Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes

Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with ipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (Tm). Surfactants also removed the lipid pre-transition but reduced Tm and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower Tm. The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced Tm and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The Tm and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2 mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings.

Natural food and beverage flavour enhancers

Flavour enhancers are of great importance to the food industry and the consumer, in terms of achieving strong, balanced and preferred product flavour. The understanding and use of flavour enhancers can help to avoid excessive use of individual ingredients such as salt or specific character impact flavours. This chapter first discusses savoury flavour enhancement through the use of ingredients rich in amino acids and 5’nucleotides. It later includes the potential role of peptides and Maillard derived compounds. The role of volatile flavour compounds in the enhancement of salt and sweet taste is also discussed.

Liquid AP-UV-MALDI enables stable ion yields of multiply charged peptide and protein ions for sensitive analysis by mass spectrometry

In biological mass spectrometry (MS), two ionization techniques are predominantly employed for the analysis of larger biomolecules, such as polypeptides. These are nano-electrospray ionization [1, 2] (nanoESI) and matrix-assisted laser desorption/ionization [3, 4] (MALDI). Both techniques are considered to be “soft”, allowing the desorption and ionization of intact molecular analyte species and thus their successful mass-spectrometric analysis. One of the main differences between these two ionization techniques lies in their ability to produce multiply charged ions. MALDI typically generates singly charged peptide ions whereas nanoESI easily provides multiply charged ions, even for peptides as low as 1000 Da in mass. The production of highly charged ions is desirable as this allows the use of mass analyzers, such as ion traps (including orbitraps) and hybrid quadrupole instruments, which typically offer only a limited m/z range (< 2000–4000). It also enables more informative fragmentation spectra using techniques such as collisioninduced dissociation (CID) and electron capture/transfer dissociation (ECD/ETD) in combination with tandem MS (MS/MS). [5, 6] Thus, there is a clear advantage of using ESI in research areas where peptide sequencing, or in general, the structural elucidation of biomolecules by MS/MS is required. Nonetheless, MALDI with its higher tolerance to contaminants and additives, ease-of-operation, potential for highspeed and automated sample preparation and analysis as well as its MS imaging capabilities makes it an ionization technique that can cover bioanalytical areas for which ESI is less suitable. [7, 8] If these strengths could be combined with the analytical power of multiply charged ions, new instrumental configurations and large-scale proteomic analyses based on MALDI MS(/MS) would become feasible.

Effects of variety and nutrient availability on the acrylamide-forming potential of rye grain

Acrylamide is a probable human carcinogen that forms in plant-derived foods when free asparagine and reducing sugars react at high temperatures. The identification of rye varieties with low acrylamide-forming potential or agronomic conditions that produce raw material with low acrylamide precursor concentrations would reduce the acrylamide formed in baked rye foods without the need for additives or potentially costly changes to processes. This work compared five commercial rye varieties grown under a range of fertilisation regimes to investigate the effects of genotype and nutrient (nitrogen and sulphur) availability on the accumulation of acrylamide precursors. A strong correlation was established between the free asparagine concentration of grain and the acrylamide formed upon heating. The five rye varieties accumulated different concentrations of free asparagine in the grain, indicating that there is genetic control of this trait and that variety selection could be useful in reducing acrylamide levels in rye products. High levels of nitrogen fertilisation were found to increase the accumulation of free asparagine, showing that excessive nitrogen application should be avoided in order not to exacerbate the problem of acrylamide formation. This effect of nitrogen was mitigated in two of the varieties by the application of sulphur.

