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© 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in theEGCGgroup and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. Peer Reviewed Article signat per 26 autors/es: Cécile Cieuta-Walti, Aida Cuenca-Royo, Klaus Langohr, Claire Rakic, Ma Ángeles López-Vílchez, Julián Lirio, Domingo González-Lamuño Leguina, Teresa Bermejo González, Jordi García García, Maria Rimblas Roure, Ana Aldea-Perona, Laura Forcano, Maria Gomis-Gonzalez, Sebastià Videla Cés, Florence Lacaille, Aimé Ravel, Clotilde Mircher, Hervé Walti, Nathalie Janel, Julien Dairou, Marilyne Lévy, Sophie Durand, Mara Dierssen, Silvia Sacco, Rafael de la Torre Fornell, PERSEUS Study Group

Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Methods Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. Results An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment. Conclusion These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Background Although 3,4-methylenedioxymethamphetamine (MDMA) has a long history in recreational settings, research on its composition (purity and adulteration) has focused only on tablets even though crystal format is readily available for users. Methods Drug specimens collected between January 2000 and December 2014 were analyzed at Energy Control's facilities. All samples were voluntarily provided by drug users. Sample identification was made with thin layer chromatography and gas chromatography coupled to mass spectrometry, and quantification with ultraviolet spectrophotometry (only in unadulterated samples). Results Between January 2000 and December 2014, 6200 samples purchased as ecstasy by their users were analyzed. Crystals were the most frequent format (60.6%) followed by tablets (38.8%). During the study period, the proportion of samples containing only MDMA was higher in crystals than in tablets. Compared with tablets, adulterated crystal samples contained the same number of adulterants but more combinations of different substances. Although caffeine was commonly detected as adulterant both in crystals and tablets, other substances such as phenacetin, lidocaine, dextrometorphan or methamphetamine were detected almost exclusively in crystal samples. The amount of MDMA in crystal samples remained stable unlike tablets for which a huge increase in MDMA dose was observed since 2010. Conclusion Crystal samples of ecstasy showed clear differences compared to ecstasy tablets and this must be taken into account both in research and harm reduction.

Antioxidant activity of phenolic extract isolated from Tunisian walnut (Juglans regia L.) fruits has been investigated. Preliminarily, composition of walnut kernels was determined. Fat content varied from 53.5 to 66.9% (w/w), while total phenol ranged from 1.2 to 5.2 g/100 g of kernel as gallic acid equivalent (GAE). High amounts of ellagic acid (EA) and its derivatives were evidenced by HPLC analysis of the phenolic extract. Walnut fat showed induction time ranging from 2.5 to 3.7 h at 110 °C (rancimat test) and these values unchanged by adding 300 mg/kg of kernel phenolic extract which so showed to have no antioxidant effect. In addition, activities of the ellagic and gallic acids and trolox were compared in vitro by using the Folin–Ciocalteu’s, rancimat and DPPH radical scavenging methods. EA exhibited an antioxidant and radical scavenging activity significantly lower than other tested substances. In conclusion, EA showed to have a negligible role in preventing walnut fat oxidation.

Drugs are incorporated into sweat by passive diffusion and transdermal migration. The proof of principle of drug testing in sweat has been developed in the past 25 years. Numerous devices and approaches have been developed for the collection of sweat. The potential application of sweat analysis for on-site drug testing at the roadside is limited by the nonavailability of adequate analytical devices. Their major limitation is the lack of sensitivity to some drug classes, an aspect that has been improving over the years. Adequate analytical methodology has been developed for drug analysis both in sweat patches and skin swabs. Immunoassays directed at the detection of parent drugs combined with highly sensitive chromatographic coupled to mass spectrometry analytical methods is the most common analytical approach. In particular, the sweat patch drug testing approach has been proven to be an alternative to urine testing in substance abuse treatment and probation programs. Some of the advantages include a wider detection window, easier sample collection, and reduced opportunities for sample tampering. There are still some pending studies on environmental skin contamination, drug absorption/loss through patch membrane, and drug reabsorption from patches that limit the routine application of drug testing in sweat to some extent. Keywords: sweat; drugs of abuse; patches; drug testing; immunoassays; mass spectrometry

Results from epidemiological studies support the relationship between the consumption of phenolic-rich food and a low incidence of coronary heart disease (1)(2). The lower incidences of coronary heart disease and certain cancers in Mediterranean countries have been associated with diet, of which fruits, vegetables, legumes, and grains are the usual components and the major fat component is olive oil (3). The Mediterranean dietary pattern has been also shown to be effective in secondary prevention of coronary heart disease (4). Virgin olive oil is rich in phenolic compounds with strong antioxidant properties that protect olive oil from autooxidation (5). In addition, olive oil phenolic compounds have been shown to delay in vitro metal-induced and radical-dependent LDL oxidation (6)(7). Among the phenolic compounds in olive oil is tyrosol (4-hydroxyphenylethanol), which is also present in other dietary sources (8)(9) and has mild antioxidant properties (10)(11)(12). However, information on the bioavailability of dietary phenolic compounds in humans is scarce (13)(14). In bioavailability studies of phenolic compounds, one of the main problems is the estimation of the dose administered because these substances can be present in multiple forms in food. In the specific case of olive oil, phenolic compounds may be in the form of glycosides, polymers, and esters (12)(15). To our knowledge, the bioavailability of tyrosol from nonsupplemented dietary sources has not been described previously. Eight healthy volunteers were recruited (five men and three women; age range, 25–52 years). The local ethics committee, CEIC-IMAS (register no. 98/798/I), approved the protocol, and participants signed an informed consent. All volunteers could be considered healthy on the basis of physical examination and standard biochemical and hematological tests. Subjects had an mean weight of 75 ± 13.47 kg (men, 83.2 ± 4.4 kg; women, …

Objetivo: recopilar y analizar la informacion sobre los efectos de la MDMA obtenida en estudios controlados en humanos. Metodo: la mayoria de ensayos analizados han sido de diseno enmascarado a doble ciego, cruzados, con asignacion aleatoria a la secuencia de tratamientos, y controlados con placebo y/o farmaco patron. Resultados: ademas del incremento de la presion y frecuencia cardiaca, la MDMA incrementa el consumo miocardico de oxigeno sin efectos inotropicos y puede incrementar el intervalo QTc en el ECG. El aumento de temperatura no fue significativo frente a placebo. Produce euforia, bienestar y activacion. No se han descrito ni alucinaciones ni ilusiones. En el EEG aumenta la actividad beta y disminuye la alfa. Aumenta de forma dosis-dependiente las concentraciones de ACTH, cortisol, prolactina, dihidroepiandrosterona y vasopresina. Inmunologicamente su efecto parece ser inmunosupresor. Su farmacocinetica parece ser no-lineal con tendencia a la acumulacion a dosis alta. Conclusiones: los estudios controlados han permitido conocer mejor la MDMA, profundizando en sus efectos subjetivos, y aportando datos originales en cuanto a cambios hormonales e inmunologicos. Se necesitan mas estudios para determinar cientificamente los efectos y toxicidad de la MDMA.