Passive exposure to electronic cigarette aerosol in pregnancy: A case study of a family.

BACKGROUND: Passive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. METHODS: This prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. RESULTS: Samples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. CONCLUSIONS: We detected low but not negligible concentrations of e-cigarette-related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.

How binomial (traditional rainfed olive grove-Crocus sativus) crops impact the soil bacterial community and enhance microbial capacities.

Intercropping can favour the yield of the main crop. However, because of the potential competition among woody crops, this system is rarely used by farmers. To increase knowledge about the intercropping system, we have explored three different combinations of alley cropping in rainfed olive groves compared to conventional management (CP): (i) Crocus sativus (D-S); (ii) Vicia sativa/Avena sativa in annual rotation (D-O); and (iii) Lavandula x intermedia (D-L). Different soil chemical properties were analyzed to evaluate the effects of alley cropping, while 16S rRNA amplification and enzymatic activities were determined to study the changes that occurred in soil microbial communities and activity. In addition, the influence of intercropping on the potential functionality of the soil microbial community was measured. Data revealed that the intercropping systems highly affected the microbial community and soil properties. The D-S cropping system increased soil total organic carbon and total nitrogen that were correlated with the bacterial community, indicating that both parameters were the main drivers shaping the structure of the bacterial community. The D-S soil cropping system had significantly higher relative abundances of the phyla Bacteroidetes, Proteobacteria, and Patescibacteria compared to the other systems and the genera Adhaeribacter, Arthrobacter, Rubellimicrobium, and Ramlibacter, related to C and N functions. D-S soil was also related to the highest relative abundances of Pseudoarthrobacter and Haliangium, associated with the plant growth-promoting effect, antifungal activity, and a potential P solubilizer. A potentially increase of C fixation and N fixation in soils was also observed in the D-S cropping system. These positive changes were related to the cessation of tillage and the development of a spontaneous cover crop, which increased soil protection. Thus, management practices that contribute to increasing soil cover should be encouraged to improve soil functionality.

Methylobacterium symbioticum sp. nov., a new species isolated from spores of Glomus iranicum var. tenuihypharum.

Strain SB0023/3 T, isolated from spores of the arbuscular mycorrhizal fungus Glomus iranicum var. tenuihypharum, was analysed to determine whether it represents a new species. It was studied for its applicability in the field of agriculture to reduce the input of nitrogen fertilizers. Comparative analysis of the 16S rRNA gene sequence shows the strain to be affiliated to the genus Methylobacterium, the closest similarities (98.7%) being shared with Methylobacterium dankookense. Further phylogenomic analysis through Up-to-date Bacterial Core Gene (UBCG) confirmed Methylobacterium dankookense as its closest relative. Average Nucleotide Identity (ANI) and in silico DNA-DNA hybridization (DDH) were lower than 92% and 44%, respectively, of the values shown by its phylogenetic relatives. Its genome had an approximate length of 6.05 Mb and the G + C content of the genome was 70.1 mol%. The main cellular fatty acid was Summed Feature 8 (C18:1ω7c and/or C18:1ω6c). It is a Gram-staining-negative, pink-pigmented, strictly aerobic and facultative methylotroph; it grows at 28 ºC and can grow at up to 3% salinity in the presence of sodium chloride. All the data collected support the naming of a novel species to accommodate the strain SB0023/3 T, for which the name Methylobacterium symbioticum sp. nov. is proposed. The type strain is SB0023/3 T (=CECT 9862 T =PYCC 8351 T).

Impact of foliar fungicides on target and non-target soil microbial communities in cucumber crops.

The application of foliar fungicides to horticultural crops has raised public concerns worldwide. In fact, it has been demonstrated that such fungicides have an impact on non-target microorganisms in the rhizosphere. Fluopyram, triadimenol and penthiopyrad are three broad-spectrum fungicides recommended to control foliar diseases. In our experiment, these fungicides were applied to a cucumber crop to mainly control downy mildew caused by Pseudoperonospora cubensis and grey mold caused by Botrytis cinerea. At the same time, we found that these treatments also controlled other fungal pathogens affecting cucumber crops, particularly penthiopyrad, which was more effective. Once the fungicide application period was over, the effect decreased, although fungicide traces remained in the soil. Furthermore, microbial soil community analysis indicated that both fungicide treatments affect fungal communities to a greater extent than bacterial communities.

Agroindustrial composts to reduce the use of peat and fungicides in the cultivation of muskmelon seedlings.

