The impact of agricultural management on selected soil properties in citrus orchards in Eastern Spain: A comparison between conventional and organic citrus orchards with drip and flood irrigation. , 581, 153-160.

The agricultural management of citrus orchards is changing from flood irrigated managed orchards to drip irrigated organic managed orchards. Eastern Spain is the oldest and largest European producer of citrus, and is representative of the environmental changes triggered by innovations in orchard management. In order to determine the impact of land management on different soil quality parameters, twelve citrus orchards sites were selectedwith different land and irrigation management techniques. Soil samples were taken at two depths, 0-2 cmand 5-10 cm for studying soil quality parameters under the different treatments. Half of the studied orchardswere organicallymanaged and the other sixwere conventionally managed, and for each of these six study sites three fields were flood irrigated plots and the other three drip irrigated systems. The outcome of the studied parameters was that soil organic matter (SOM) and aggregate stability were higher for organic farms. Bulk density and pH were only significantly different for organic farms when drip irrigation was applied in comparison with flooded plots. C/N ratio did not vary significantly for the four treatments. Although there are some points of discussion, this research shows that a combination of different management decisions leads to improvement of a couple of soil quality parameters. Organic management practiceswere found to be beneficial for soil quality, compared to conventional management for soils with comparable textures and applied irrigation water

Finding guidelines for cabbage intercropping systems design as a first step in a meta-analysis relay for vegetables

Modern agriculture has been focused on optimizing production, neglecting supporting and regulating ecosystem services. Meta-analyses have demonstrated the potential of intercropping to deliver multiple ecosystem services. However, guidelines for the design and management of such systems remain unclear, especially for the understudied vegetable-based intercropping systems. Given the diversity of vegetable crops, we propose a ‘relay’ of classical crop-specific meta-analyses to capitalize on vegetable intercropping research. Each ‘leg’ in the relay analyzes the effects of companion crops on a focal crop, and over the course of subsequent legs, the network of interactions among the different crops is built. In this study we start what we aspire to be the meta-analysis relay, focusing on cabbage (Brassica oleracea ssp.) and the delivery of the provisioning services Productivity, Product Quality (grade and pest injury in cabbage products), and Yield Stability across different companion species, spatio-temporal configurations, and management practices. We identified 76 studies from all inhabited continents across 81 field sites, comprising 892 data records, of which 689 remained after cleaning. We show that intercropping reduced cabbage productivity (−7% on average, P < 0.05) but also pest injury (−48%, P < 0.001) relative to sole cabbage systems. Cabbage grade on the contrary was not significantly improved by intercropping (+1%, P = 0.71). Effects on yield stability varied widely as only few data records were available from trials conducted over more than two years, pointing to the need for longer-term experimentation. Greater productivity was associated with companion species with a low growth habit or types sown at or after planting of the cabbage crop thus limiting competition with cabbage at early development stages. The decrease in pest injuries was associated with intercropping patterns involving strong inter-plant interactions (i.e., mixed, row, and additive) and companion species that supported biodiversity such as living mulches. Overall, beneficial effects of intercropping tended to be more evident in organic production systems, possibly because synthetic inputs may have hidden regulating effects. Cabbage growers and agricultural advisors can use these guidelines when designing intercrop systems specific to their needs. Applying the approach to other crops and agro-ecosystem services as part of the proposed meta-analysis relay will foster comprehensive understanding of vegetable intercropping systems interactions

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence

Effect of the first wave of COVID-19 on Poison Control Centre activities in 21 European countries : an EAPCCT initiative

Peer reviewe

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS

Drugs of abuse modulate dopaminergic neurotransmission : effects on exocytosis and neurotransmitter receptor function

