Determinants of fetal exposure to polyfluoroalkyl compounds in Baltimore, Maryland

Polyfluoroalkyl compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), are ubiquitous, man-made chemicals. Human data suggest that in utero exposures to these chemicals occur and some evidence of developmental toxicity in animals exists. To assess the distribution and determinants of fetal exposure to PFCs, we analyzed cord serum samples from 299 singleton newborns delivered between 2004 and 2005 in Baltimore, MD for 10 PFCs by employing on-line solid-phase extraction coupled with reversed-phase high-performance liquid chromatography-tandem mass spectrometry. PFOS and PFOA were detected in 99 and 100% of umbilical cord sera, with geometric mean concentrations of 4.9 and 1.6 ng/mL, respectively. PFOS and PFOA concentrations were highly correlated (Pearson's r = 0.64 after natural log transformation, p < 0.01). Eight other PFCs were detected less frequently and at lower concentrations than PFOS and PFOA. Geometric mean concentrations of PFOS for Asians (6.0 ng/mL) and Blacks (5.1 ng/mL) were higher than those for Whites (4.2 ng/mL), while PFOA levels were more evenly distributed by race. Other maternal demographic and socioeconomic characteristics, including age, education, marital status, and living in the city limits were not significantly associated with cord concentrations. Our findings suggest that in utero exposure to PFOS and PFOA is ubiquitous in a population of babies born in Baltimore, MD.     

Effect of Ultrafiltration on Anthocyanin and Flavonol Content of Black Currant Juice (Ribes nigrum L.)

This paper evaluates the efficiency of ultrafiltration and the effects of processing on the total anthocyanin and flavonol contents of black currant juice at chosen operational conditions. Ultrafiltration of black currant juices was carried out using Biomax 100?kDa polyethersulfone membrane. Ultrafiltration was used to process the juice prior concentration by reverse osmosis; with the aim to enhance the efficiency of the concentration process in terms of permeate flux. To avoid the fouling of the membrane, the juices were depectinized with Panzym Super E liquid enzyme preparation. The ultrafiltration was carried out at a transmembrane pressure of 2?bars and the operating temperature of 25?°C. The effect of processing on the valuable anthocyanin and flavonol content of the juices was evaluated based on the results of high-performance liquid chromatography analyses. The article includes detailed analyses of anthocyanin and flavonol compounds of the enzyme treated and ultrafiltered juice as compared with the original juice. The results indicate that, due to the enzymatic treatment, the valuable compound content of the juice increases. However, the ultrafiltration process resulted in a significant loss of a valuable content; 54% of total flavonol and 50% of total anthocyanins maintained in ultrafiltered juice when compared to the feed samples.     

Simultaneous measurement of urinary bisphenol A and alkylphenols by automated solid-phase extractive derivatization gas chromatography/mass spectrometry

Bisphenol A (BPA) and alkylphenols (APs) are widely used industrial chemicals. BPA is used to manufacture polycarbonate plastic and epoxy resins; APs are used to make alkylphenol ethoxylates, common nonionic surfactants. BPA and APs can leach into the environment during industrial production and after degradation of the polycarbonate plastics and nonionic surfactants. Environmental exposure to these phenolic compounds has been associated with adverse reproductive and developmental effects in wildlife. We developed a sensitive and robust method for measuring BPA and six APs; 3-tert-butylphenol, 4-tert-butylphenol, 4-n-octylphenol, 4-tert-octylphenol, 4-n-nonylphenol, and technical-grade nonylphenol in urine. The method is based on the use of automated solid-phase extraction (SPE) coupled to isotope dilution-gas chromatography/mass spectrometry (GC/MS). During the automated SPE process, the phenols are both extracted from the urine matrix and derivatized, using pentafluorobenzyl bromide, on commercially available styrene-divinylbenzene copolymer-based SPE cartridges. After elution from the SPE column, the derivatized phenols in the SPE eluate are analyzed by GC/MS. The method, validated on spiked pooled urine samples and on urine samples from exposed persons, has limits of detection of approximately 0.1 ng in 1 mL of urine.     