BACKGROUND: Environmental concerns about peat extraction in wetland ecosystems have increased. Therefore, there is an international effort to evaluate alternative organic substrates for the partial substitution of peat. The aim of this work was to use different composts (C1-C10) obtained from the fruit and vegetable processing industry (pepper, carrot, broccoli, orange, artichoke residues, sewage sludge (citric and pepper) and vineyard pruning wastes) to produce added-value composts as growing media with suppressive effect against Fusarium oxysporum f.sp. melonis (FOM) in muskmelon. RESULTS: Composts showed values of water-soluble carbon fractions and dehydrogenase activity that allowed them to be considered mature and stabilized. All compost treatments produced significantly (F = 7.382; P < 0.05) higher fresh shoot weight than peat, treatment T-C2 showing the highest values. Treatments T-C5, T-C7 and T-C8 showed percentages of disease incidence that were significantly (F = 16.052; P < 0.05) the lowest, relative to peat, followed by T-C6, T-C10, T-C1 and T-C9 with values below 50%. CONCLUSION: Composts produced are suitable components of mixed compost-peat growing media, providing a 50% substitution of peat. Furthermore, some of these composts also showed an added value as a suppressive organic medium against Fusarium wilt in muskmelon seedling, a fact probably related to high pH and pepper wastes and high content of pruning waste as initial raw materials. © 2016 Society of Chemical Industry.

Identification of predictor parameters to determine agro-industrial compost suppressiveness against Fusarium oxysporum and Phytophthora capsici diseases in muskmelon and pepper seedlings.

BACKGROUND: The lack of reliable prediction tools for evaluation of the level and specificity of compost suppressiveness limits its application. In our study, different chemical, biological and microbiological parameters were used to evaluate their potential use as a predictor parameter for the suppressive effect of composts against Fusarium oxysporum f. sp. melonis (FOM) and Phytophthora capsici (P. capsici) in muskmelon and pepper seedlings respectively. Composts were obtained from artichoke sludge, chopped vineyard pruning waste and various agro-industrial wastes (C1: blanched artichokes; C2: garlic waste; C3: dry olive cake). RESULTS: Compost C3 proved to offer the highest level of resistance against FOM, and compost C2 the highest level of resistance against P. capsici. Analysis of phospholipid fatty acids isolated from compost revealed that the three composts showed different microbial community structures. Protease, NAGase and chitinase activities were significantly higher in compost C3, as was dehydrogenase activity in compost C2. CONCLUSION: The use of specific parameters such as general (dehydrogenase activity) and specific enzymatic activities (protease, NAGase and chitinase activities) may be useful to predict compost suppressiveness against both pathogens. The selection of raw materials for agro-industrial composts is important in controlling Fusarium wilt and Phytophthora root rot.

Combined effect of an agro-industrial compost and light spectra composition on yield and phytochemical profile in mizuna and pak choi microgreens.

This work aimed to evaluate the growth of two species of microgreens (mizuna and pak choi), using agro-industrial compost as growing media in two different mixes versus one hundred percent peat, under two different LED illumination spectra (LED 1 and LED 2) in a 14 h photoperiod. The experiment was carried-out for two times. Biomass yield, glucosinolates, and phenolic compounds, and nitrate (NO3-) content were analysed in leaf tissues. In both species, the highest fresh and dry biomass production was in compost:peat (50:50%) and LED 2 (Blue/Red/Far Red). In general, compost had a greater influence on nitrate content than light, but in the microgreen pak choi, the anthocyanin content was inhibited by the compost treatment. In the other hand both LED illumination had a positive effect on mizuna for glucosinolates and anthocyanins, and LED 2 also showed a positive effect on pak choi for anthocyanin. Therefore, the use of agri-food compost: peat (50:50%) with LED 2 (blue/red) lighting treatment to obtain microgreens in indoor crops is a plausible technology that provides nutritionally and phytochemically rich crops.

Analytical strategy to assess the microbial degradation of poly(butylene-adipate-co-terephthalate)/poly(lactic acid) films.

