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https://www.readbyqxmd.com/read/28213850/gamma-hydroxybutyrate-ghb-content-in-hair-samples-correlates-negatively-with-age-in-succinic-semialdehyde-dehydrogenase-deficiency
#1
S S Johansen, X Wang, D Sejer Pedersen, P L Pearl, J-B Roullet, G R Ainslie, K R Vogel, K M Gibson
Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28186869/sedative-hypnotic-drug-withdrawal-syndrome-recognition-and-treatment
#2
Cynthia Santos, Ruben E Olmedo
Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents...
March 2017: Emergency Medicine Practice
https://www.readbyqxmd.com/read/28139340/ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-determination-of-ghb-ghb-glucuronide-in-plasma-and-cerebrospinal-fluid-of-narcoleptic-patients-under-sodium-oxybate-treatment
#3
Roberta Tittarelli, Simona Pichini, Daniel S Pedersen, Roberta Pacifici, Monica Moresco, Fabio Pizza, Francesco Paolo Busardò, Giuseppe Plazzi
Sodium oxybate (Xyrem(®)), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment...
January 25, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28125446/inpatient-gamma-hydroxybutyrate-detoxification-a-case-report-describing-day-to-day-therapeutic-management
#4
Louis von Theobald, Morgane Rousselet, Jennyfer Cholet, Hélène Debar, David Boels, Caroline Victorri-Vigneau, Marie Grall-Bronnec
BACKGROUND: Gamma-hydroxybutyrate (GHB) is a synthetic drug increasingly used by consumers of psychoactive substances. The sought after psychoactive effects of GHB have resulted in an increase in recreational use in Europe. GHB is considered to have a high dependence potential, and abrupt discontinuation after long-term use can result in a severe withdrawal syndrome. Despite a large number of publications related to GHB withdrawal and detoxification, to date, no evidence-based protocol or consensual international therapeutic guidelines are available (over and above the administration of benzodiazepines)...
January 25, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28119166/in-vitro-toxicological-evaluation-of-ncs-382-a-high-affinity-antagonist-of-%C3%AE-hydroxybutyrate-ghb-binding
#5
K R Vogel, G R Ainslie, J-B Roullet, A McConnell, K M Gibson
γ-Hydroxybutyric acid (GHB), a minor metabolite of the inhibitory neurotransmitter GABA, can accumulate to significant concentrations in the heritable disorder of GABA degradation, succinic semialdehyde dehydrogenase (SSADH) deficiency (SSADHD). Moreover, GHB may be employed in therapeutic settings (treatment of narcolepsy), as well as instances of illicit activity, including acquaintance sexual assault and the induction of euphoria. High-affinity binding sites for GHB in the brain have been identified, although the absolute identity of these receptors remains unclear...
January 22, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28111035/postmortem-concentrations-of-gamma-hydroxybutyrate-ghb-in-peripheral-blood-and-brain-tissue-differentiating-between-postmortem-formation-and-antemortem-intake
#6
Ragnar Thomsen, Brian Schou Rasmussen, Sys Stybe Johansen, Kristian Linnet
Gamma-hydroxybutyrate (GHB) is a recreational drug, a drug of abuse, as well as an endogenous molecule in mammals. The drug has become infamous as a tool for drug-facilitated sexual assault. GHB is found in low concentrations in living humans, while at postmortem the concentration of GHB rises due to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy...
January 5, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28110168/ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-uhplc-ms-ms-for-determination-of-ghb-precursors-and-metabolites-in-different-specimens-application-to-clinical-and-forensic-cases
#7
Francesco Paolo Busardò, Chrystalla Kyriakou, Emilia Marchei, Roberta Pacifici, Daniel Sejer Pedersen, Simona Pichini
Gamma-hydroxybutyric acid (GHB) acts as a precursor and metabolite of the inhibitory central nervous system (CNS) neurotransmitter gamma-aminobutyric acid (GABA). Sodium salt of GHB has been used as a medication for narcolepsy and alcohol withdrawal. Moreover, GHB and its precursor gamma-butyrolactone (GBL), are illegal recreational drugs of abuse. A procedure based on ultra-high-performance liquid chromatography tandem mass spectrometry has been developed and validated in plasma, urine, cerebrospinal fluid and hair for acute and chronic exposure to GHB and in seized preparations coming from black market...