Lactulose and Lactobacillus plantarum, a potential complementary synbiotic to control postweaning colibacillosis in piglets

The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of Lactobacillus plantarum, or their synbiotic combination to control postweaning colibacillosis in pigs was evaluated using an enterotoxigenic Escherichia coli (ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control diet (CTR), that diet supplemented with L. plantarum (2 × 10(10) CFU · day(-1)) (LPN), that diet supplemented with 10 g · kg(-1) lactulose (LAC), or a combination of the two treatments (SYN). After 7 days, the pigs were orally challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge (PC). Inclusion of lactulose improved the average daily gain (ADG) (P < 0.05) and increased lactobacilli (P < 0.05) and the percentage of butyric acid (P < 0.02) in the colon. An increase in the ileum villous height (P < 0.05) and a reduction of the pig major acute-phase protein (Pig-MAP) in serum (P < 0.01) were observed also. The inclusion of the probiotic increased numbers of L. plantarum bacteria in the ileum and colon (P < 0.05) and in the total lactobacilli in the colon and showed a trend to reduce diarrhea (P = 0.09). The concentrations of ammonia in ileal and colonic digesta were decreased (P < 0.05), and the villous height (P < 0.01) and number of ileal goblet cells (P < 0.05) increased, at day 10 PC. A decrease in plasmatic tumor necrosis factor alpha (TNF-α) (P < 0.01) was also seen. The positive effects of the two additives were combined in the SYN treatment, resulting in a complementary synbiotic with potential to be used to control postweaning colibacillosis.

Electron doping and phonon scattering in Ti1+xS2 thermoelectric compounds

Bulk polycrystalline samples in the series Ti1+xS2 (x = 0 to 0.05) were prepared using high temperature synthesis from the elements and spark plasma sintering. X-ray structure analysis shows that the lattice constant c expands as titanium intercalates between TiS2 slabs. For x=0, a Seebeck coefficient close to -300 μV/K is observed for the first time in TiS2 compounds. The decrease in electrical resistivity and Seebeck coefficient that occurs upon Ti intercalation (Ti off stoichiometry) supports the view that charge carrier transfer to the Ti 3d band takes place and the carrier concentration increases. At the same time, the thermal conductivity is reduced by phonon scattering due to structural disorder induced by Ti intercalation. Optimum ZT values of 0.14 and 0.48 at 300K and 700K, respectively, are obtained for x=0.025.

Ordered-defect sulfides as thermoelectric materials

The thermoelectric behaviour of the transition-metal disulphides n-type NiCr2S4 and p-type CuCrS2 is investigated. Materials prepared by high-temperature reaction were consolidated using cold-pressing and sintering, hot-pressing (HP) in graphite dies or spark-plasma sintering (SPS) in tungsten carbide dies. The consolidation conditions have a marked influence on the electrical transport properties. In addition to the effect on sample density, altering the consolidation conditions results in changes to the sample composition, including the formation of impurity phases. Maximum room-temperature power factors are 0.18 mW m-1 K-2 and 0.09 mW m-1 K-2 for NiCr2S4 and CuCrS2, respectively. Thermal conductivities of ca. 1.4 and 1.2 W m-1 K-1 lead to figures of merit of 0.024 and 0.023 for NiCr2S4 and CuCrS2, respectively.

Stability of dobutamine 500 mg in 50 ml syringes prepared using a Central Intravenous Additive Service

Objectives A pharmacy Central Intravenous Additives Service (CIVAS) provides ready to use injectable medicines. However, manipulation of a licensed injectable medicine may significantly alter the stability of drug(s) in the final product. The aim of this study was to develop a stability indicating assay for CIVAS produced dobutamine 500 mg in 50 ml dextrose 1% (w/v) prefilled syringes, and to allocate a suitable shelf life. Methods A stability indicating high performance liquid chromatography (HPLC) assay was established for dobutamine. The stability of dobutamine prefilled syringes was evaluated under storage conditions of 4°C (protected from light), room temperature (protected from light), room temperature (exposed to light) and 40°C (protected from light) at various time points (up to 42 days). Results An HPLC method employing a Hypersil column, mobile phase (pH=4.0) consisting of 82:12:6 (v/v/v) 0.05 M KH2PO4:acetonitrile:methanol plus 0.3% (v/v) triethylamine with UV detection at λ=280 nm was specific for dobutamine. Under different storage conditions only samples stored at 40°C showed greater than 5% degradation (5.08%) at 42 days and had the shortest T95% based on this criterion (44.6 days compared with 111.4 days for 4°C). Exposure to light also reduced dobutamine stability. Discolouration on storage was the limiting factor in shelf life allocation, even when dobutamine remained within 5% of the initial concentration. Conclusions A stability indicating HPLC assay for dobutamine was developed. The shelf life recommended for the CIVAS product was 42 days at 4°C and 35 days at room temperature when protected from light.

