Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic.

An immunoaffinity clean-up material based on a monoclonal antibody (mAb) has been prepared for concentrating and purifying bisphenol A (BPA) in 14 kinds of foodstuffs at trace level. Haptens and immunogen of bisphenol A have been synthesized and comprehensively characterized. An mAb towards BPA was prepared and cross-reactivities with 14 BPA analogues were below 5%. The prepared antibody was coupled to N-hydroxysuccinimide-activated Sepharose 4B to manufacture an immunoaffinity column (IAC), which was applied to purify BPA in 14 kinds of foodstuffs. The analyte was then detected by means of ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Under the optimized conditions, compared with two traditional SPE clean-up methods, the IAC showed better selectivity (matrix effect <16.8%) and higher sensitivity. The limits of detection for BPA in 14 kinds of foodstuffs ranged from 0.001 μg L-1to 0.01 μg kg-1, and the limits of quantification were in the range from 0.003 μg L-1to 0.04 μg kg-1. The recoveries of BPA from spiked samples ranged from 82.0% to 104.9%, with RSDs below 13.8%. Besides, the IAC exhibited good reusability, with 40% column capacity remaining and no significant loss of recovery after 25 application cycles in real sample detection. These results demonstrated that the developed IAC-UPLC-MS/MS approach has wide applicability for purifying and detecting BPA in various foodstuffs.

The neurotoxicity of polybrominated diphenyl ethers (PBDEs) has been of concern. Acetylcholinesterase (AChE) is a critical enzyme in the central and peripheral nervous system related to neurotoxicity. The interaction between BDE-47, BDE-209, and AChE was investigated through fluorescence and UV-vis spectra combined with molecular docking. Both BDE-47 and BDE-209 bound with AChE and changed the microenvironment of some amino acid residues, resulting in a change of AChE conformation. Hydrophobic interaction is the main binding force between BDE-47, BDE-209, and AChE, and electrostatic interaction exists according to the thermodynamic parameters of the interaction between them. A hydrophobic interaction of BDE-47-AChE and BDE-209-AChE has been confirmed through molecular docking to dominate the binding force. The binding constants of BDE-47-AChE and BDE-209-AChE were 4.2 × 104and 4.1 × 104 L/mol, respectively, and the lowest binding energies of BDE-47-AChE and BDE-209-AChE were -7.8 and -5.9 kJ/mol, respectively. BDE-47 is more likely to bind with AChE than BED-209.

Antidepressants are among the most prescribed pharmaceuticals throughout the world. Their presence has already been detected in several aquatic ecosystems worldwide and their effects on non-target organisms justify the growing concern of both the public and regulatory authorities. These emerging pollutants do not occur as isolated compounds but rather as multi-component mixtures, which may lead to increased adverse effects compared to individual compounds. Freshwater and marine algae seem particularly sensitive to pharmaceuticals, including antidepressants. Studies assessing the toxicity of antidepressant mixture to algae focused mainly on binary mixtures of selective serotonin reuptake inhibitors. In the present experiment, the freshwater algae Raphidocelis subcapitata (formerly known as Pseudokirchneriella subcapitata) and the marine diatom Skeletonema marinoi were exposed to equitoxic mixtures of 9 antidepressants (fluvoxamine, fluoxetine, sertraline, duloxetine, venlafaxine, clomipramine, amitriptyline, and citalopram) at different concentrations. The growth inhibition was measured. Results showed that the toxicity of this mixture was higher than the effects of each individual component, highlighting simple additivity or synergistic effects, whereas tested concentrations were below the 10% inhibition concentration (IC10) of each compound. Moreover, the QSAR analysis highlighted that antidepressants would act through narcosis (non-specific mode of action) towards the two species of algae. However, more specific effects can be observed by differentiating compounds with a primary/secondary amine from those with a tertiary amine. These mixture effects on algal species have to be assessed, especially since any impacts on phytoplankton could ultimately impact higher trophic levels (less food, secondary poisoning).