Plastic is widely used in agricultural applications, but its waste has an adverse environmental impact and a long-term detrimental effect. The development of biodegradable plastics for agricultural use is increasing to mitigate plastic waste. The most commonly used biodegradable plastic is poly(butylene adipate co-terephthalate)/poly(lactic acid) (PBAT/PLA) polymer. In this study, an analytical procedure based on dispersive liquid-liquid microextraction (DLLME) followed by gas chromatography-mass spectrometry (GC-MS) in combination with chemometrics has been optimized to assess the degradation level of PBAT/PLA films by monitoring their characteristic degradation products. Carboxylic acids (benzoic, phthalic, adipic, heptanoic, and octadecanoic acids) and 1,4-butanediol have been found to be potential markers of PBAT/PLA degradation. The DLLME-GC-MS analytical approach has been applied for the first time to assess the degradation efficiency of several microorganisms used as degradation accelerators of PBAT/PLA based on the assigned potential markers. This analytical strategy has shown higher sensitivity and precision than standard techniques, such as elemental analysis, allowing us to detect low degradation levels.

Changes induced by Trichoderma harzianum in suppressive compost controlling Fusarium wilt.

The addition of species of Trichoderma to compost is a widespread technique used to control different plant diseases. The biological control activity of these species is mainly attributable to a combination of several mechanisms of action, which may affect the microbiota involved in the suppressiveness of compost. This study was therefore performed to determine the effect of inoculation of Trichoderma harzianum (T. harzianum) on compost, focusing on bacterial community structure (16S rRNA) and chitinase gene diversity. In addition, the ability of vineyard pruning waste compost, amended (GCTh) or not (GC) with T. harzianum, to suppress Fusarium wilt was evaluated. The addition of T. harzianum resulted in a high relative abundance of certain chitinolytic bacteria as well as in remarkable protection against Fusarium oxysporum comparable to that induced by compost GC. Moreover, variations in the abiotic characteristics of the media, such as pH, C, N and iron levels, were observed. Despite the lower diversity of chitinolytic bacteria found in GCTh, the high relative abundance of Streptomyces spp. may be involved in the suppressiveness of this growing media. The higher degree of compost suppressiveness achieved after the addition of T. harzianum may be due not only to its biocontrol ability, but also to changes promoted in both abiotic and biotic characteristics of the growing media.

Agronomical Practices and Management for Commercial Cultivation of Portulaca oleracea as a Crop: A Review.

Soil is an essential resource, and its degradation is challenging modern agriculture, while its impact is expected to increase in the near future. One of the strategies to address this issue is to incorporate new alternative crops able to tolerate arduous conditions, as well as for the use of sustainable agricultural practices in order to recover and/or improve soil health. Additionally, the increasing market for new functional/healthy natural foods promotes the search for potential alternative crop species with promising bioactive compounds content. For this purpose, wild edible plants are a key option because they have already been consumed for hundreds of years in traditional gastronomy and there is well-established evidence of their health-promoting effects. Moreover, since they are not a cultivated species, they are able to grow under natural conditions without human intervention. Among them, common purslane is an interesting wild edible species and a good candidate for integration in commercial farming systems. With worldwide spread, it is able to tolerate drought, salinity and heat stress and is already used in traditional dishes, while it is highly appreciated for its high nutritional value due to its bioactive compound content, especially omega-3 fatty acids. In this review, we aim to present the breeding and cultivation practices of purslane, as well as the effects of abiotic stressors on yield and chemical composition of the edible parts. Finally, we present information that helps to optimize purslane cultivation and facilitate its management in degraded soils for their exploitation in the existing farming systems.

Effects of inorganic and compost tea fertilizers application on the taxonomic and functional microbial diversity of the purslane rhizosphere.

Introduction: Soil fertility is a major determinant of plant-microbial interactions, thus, directly and indirectly affecting crop productivity and ecosystem functions. In this study, we analysed for the first time the effects of fertilizer addition on the cropping of purslane (Portulaca oleracea) with particular attention to the taxonomic and functional characteristics of their associated soil microbiota. Methods: We tested the effects of different doses of inorganic fertilization differing in the amount of N:P:K namely IT1 (300:100:100); IT2 (300:200:100); IT3 (300:200:200); and IT4 (600:100:100) (ppm N:P:K ratio) and organic fertilization (compost tea) which reached at the end of the assay the dose of 300 ppm N. Results and discussion: Purslane growth and soil quality parameters and their microbial community structure, abundance of fungal functional groups and prevailing bacterial metabolic functions were monitored. The application of compost tea and inorganic fertilizers significantly increased the purslane shoot biomass, and some soil chemical properties such as pH and soil enzymatic activities related to C, N and P biogeochemical cycles. The bacterial and fungal community compositions were significantly affected by the organic and chemical fertilizers input. The majority of inorganic fertilization treatments decreased the fungal and bacterial diversity as well as some predictive bacterial functional pathways. Conclusions: These findings suggest that the inorganic fertilization might lead to a change of microbial functioning. However, in order to get stronger evidence that supports the found pattern, longer time-frame experiments that ideally include sampling across different seasons are needed. Thus, further research is still needed to investigate the effects of fertilizations on purslane productivity under commercial field conditions.