Acrylamide concentrations in potato crisps in Europe from 2002 to 2011

A dataset of manufacturers' measurements of acrylamide levels in 40,455 samples of fresh sliced potato crisps from 20 European countries for years 2002 to 2011 was compiled. This dataset is by far the largest ever compiled relating to acrylamide levels in potato crisps. Analysis of variance was applied to the data and showed a clear, significant downward trend for mean levels of acrylamide, from 763 +/- 91.1 ng g(-1) (parts per billion) in 2002 to 358 +/- 2.5 ng g(-1) in 2011; this was a decrease of 53% +/- 13.5%. The yearly 95th quantile values were also subject to a clear downward trend. The effect of seasonality arising from the influence of potato storage on acrylamide levels was evident, with acrylamide in the first 6 months of the year being significantly higher than in the second 6 months. The proportion of samples containing acrylamide at a level above the indicative value of 1000ngg(-1) for potato crisps introduced by the European Commission in 2011 fell from 23.8% in 2002 to 3.2% in 2011. Nevertheless, even in 2011, a small proportion of samples still contained high levels of acrylamide, with 0.2% exceeding 2000ngg(-1).

Structural stability of the synthetic thermoelectric ternary and nickel-substituted tetrahedrite phases

The purity and structural stability of the high thermoelectric performance Cu12Sb4S13 and Cu10.4Ni1.6Sb4S13 tetrahedrite phases, synthesized by solid–liquid–vapor reaction and Spark Plasma Sintering, were studied at high temperature by Rietveld refinement using high resolution X-ray powder diffraction data, DSC/TG measurements and high resolution transmission electron microscopy. In a complementary study, the crystal structure of Cu10.5Ni1.5Sb4S13 as a function of temperature was investigated by powder neutron diffraction. The temperature dependence of the structural stability of ternary Cu12Sb4S13 is markedly different to that of the nickel-substituted phases, providing clear evidence for the significant and beneficial role of nickel substitution on both sample purity and stability of the tetrahedrite phase. Moreover, kinetic effects on the phase stability/decomposition have been identified and discussed in order to determine the maximum operating temperature for thermoelectric applications. The thermoelectric properties of these compounds have been determined for high density samples (>98%) prepared by Spark Plasma Sintering and therefore can be used as reference values for tetrahedrite samples. The maximum ZT of 0.8 was found for Cu10.4Ni1.6Sb4S13 at 700 K.

Thermoelectric materials: a new rapid synthesis process for non-toxic and high-performance tetrahedrite compounds

The feasibility to synthesize, in large quantity, pure and non-toxic tetrahedrite compounds using high-energy mechanical-alloying from only elemental precursors is reported in the present paper for the first time. Our processing technique allows a better control of the final product composition and leads to high thermoelectric performances (ZT of 0.75 at 700 K), comparable to that reported on sealed tube synthesis samples. Combined with spark plasma sintering, the production of highly pure and dense samples is achieved in a very short time, at least 8 times shorter than in conventional liquid-solid-vapor synthesis process. The process described in this paper is a promising way to produce high performance tetrahedrite materials for cost-effective and large-scale thermoelectric applications.

