The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

UNASSIGNED: \"Activation syndrome\" represents a cluster of symptoms of excessive emotional arousal or behavioral activation, which emerges after the first few weeks of antidepressant treatment or a dose increase and resolves with dose reduction or cessation of treatment. It was reported after treatment with selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor group of agents, but no case of activation syndrome has been reported with the norepinephrine reuptake inhibitor group. Atomoxetine is a norepinephrine reuptake inhibitor and nonstimulant and is used to manage symptoms of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine-related symptoms of mania and hypomania were reported in literature previously. Here, we report a case of activation syndrome arising after atomoxetine (ATX) dose titration in a prepubertal male child with ADHD. Differentiation of activation symptoms from mania/hypomania symptoms after treatment with ATX may be important for the clinicians to manage the adverse effects and understand the risk factors behind activation syndrome with use of ATX in children and adolescents diagnosed with ADHD.

Atomoxetine is a norepinephrine reuptake inhibitor used for treatment of attention-deficit/hyperactivity disorder. Prescribing information from the manufacturer lists genitourinary-related adverse events such as urinary hesitancy/retention and priapism as precautions for atomoxetine. We report a case of urinary hesitancy with milky, white-colored discharge associated with atomoxetine use in a 42-year-old male. The onset of genitourinary symptoms occurred within 2 days of atomoxetine 40 mg daily initiation. Laboratories, urinalysis, sexually transmitted infection analysis, and genital examinations were all unremarkable. Within 2 days of atomoxetine discontinuation, the genitourinary symptoms were no longer present. We calculated a Naranjo adverse event score of 5, indicating atomoxetine probably caused the genitourinary adverse events. A review of literature suggests that urine outflow obstruction-related adverse events occur more commonly in men compared to women. Discontinuation of atomoxetine appears to lead to rapid resolution of the adverse events. Additionally, spontaneous ejaculation and sexual side effects rarely occur with atomoxetine. Clinicians should educate and monitor patients explicitly for genitourinary-related adverse events, as they may not be spontaneously reported.

Background: Aflatoxins (AFs) have attracted increasing amounts of attention in recent years for their high toxicity. Previously, AF-polluted Chinese Patent Medicines (CPMs) were ignored, but their quality, safety, and efficacy might be influenced by the toxic compounds. Objective: The objective is to develop a simple, low-cost, and efficient method for quantitative analysis of aflatoxins B1 (AFB1) and B₂ (AFB₂) in CPMs to ensure their safe use. Methods: A simple, modified, magnetic nanoparticle-based solid-phase extraction (SPE) combined with HPLC-fluorescence detection for the determination of trace amounts of AFB1 and AFB₂ was established. The main parameters affecting the efficiency of modified magnetic nanoparticle-based SPE, such as pH of sample solution, adsorbent amount, adsorption time, and desorption condition, were investigated. Results: Under the optimum conditions, AFB1 and AFB₂ were linear in the ranges of 0.3-10 and 0.04-3 ng/mL with the correlation coefficient (R) of 0.9998 and 0.9999, respectively. Their intraday precisions were 1.16 and 2.30% and the interday precisions were 1.28 and 1.87% for AFB1 and AFB₂, respectively. The developed SPE was applied for AFB1 and AFB₂ extraction in three commercially available Fupuganmao granule samples, and the results were compared with the official immunoaffinity column chromatography method. Conclusions: The method provided a preferable candidate for the determination approach of AF measurement in CPMs. Highlights: Amine-functionalized magnetic nanoparticles were successfully applied to SPE for adsorbing AFB1 and AFB₂ in CPMs for the first time.

