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Ipê is a plant of the Bignoniaceae family. Among the compounds extracted from this tree, lapachol is notable because its structural modification allows the production of β-lapachone, which has anticancer properties. The objective of this work was to test this hypothesis at a cellular level in vitro and assess its potential safety for use. The following tests were performed: MTT cell viability assay, apoptotic index determination, comet assay, and micronucleus test. The results showed that β-lapachone had a high cytotoxic capacity for all cell lines tested: ACP02 (gastric adenocarcinoma cells), MCF7 (breast carcinoma cells), HCT116 (colon cancer cells) and HEPG2 (hepatocellular carcinoma cells). Regarding genotoxicity, the exposure of cells to sublethal doses of β-lapachone induced DNA damage (assessed by the comet assay) and nuclear abnormalities, such as nucleoplasmic bridges and nuclear buds (assessed by the micronucleus test). All tested cell lines responded similarly to β-lapachone, except for ACP02 cells, which were relatively resistant to the cytotoxic effects of the compound in the MTT test. Our results collectively indicate that although β-lapachone showed antiproliferative activity against cancer cell lines, it also caused harmful effects in these cells, suggesting that the use of β-lapachone in treating cancer should be carried out with caution.

From Eleutherine plicata , naphthoquinones, isoeleutherine, and eleutherol were isolated, and previous studies have reported the antioxidant activity of these metabolites. The present work evaluated the role of oxidative changes in mice infected with Plasmodium berghei and treated with E. plicata extract, fraction, and isolated compounds, as well as to verify possible oxidative changes induced by these treatments. E. plicata extracts were prepared from powder from the bulbs, which were submitted to maceration with ethanol, yielding the extract (EEEp), which was fractionated under reflux, and the dichloromethane fraction (FDMEp) was submitted for further fractionation, leading to the isolation of isoeleutherine, eleutherine, and eleutherol. The antimalarial activity was examined using the suppressive test, evaluating the following parameters of oxidative stress: trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH). Furthermore, the molecular docking of naphthoquinones, eleutherol, eleutherine, and isoeleutherine interactions with antioxidant defense enzymes was investigated, which was favorable for the formation of the receptor-ligand complex, according to the re-rank score values. Eleutherine and isoeleutherine are the ones with the lowest binding energy for catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx1), showing themselves as possible targets of these molecules in the involvement of redox balance. Data from the present study showed that treatments with E. plicata stimulated an increase in antioxidant capacity and a reduction in oxidative stress in mice infected with P. berghei , with naphthoquinones being responsible for reducing oxidative changes and disease severity.

This study evaluated the genotoxicity of Ethanol Extract (EEEp), Dichloromethane Fraction (FDCMEp) and isoeleutherin isolated from Eleutherine plicata , using the micronucleus test and the impact of structural alterations on toxicity and molecular docking (topoisomerase II and DNA complex). The extract was obtained by maceration and fractionation in a chromatography column. The genotoxicity was evaluated by the micronucleus test in human hepatoma cells (HepG2). Isoeleutherin was the starting molecule in the search for analogues by structural similarity, using the ZINC and e-Molecules databases. Isoeleutherin and analogues were subjected to in silico toxicity prediction, and compounds free of toxicological risks (CP13, CP14, CP17 and isoeleutherin) were selected for molecular docking in Topoisomerase II (PDB: 1ZXM). In the micronucleus test, isoeleutherin was less genotoxic. Among the 22 isoeleutherin analogues there were variations in the toxicity profile. Molecular docking studies showed that the compounds have good complementarity in the active site with important hydrogens bonds. Therefore, the structural changes of isoeleutherin led to the obtaining of a molecule with a lower mutagenic potential, and the CP13 can be considered a prototype compound for the development of new molecules with pharmacological potential.