Thermoelectric properties of TiS2 mechanically alloyed compounds

Bulk polycrystalline samples in the series Ti1−xNbxS2 (0 ≤ x ≤ 0.075) were prepared using mechanical alloying synthesis and spark plasma sintering. X-ray diffraction analysis coupled with high resolution transmission electron microscopy indicates the formation of trigonal TiS2 by high energy ball-milling. The as-synthesized particles consist of pseudo-ordered TiS2 domains of around 20–50 nm, joined by bent atomic planes. This bottom-up approach leads, after spark plasma sintering, to homogeneous solid solutions, with a niobium solubility limit of x = 0.075. Microstructural observations evidence the formation of small crystallites in the bulk compounds with a high density of stacking faults. The large grain boundary concentration coupled with the presence of planar defects, leads to a substantial decrease in the thermal conductivity to 1.8 W/mK at 700 K. This enables the figure of merit to reach ZT = 0.3 at 700 K for x = 0.05, despite the lower electron mobility in mechanically alloyed samples due to small crystallite/grain size and structural defects.

Up-scaled synthesis process of sulphur-based thermoelectric materials

The scale up of Spark Plasma Sintering (SPS) for the consolidation of large square monoliths (50 × 50 × 3 mm3) of thermoelectric material is demonstrated and the properties of the fabricated samples compared with those from laboratory scale SPS. The SPS processing of n-type TiS2 and p-type Cu10.4Ni1.6Sb4S13 produces highly dense compacts of phase pure material. Electrical and thermal transport property measurements reveal that the thermoelectric performance of the consolidated n- and p-type materials is comparable with that of material processed using laboratory scale SPS, with ZT values that approach 0.8 and 0.35 at 700 K for Cu10.4Ni1.6Sb4S13 and TiS2, respectively. Mechanical properties of the consolidated materials shows that large-scale SPS processing produces highly homogeneous materials with hardness and elastic moduli that deviate little from values obtained on materials processed on the laboratory scale.

Emission of polycyclic aromatic hydrocarbons from gasohol and ethanol vehicles

The exhaust emission of the polycyclic aromatic hydrocarbons (PAHs) considered toxic to human health were investigated on two spark ignition light duty vehicles, one being gasohol (Gasohol, in Brazil, is the generic denomination for mixtures of pure gasoline plus 20-25% of anhydrous ethyl alcohol fuel (AEAF).)-fuelled and the other a flexible-fuel vehicle fuelled with hydrated ethanol. The influence of fuel type and quality, aged lubricant oil type and use of fuel additives on the formation of these compounds was tested using standardized tests identical to US FTP-75 cycle. PAH sampling and chemical analysis followed the basic recommendations of method TO-13 (United States. Environmental Protection Agency, 1999. Compendium Method TO-13A - Determination of polycyclic Aromatic hydrocarbons (PAH) in Ambient Air Using Gas Chromatography/Mass Spectrometry (CG/MS). Center for environmental research information, Cincinnati, p. 78), with the necessary modification for this particular application. Results showed that the total PAH emission factor varied from 41.9 mu g km(-1) to 612 mu g km(-1) in the gasohol vehicle, and from 11.7 mu g km(-1) to 27.4 mu g km(-1) in the ethanol-fuelled vehicle, a significant difference in favor of the ethanol vehicle. Generally, emission of light molecular weight PAHs was predominant, while high molecular weights PAHs were not detected. In terms of benzo(a)pyrene toxicity equivalence, emission factors varied from 0.00984 mu g TEQ km(-1) to 4.61 mu g TEQ km(-1) for the gasohol vehicle and from 0.0117 mu g TEQ km(-1) to 0.0218 mu g TEQ km(-1) in the ethanol vehicle. For the gasohol vehicle, results showed that the use of fuel additive causes a significant increase in the emission of naphthalene and phenanthrene at a confidence level of 90% or higher; the use of rubber solvent on gasohol showed a reduction in the emission of naphthalene and phenanthrene at the same confidence level; the use of synthetic oil instead of mineral oil also contributed significantly to a decrease in the emission of naphthalene and fluorene. In relation to the ethanol vehicle, the same factors were tested and showed no statistically significant influence on PAH emission. (c) 2008 Elsevier Ltd. All rights reserved.