Assessment of gunshot residue detection on a large variety of surfaces by portable LIBS system for crime scene application.

The application of Laser-Induced Breakdown Spectroscopy (LIBS) in forensic science has garnered increasing attention. The ability to perform real-time, on-site analysis of Gunshot Residue (GSR) particles and potential elements originating from bullets or projectile cores on various surfaces holds the potential to assist in resolving firearms-related cases. This includes facilitating trajectory determination by locating distinct impact points and identifying the types of ammunition used. This study evaluates the utilization of a portable LIBS device for ballistic forensic purposes. Additionally, it focuses on the assessment of potential false positives and false negatives arising from the different materials where the shots have been fired. Since the system performs laser ablation of both surface particles and the substrate, it emphasizes the importance of conducting preliminary screening in an area with the same composition as the impact zone to minimize potential false positives during direct surface analysis. Furthermore, the results demonstrate the capability to detect the constituent elements of characteristic gunshot residue particles (GSR particles): lead (Pb), antimony (Sb), and barium (Ba) adhering to bullets, as well as the principal elements composing the jacket or core of the projectile: lead (Pb), copper (Cu), and zinc (Zn) through direct analysis, without the need for a sampling kit, on different surfaces such as walls, furniture, or fabrics. Analyses conducted a month after the shots were fired indicate the potential for finding residues in the vicinity of the bullet hole. Analyses conducted a month after the shots were fired indicate the possibility of finding residues in the area around the bullet hole.

Assessing the shooting distance of lead-free ammunition regardless of composition using Laser Induced Breakdown Spectroscopy.

At present, it is challenging to accurately determine firearm shooting distances in the case that lead-free ammunition is involved, largely because different manufacturers use different primer compositions. Laser-induced breakdown spectroscopy (LIBS) allows the simultaneous detection of multiple elements with high sensitivity and so may represent a solution to this problem. Previous studies have, in fact, demonstrated that LIBS can be used to determine shooting distances when working with gunshot residues from conventional ammunition based on scanning fabric surfaces. The present study confirms that the shooting distance can be ascertained using LIBS to detect copper originating from the ammunition casing and projectile but not the primer on fabric surfaces. This estimation can be performed regardless of the primer composition of lead-free ammunition. Key points: Evaluation of gunshot residue from lead-free ammunition using scanning electron microscopy-energy dispersive X-ray analysis indicated that 40% of the particles contained copper.The iForenLIBS system allowed the detection of copper-containing particles on fabric surfaces after firing at different distances with high sensitivity.Laser-induced breakdown spectroscopy can determine the shooting distance of lead-free ammunition through copper detection even in ammunition that does not used this element in the primer.This technique can generate density maps allowing the evaluation of short, medium, and long-range shooting distances.

Bacterial and fungal community dynamics during different stages of agro-industrial waste composting and its relationship with compost suppressiveness.

Composting is an advantageous and efficient process for recycling organic waste and producing organic fertilizers, and many kinds of microorganisms are involved in obtaining quality compost with suppressive activity against soil-borne pathogens. The aim of this work was to evaluate the main differences in the effects of three composting piles on the whole bacterial and fungal communities of baby-leaf lettuce crops and to determine the specific communities by high-throughput sequencing related to suppressiveness against the soil-borne plant pathogen Pythium irregulare- (P. irregulare). Compost pile A was composed of 47% vineyard pruning waste, 34% tomato waste and 19% leek waste; pile B was composed of 54% vineyard pruning waste and 46% tomato waste; and pile C was composed of 42% vineyard pruning waste, 25% tomato waste and 33% olive mill cake. The temperature and the chemical properties of the piles were monitored throughout the composting process. In addition, the potential suppressive capacity of the three composts (C_A, C_B and C_C) against P. irregulare in baby-leaf lettuce was assessed. We found that the bacterial community changed according to the composting phases and composting pile and was sensitive to chemical changes throughout the composting process. The fungal community, on the other hand, did not change between the composting piles and proved to be less influenced by chemical properties, but it did change, principally, according to the composting phases. All composts obtained were considered stable and mature, while compost C_C showed higher maturity than composts C_A and C_B. During composting, the three piles contained a greater relative abundance of Bacterioidetes, Proteobacterias and Actinobacterias related to the suppression of soil-borne pathogens such as Pythium irregulare. Composts C_A and C_B, however, showed higher suppressiveness against P. irregulare than compost C_C. Deeper study showed that this observed suppressiveness was favored by a higher abundance of genera that have been described as potential suppressive against P. irregulare, such as Aspergillus, Penicillium, Truepera and Luteimonas.

