and oxygen is hindered in presence of ZnO compared with the blank. Such "stabilization" could be attributable to ZnO dissolution and complexation between Zn2+ ions and DTT.

Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans.

BACKGROUND: The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control, time course, and onset of hunger in humans. OBJECTIVE: We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total, endogenous, and exogenous carbohydrate oxidation rates. DESIGN: Two diets with either a high (H diet) or a low (L diet) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber. Substrate utilization was assessed by whole-body indirect calorimetry. In a subgroup of 8 subjects, endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate. Subjective feelings of hunger were estimated with use of visual analogue scales. RESULTS: Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets. However, there was a significant effect of diet (P: = 0.03) on the carbohydrate oxidation pattern: the H diet elicited a lower and delayed rise of postprandial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet. The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets (r = -0.67, P: = 0. 006). Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet. CONCLUSIONS: The pattern of carbohydrate utilization is involved in the modulation of hunger feelings. The greater suppression of hunger after the H diet than after the L diet may be helpful, at least over the short term, in individuals attempting to better control their food intake.

The effect of different proportions of males and females over the Chrysomya albiceps (Wiedemann 1819) (Diptera, Calliphoridae) biotic potential and longevity under laboratory conditions

Chrysomya albiceps specimens were derived from colonies kept under laboratory conditions. The oviposition period, total number of eggs-mass and the weight of the eggs-mass (average/female) presented significant differences between colonies regarding the sexual ratio of 1male/1female (situation I), when compared to the other ratios (1male/3female, situation II), (1male/5female, situation III), (3male/1female, situation IV) and (5 male/1female, situation V). It was ascertained that the increase in the proportion of females, resulted in higher weight and greater number of ovipositions and lenghtening of the period of oviposition, leads to a decrease in their lifespan.

Prevalence of and potential influencing factors for alcohol dependence in europe.

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

A cognitive attempt to understanding female entrepreneurial potential: the role of social norms and culture

This article analyzes the different perceptions of both male and female potential entrepreneurs from three European regions differing in their respective level of economic development and entrepreneurial culture. We use an extended cognitive model of entrepreneurial intentions based on the theory of planned behaviour, the theory of normative social behaviour and social capital literature. Results show females have lower self-efficacy and entrepreneurial attraction than males, thus leading to lower entrepreneurial intention. Differences between the three subsamples are small when males are studied. However, female entrepreneurial intentions and perceptions are more affected by the cultural context.

The Potential for Dispersal of Onchocerciasis in Ecuador in Relation to the Distribution of the Vector Simulium exiguum (Diptera:Simuliidae)

The future dispersal of onchocerciasis in Ecuador is dependent on the distribution of cytotypes of the vector species complex Simulium exiguum. Over the last 14 years, collections of larvae have been made from over 25 rivers, between 80-1600 m altitude, from various sites on both sides of the Andes. Analysis of larval polytene chromosomes was used to determine the distributions of each cytotype. On the western side of the Andes, the Cayapa cytotype (the only cytotype directly incriminated as a vector) has a distribution from Santo Domingo de los Colorados northwards. The Quevedo and Bucay cytotypes occur from Santo Domingo de los Colorados southwards. On the eastern side of the Andes, the Aguarico cytotype occurs in the Rio Aguarico and a new cytotype is present in the tributaries of the Rio Napo. Whether the disease will spread south of Santo Domingo and on the eastern side of the Andes depends on vector capacity of the cytotypes and the dispersal patterns of individuals infected with onchocerciasis. At present the Aguarico, Bucay and Quevedo cytotypes are known to be efficient hosts, but their biting preferences and biting densities have not yet been evaluated

EIU in the rat promotes the potential of syngeneic retinal cells injected into the vitreous cavity to induce PVR.

PURPOSE: To determine whether syngeneic retinal cells injected in the vitreous cavity of the rat are able to initiate a proliferative process and whether the ocular inflammation induced in rats by lipopolysaccharide (LPS) promotes this proliferative vitreoretinopathy (PVR). METHODS: Primary cultured differentiated retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells isolated from 8 to 12 postnatal Lewis rats were injected into the vitreous cavity of 8- to 10-week-old Lewis rats (10(5) cells/eye in 2 microlieter sterile saline), with or without the systemic injection of 150 microgram LPS to cause endotoxin-induced uveitis (EIU). Control groups received an intravitreal injection of 2 microliter saline. At 5, 15, and 28 days after cell injections, PVR was clinically quantified, and immunohistochemistry for OX42, ED1, vimentin (VIM), glial fibrillary acidic protein (GFAP), and cytokeratin was performed. RESULTS: The injection of RMG cells, alone or in combination with RPE cells, induced the preretinal proliferation of a GFAP-positive tissue, that was enhanced by the systemic injection of LPS. Indeed, when EIU was induced at the time of RMG cell injection into the vitreous cavity, the proliferation led to retinal folds and localized tractional detachments. In contrast, PVR enhanced the infiltration of inflammatory cells in the anterior segment of the eye. CONCLUSIONS: In the rat, syngeneic retinal cells of glial origin induce PVR that is enhanced by the coinduction of EIU. In return, vitreoretinal glial proliferation enhanced the intensity and duration of EIU.

Evaluation of Chemical and Physical-morphological Factors as Potential Determinants of Biomphalaria pfeifferi (Krauss, 1848) Distribution

This study was carried out in five sites along a small perennial river system in south-central Tanzania, which had been identified as the focus for transmission of intestinal schistosomiasis in the area. Malacological surveys preceding the study showed a focal distribution of Biomphalaria pfeifferi, intermediate host snail of Schistosoma mansoni, the snails being present in three sites but absent from the other two sites. The objective of this study was to evaluate to what extent chemical and/or physical-morphological factors determine the distribution of B. pfeifferi between these five sites. It was found that none of the chemical constituents in the waters examined were outside the tolerance range of B. pfeifferi snails. Moreover, the composition of water from B. pfeifferi-free sites was not different from that in those sites where snails occurred. Furthermore, none of the physical-morphological constituents seemed likely to be a determinant for the absence of B. pfeifferi. In view of these findings, and those of previous studies, it is concluded that the focal distribution of B. pfeifferi cannot be associated with a single environmental factor and is rather the result of more complex interactions of habitat factors