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https://www.readbyqxmd.com/read/28714673/direct-monitoring-of-exogenous-ghb-in-body-fluids-by-nmr-spectroscopy
#1
Martina Palomino-Schätzlein, Yaoyao Wang, Teodor Parella, Cristina Legido-Quigley, Míriam Pérez-Trujillo
γ-Hydroxybutyric acid (GHB) is a popular drug increasingly associated to cases of drug-facilitated sexual assault (DFSA). Currently, expanding procedures of analysis and having forensic evidence of GHB intake at a long term are mandatory. Up to now, most studies have been performed using GC-MS and LC-MS as analytical platforms, which involve significant manipulation of the sample and, often, indirect measurements. In this work, procedures used in NMR-based metabolomics were applied to a GHB clinical trial on urine and serum...
July 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28683403/monastrol-a-3-4-dihydropyrimidin-2-1h-thione-as-structural-scaffold-for-the-development-of-modulators-for-ghb-high-affinity-binding-sites-and-%C3%AE-1%C3%AE-2%C3%AE-gabaa-receptors
#2
Maria Damgaard, Anas Al-Khawaja, Mia Nittegaard-Nielsen, Rebekka F Petersen, Petrine Wellendorph, Bente Frølund
The α4βδ subtype of the γ-aminobutyric acid (GABA) type A receptors (GABAARs) has been shown to be implicated in high-affinity binding of the neuromodulator γ-hydroxybutyric acid (GHB), but may not be the only GHB high-affinity binding sites. Monastrol has been identified as a modulator of GHB high-affinity binding and is furthermore reported as an allosteric modulator selective for the α1β2δ GABAARs. Therefore, structural determinants for selectivity at the two targets were investigated. 39 structural diverse monastrol analogues were synthesized by employing the Biginelli cyclocondensation and examined for modulation of GHB high-affinity binding using the GHB-specific ligand [(3)H]NCS-382 [(E,RS)-6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid] in rat brain homogenate...
June 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28668666/ghb-levels-in-breast-milk-of-women-with-narcolepsy-with-cataplexy-treated-with-sodium-oxybate
#3
Emily C Barker, Michelle Puchowicz, John Letterio, Kristine Higgins, Katherine M Sharkey
OBJECTIVE: To determine GHB levels in breast milk of women taking sodium oxybate (Xyrem) for treatment of narcolepsy and cataplexy. METHODS: Two women with narcolepsy and cataplexy treated with sodium oxybate before pregnancy collected breast milk for analysis of GHB concentration after resuming sodium oxybate postpartum. One woman collected samples across two consecutive nights (doses: 3.0 gm and 4.5 gm twice per night) five months after delivering her first child; the other collected samples on three separate days (doses: 2...
June 1, 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28664505/ssadh-deficiency-in-an-italian-family-a-novel-aldh5a1-gene-mutation-affecting-the-succinic-semialdehyde-substrate-binding-site
#4
Sara Leo, Concetta Capo, Bianca Maria Ciminelli, Federico Iacovelli, Giovanna Menduti, Silvia Funghini, Maria Alice Donati, Mattia Falconi, Luisa Rossi, Patrizia Malaspina
SSADH deficiency (SSADHD) is a rare autosomal recessively inherited metabolic disorder. It is associated with mutations of ALDH5A1 gene, coding for the homotetrameric enzyme SSADH. This enzyme is involved in γ-aminobutyric acid (GABA) catabolism, since it oxidizes succinic semialdehyde (SSA) to succinate. Mutations in ALDH5A1 gene result in the abnormal accumulation of γ-hydroxybutyrate (GHB), which is pathognomonic of SSADHD. In the present report, diagnosis of SSADHD in a three-month-old female was achieved by detection of high levels of GHB in urine...
June 29, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28662343/effect-of-chronic-%C3%AE-hydroxybutyrate-ghb-administration-on-ghb-toxicokinetics-and-ghb-induced-respiratory-depression
#5
Bridget L Morse, Gurkishan S Chadha, Melanie A Felmlee, Kristin E Follman, Marilyn E Morris
BACKGROUND: γ-hydroxybutyrate (GHB) has a high potential for illicit use; overdose of this compound results in sedation, respiratory depression and death. Tolerance to the hypnotic/sedative and electroencephalogram effects of GHB occurs with chronic GHB administration; however, tolerance to respiratory depression has not been evaluated. GHB toxicodynamic effects are mediated predominantly by GABAB receptors. Chronic treatment may affect monocarboxylate transporters (MCTs) and alter the absorption, renal clearance and brain uptake of GHB...