Automated on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine

We developed a method using isotope dilution on-line solid-phase extraction (SPE) coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination in urine of nine environmental phenolic compounds: Bisphenol A; 4-tert-octylphenol; o-phenylphenol; 2,4-dichlorophenol; 2,5-dichlorophenol; 2,4,5-trichlorophenol; 2,4,6-trichlorophenol; benzophenone-3 (2-hydroxy-4-metoxybenzophenone); and triclosan (2,4,4'-trichloro-2'-hydroxyphenyl ether). A unique fully automated column-switching system, constructed using 1 autosampler, 2 HPLC pumps, and a 10-port switching valve, was designed to allow for concurrent SPE-HPLC operation with peak focusing. The phenols present in 100 microL of urine were retained and concentrated on a C18 reversed-phase size-exclusion SPE column. Then, the phenols were "back-eluted" from the SPE column and diluted through a mixing Tee before being separated from other urine matrix components using a pair of monolithic HPLC columns. The phenols were detected by negative ion-atmospheric pressure chemical ionization-MS/MS. The efficient preconcentration of the phenols by the SPE column, analyte peak focusing by the dilution, and minimal ion suppression in the LC/MS interface by the buffer-free mobile phases resulted in limits of detection as low as 0.1-0.4 ng/mL for most analytes. The method was validated on spiked pooled urine samples and on urine samples from 30 adults with no known occupational exposure to environmental phenols. The method can be used for quick and accurate analysis of large numbers of samples in epidemiologic studies for assessing the prevalence of human exposure to environmental phenols.     

Exploration of Somatostatin Binding Mechanism to Somatostatin Receptor Subtype 4

Somatostatin (also named as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor) is a regulatory peptide important for the proper functioning of the endocrine system, local inflammatory reactions, mood and motor coordination, and behavioral responses to stress. Somatostatin exerts its effects via binding to G-protein-coupled somatostatin receptors of which the fourth subtype (SSTR4) is a particularly important receptor mediating analgesic, anti-inflammatory, and anti-depressant effects without endocrine actions. Thus, SSTR4 agonists are promising drug candidates. Although the knowledge of the atomic resolution-binding modes of SST would be essential for drug development, experimental elucidation of the structures of SSTR4 and its complexes is still awaiting. In the present study, structures of the somatostatin–SSTR4 complex were produced using an unbiased, blind docking approach. Beyond the static structures, the binding mechanism of SST was also elucidated in the explicit water molecular dynamics (MD) calculations, and key binding modes (external, intermediate, and internal) were distinguished. The most important residues on both receptor and SST sides were identified. An energetic comparison of SST binding to SSTR4 and 2 offered a residue-level explanation of receptor subtype selectivity. The calculated structures show good agreement with available experimental results and indicate that somatostatin binding is realized via prerequisite binding modes and an induced fit mechanism. The identified binding modes and the corresponding key residues provide useful information for future drug design targeting SSTR4.     

Stereoselective Synthesis and Application of Gibberellic Acid-Derived Aminodiols

A series of gibberellic acid-based aminodiols was designed and synthesized from commercially available gibberellic acid. Exposure of gibberellic acid to hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate, ethyl allo-gibberate, was prepared according to literature methods. Epoxidation of key intermediate and subsequent ring-opening of the corresponding epoxide with different nucleophiles resulted in N-substituted aminodiols. The regioselective ring closure of N-benzyl-substituted aminodiol with formaldehyde was also investigated. All aminodiol derivatives were well characterized using modern spectroscopic techniques and evaluated for their antiproliferative activity against a panel of human cancer cell lines. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems. The results indicated that aminodiols containing aromatic rings on their nitrogen substituents displayed significant cytotoxic effects. Among these agents, N-naphthylmethyl-substituted aminodiols were found to be the most potent candidates in this series. One of these molecules exhibited a modest cancer selectivity determined by non-cancerous fibroblast cells. A docking study was also made to exploit the observed results.     

A Multiple Interactive Continua Model (MINC) to Simulate Reactive Mass Transport in a Post-Mining Coal Zone: A Case Study of the Ibbenbüren Westfield

We tested the suitability of the multiple interactive continua approach (MINC) to simulate reactive mass transport in a disturbed post-mining coal zone. To the authors’ knowledge, this approach has not been employed in such mining settings despite its relative success in other environmental fields. To this end, TOUGHREACT software was used to set up a MINC model of the unsaturated overburden of the Ibbenbüren Westfield. With it, we examined and evaluated water–rock interactions in both the fractured and porous continua as the main driver of elevated hydrogen, iron, sulfate, and chloride concentrations in the coal mine groundwater. Long and seasonal geochemical signatures were obtained by formulating and applying a five-stage modelling process that depicts the mining history of the area. The simulation results agree well with the concentrations and discharge trends measured in the mine drainage. Oxygen and meteoric water flow through the fractured continuum, leading to a high and steady release of hydrogen, iron, and sulfate ions derived from pyrite oxidation in the matrix continua closest to the fractures. Likewise, high chloride concentrations resulted from the mixing and gradual release of relatively immobile solutes in the matrix as they interacted with percolating water in the fracture. In both cases, the use of a multiple continua approach was essential to resolve sharp gradients for advection and faster kinetic reactions, while reducing the model’s dependence on block size for diffusive transport at the fracture–matrix interface. The model further allows for the calculation and analysis of solute exchange and transport in the unsaturated overburden resulting from rebound and imbibition processes, something pioneering when compared to other models in the field.