January 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28107969/a-new-paper-based-analytical-device-for-detection-of-glucose-6-phosphate-dehydrogenase-deficiency
#8
Phuritat Kaewarsa, Wanida Laiwattanapaisal, Attakorn Palasuwan, Duangdao Palasuwan
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic haemolytic disorder. Most persons with G6PD deficiency are asymptomatic, but exposure to oxidant drugs, such as the anti-malarial drug primaquine, may induce haemolysis, which is commonly found in Asian countries. A reliable test is necessary for diagnosing the deficiency to prevent an acute haemolytic crisis. This study proposes a novel quantitative method to detect G6PD deficiency using paper-based analytical devices (G6PDD-PAD). Wax printing was utilized for fabricating circular reaction zone patterns in paper...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28098924/-hypernatremia-caused-by-treatment-with-ghb-obtained-via-a-doctor-s-prescription
#9
I M Rood, C G W Seijger, J A van Waarde, M M R de Maat, J C Verhave, M J Blans
In the last few years, gamma hydroxybutyric acid (GHB) has been used increasingly as a party drug; this has led to a marked increase in the number of requests for professional help with the treatment of GHB addiction. Pharmaceutical GHB (sodium oxybate, the sodium-salt of GHB), registered for cataplexia in narcolepsy patients, is used off-label to treat the withdrawal symptoms associated with GHB addiction. Pharmaceutical GHB has a high sodium load. In this report we present the cases of two patients who developed symptomatic hypernatremia following treatment with pharmaceutical GHB and who thereafter needed intensive care for the severe withdrawal symptoms that they experienced...
2017: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/28095676/radiosynthesis-and-evaluation-of-11-c-3-hydroxycyclopent-1-enecarboxylic-acid-as-potential-pet-ligand-for-the-high-affinity-%C3%AE-hydroxybutyric-acid-binding-sites
#10
Claus H Jensen, Hanne D Hansen, Tina Bay, Stine B Vogensen, Szabolcs Lehel, Louise Thiesen, Christoffer Bundgaard, Rasmus P Clausen, Gitte M Knudsen, Matthias M Herth, Petrine Wellendorph, Bente Frølund
γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28065555/stability-of-endogenous-ghb-in-vitreous-humor-vs-peripheral-blood-in-dead-bodies
#11
Francesco Paolo Busardò, Giulio Mannocchi, Raffaele Giorgetti, Manuela Pellegrini, Giovanni Baglio, Simona Zaami, Enrico Marinelli, Simona Pichini
For the first time, the stability of GHB was tested in post-mortem peripheral blood and vitreous humor samples, collected from 22 dead bodies at two different times: at the external body examination at the place of death and then during autopsy. An ad hoc method for the detection and quantification of GHB in vitreous humor by gas chromatography coupled to mass spectrometry (GC-MS) was developed and validated, with a good linearity between 0.1 and 50μg/mL (r(2)=0.991) and a precision and accuracy always better than 10% and an analytical recovery higher than 90%...
December 26, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28032215/a-driver-role-for-gaba-metabolism-in-controlling-stem-and-proliferative-cell-state-through-ghb-production-in-glioma
#12
Elias A El-Habr, Luiz G Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation...
December 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28018340/analysis-of-the-interaction-between-globular-head-modules-of-human-c1q-and-its-candidate-receptor-gc1qr
#13
Lina Pednekar, Ansar A Pathan, Basudev Paudyal, Anthony G Tsolaki, Anuvinder Kaur, Suhair M Abozaid, Lubna Kouser, Haseeb A Khan, Ellinor I Peerschke, Mohamed H Shamji, Gudrun Stenbeck, Berhane Ghebrehiwet, Uday Kishore
The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight into the pleiotropic functions of gC1qR, this study was undertaken to identify the gC1qR-binding site on the gC1q domain, using the recombinant ghA, ghB, and ghC modules and their substitution mutants...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28004314/pharmacological-treatment-in-%C3%AE-hydroxybutyrate-ghb-and-%C3%AE-butyrolactone-gbl-dependence-detoxification-and-relapse-prevention
#14
REVIEW
Rama M Kamal, Martijn S van Noorden, Wim Wannet, Harmen Beurmanjer, Boukje A G Dijkstra, Arnt Schellekens
The misuse of γ-hydroxybutyrate (GHB) for recreational purposes has resulted in an increase in GHB-related problems such as intoxications, dependence and withdrawal in several countries in Europe, Australia and the US over the last decade. However, prevalence rates of misuse of GHB and its precursor, γ-butyrolactone (GBL), are still relatively low. In this qualitative review paper, after a short introduction on the pharmacology of GHB/GBL, followed by a summary of the epidemiology of GHB abuse, an overview of GHB dependence syndrome and GHB/GBL withdrawal syndrome is provided...