June 29, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28653244/%C3%AE-hydroxybutyric-acid-ghb-pharmacokinetics-and-pharmacodynamics-semi-mechanistic-and-physiologically-relevant-pk-pd-model
#6
Rutwij A Dave, Kristin E Follman, Marilyn E Morris
An overdose of γ-hydroxybutyric acid (GHB), a drug of abuse, results in fatality caused by severe respiratory depression. In this study, a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize monocarboxylate transporter 1 (MCT1)-mediated transport of GHB, as well as effects of GHB on respiration frequency, for IV doses of 200, 600, and 1500 mg/kg in rats. The proposed PK/PD model for GHB consists of nonlinear metabolism of GHB in the liver, MCT1-mediated renal reabsorption with physiologically relevant concurrent fluid reabsorption, MCT1-mediated uptake into the brain, and direct effects of binding of GHB to GABAB receptors on the PD parameter, respiration frequency...
June 26, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28649510/targeted-screening-of-succinic-semialdehyde-dehydrogenase-deficiency-ssadhd-employing-an-enzymatic-assay-for-%C3%AE-hydroxybutyric-acid-ghb-in-biofluids
#7
C Wernli, S Finochiaro, C Volken, H Andresen-Streichert, A Buettler, D Gygax, G S Salomons, E E Jansen, G R Ainslie, K R Vogel, K M Gibson
HYPOTHESIS: An enzymatic assay for quantification of γ-hydroxybutyric acid (GHB) in biofluids can be employed for targeted screening of succinic semialdehyde dehydrogenase deficiency (SSADHD) in selected populations. RATIONALE: We used a two-tiered study approach, in which the first study (proof of concept) examined 7 urine samples derived from patients with SSADHD and 5 controls, and the second study (feasibility study) examined a broader sample population of patients and controls, including plasma...
June 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28627831/whole-blood-thiopurine-s-methyltransferase-genotype-and-phenotype-concordance-in-iranian-kurdish-ulcerative-colitis-uc-patients
#8
Fariborz Bahrehmand, Asad Vaisi-Raygani, Amir Kiani, Homayoun Bashiri, Mahdi Zobeiri, Maryam Tanhapour, Tayebeh Pourmotabbed
BACKGROUND: Thiopurine methyl transferase (TPMT), a drug-metabolizing enzyme, catalyzes methylation and consequently, the metabolism of thiopurine compounds used for treatment of inflammatory bowel disease (IBD). Individuals who are homozygous recessive or have extremely low TPMT activity need to avoid thiopurines because of concern for significant leukopenia. The aim of this research was to determine TPMT phenotypes and genotypes in IBD patients to predict the risk of thiopurine toxicity before treatment...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28602470/further-evidence-for-ghb-naturally-occurring-in-common-non-alcoholic-beverages
#9
Simon P Elliott, Paolo Fais
GHB has been implicated in many cases of suspected surreptitious administration with the purpose of increasing victim vulnerability to sexual assault. Low amounts of endogenous (or naturally occurring) GHB, which do not reach pharmacologically active levels, have been detected in alcoholic and non-alcoholic beverages. Due to the continued requirement to obtain data on the presence of endogenous GHB in various beverage types, GHB concentrations were measured in a series of non-alcoholic beverages. Tonic water and lemon flavoured tonic water beverages were analysed at 0, 24 and 96h after the bottle opening using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) on an Agilent 6890/7000C Triple Quadrupole...
May 20, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28579487/intoxication-by-gamma-hydroxybutyrate-and-related-analogues-clinical-characteristics-and-comparison-between-pure-intoxication-and-that-combined-with-other-substances-of-abuse
#10
Òscar Miró, Miguel Galicia, Paul Dargan, Alison M Dines, Isabelle Giraudon, Fridtjof Heyerdahl, Knut E Hovda, Christopher Yates, David M Wood
OBJECTIVE: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse. METHOD: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes...
June 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28561068/gamma-hydroxybutyrate-increases-resting-state-limbic-perfusion-and-body-and-emotion-awareness-in-humans
#11
Oliver G Bosch, Fabrizio Esposito, Michael M Havranek, Dario Dornbierer, Robin von Rotz, Philipp Staempfli, Boris B Quednow, Erich Seifritz
Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations...
May 31, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28534145/alterations-in-gene-expression-after-gamma-hydroxybutyric-acid-intake-a-pilot-study
#12
Lena-Maria Mehling, Annika Spottke, Anna Heidbreder, Peter Young, Burkhard Madea, Cornelius Hess, Cornelius Courts
Gamma-hydroxybutyric acid (GHB) acts as an agonist of the GABAB receptor, where GHB induces a depressant effect in the central nervous system. Besides its therapeutic application, GHB is also used as a date rape drug. However, the detection of GHB ingestion proves to be difficult due to its narrow detection window. The aim of this pilot study was to assess differential gene expressions after GHB intake to identify potential biomarkers for the detection of GHB intake. To this aim, alteration in gene expression of ALDH5A1, AKR7A2, EREG, and PEA15 was investigated via quantitative PCR (qPCR)...
