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1

Gamma Hydroxybutyric Acid (GHB) Intoxication  

Microsoft Academic Search

Gamma-aminobutyric acid (GABA) was discovered as the predominant inhibitory central nervous sys- tem (CNS) neurotransmitter in 1956. This prompted a search for a GABA analog that would cross the blood-brain barrier for possible therapeutic use. During this search, gamma-hydroxybutyric acid (GHB) was found in the brain and subsequently synthesized in the laboratory in 1964. 1,2 Since its discovery, GHB has

Phillip E. Mason; William P. Kerns II

2002-01-01

2

Gamma-Hydroxybutyrate (GHB)  

MedlinePLUS

... fX rush Organic quaalude Oxy-sleep Poor man's heroin Remforce Revivarant Salty water Scoop Soap Somatomax PM Somsanit Vita-G Water Wolfies Zonked Should I be worried about GHB? Yes. Because GHB has no color or smell, it can easily be slipped into drinks and food. Even a very small amount of GHB may ...

3

Gamma hydroxybutyric acid (GHB) intoxication.  

PubMed

Gamma hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. In the past decade it has become very popular as a dietary supplement and recreational drug. Acute overdose leads to profound alteration of mental status and variable amounts of respiratory depression. With proper management, most patients recover fully within six hours. However, respiratory arrest and death have been reported in severe GHB intoxication. In addition to acute overdose, there is a GHB withdrawal syndrome that is similar to sedative/hypnotic and ethanol withdrawal. Recently several congeners of GHB, gamma butyrolactone and 1,4-butanediol, have emerged as drugs of abuse and show toxidromes similar to GHB. Emergency physicians should be familiar with the presentation and management of GHB-related emergencies. PMID:12093716

Mason, Phillip E; Kerns, William P

2002-07-01

4

Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review  

Microsoft Academic Search

Aim: To examine the clinical course of gamma-hydroxybutyrate (GHB) withdrawal and generate management guidelines. Design: Review and analysis of all published reports of GHB or GHB precursor withdrawal identified from electronic searches. Findings: In total, 38 cases of GHB (n=28) or GHB precursor (n=10) withdrawal were identified, 36 of which were from the US. A rapidly deteriorating course into delirium

Michael McDonough; Noel Kennedy; Anthony Glasper; Jenny Bearn

2004-01-01

5

Metabolic GHB precursor succinate binds to gamma-hydroxybutyrate receptors: characterization of human basal ganglia areas nucleus accumbens and globus pallidus.  

PubMed

Binding of the metabolic gamma-hydroxybutyrate (GHB) precursor succinate to NCS-382-sensitive [3H]GHB-labeled sites in crude synaptosomal or purified synaptic membrane fractions prepared from the human nucleus accumbens (NA), globus pallidus (GP) and rat forebrain has been shown. This site can be characterized by binding of ethyl hemisuccinate and gap-junction blockers, including carbenoxolone hemisuccinate and beta-GRA. There was no significant binding interaction between GABAB receptor ligands (CGP 55845, (R)-baclofen) and these [3H]GHB-labeled sites. GHB, NCS-382 and succinate binding profile of [3H]GHB-labeled sites in rat forebrain, human NA or GP synaptic membranes were similar. The synaptic fraction isolated from the rat forebrain was characterized by GHB binding inhibition constants: Ki,NCS-382 = 1.2 +/- 0.2 microM, Ki,GHB = 1.6 +/- 0.3 microM and Ki,SUCCINATE = 212 +/- 66 microM. In crude membranes containing mainly extrasynaptic membranes, distinct GHB and GABAB receptor sites were found in the NA. By contrast, extrasynaptic GABAB receptor sites of rat forebrain and GP were GHB- and succinate-sensitive, respectively. The heterogeneity of GABAB sites found in native membranes indicates GABAB receptor-dependent differences in GHB action. Based on these findings, we suggest that succinate (and possibly drugs available as succinate salt derivatives) can mimic some of the actions of GHB. PMID:16673403

Molnár, Tünde; Fekete, Erzsébet Kútiné; Kardos, Julianna; Simon-Trompler, Edit; Palkovits, Miklós; Emri, Zsuzsa

2006-07-01

6

Identification and quantitation of gamma-hydroxybutyrate (NaGHB) by nuclear magnetic resonance spectroscopy.  

PubMed

The most common means of identification of gamma-hydroxybutyrate (NaGHB) involves using Fourier transform infrared spectroscopy (FTIR) or gas chromatography-mass spectrometry (GC-MS) of a suitable derivative. However, these methods may be complicated by possible shifts in chemical equilibrium between gamma-hydroxybutyric acid (GHB), GHB salts and the precursor lactone, gamma-butyrolactone (GBL). This paper addresses the technique of proton and carbon nuclear magnetic resonance spectroscopy (1H and 13C NMR) for the direct and accurate identification of GHB and GBL. The application of 1H NMR for GHB quantitation is also discussed. PMID:12664985

Chew, Shirley L; Meyers, John A

2003-03-01

7

Behavioral effects and pharmacokinetics of gamma-hydroxybutyrate (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons  

PubMed Central

Rationale Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions. Objectives The first study compared the behavioral effects of GBL (32?240 mg/kg) and 1,4-BD (32?240 mg/kg) with each other and to effects previously reported for GHB (32?420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD. Methods Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD. Results Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration. Conclusions GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB.

