- Email: [email protected]
Fatal poisonings caused by NPS, new psychoactive substances
S24
Abstracts / Toxicology Letters 238S (2015) S15–S29
showed linear pharmacokinetics in rats, and 4-OH-3-MeOH-PV was the predominant metabolite. Our results suggest that the parent compound mediates motor stimulation after systemic MDPV administration, but additionally, metabolites may be inhibitory, may not be active, or may not pass the blood–brain barrier. Supported by the National Institutes of Health, Intramural Research Program, NIDA.
ing adverse effects. Indeed, it seems that many of the NPS are more acutely dangerous than the established drugs of abuse. Over the years we have experienced clusters or outbreaks of deaths from NPS such as PMMA, 5-IT, methoxetamine, MDPV, mephedrone, methedrone, AH-7921, MT-45, as well as the commonly abused synthetic cannabinoids. In this lecture, I will address the toxicology of NPS exemplified by case reports from a post mortem perspective.
http://dx.doi.org/10.1016/j.toxlet.2015.08.199
http://dx.doi.org/10.1016/j.toxlet.2015.08.201
S06-4 Sources of Data on the Acute Toxicity Associated with the use of New Psychoactive Substance (NPS)
Symposium S07: MicroRNAs – Mediators and Markers of Chemically-Induced Toxicity
P.I. Dargan 1,2
S07-1 miRNAs in toxicology: The link to epigenetic effects
1 Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, United Kingdom 2 King’s College London, London, United Kingdom
T. Gant ∗ , E. Marcxylo
There has been increasing availability and use of a wide range of different new psychoactive substances (NPS) in Europe and elsewhere in the world over the last decade. Initially when these NPS become available there is often little information available on their pharmacology or potential for acute toxicity. There is limited systematic data collected in Europe on the acute toxicity of NPS (and classical, established recreational drugs). This talk will summarise some of the common sources of data that can be used to put together a picture on the acute toxicity of NPS. These include in vitro pharmacology studies, animal studies, information from internet user discussion forums, data from poisons information services and case reports/case series. None of these sources gives the full picture and each have their limitations. Data traingulation of data from these sources can help to overcome these limitations and enable clinicians and legislative authorities to determine the potential for toxicity associated with emerging NPS.
miRNAs and associated non protein coding RNA species are considered part of the epigenetic machinery of the cell which also includes DNA and histone modifications. While DNA and histone modifications alter gene transcription, miRNAs operate by altering protein translation from mRNAs by a direct interaction with the mRNA 3 untranslated region. The transcription of miRNA species themselves from the genome can be altered as a result of DNA and histone epigenetic modifications. Epigenetic change at both the DNA and RNA level are considered important in many aspects of toxicology but particularly in mechanisms, fertilisation and development, adaptation, and as biomarkers. With respect to biomarkers they can acts both as a quantitative measure of pathophysiology and, in body fluids, as an indicator of damage happening elsewhere. miRNAs can also have effects beyond the organisms because of their established importance in the zygote after transfer in via the gametes. We have previously shown that smoking behaviour in men can affect miRNAs in sperm (Epigenetics. 2012 May;7(5):432–9) and while there is no evidence to date that these changes have an adverse effect on the foetus this work does indicate how environmental hazards can affect gamete miRNA composition. These changes could then potentially cause an effect in subsequent generations by changing the balance of critical early gene expression in the zygote. In this lecture we will explore the multiple roles for miRNAs in toxicology and their regulation by other epigenetic changes in the cell. In particular we will look at the role for miRNAs in transferring epigenetic marks in the gamete, the effect of environmental influences on their expression in the gamete cells and the potential impact of this for the zygote and foetus.
http://dx.doi.org/10.1016/j.toxlet.2015.08.200
S06-5 Fatal poisonings caused by NPS, new psychoactive substances R. Kronstrand National Board of Forensic Medicine, Forensic Toxicology, Linkoping, Sweden The term designer drugs have been used for many years as a synonym for a range of phenylethylamines and later, tryptamines. Today, however, designer drugs appear in most of the common groups of drugs of abuse. In addition to the amphetamine analogs there are cannabinoid analogs, cocaine analogs, opioid analogs, benzodiazepine analogs and some more difficult to categorize at all. The term has also changed into new psychoactive substances (NPS). The drug panorama changes quickly and unpredictably and the clinical and forensic toxicology laboratories must put in tremendous effort to keep up with these emerging drugs. The technique LC-Q-TOF seems to have analytical advantages that make it an alternative both for quick, broad screening in a clinical setting as well as for confirmatory analyses in blood to enable forensic interpretation in fatal intoxications. Even though many of the NPS are advertised as safe alternatives, the safety is mainly concerned with not getting caught with a scheduled drug rather than not having life threaten-
Public Health England, Fermie Avenue, Didcot, United Kingdom
http://dx.doi.org/10.1016/j.toxlet.2015.08.163
S07-2 MiRNAs in drug induced steatosis and its link to human non-alcoholic fatty liver disease J. Borlak Hannover Medical School, Centre for Pharmacology and Toxicology, Hannover, Germany Background: Drug induced steatosis (DIS) results from cellular stress and mitochondrial dysfunction and is characterized by excessive triglyceride accumulation in form of lipid droplets within hepatocytes. Here, we hypothesized distinct transcriptional regu-
Abstracts / Toxicology Letters 238S (2015) S15–S29
showed linear pharmacokinetics in rats, and 4-OH-3-MeOH-PV was the predominant metabolite. Our results suggest that the parent compound mediates motor stimulation after systemic MDPV administration, but additionally, metabolites may be inhibitory, may not be active, or may not pass the blood–brain barrier. Supported by the National Institutes of Health, Intramural Research Program, NIDA.