May 22, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28531770/treatment-consumption-and-treatment-re-enrollment-in-ghb-dependent-patients-in-the-netherlands
#13
Martijn S van Noorden, Ton Mol, Jeroen Wisselink, Wil Kuijpers, Boukje A G Dijkstra
BACKGROUND: The objective of this study was to assess treatment consumption and re-enrollment in treatment in patients with gamma-hydroxybutyrate (GHB)-dependence in Dutch Addiction Treatment Centers (ATCs) in comparison with other addictions. METHODS: A cohort-study using nationwide administrative data from regular Dutch ATCs associated with the Dutch National Alcohol and Drugs Information System (LADIS), covering an estimated 95% of ATCs. We selected in- and out-patients with alcohol, drug and/or behavioral addictions with a first treatment episode in 2008-2011 and consecutive treatments until 2013 (n=71,679)...
May 16, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28527983/when-a-death-apparently-associated-to-sexual-assault-is-instead-a-natural-death-due-to-idiopathic-hypereosinophilic-syndrome-the-importance-of-gamma-hydroxybutyric-acid-analysis-in-vitreous-humor
#14
Francesco Paolo Busardò, Francesca Portelli, Angelo Montana, Maria Concetta Rotolo, Simona Pichini, Emiliano Maresi
We here report a case involving a 21-year-old female, found dead in a central square of a city in the south of Italy. Initial evidences and circumstances were suggestive of a death associated with a sexual assault. Two peripheral blood and two vitreous humor samples were collected for the purpose of gamma-hydroxybutyric acid (GHB) testing from the dead body at two different post-mortem intervals (PMIs): approximately 2 (t0) and 36 (t1) hours. The obtained results showed that, between t0 and t1, there was an increase of GHB concentrations in peripheral blood and vitreous humor of 66...
May 2017: Legal Medicine
https://www.readbyqxmd.com/read/28480587/melatonin-successfully-rescues-hippocampal-bioenergetics-and-improves-cognitive-function-following-drug-intoxication-by-promoting-nrf2-are-signaling-activity
#15
Li-You Chen, Ting-Yi Renn, Wen-Chieh Liao, Fu-Der Mai, Ying-Jui Ho, George Hsiao, Ai-Wei Lee, Hung-Ming Chang
Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury...
May 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28460656/gamma-hydroxybutyrate-ghb-an-unusual-cause-of-high-anion-gap-metabolic-acidosis
#16
Laurence Carlier, Vincent Van Belleghem, Kathleen Croes, Frederik Hooft, Matthias Desmet, Olivier Heylen, Stijn Lambrecht, Stefaan Carlier
The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence. In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause. GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy...
May 2, 2017: CJEM
https://www.readbyqxmd.com/read/28457331/beneficial-effects-of-novel-cross-linked-hemoglobin-yq23-on-hemorrhagic-shock-in-rats-and-pigs
#17
Tao Li, Guangming Yang, Yu Zhu, Fei Chuen Tzang, Sze-Hang Lau, Sui-Yi Kwok, Bing L Wong, Liangming Liu
BACKGROUND: To overcome the problems of previously reported hemoglobin-based oxygen carriers, we developed a stabilized nonpolymeric cross-linked tetrameric hemoglobin solution (YQ23). The aims of this study were to investigate the oxygen carrying and releasing properties of this novel hemoglobin-based oxygen carrier and to determine whether it has beneficial effects for hemorrhagic shock. METHODS: Using a hemorrhagic shock model in Sprague-Dawley rats and mini-pigs, we tested the effects of infusing 0...
April 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28429067/neuronal-oscillations-and-synchronicity-associated-with-gamma-hydroxybutyrate-during-resting-state-in-healthy-male-volunteers
#18
Robin von Rotz, Michael Kometer, Dario Dornbierer, Jürg Gertsch, M Salomé Gachet, Franz X Vollenweider, Erich Seifritz, Oliver G Bosch, Boris B Quednow
RATIONALE: Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, an anesthetic agent, and a treatment for neuropsychiatric disorders. In previous electroencephalography (EEG) studies, GHB was shown to induce an electrophysiological pattern of "paradoxical EEG-behavioral dissociation" characterized by increased delta and theta oscillations usually associated with sleep during awake states. However, no detailed source localization of these alterations and no connectivity analyses have been performed yet...
April 20, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28425102/fatal-overdose-of-gamma-hydroxybutyrate-acid-after-ingestion-of-1-4-butanediol
#19
Erwan Le Garff, Vadim Mesli, Raphael Cornez, Christophe Demarly, Gilles Tournel, Valery Hédouin
We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was ingested by a young and "naïve" gamma-hydroxybutyrate (GHB) consumer during a party with the co-ingestion of alcohol, cannabis, and methylene-dioxy-methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB...
April 20, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28350147/-reaction-on-hypernatremia-caused-by-treatment-with-ghb-obtained-via-a-doctor-s-prescription
#20
M S van Noorden
No abstract text is available yet for this article.
2017: Tijdschrift Voor Psychiatrie
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