Although the evaluation of the uncertainty of an analytical method is a mandatory step in the method's validation, its applicability to the monitoring of trace compounds in complex samples is not simple, nor is it part of the routine of most laboratories, namely those dedicated to research. This manuscript focuses on the full validation of an analytical procedure for determining trace concentrations of twenty-four pharmaceutical active compounds (PhACs) in wastewaters using solid-phase extraction (SPE) and ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The method optimization was performed on different wastewater matrices, namely influents and final effluents from two distinct wastewater treatment plants (WWTPs). Matrix effects and extraction efficiency (absolute recovery) of the developed method were determined. Validation was performed to obtain the method's linearity/working range, precision, trueness, method detection limits (MDLs) and method quantification limits (MQLs). The expanded uncertainty of the data obtained was estimated according to the requirements of international procedures dedicated to the expression of uncertainty. Different approaches for the estimation of uncertainty were applied. The validated method was used in the analysis of target PhACs in wastewater samples collected at two WWTPs. The obtained results facilitated the introduction of a validated method for routine measurement of PhACs in wastewater samples and allowed method accreditation by the competent national authority.

Malaria is a disease that affects thousands of people around the world every year. Its pathogenesis is associated with the production of reactive oxygen and nitrogen species (RONS) and lower levels of micronutrients and antioxidants. Patients under drug treatment have high levels of oxidative stress biomarkers in the body tissues, which limits the use of these drugs. Therefore, several studies have suggested that RONS inhibition may represent an adjuvant therapeutic strategy in the treatment of these patients by increasing the antioxidant capacity of the host. In this sense, supplementation with antioxidant compounds such as zinc, selenium, and vitamins A, C, and E has been suggested as part of the treatment. Among dietary antioxidants, lycopene is the most powerful antioxidant among the main carotenoids. This review aimed to describe the main mechanisms inducing oxidative stress during malaria, highlighting the production of RONS as a defense mechanism against the infection induced by the ischemia-reperfusion syndrome, the metabolism of the parasite, and the metabolism of antimalarial drugs. Furthermore, the effects of lycopene on several diseases in which oxidative stress is implicated as a cause are outlined, providing information about its mechanism of action, and providing an evidence-based justification for its supplementation in malaria.

Malaria is an infectious disease and a serious public health problem in the world, with 3.3 billion people in endemic areas in 100 countries and about 200 million new cases each year, resulting in almost 1 million deaths in 2018. Although studies look for strategies to eradicate malaria, it is necessary to know more about its pathophysiology to understand the underlying mechanisms involved, particularly the redox balance, to guarantee success in combating this disease. In this review, we addressed the involvement of oxidative stress in malaria and the potential benefits of antioxidant supplementation as an adjuvant antimalarial therapy.

This study evaluated the morphological changes caused by fractions and subfractions, obtained from barks of Aspidosperna nitidum, against L. (L.) amazonensis promastigotes. The ethanolic extract (EE) obtained through the maceration of trunk barks was subjected to an acid-base partition, resulting the neutral (FN) and the alkaloid (FA) fractions, and fractionation under reflux, yielded hexane (FrHEX), dichloromethane (FrDCL), ethyl acetate (FrACoET), and methanol (FrMEOH) fractions. The FA was fractionated and three subfractions (SF5-6, SF8, and SF9) were obtained and analyzed by HPLC-DAD and 1 H NMR. The antipromastigote activity of all samples was evaluated by MTT, after that, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for the active fractions were performed. Chromatographic analyzes suggest the presence of alkaloids in EE, FN, FA, and FrDCL. The fractionation of FA led to the isolation of the indole alkaloid dihydrocorynantheol (SF8 fractions). The SF5-6, dihydrocorynantheol and SF-9 samples were active against promastigotes, while FrDCL was moderately active. The SEM analysis revealed cell rounding and changes in the flagellum of the parasites. In the TEM analysis, the treated promastigotes showed changes in flagellar pocket and kinetoplast, and presence of lipid inclusions. These results suggest that alkaloids isolated from A. nitidum are promising as leishmanicidal., (© 2022. The Author(s).)