An isotope-dilution ultra-performance liquid chromatography-electrospray tandem mass spectrometry method combined with dansylation was established to sensitively quantify four steroid estrogens (estrone, 17α-estradiol, 17β-estradiol and 17α-ethynylestradiol) and bisphenol A in sewage influent and effluent. A simple hexane extraction was performed from a small volume (10 mL), followed by dansyl chloride derivatization and purification with a silica cartridge. The method effectively reduced the matrix effects in sample extract and permitted the selective and sensitive determination of target compounds from complicated matrices. The detection limits of the method for steroid estrogens were 0.20-0.90 ng L-1 in influent and 0.10-0.20 ng L-1 in effluent samples. For bisphenol A, the limits detection of the method were 20 and 0.80 for influent and effluent samples, respectively. Recoveries of 85%-96% were observed in all matrices. The method was applied to analyze residual estrogens and bisphenol A in sewage influent and effluent samples from Beijing, China. The concentrations of bisphenol A (636-1200 ng L-1) were up to 250 times higher than those of steroid estrogens. Estrone was the dominant estrogen in influent and effluent samples, while similar concentrations of 17α-estradiol and 17β-estradiol were detected in all samples.

Attempted murder by repeated poisoning is quite rare. The authors describe the case of a 62-year-old man who was admitted to an intensive care unit (ICU) for neurological disturbances complicated by inhalation pneumopathy. He presented a loss of consciousness while his wife was visiting him at the ICU (H0). Forty-eight hours later (H48), police officers apprehended the patient's wife pouring a liquid into his fruit salad at the hospital. Toxicological analyses of a blood sample and the infusion equipment (H0), as well as the fruit salad and its container (H48), confirmed the attempted poisoning with cyamemazine (H0) and hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair analysis was requested and the medical records of the 6 previous months were also examined. Two 6-cm brown hair strands were sampled and the victim's medical record was seized in order to determine the treatments he had been given during the previous six months. Segmental hair testing on two 6-cm brown hair was conducted by GC-MS, LC-DAD and LC-MS/MS (0-2/2-4/4-6 cm; pg/mg). Haloperidol (9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that had never been part of the victim's treatment were detected, as well as some benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also detected in all the segments (9960/1610/2367) though only a single dose administration was reported in the medical records. The toxicological analyses performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition, comparison of the results in hair analysis with the medical records confirmed repeated poisoning attempts over the previous six months, and thus explain the origin of the disorders presented by the victim. This case serves to remind us that repeated attempted murder can be difficult to diagnose and that hair analysis can be an effective way to detect such attempts.

A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced β-amyloid (Aβ) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation.

There is growing public concern about the global expansion of harmful algal bloom species (HABs), with dinoflagellate microalgae comprising the major portion of the harmful taxa. These motile, unicellular organisms have a lifecycle involving sexual reproduction and resting cyst formation whereby cysts can germinate from sediments and 'seed' planktonic populations. Thus, investigation of dinoflagellate cyst (dinocyst) distribution in sediments can provide significant insights into HAB dynamics and contribute to indices of habitat quality. Species composition and abundance of dinocysts in relation to sediment characteristics were studied at 18 stations in two densely populated temperate Australian estuaries, Sydney Harbour (Parramatta River/Port Jackson; PS) and Botany Bay (including Georges River; GB). Eighteen dinocyst taxa were identified, dominated by Protoceratium reticulatum and Gonyaulax sp.1 in the PS estuary, together with Archaeperidinium minutum and Gonyaulax sp.1 in the GB estuary. Cysts of Alexandrium catenella, which is one of the causative species of paralytic shellfish poisoning (PSP), were also detected in both estuaries. Out of the measured sediment characteristics (TOC, Cd, Cr, Cu, Fe, Pb, Mn, Ni, Zn and polycyclic aromatic hydrocarbons), TOC was the parameter explaining most of the variation in dinocyst assemblages and was positively correlated to most of the heavy metals. Given the significant relationship between sediment TOC and dinocyst abundance and heavy metal concentrations, this study suggests that sediment TOC could be broadly used in risk management for potential development of algal blooms and sediment contamination in these estuaries.