Association between biomarkers of tobacco consumption and lung cancer risk among daily smokers.

BACKGROUND: Biomarkers of tobacco consumption may play a role in the lung cancer risk assessment. However, the role of salivary biomarkers has not been well studied. The aim of this study is to assess the use of salivary biomarkers of tobacco consumption as lung cancer screening criterion. RESEARCH DESIGN AND METHODS: Data came from the Determinants of cotinine phase 3 project (Barcelona, 2013-2014). We compared the concentrations of TSNAs, including NNAL, NNN and NNK, and cotinine, in saliva samples of 142 daily smokers from the general population according to their risk of lung cancer. High risk of lung cancer was defined as per the inclusion criteria in the US National Lung Screening Trial (NLST) and in the Dutch-Belgian lung cancer screening trial (NELSON). RESULTS: Among daily smokers accomplishing the age criterion for lung cancer screening, salivary concentrations of cotinine, NNAL and NNK adjusted for sex were significantly higher (p-value < 0.05) in daily smokers at high risk of lung cancer compared to smokers not at high risk according to both NELSON and NLST criteria. CONCLUSIONS: Saliva concentrations of cotinine, NNAL and NNK may be used as additional criteria for lung cancer screening. Further research on this topic is guaranteed.

Melon/cowpea intercropping pattern influenced the N and C soil cycling and the abundance of soil rare bacterial taxa.

The high use of pesticides, herbicides, and unsustainable farming practices resulted in losses of soil quality. Sustainable farming practices such as intercropping could be a good alternative to traditional monocrop, especially using legumes such as cowpea (Vigna unguiculata L. Walp). In this study, different melon and cowpea intercropping patterns (melon mixed with cowpea in the same row (MC1); alternating one melon row and one cowpea row (MC2); alternating two melon rows and one cowpea row (MC3)) were assayed to study the intercropping effect on soil bacterial community through 16S rRNA region in a 3-year experiment. The results indicated that intercropping showed high content of total organic carbon, total nitrogen and ammonium, melon yield, and bacterial diversity as well as higher levels of beneficial soil microorganisms such a Pseudomonas, Aeromicrobium, Niastella, or Sphingomonas which can promote plant growth and plant defense against pathogens. Furthermore, intercropping showed a higher rare taxa diversity in two (MC1 and MC2) out of the three intercropping systems. In addition, N-cycling genes such as nirB, nosZ, and amoA were more abundant in MC1 and MC2 whereas the narG predicted gene was far more abundant in the intercropping systems than in the monocrop at the end of the 3-year experiment. This research fills a gap in knowledge about the importance of soil bacteria in an intercropping melon/cowpea pattern, showing the benefits to yield and soil quality with a decrease in N fertilization.

Trichoderma harzianum and Glomus intraradices modify the hormone disruption induced by Fusarium oxysporum infection in melon plants.

The plant hormones salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA) are known to play crucial roles in plant disease and pest resistance. Changes in the concentrations of these plant hormones in melon plant shoots, as a consequence of the interaction between the plant, the pathogen Fusarium oxysporum, the antagonistic microorganism Trichoderma harzianum, and the arbuscular mycorrhizal fungus Glomus intraradices were investigated. Attack by F. oxysporum activated a defensive response in the plant, mediated by the plant hormones SA, JA, ET, and ABA, similar to the one produced by T. harzianum. When inoculated with the pathogen, both T. harzianum and G. intraradices attenuated the plant response mediated by the hormones ABA and ET elicited by the pathogen attack. T. harzianum was also able to attenuate the SA-mediated response. In the three-way interaction (F. oxysporum-T. harzianum-G. intraradices), although a synergistic effect in reducing disease incidence was found, no synergistic effect on the modulation of the hormone disruption induced by the pathogen was observed. These results suggest that the induction of plant basal resistance and the attenuation of the hormonal disruption caused by F. oxysporum are both mechanisms by which T. harzianum can control Fusarium wilt in melon plants; while the mechanisms involving G. intraradices seem to be independent of SA and JA signaling.