Twenty-four pharmaceutical active compounds (PhACs) were evaluated in the soft tissues of clams Ruditappes decussatus exposed along a 1.5-km dispersal gradient of the treated effluent from an urban wastewater treatment plant discharging in Ria Formosa, and compared with those in the marine waters and discharged effluents. The clams were exposed for 1 month, in June-July 2016, 2017 and 2018. PhACs were quantified by high performance liquid chromatography coupled to tandem mass spectrometry after the quick, easy, cheap, effective, rugged and safe (QuEChERS) method (clams) or solid-phase extraction (water samples). The most representative PhACs in the effluents and receiving waters (regardless of the tidal dilution effect) were diclofenac, carbamazepine and caffeine (on average ≤ 2 μg/L) and only caffeine exhibited significant inter-annual differences, with higher values in 2017. In turn, the most bioaccumulated PhACs in clams were caffeine (0.54-27 ng/g wet weight, significantly higher in 2016) and acetaminophen (0.37-3.7 ng/g wet weight, significant lower in 2016). A multivariate principal component analysis showed (i) PhAC bioaccumulation primarily depended on biotic factors (clams length and weight), (ii) PhAC physicochemical properties Log K ow , pKa and water solubility interplaying with water abiotic variables were more relevant for explaining data variability in water than the physical dilution/tidal mixing, (iii) this process, reflected by the salinity gradient, had a tertiary role in data variation, responsible for spatial discrimination of marine waters. This study provides a better understanding of PhACs bioaccumulation by clams Ruditapes decussatus in real environmental conditions, under the influence of urban treated effluent dispersal in Ria Formosa coastal lagoon, a major producer of bivalves, ultimately disentangling key factors of PhAC bioaccumulation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The hexane and ethanol extracts from Himatanthus bracteatus (Apocynaceae) stems were evaluated for antiviral activity against Zika virus, yellow fever virus and dengue virus 2 and for cytotoxicity in Vero cells by MTT assay. The ethanol extract showed good antiviral activity against the three viruses with selective indexes (SI) > 10 and its fractionation led to the isolation of the known plumieride that was active only against Zika virus (SI of 15.97).

Pharmaceutical active compounds (PhACs) belonging to analgesics, antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs) therapeutic classes were monitored in wastewater influents and effluents from two Portuguese urban wastewater treatment plants (UWWTPs) for 24 months. Both facilities were chosen due to their effluents are discharged in highly touristic and sensitive areas, Tagus river and Ria Formosa coastal lagoon, respectively. Target PhACs, acetaminophen, diclofenac, ibuprofen, naproxen, sulfadiazine, and sulfamethoxazole were measured using solid-phase extraction (SPE) coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS). PhACs occurrence in the influents was higher than 98%, with acetaminophen presenting the highest concentrations, with values between 16.3 µg/L and 124 µg/L. In the effluents, distinct behavior was observed with diclofenac and sulfamethoxazole showing recalcitrant characteristics, whereas acetaminophen, ibuprofen, and naproxen showed removal efficiencies above 95%. Acetaminophen and ibuprofen amount in influents showed consistently higher concentration levels in autumn (in Beirolas and Faro Nw UWWTPs) and winter (only in Beirolas UWWTP) seasons. These seasonal trends were observed to a greater extent in Beirolas UWWTP than in Faro Nw UWWTP. This study enabled the comprehensive definition of a behavior pattern for these target contaminants, contributing to better characterization and build-up a library of PhACs occurrence. It also allowed a robust seasonal profiling of the target compounds due to the high number of samples analyzed by each season and a longer monitoring campaign, making the obtained results more significant., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Eleutherine plicata has been shown to be a promising medicinal plant, and its activity has been associated with naphthoquinones. The present study aimed at evaluating the cytotoxicity, genotoxicity, and oral toxicity of the ethanol extract (EEEp), dichloromethane fraction (FDMEp) of E. plicata , and isoeleutherin. For the cytotoxicity evaluation, the viability test (MTT) was used. Genotoxicity was accessed through the Comet assay (alkaline version), acute and subacute oral toxicities were also evaluated. The antioxidant capacity of the samples in the wells where the cells were treated with E. plicata was evaluated. Furthermore, the participation of caspase-8 in the possible mechanism of action of isoeleutherin, eleutherin, and eleutherol was also investigated through a docking study. FDMEp and isoeleutherin were cytotoxic, with higher rates of DNA fragmentation observed for FDMEp and isoeleutherin, and all samples displayed higher antioxidant potential than the control. In the acute oral toxicity test, EEEp, FDMEp, and isoeleutherin did not cause significant clinical changes. In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. The three compounds bound similarly to caspase-8. Despite the results of cytotoxicity, in vitro studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8., (© 2021 Published by Elsevier B.V.)