An extensive amount of literature is available on drugs of abuse. However, current knowledge on cellular and molecular mechanisms of actions is insufficient and hampers treatment of intoxicated patients. Drugs of abuse cause 100.000 hospital admissions yearly only in the US. Therefore, we investigated theeffects commonly used illicit drugs have on dopaminergic neurotransmission. Most tested drugs induced opposite effects, e.g., decreasing cholinergic input (possibly decreasing dopaminergic output) combined with decreasing GABA-ergic input (possibly increasing dopaminergic output). Predicting the ultimate effects in vivo is difficult and will depend on the investigated brain area, the drug concentration and other, not investigated, inputs on the dopaminergic system. In our studies, amphetamine did not induce changes in the basal intracellular calcium concentration ([Ca2+]i) or dopamine exocytosis. However, at a high amphetamine concentration, voltage-gated calcium channels (VGCCs) were inhibited, GABA-ergic input was increased and cholinergic input was decreased. All these mechanisms can contribute to reducing dopamine release following exposure to high concentrations of amphetamine. At a lower, recreational concentration, amphetamine increased cholinergic input, which could increase dopaminergic output. Methamphetamine inhibited VGCCs and cholinergic input at a high concentration, possibly reducing dopaminergic output. However, GABA-ergic input was either decreased or unaffected, which could respectively increase or not affect dopaminergic output. At a lower, recreational concentration, methamphetamine increased cholinergic input, possibly contributing to higher dopamine levels. We also observed 3,4-methylenedioxymethamphetamine (MDMA)- and 3,4-methylenedioxy-amphetamine (MDA)-induced inhibitions of VGCCs, depolarization-evoked dopamine release and cholinergic input at high concentrations. Metabolism could increase MDMAs neurotoxic effects since its metabolite MDA was more potent. Also, MDA potentiates GABA-ergic input (at high GABA receptor occupancy), further decreasing DA release. However, at low GABA receptor occupancy, both MDMA and MDA inhibit GABA-ergic input. This mechanism possibly contributes to drug-induced increases in extracellular dopamine levels. Meta-chlorophenylpiperazine (mCPP) has been suggested as a safe alternative to MDMA. However, of all tested drugs, mCPP induced the strongest effects on all endpoints measured in our studies. At a high concentration, mCPP almost completely inhibited depolarization-evoked and ACh-evoked increases in [Ca2+]i. Thus, mCPP inhibits VGCCs and cholinergic input. Furthermore, mCPP increased GABA-ergic input (at high receptor occupancy). All these mechanisms could contribute to a decrease in dopamine release. However, mCPP decreased GABA-ergic input at low receptor occupancy, which could enhance dopamine release. Overall, drugs of abuse can modulate the dopaminergic system. The degree of modulation depends on the type and concentration of the drug as well as on the concentration of the endogenous receptor ligands. Therefore, a spectrum of effects is expected, and reported, following in vivo exposure. Consequently, predicting the effects methamphetamine, amphetamine, MDMA, MDA and mCPP will induce in the in vivo situation is difficult. However, cholinergic and GABA-ergic receptors represent novel treatment targets as these systems provide a significant input on dopaminergic neurons and we have shown drug-induced effects on these inputs

Effect fingerprinting of new psychoactive substances (NPS) : What can we learn from in vitro data?

The use of new psychoactive substances (NPS) is increasing and currently > 600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP). Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT2receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABAAreceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure. Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks

Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions

Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates the triage and treatment of MDMA users needing medical care. The user's genetic profile and interactions resulting from polydrug use are key factors that modulate the individual response to MDMA and influence MDMA pharmacokinetics and dynamics, and thus clinical outcome. Polymorphisms in CYP2D6, resulting in poor metabolism status, as well as co-exposure of MDMA with specific substances (e.g. selective serotonin reuptake inhibitors (SSRIs)) can increase MDMA plasma levels, but can also decrease the formation of toxic metabolites and subsequent cellular damage. While pre-exposure to e.g. SSRIs can increase MDMA plasma levels, clinical effects (e.g. blood pressure, heart rate, body temperature) can be reduced, possibly due to a pharmacodynamic interaction at the serotonin reuptake transporter (SERT). Pretreatment with inhibitors of the dopamine or norepinephrine reuptake transporter (DAT or NET), 5-HT(2A) or α-β adrenergic receptor antagonists or antipsychotics prior to MDMA exposure can also decrease one or more MDMA-induced physiological and/or subjective effects. Carvedilol, ketanserin and haloperidol can reduce multiple MDMA-induced clinical and neurotoxic effects. Thus besides supportive care, i.e. sedation using benzodiazepines, intravenous hydration, aggressive cooling and correction of electrolytes, it is worthwhile to investigate the usefulness of carvedilol, ketanserin and haloperidol in the treatment of MDMA-intoxicated patients