If you play with fire, you may get burned.

This article reports an interesting doping case in the late 1990s involving the physical tampering of a urine sample containing a prohibited substance, by adding an alcoholic beverage. The regulations and knowledge available at that time allowed consideration of the case as a sanctioned manipulation and the prohibited substance as an additional element that explained the reasons for it. The development of the case involved some aspects that appeared for the first time in doping control. These include, among others, the participation of an enologist as part of the B sample confirmation, forensic inspection of the sample container, the early development of gas chromatography/combustion/isotopic ratio mass spectrometry (GC/C/IRMS), and the first public hearing by the Court of Arbitration for Sport (CAS), which allowed a wide following of the developments of the case. The information was especially interesting for the general public as the athlete had had, at that time, great Olympic success.

LC-MS/MS method for the quantification of new psychoactive substances and evaluation of their urinary detection in humans for doping control analysis.

The constant legal adaptation of new psychoactive substances (NPS), challenges their evaluation in different fields. In sports, NPS are prohibited in competition with a reporting limit (RL) of 50 ng/mL for the parent compound or a metabolite. However, there is a lack of comprehensive methodologies and excretion studies for monitoring NPS. This work aims to develop an analytical methodology for the NPS quantification and to evaluate the suitability of monitoring the urinary parent stimulants after NPS misuse. A method for the quantification of 14 common NPS was developed and validated. The method was found to be linear in the range 1-1000 ng/mL, and was shown to be accurate and precise. A lowest limit of quantification (LLOQ) of 1 ng/mL was established for all analytes except for benzylpiperazine (5 ng/mL). The method was able to confirm the identity of the analytes at the LLOQ for most NPS. The methodology was applied to the quantification of the parent compound in urine samples collected from an observational study where several healthy volunteers (n ≥ 6 per drug) ingested active doses of mephedrone (MEPH), methylone (MDMC), 2,5-dimetoxy-4-ethylphenetylamine (2C-E), or 6-(2-aminopropyl)benzofuran (6-APB). It was observed that for MDMC and 6-APB, the quantification of the urinary parent drug at the current RL is a proper strategy for detecting their misuse. However, this strategy seems to be insufficient for evaluating MEPH and 2C-E misuse. Monitoring the most abundant metabolite of MEPH (4'-carboxy-MEPH) and the reduction of the RL to 10 ng/mL for the 2C-E evaluation are proposed.

Neurotoxic thioether adducts of 3,4-methylenedioxymethamphetamine identified in human urine after ecstasy ingestion.

3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely misused synthetic amphetamine derivative and a serotonergic neurotoxicant in animal models and possibly humans. The underlying mechanism of neurotoxicity involves the formation of reactive oxygen species although their source remains unclear. It has been postulated that MDMA-induced neurotoxicity is mediated via the formation of bioreactive metabolites. In particular, the primary catechol metabolites, 3,4-dihydroxymethamphetamine (HHMA) and 3,4-dihydroxyamphetamine (HHA), subsequently cause the formation of glutathione and N-acetylcysteine conjugates, which retain the ability to redox cycle and are serotonergic neurotoxicants in rats. Although the presence of such metabolites has been recently demonstrated in rat brain microdialysate, their formation in humans has not been reported. The present study describes the detection of 5-(N-acetylcystein-S-yl)-3,4-dihydroxymethamphetamine (N-Ac-5-Cys-HHMA) and 5-(N-acetylcystein-S-yl)-3,4-dihydroxyamphetamine (N-Ac-5-Cys-HHA) in human urine of 15 recreational users of MDMA (1.5 mg/kg) in a controlled setting. The results reveal that in the first 4 h after MDMA ingestion approximately 0.002% of the administered dose was recovered as thioether adducts. Genetic polymorphisms in CYP2D6 and catechol-O-methyltransferase expression, the combination of which are major determinants of steady-state levels of HHMA and 4-hydroxy-3-methoxyamphetamine, probably explain the interindividual variability seen in the recovery of N-Ac-5-Cys-HHMA and N-Ac-5-Cys-HHA. In summary, the formation of neurotoxic thioether adducts of MDMA has been demonstrated for the first time in humans. The findings lend weight to the hypothesis that the bioactivation of MDMA to neurotoxic metabolites is a relevant pathway to neurotoxicity in humans.