Achromobacter denitrificans strain PR1, previously found to harbour specific degradation pathways with high sulfamethoxazole (SMX) degradation rates, was bioaugmented into laboratory-scale membrane bioreactors (MBRs) operated under aerobic conditions to treat SMX-containing real domestic wastewater. Different hydraulic retention times (HRTs), which is related to reaction time and loading rates, were considered and found to affect the SMX removal efficiency. The availability of primary substrates was important in both bioaugmented and non-bioaugmented activated sludge (AS) for cometabolism of SMX. High HRT (24 h) resulted in low food to microorganism ratio (F/M) and low SMX removal, due to substrate limitation. Decrease in HRT from 24 h to 12 h, 6 h and finally 4 h led to gradual increases in primary substrates availability, e.g. organic compounds and ammonia, resulted in increased SMX removal efficiency and degradation rate, and is more favorable for high-rate wastewater treatment processes. After inoculation into the MBRs, the bioaugmentation strain was sustained in the reactor for a maximum of 31 days even though a significant decrease in abundance was observed. The bioaugmented MBRs showed enhanced SMX removal, especially under SMX shock loads compared to the control MBRs. The results of this study indicate that re-inoculation is required regularly after a period of time to maintain the removal efficiency of the target compound., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances., Aim of the Study: In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE)., Materials and Methods: The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE 2 levels, were performed the carrageenan or PGE 2 -induced hyperalgesia tests., Results: The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented an antihyperalgic effect at all hours of the carrageenan-induced hyperalgesia test. However, this dose of CGE was not able to reduce the hyperalgesia induced by PGE 2 , suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE 2 levels., Conclusion: The anacardic acids are the predominant phytoconstituents identified in the CGE. The action mechanisms of CGE suggest the reduction in the PGE 2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition, independent of the presence of polysaccharides., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases. Crude extract (E-HU) was prepared from H. umbellata subterraneous parts and fractionated by liquid-liquid partition, resulting hexane fraction (HF-HU), dichloromethane fraction (DF-HU), ethyl acetate fraction (EAF-HU) and aqueous fraction (AF-HU). The hibalactone (HU-1) was isolated from the DF-HU and its structure was elucidated by 1 H NMR and 13 C NMR Spectroscopy, mass spectrometry and crystallographic x-ray analysis. The formalin-induced nociception was used to evaluate antinociceptive activity; carrageenan-induced edema and pleurisy tests to evaluate anti-inflammatory activity and light-dark box to evaluate anxiolytic-like activity in mice. The acute oral treatments with E-HU (1000mg/kg), DF-HU (150mg/kg), EAF-HU (400mg/kg) and HU-1 (33mg/kg) decreased the licking time in both phases of the formalin test. In the carrageenan-induced inflammation models, the treatment with the same doses of E-HU, DF-HU, EAF-HU and HU-1 reduced the paw edema formation and leukocytes account into pleural cavity. In silico findings suggest that hibalactone present anti-inflammatory activity by interacting with the enzymes 5-lipoxygenase and cyclooxygenase-2. In the light dark box, the treatments with DF-HU, EAF-HU and HU-1 revealed an anxiolytic like effect. Thus, the E-HU and fractions of H. umbellata showed antinociceptive, anti-inflammatory and anxiolytic like activities, as also hibalactone, a possible phytoconstituent responsible for the biological effects of this specie., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Wastewater treatments can eliminate or remove a substantial amount of pharmaceutical active compounds (PhACs), but there may still be significant concentrations of them in effluents discharged into surface water bodies. Beirolas wastewater treatment plant (WWTP) is located in the Lisbon area and makes its effluent discharges into Tagus estuary (Portugal). The main objective of this study is to quantify a group of 32 PhACs in the different treatments used in this WWTP. Twelve sampling campaigns of wastewater belonging to the different treatments were made in 2013-2014 in order to study their removal efficiency. The wastewaters were analysed by solid phase extraction (SPE) and ultra-performance liquid chromatography coupled with tandem mass detection (UPLC-MS/MS). The anti-diabetics were the most frequently found in wastewater influent (WWI) and wastewater effluent (WWE) (208 and 1.7 μg/L, respectively), followed by analgesics/antipyretics (135 μg/L and < LOQ, respectively), psychostimulants (113 and 0.49 μg/L, respectively), non-steroidal anti-inflammatory drugs (33 and 2.6 μg/L, respectively), antibiotics (5.2 and 1.8 μg/L, respectively), antilipidemics (1.6 and 0.24 μg/L, respectively), anticonvulsants (1.5 and 0.63 μg/L, respectively) and beta blockers (1.3 and 0.51 μg/L, respectively). A snapshot of the ability of each treatment step to remove these target PhACs is provided, and it was found that global efficiency is strongly dependent on the efficiency of secondary treatment. Seasonal occurrence and removal efficiency was also monitored, and they did not show a significant seasonal trend.