January 2017: CNS Drugs
https://www.readbyqxmd.com/read/27936427/an-observed-rise-in-%C3%AE-hydroxybutyrate-associated-deaths-in-london-evidence-to-suggest-a-possible-link-with-concomitant-rise-in-chemsex
#15
Joanna Hockenhull, Kevin G Murphy, Sue Paterson
BACKGROUND: Gamma-hydroxybutyrate (GHB) is the drug most linked to acute harm out of those used in chemsex, the incidence of which is reported to be increasing. However, there have been few systematic studies of the harms associated with GHB use. We investigated GHB-associated deaths from London coroners' jurisdictions between 2011 and 2015. METHODS: Blood and urine samples were collected by pathologists and submitted for toxicological analysis at the request of coroners...
January 2017: Forensic Science International
https://www.readbyqxmd.com/read/27923198/detoxification-with-titration-and-tapering-in-gamma-hydroxybutyrate-ghb-dependent-patients-the-dutch-ghb-monitor-project
#16
Boukje A G Dijkstra, Rama Kamal, Martijn S van Noorden, Hein de Haan, Anton J M Loonen, Cor A J De Jong
BACKGROUND AND AIMS: Gamma-hydroxybutyrate (GHB) detoxification procedures have been insufficiently studied for effectiveness and safety. Based on case reports, benzodiazepines are generally regarded as first-choice agents in GHB detoxification. Detoxification by titration and tapering (DeTiTap) with pharmaceutical GHB in an open-label consecutive case series of 23 GHB-dependent patients showed to be feasible, effective and safe. This study further explored the feasibility, effectiveness and safety of this detoxification procedure in a large group of patients...
January 1, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27891231/a-pharmacokinetic-evaluation-and-metabolite-identification-of-the-ghb-receptor-antagonist-ncs-382-in-mouse-informs-novel-therapeutic-strategies-for-the-treatment-of-ghb-intoxication
#17
Garrett R Ainslie, K Michael Gibson, Kara R Vogel
Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27845883/salivary-flow-rate-buffer-capacity-and-urea-concentration-in-adolescents-with-type-1-diabetes-mellitus
#18
Ivana Maria Saes Busato, Carlos Cesar De Antoni, Thiago Calcagnotto, Sérgio Aparecido Ignácio, Luciana Reis Azevedo-Alanis
BACKGROUND: The objective of the study was to analyze salivary flow rate, urea concentration, and buffer capacity in adolescents with type 1 diabetes mellitus (type 1 DM) in two different stages. METHODS: This study was performed on adolescents (14-19 years), allocated between two groups: type 1 DM group comprised 32 adolescents with type 1 DM, and non-type 1 DM group comprised 32 nondiabetics. The adolescents in type 1 DM group were evaluated at a baseline (T0) and after 15 months (T1), and those in non-type 1 DM group were only evaluated at T0...
December 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/27829545/a-novel-formula-sang-tong-jian-improves-glycometabolism-and-ameliorates-insulin-resistance-by-activating-pi3k-akt-pathway-in-type-2-diabetic-kkay-mice
#19
Meiyu Kuai, Yu Li, Xin Sun, Zhi Ma, Chao Lin, Yi Jing, Ying Lu, Qi Chen, Xiang Wu, Xueyun Kong, Huimin Bian
AIMS: Sang-Tong-Jian (STJ), a novel formula composed of flavonoids and alkaloids derived from mulberry leaf, has been found to reduce blood glucose levels in rats with type 2 diabetes mellitus (T2DM) in our previous studies. However, the precise mechanisms remain unknown. Insulin resistance is the main characteristic of T2DM, which may be due to impairment of the PI3K/AKT signaling pathway. In this study, we investigated the effects of STJ on glycometabolism and insulin resistance in KKAy mice...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27807735/-treatment-of-fibromyalgia-syndrome-with-gamma-hydroxybutyrate-a%C3%A2-randomized-controlled-study
#20
E Reuter, S Tafelski, K Thieme, C West, U Haase, L Beck, M Schäfer, C Spies
BACKGROUND: The etiology of fibromyalgia syndrome is not yet fully understood. Current hypotheses suggest a potential role of gamma-hydroxybutyrate (GHB) in influencing endocrinological abnormalities in patients with fibromyalgia. OBJECTIVE: The aim of the study was to investigate whether low dose GHB as a growth-hormone releasing substance reduces pain intensity and improves depressive mood, physical impairment and sleep quality in outpatients with fibromyalgia...
November 2, 2016: Der Schmerz
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