161,816 research outputs found

    Gap analysis of nickel bioaccessibility and bioavailability in different food matrices and its impact on the nickel exposure assessment

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    The metal nickel is well known to cause nickel allergy in sensitive humans by prolonged dermal contact to materials releasing (high) amounts of nickel. Oral nickel exposure via water and food intake is of potential concern. Nickel is essential to plants and animals and can be naturally found in food products or contamination may occur across the agro-food chain. This gap analysis is an evaluation of nickel as a potential food safety hazard causing a risk for human health. In the first step, the available data regarding the occurrence of nickel and its contamination in food and drinks have been collected through literature review. Subsequently, a discussion is held on the potential risks associated with this contamination. Elevated nickel concentrations were mostly found in plant-based foods, e.g. legumes and nuts in which nickel of natural origin is expected. However, it was observed that dedicated and systematic screening of foodstuffs for the presence of nickel is currently still lacking. In a next step, published studies on exposure of humans to nickel via foods and drinks were critically evaluated. Not including bioaccessibility and/or bioavailability of the metal may lead to an overestimation of the exposure of the body to nickel via food and drinks. This overestimation may be problematic when the measured nickel level in foods is high and bioaccessibility and/or bioavailability of nickel in these products is low. Therefore, this paper analyzes the outcomes of the existing dietary intake and bioaccessibility/bioavailability studies conducted for nickel. Besides, the available gaps in nickel bioaccessibility and/or bioavailability studies have been clarified in this paper. The reported bioaccessibility and bioavailability percentages for different food and drinks were found to vary between < LOD and 83% and between 0 and 30% respectively. This indicates that of the total nickel contained in the foodstuffs only a fraction can be absorbed by the intestinal epithelium cells. This paper provides a unique critical overview on nickel in the human diet starting from factors affecting its occurrence in food until its absorption by the body

    Influence and interactions of multi-factors on the bioavailability of PAHs in compost amended contaminated soils

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    Compost amendment to contaminated soils is a potential approach for waste recycling and soil remediation. The relative importance and interactions of multiple factors on PAH bioavailability in soils were investigated using conjoint analysis and five-way analysis of variance. Results indicated that soil type and contact time were the two most significant factors influencing the PAH bioavailability in amended soils. The other two factors (compost type and ratio of compost addition) were less important but their interactions with other factors were significant. Specifically the 4-factor interactions showed that compost addition stimulated the degradation of high molecular PAHs at the initial stage (3 month) by enhancing the competitive sorption within PAH groups. Such findings suggest that a realistic decision-making towards hydrocarbon bioavailability assessment should consider interactions among various factors. Further to this, this study demonstrated that compost amendment can enhance the removal of recalcitrant hydrocarbons such as PAHs in contaminated soils

    How proteins bind macrocycles

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    The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this knowledge gap, we analyze the binding modes of a representative set of MC-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic MC libraries with structural and physicochemical features likely to favor strong binding to protein targets as well as good bioavailability. We additionally provide evidence that large, natural product-derived MCs can bind targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product-inspired synthetic MCs can expand the number of proteins that are druggable by synthetic small molecules.R01 GM094551 - NIGMS NIH HHS; GM064700 - NIGMS NIH HHS; GM094551 - NIGMS NIH HHS; R01 GM064700 - NIGMS NIH HHS; GM094551-01S1 - NIGMS NIH HH

    A method for improving Centre for Environmental Studies (CML) characterisation factors for metal (eco)toxicity - the case of zinc gutters and downpipes