Microcystin-leucine arginine (MC-LR) is the most abundant and toxic secondary metabolite produced by freshwater cyanobacteria. This toxin has a high potential hazard health due to potential interactions with liver, kidney and the nervous system. The aim of this work was the design of a simple and environmentally friendly electrochemical system based on highly efficient nanostructured electrodes for the removal of MC-LR in tap water. Titania nanoparticles were deposited on carbon (graphite) under a simple and efficient microwave assisted approach for the design of the electrode, further utilized in the electrochemical remediation assays. Parameters including the applied voltage, time of removal and pH (natural tap water or alkaline condition) were investigated in the process, with results pointing to a high removal efficiency for MC-LR (60% in tap water and 90% in alkaline media experiments, under optimized conditions)., Competing Interests: The authors declare no competing financial interests.

The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl 2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K + channels observed in the vasorelaxant effect., (© 2016 John Wiley & Sons A/S.)

The water constituents that are currently subject to legal control are only a small fraction of the vast number of chemical substances and microorganisms that may occur in both the environment and water resources. The main objective of the present study was to study the health impact resulting from exposure to a mixture of pharmaceuticals that have been detected in tap water at low doses. Analyses of atenolol, caffeine, erythromycin, carbamazepine, and their metabolites in blood, urine, feces, fat tissue, liver, and kidney after exposure to a mixture of these pharmaceuticals in treated drinking water were performed. The effects of this exposure were assessed in rats by measuring biochemical markers of organ injury or dysfunction. Simultaneously, the selected pharmaceuticals were also quantified in both physiological fluids and organ homogenates by liquid chromatography-tandem mass spectrometry (performed in multiple reaction monitoring mode and full scan mode). Following exposure of rats to a concentration of a pharmaceutical which was 10 times higher than the concentration known to be present in tap water, trace levels of some pharmaceuticals and their metabolites were detected in biological samples. This exposure did, however, not lead to significant organ injury or dysfunction. Thus, the authors report an experimental model that can be used to characterize the safety profile of pharmaceuticals in treated drinking water using a multiorgan toxicity approach. Environ Toxicol Chem 2016;35:2674-2682. © 2016 SETAC., (© 2016 SETAC.)