OBJECTIVE: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have an increased risk of injuries. Attention-deficit/hyperactivity disorder is often treated with medication, but the evidence regarding prevention of injuries is inconclusive.
OBJECTIVE: To determine via a case-only design whether the use of methylphenidate hydrochloride or atomoxetine hydrochloride reduces the risk of injuries among children and adolescents with ADHD.
METHODS: We used the German Pharmacoepidemiological Research Database, which includes records from about 17 million insurees (approximately 20% of the population) from 4 statutory health insurance providers in Germany to identify children aged 3 to 17 years with new diagnoses of ADHD in 2005 and 2006. We identified 37,650 children with ADHD based on inpatient and outpatientdiagnostic codes (F90.0, F90.1, and F90.9) from the German modification of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Among them, we identified those with an inpatient injury diagnosis during follow-up until 2009. A total of 2128 children with any injury diagnosis at hospitalization, 821 of whom had a brain injury diagnosis, were included in the analysis. We applied the self-controlled case series design to control for time-invariant characteristics of the patients and time trends in the exposure.
METHODS: Treatment with methylphenidate or atomoxetine based on prescription data.
METHODS: Hospitalization because of any injury or brain injury according to the injury mortality diagnosis matrix.
RESULTS: Incidence rate ratios for the periods with medication compared with nonmedicated periods were 0.87 (95% CI, 0.74-1.02) for hospitalization with any injuries and 0.66 (95% CI, 0.48-0.91) for brain injuries only in the full sample. These estimates remained stable in sensitivity analyses restricting the sample to a narrower age range or to patients with a single hospitalization. There was no indication that medication prescriptions are increased after hospitalizations.
CONCLUSIONS: No significant risk reduction for hospitalizations with injury diagnoses was observed during periods of ADHD medication, but there was a preventive effect on the risk of brain injuries (34% risk reduction). The effects were controlled for time-invariant characteristics of the patients by the study design.

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Nutrient import across Gram-negative bacteria\'s outer membrane is powered by the proton-motive force, delivered by the cytoplasmic membrane protein complex ExbB-ExbD-TonB. Having purified the ExbB4-ExbD2 complex in the detergent dodecyl maltoside, we substituted amphipol A8-35 for detergent, forming a water-soluble membrane protein/amphipol complex. Properties of the ExbB4-ExbD2 complex in detergent or in amphipols were compared by gel electrophoresis, size exclusion chromatography, asymmetric flow field-flow fractionation, thermal stability assays, and electron microscopy. Bound detergent and fluorescently labeled amphipol were assayed quantitatively by 1D NMR and analytical ultracentrifugation, respectively. The structural arrangement of ExbB4-ExbD2 was examined by EM, small-angle X-ray scattering, and small-angle neutron scattering using a deuterated amphipol. The amphipol-trapped ExbB4-ExbD2 complex is slightly larger than its detergent-solubilized counterpart. We also investigated a different oligomeric form of the two proteins, ExbB6-ExbD4, and propose a structural arrangement of its transmembrane α-helical domains.

During preclinical and early phase clinical studies of drug candidates, exposure to metabolites should be monitored to determine whether safety conclusions drawn from studies in animals can be extrapolated to humans. Metabolites accounting for more than 10% of total exposure to drug-related material (DRM) in humans are of regulatory concern, and for any such metabolites, adequate exposure should be demonstrated in animals before large-scale phase 3 clinical trials are conducted. We have previously identified six metabolites, M1-M6, of the gastroesophageal reflux inhibitor lesogaberan. In this study, we measured exposure in humans, rats, and beagle dogs to lesogaberan and these metabolites. Plasma samples were taken at various time points after lesogaberan dosing in two clinical and three preclinical studies. Concentrations of lesogaberan and its metabolites were measured, and exposures during a single dosing interval were calculated. The parent compound and metabolites M1, M2, M4, and M5 were together shown to constitute all significant exposure to DRM in humans. Only M4 and M5 were present at levels of regulatory concern (10.6% and 18.9% of total exposure to DRM, respectively, at steady state). Absolute exposure to M5 was greater in rats during toxicology studies than the highest absolute exposure observed in humans at steady state (117.0 µmol × h/liter vs. 52.2 µmol × h/liter). In contrast, exposure to M4 in rats was less than 50% of the highest absolute exposure observed in humans. Further safety testing of this metabolite may therefore be required.

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