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    Background, aim and scope - The environmental impact of building products made from heavy metals has been a topic of discussion for some years. This was fuelled by results of life cycle assessments (LCAs), where the emission of heavy metals strongly effected the results. An issue was that the characterisation factors of the Centre for Environmental Studies (CML) 2000 life cycle impact assessment (LCIA) methodology put too much emphasis on the impact of metal emissions. We adjusted Zn characterisation factors according to the most recent insights in the ecotoxicity of zinc and applied them in an LCA using zinc gutters and downpipes as an example. Materials and methods - The CML 2000 methodology was used to assess the environmental impact of the zinc products. To adjust the Zn characterisation factors, the uniform system for the evaluation of substances (USES)–LCA model and the biotic ligand model were used. Results and discussion - The first correction was based on updating the effect values for zinc. This resulted in a reduction of the characterisation factors for zinc to 42% of their original values. Additional correcting for the bioavailability of zinc leads to final Zn characterisation factors for the freshwater aquatic ecotoxicity potential (FAETP), the marine aquatic ecotoxicity potential (MAETP) and the terrestrial ecotoxicity potential (TETP) of 25%, 42% and 0.006%, respectively, of the original values. The CML 2000 LCIA methodology is based on the predicted no-effect concentration (PNEC) of a substance. PNEC is not value-free as political considerations are used to decide on it. Using a more robust toxicity measure as the hazardous concentration at which 50% of the species is affected (HC50) will provide value-free results. The production of standard high-grade zinc shows main contributions to six of the ten environmental impact categories. The recycling of zinc at the end of the life cycle shows beneficial effects for these same categories. Despite the reduction of the characterisation factor of Zn, the runoff emissions of Zn are still dominant. Conclusions and recommendations - To improve LCA characterisation factors for ecotoxicity in the CML 2000 methodology, it is recommended to use either the geometric mean of the effect data or the HC50. The HC50 should be based upon the EC50 values from chronic ecotoxicity tests. It is proposed to include the bioavailability of metals in LCA in three steps: (1) separate soluble fraction, (2) separate dissolved fraction and (3) separate bioavailable fraction. The issue of essentiality could not be resolved in this study. However, this could be accounted for by leaving out the fraction of the emission below the maximum permissible admissio

    Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential

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    The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility

    Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

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    Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

    Polyelectrolyte multilayer assembly bearing ketoprofen for transdermal delivery

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    A novel microencapsulation technology based on layer-by-layer assembly has been extensively studied and used for controlled delivery of drug microcrystal having poor aqueous solubility and low bioavailability. A non-steroidal anti-inflammatory drug ketoprofen (KF)was selected for encapsulation using biodegradable and biocompatible polyions and synergistically the fabricated system was embedded in gel matrix for topical application. Topical application of the drugs at the pathological sites offer potential advantages of delivering the drug directly to the site of action and thus producing high tissue concentrations of the drug

    QUANTIFICATION OF POTENTIAL ARSENIC BIOAVAILABILITY IN SPATIALLY VARYING GEOLOGIC ENVIRONMENTS AT THE WATERSHED SCALE USING CHELATING RESINS

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    Potential arsenic toxicity in different geologic environments is dependent on total arsenic concentration and arsenic bioavailability. It is important to identify the geologic environments that may sequester arsenic because these systems can act as long-term sources for arsenic as well as retard transport and limit toxicity. Bioavailability is defined as the readiness of a compound or element to be taken up by organisms (Gregorich et al., 2001), while potential bioavailability is possible uptake of a compound or element by organisms. The objective of this research is to quantify the potential bioavailability of arsenic in laboratory microcosms and in different geologic environments in the Nueces and San Antonio River Watersheds, Texas, using a chelating resin as an infinite sink. To assess the applicability of chelating resins to estimate potential arsenic bioavailability in the field, iron-loaded DOWEX M4195 resin was used to extract arsenic from solutions and sediments (pond sediment, river sediment, and ephemeral stream sediment). The average percentage of arsenic sorbed from solution was 66% ± 0.16. Competition studies between arsenate, phosphate, and vanadate suggest there is moderate competition, reducing overall arsenic sorption to the resin in the presence of competing ions. Iron-loaded resin was then exposed to sediment samples spiked with increasing amounts of arsenic over 15, 30, 60 and 90 days. Results of the sediment study showed 1) increased arsenic sorption to the resin over time, 2) small variations of potential bioavailable arsenic among geologically different sediments, and 3) evidence of arsenic sequestration. Field devices that housed iron-loaded resin were used to extract potentially bioavailable arsenic from sediment in six different geologic environments (i.e. lake, river, perennial stream, ephemeral stream, pond, and wetland) in the watersheds over a twenty-eight day period. The wetland (15.7 mmol As/g wet resin) and perennial stream sediments (11.0 mmol As/g wet resin) represented the maximal and minimal calculated potential bioavailability, respectively. However, the potentially bioavailable index calculated from mmol As/g wet resin extracted from field environments and mmol As/ g sediment in digested samples showed sequestration would be high in the wetland environment and high bioavailability in the perennial stream and river environments
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