Sulfonamides (SAs) are one class of the most widely used antibiotics around the world and have been frequently detected in municipal wastewater and surface water in recent years. Their transformation in waste water treatment plants (WWTP) and in water treatment plants (WTP), as well as, their fate and transport in the aquatic environment are of concern. The reaction of six sulfonamides (sulfamethoxazole, sulfapyridine, sulfamethazine, sulfamerazine, sulfathiazole and sulfadiazine) with free chlorine was investigated at a laboratory scale in order to identify the main chlorination by-products. A previously validated method, liquid chromatography/mass spectrometry, was used to analyse SAs and their chlorination by-products. At room temperature, pH 6-7, reaction times of up to 2 h and an initial concentration of 2 mg/L of free chlorine, the majority of SAs suffered degradation of around 65%, with the exception of sulfamethoxazole and sulfathiazole (20%). The main reaction of SAs with free chlorine occurred in the first minute., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A monitoring study of 31 pharmaceuticals along Lisbon's drinking water supply system was implemented, which comprised the analysis of 250 samples including raw water (surface water and groundwater), and drinking water. Of the 31 pharmaceutical compounds, only sixteen were quantified in the analyzed samples, with levels ranging from 0.005 to 46 ng/L in raw water samples and 0.09-46 ng/L in drinking water samples. The human health risk assessment performed showed that appreciable risks to the consumer's health arising from exposure to trace levels of pharmaceuticals in drinking water are extremely unlikely, as RQs values were all below 0.001. Also, pharmaceuticals were selected as indicators to be used as a tool to control the quality of raw water and the treatment efficiency in the drinking water treatment plants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus., Methods: Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity--TEAC; lipid peroxidation--TBARS, and nitrites and nitrates--NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice., Results: Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies., Conclusions: The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.

[S,S]-ethylenediamine-N,N'-diglutaric acid (EDDG) has been gaining interest in the industrial sector as a promising chelator. In this study, the effective metal complexing capacity of EDDG over a wide pH range was modelled and its biodegradability assessed. Results showed that EDDG could effectively bind to several metallic ions in a wide pH range and was completely biodegraded after approximately 15 days by un-acclimatized sludge. To confirm its biodegradability, an accurate quantification method based on the combination of liquid chromatography and tandem quadrupole mass spectrometry (LC-MS/MS) was developed. Good linearity of the detector response was found for EDDG at concentrations ranging from 0.15 to 1.2 mg/L.

A procedure based on solid-phase microextraction (SPME) and gas chromatography coupled with mass spectrometry (GC-MS) was developed and validated in order to analyse 10 phenols in water samples. The optimised conditions were obtained using polyacrylate fibre (PA), 20ml of sample volume, 10% NaCl, pH 4.0 and direct extraction at 35 degrees C and 1000rpm, for 40min. The linear range and quantification limits for these compounds by SPME-GC-MS were defined. An evaluation of the main uncertainty sources of this method is included, which allows expanded uncertainties in the 9.4-35% range for the majority of the compounds. The main source of uncertainty is associated with matrix effects. The validated method is suitable for monitoring the production and distribution of potable water and was used, in field trials, for the analysis of samples from main intakes of water (surface or underground) and from water supply system of a large area (Lisbon and neighbour municipalities).

The analysis of pesticides in water samples is a problem of primary concern for quality control laboratories due to the toxicity level of these compounds and their public health risk. In order to evaluate the impact of pesticides in the Lisbon drinking water supply system, following the requirements of the European Union Directive 98/83/EC, we developed and validated an analytical method based on the combination of solid-phase extraction with liquid chromatography and tandem mass spectrometry. In this work, several pesticides were studied: imidacloprid, dimethoate, cymoxanil, carbendazime, phosmet, carbofuran, isoproturon, diuron, methidathion, linuron, pyrimethanil, methiocarbe, tebuconazole and chlorpyrifos. Several parameters of the electrospray source were optimized in order to get the best formation conditions of the precursor ion for each pesticide, namely capillary and extractor voltage, cone voltage, cone gas flow rate and desolvation gas flow rate. After optimization of the collision cell energy of the triple quadrupole, two different precursor ion-product ion transitions were selected for each pesticide, one for quantification and one for qualification, and these ions were monitored under time-scheduled multiple reaction monitoring (MRM) conditions. The selection of specific fragment ions for each pesticide guarantees a high degree of selectivity as well as additional sensitivity to quantify trace levels of these pesticides in water samples. This method showed excellent linearity ranges for all pesticides, with correlation coefficients greater than 0.9989. Determination limits (between 0.0041 and 0.0480 microg/L), precision (RSD <9.18%), accuracy and recovery studies in several water samples using solid-phase extraction were also performed.