ing adverse effects. Indeed, it seems that many of the NPS are more acutely dangerous than the established drugs of abuse. Over the years we have experienced clusters or outbreaks of deaths from NPS such as PMMA, 5-IT, methoxetamine, MDPV, mephedrone, methedrone, AH-7921, MT-45, as well as the commonly abused synthetic cannabinoids. In this lecture, I will address the toxicology of NPS exemplified by case reports from a post mortem perspective.
http://dx.doi.org/10.1016/j.toxlet.2015.08.199
http://dx.doi.org/10.1016/j.toxlet.2015.08.201
S06-4 Sources of Data on the Acute Toxicity Associated with the use of New Psychoactive Substance (NPS)
Symposium S07: MicroRNAs – Mediators and Markers of Chemically-Induced Toxicity
P.I. Dargan 1,2
S07-1 miRNAs in toxicology: The link to epigenetic effects
1 Guy’s and St Thomas’ NHS Foundation Trust and King’s Health Partners, London, United Kingdom 2 King’s College London, London, United Kingdom
T. Gant ∗ , E. Marcxylo
There has been increasing availability and use of a wide range of different new psychoactive substances (NPS) in Europe and elsewhere in the world over the last decade. Initially when these NPS become available there is often little information available on their pharmacology or potential for acute toxicity. There is limited systematic data collected in Europe on the acute toxicity of NPS (and classical, established recreational drugs). This talk will summarise some of the common sources of data that can be used to put together a picture on the acute toxicity of NPS. These include in vitro pharmacology studies, animal studies, information from internet user discussion forums, data from poisons information services and case reports/case series. None of these sources gives the full picture and each have their limitations. Data traingulation of data from these sources can help to overcome these limitations and enable clinicians and legislative authorities to determine the potential for toxicity associated with emerging NPS.
miRNAs and associated non protein coding RNA species are considered part of the epigenetic machinery of the cell which also includes DNA and histone modifications. While DNA and histone modifications alter gene transcription, miRNAs operate by altering protein translation from mRNAs by a direct interaction with the mRNA 3 untranslated region. The transcription of miRNA species themselves from the genome can be altered as a result of DNA and histone epigenetic modifications. Epigenetic change at both the DNA and RNA level are considered important in many aspects of toxicology but particularly in mechanisms, fertilisation and development, adaptation, and as biomarkers. With respect to biomarkers they can acts both as a quantitative measure of pathophysiology and, in body fluids, as an indicator of damage happening elsewhere. miRNAs can also have effects beyond the organisms because of their established importance in the zygote after transfer in via the gametes. We have previously shown that smoking behaviour in men can affect miRNAs in sperm (Epigenetics. 2012 May;7(5):432–9) and while there is no evidence to date that these changes have an adverse effect on the foetus this work does indicate how environmental hazards can affect gamete miRNA composition. These changes could then potentially cause an effect in subsequent generations by changing the balance of critical early gene expression in the zygote. In this lecture we will explore the multiple roles for miRNAs in toxicology and their regulation by other epigenetic changes in the cell. In particular we will look at the role for miRNAs in transferring epigenetic marks in the gamete, the effect of environmental influences on their expression in the gamete cells and the potential impact of this for the zygote and foetus.
http://dx.doi.org/10.1016/j.toxlet.2015.08.200
S06-5 Fatal poisonings caused by NPS, new psychoactive substances R. Kronstrand National Board of Forensic Medicine, Forensic Toxicology, Linkoping, Sweden The term designer drugs have been used for many years as a synonym for a range of phenylethylamines and later, tryptamines. Today, however, designer drugs appear in most of the common groups of drugs of abuse. In addition to the amphetamine analogs there are cannabinoid analogs, cocaine analogs, opioid analogs, benzodiazepine analogs and some more difficult to categorize at all. The term has also changed into new psychoactive substances (NPS). The drug panorama changes quickly and unpredictably and the clinical and forensic toxicology laboratories must put in tremendous effort to keep up with these emerging drugs. The technique LC-Q-TOF seems to have analytical advantages that make it an alternative both for quick, broad screening in a clinical setting as well as for confirmatory analyses in blood to enable forensic interpretation in fatal intoxications. Even though many of the NPS are advertised as safe alternatives, the safety is mainly concerned with not getting caught with a scheduled drug rather than not having life threaten-
Public Health England, Fermie Avenue, Didcot, United Kingdom
http://dx.doi.org/10.1016/j.toxlet.2015.08.163
S07-2 MiRNAs in drug induced steatosis and its link to human non-alcoholic fatty liver disease J. Borlak Hannover Medical School, Centre for Pharmacology and Toxicology, Hannover, Germany Background: Drug induced steatosis (DIS) results from cellular stress and mitochondrial dysfunction and is characterized by excessive triglyceride accumulation in form of lipid droplets within hepatocytes. Here, we hypothesized distinct transcriptional regu-