In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures

The market of new psychoactive substances (NPS) is characterized by a high turnover and thus provides several challenges for analytical toxicology. The analysis of urine samples often requires detailed knowledge about metabolism given that parent compounds may either be present only in small amounts or may not even be excreted. Hence, knowledge of the metabolism of NPS is a prerequisite for the development of reliable analytical methods. The main aim of this work was to elucidate for the first time the pooled human liver S9 fraction metabolism of the nine d-lysergic acid diethylamide (LSD) derivatives 1-acetyl-LSD (ALD-52), 1-propionyl-LSD (1P-LSD), 1-butyryl-LSD (1B-LSD), N6-ethyl-nor-LSD (ETH-LAD), 1-propionyl-N6-ethyl-nor-LSD (1P-ETH-LAD), N6-allyl-nor-LSD (AL-LAD), N-ethyl-N-cyclopropyl lysergamide (ECPLA), (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ), and lysergic acid morpholide (LSM-775) by means of liquid chromatography coupled to high resolution tandem mass spectrometry. Identification of the monooxygenase enzymes involved in the initial metabolic steps was performed using recombinant human enzymes and their contribution confirmed by inhibition experiments. Overall, N-dealkylation, hydroxylation, as well as combinations of these steps predominantly catalyzed by CYP1A2 and CYP3A4 were found. For ALD-52, 1P-LSD, and 1B-LSD deacylation to LSD was observed. The obtained mass spectral data of all metabolites is essential for reliable analytical detection particularly in urinalysis and for differentiation of the LSD-like compounds as biotransformations also led to structurally identical metabolites. However, in urine of rats after the administration of expected recreational doses and using standard urine screening approaches, parent drugs or metabolites could not be detected

Subcellular distribution of dolichol phosphate

originalFil: Dallner, Gustav. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Behrens, Nicolás H.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Parodi, Armando José A.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Leloir, Luis Federico. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaBlanco y negro3 páginas en pdfLFL-PI-O-ART. Artículos científicosUnidad documental simpleAR-HYL-201

Relativistic nature of a magnetoelectric modulus of Cr_2O_3-crystals: a new 4-dimensional pseudoscalar and its measurement

Earlier, the magnetoelectric effect of chromium sesquioxide Cr_2O_3 has been determined experimentally as a function of temperature. One measures the electric field-induced magnetization on Cr_2O_3 crystals or the magnetic field-induced polarization. From the magnetoelectric moduli of Cr_2O_3 we extract a 4-dimensional relativistic invariant pseudoscalar $\widetilde{\alpha}$. It is temperature dependent and of the order of 10^{-4}/Z_0, with Z_0 as vacuum impedance. We show that the new pseudoscalar is odd under parity transformation and odd under time inversion. Moreover, $\widetilde{\alpha}$ is for Cr_2O_3 what Tellegen's gyrator is for two port theory, the axion field for axion electrodynamics, and the PEMC (perfect electromagnetic conductor) for electrical engineering.Comment: Revtex, 36 pages, 9 figures (submitted in low resolution, better quality figures are available from the authors

Unexpected Role of α-Fetoprotein in Spermatogenesis

BACKGROUND: Heat shock severely affects sperm production (spermatogenesis) and results in a rapid loss of haploid germ cells, or in other words, sperm formation (spermiogenesis) is inhibited. However, the mechanisms behind the effects of heat shock on spermatogenesis are obscure. METHODOLOGY/PRINCIPAL FINDINGS: To identify the inhibitory factor of spermiogenesis, experimental cryptorchid (EC) mice were used in this study. Here we show that α-fetoprotein (AFP) is specifically expressed in the testes of EC mice by proteome analysis. AFP was also specifically localized spermatocytes by immunohistochemical analysis and was secreted into the circulation system of EC mice by immunoblot analysis. Since spermatogenesis of an advanced mammal cannot be reproduced with in vitro, we performed the microinjection of AFP into the seminiferous tubules of normal mice to determine whether AFP inhibits spermiogenesis in vivo. AFP was directly responsible for the block in spermiogenesis of normal mice. To investigate whether AFP inhibits cell differentiation in other models, using EC mice we performed a partial hepatectomy (PH) that triggers a rapid regenerative response in the remnant liver tissue. We also found that liver regeneration is inhibited in EC mice with PH. The result suggests that AFP released into the blood of EC mice regulates liver regeneration by inhibiting the cell division of hepatocytes. CONCLUSIONS/SIGNIFICANCE: AFP is a well-known cancer-specific marker, but AFP has no known function in healthy human beings. Our findings indicate that AFP expressed under EC conditions plays a role as a regulatory factor in spermatogenesis and in hepatic generation

Measuring the Effect of Revealed Cultural Preferences on Tourism Exports

The aim of this article is to propose a novel method for measuring the effect of cultural preference on bilateral tourism receipts. The method applied is inspired from Disdier et al. (2010). Using the UNESCO classification and data on bilateral trade in cultural product, a proxy for cultural preferences is constructed. The variable is used in a gravity model for tourism export, which is estimated using a two-step procedure to avoid issues related to endogeneity. The data set used is a panel of 12 OECD countries for a period of 11 years. The variable for cultural preferences eliminates the problems with traditional methods, which by using dummy variables to account for cultural preferences, assume that the latter are time-invariant and symmetrical. The cultural variable constructed is found to be significant in explaining bilateral tourism exports with an elasticity of 0.39. © The Author(s) 2018

Measurement of gauge blocks by interferometry

The key comparison EURAMET.L-K1.2011 on gauge blocks was carried out in the framework of a EURAMET project starting in 2012 and ending in 2015. It involved the participation of 24 National Metrology Institutes from Europe and Egypt, respectively. 38 gauge blocks of steel and ceramic with nominal central lengths between 0.5 mm and 500 mm were circulated. The comparison was conducted in two loops with two sets of artifacts. A statistical technique for linking the reference values was applied. As a consequence the reference value of one loop is influenced by the measurements of the other loop although they did not even see the artifacts of the others. This influence comes solely from three "linking laboratories" which measure both sets of artifacts. In total there were 44 results were not fully consistent with the reference values. This represents 10% of the full set of 420 results which is a considerable high number. At least 12 of them are clearly outliers where the participants have been informed by the pilot as soon as possible. The comparison results help to support the calibration and measurement capabilities (CMCs) of the laboratories involved in the CIPM MRA

Exports Under the Flicker of the Northern Lights

Picture a small open economy in the North Atlantic Ocean, highly dependent on trade with the EU and NAFTA. How important are these trading blocs to the country's exports? How important is the country's location and size, and how do these affect the export sectors? A unique version of the gravity model is applied here using an inverse hyperbolic sine function. Typically, the export volume is significantly impacted by the economic size of the exporting country, but in this case it is not. This suggests that the exports from small remote economies are driven by different factors than exports from large conomies