Goodwin, A. K.; Brown, P. R.; Jansen, E. E. W.; Jakobs, C.; Gibson, K. M.; Weerts, E. M.

2009-01-01

8

Preference for gamma-hydroxybutyrate (GHB) in current users.  

PubMed

Gamma-hydroxybutyrate (GHB) is a drug with significant abuse potential. The present study aimed to assess the relative value of escalating doses of GHB to current GHB users via the Multiple Choice Procedure (MCP), and to validate that the dose rated highest with the MCP would be self-administered at a greater rate than placebo. Participants were 5 current GHB users who were not currently trying to stop using GHB. To examine the value of escalating doses of GHB, the following doses of GHB were used: 0 (placebo), 12.5, 25, 37.5, and 50 mg/kg. Participants typically assigned higher doses of GHB had higher crossover points on the MCP. During choice sessions, participants made repeated choices between administering GHB, placebo or nothing. All participants selected GHB exclusively (5 out of 5 instances) except for one participant who selected GHB on 4 out of 5 instances, thus 96% (i.e., 24/25) of choices were for active GHB. Based on these data, GHB appears likely to function as a dose-dependent reinforcer for humans based on our sample. PMID:22693361

Roll, John M; Newton, Thomas; Chudzynski, Joy; Cameron, Jennifer M; McPherson, Sterling; Fong, Timothy; Torrington, Matt

2012-05-01

9

Preference for Gamma-Hydroxybutyrate (GHB) in Current Users  

PubMed Central

Gamma-hydroxybutyrate (GHB) is a drug with significant abuse potential. The present study aimed to assess the relative value of escalating doses of GHB to current GHB users via the Multiple Choice Procedure (MCP), and to validate that the dose rated highest with the MCP would be self-administered at a greater rate than placebo. Participants were 5 current GHB users who were not currently trying to stop using GHB. To examine the value of escalating doses of GHB, the following doses of GHB were used: 0 (placebo), 12.5, 25, 37.5, and 50 mg/kg. Participants typically assigned higher doses of GHB had higher crossover points on the MCP. During choice sessions, participants made repeated choices between administering GHB, placebo or nothing. All participants selected GHB exclusively (5 out of 5 instances) except for one participant who selected GHB on 4 out of 5 instances, thus 96% (i.e., 24/25) of choices were for active GHB. Based on these data, GHB appears likely to function as a dose-dependent reinforcer for humans based on our sample.

Roll, John M; Newton, Thomas; Chudzynski, Joy; Cameron, Jennifer M; McPherson, Sterling; Fong, Timothy; Torrington, Matt

2012-01-01

10

Repeated administration of gamma-hydroxybutyric acid (GHB) to mice: assessment of the sedative and rewarding effects of GHB.  

PubMed

Because of the sedative/hypnotic and euphoric effects of gamma-hydroxybutyric acid (GHB), the recreational use of the drug has increased significantly. In the current study we investigated the sedative and rewarding effects of GHB in Swiss Webster mice. Although the acute administration of GHB (200 mg/kg) caused marked hypolocomotion, repeated administration of the drug for 6 or 14 days produced tolerance to this effect. In addition, the administration of GHB 300 mg/kg to naive mice caused catalepsy, which dissipated in mice pre-exposed to GHB (200 mg/kg). Consequently, after repeated treatment with GHB, tolerance developed to both the hypolocomotion and cataleptic effects of the drug. The administration of GHB or its precursor gamma-butyrolactone for 14 days increased the striatal content of dopamine. The sedative effects of GHB may be due to hypodopaminergic activity from inhibition of dopamine release and a subsequent increase in the intraneuronal dopamine level. The rewarding effect of GHB was assessed in the conditioned place preference paradigm. Mice treated repeatedly with 250 mg/kg for 7 days developed conditioned preference for the GHB-paired compartment of the cage, suggesting that the GHB cue is rewarding. The development of tolerance to the sedative effects of GHB coupled with the rewarding properties of the drug support the abuse potential of GHB. Further studies are necessary to determine the mechanism underlying the development of tolerance to GHB and the rewarding effect of the drug. PMID:12105120

Itzhak, Yossef; Ali, Syed F

2002-06-01

11

Reliable, Sensitive, Rapid and Quantitative Enzyme-Based Assay for Gamma-Hydroxybutyric Acid (GHB)  

Microsoft Academic Search

ABSTRACT: Several assays for gamma-hydroxybutyrate (4-hydroxybutyrate, GHB) have been developed based on the enzyme gamma- hydroxybutyrate,dehydrogenase,(GHB-DH). Enzymatic oxidation,of GHB by NAD, is coupled,to diaphorase-mediated reduction of pro-dye to yield colored product. GHB-DH from Ralstonia eutropha,was cloned and expressed,as a stable fusion protein easily purified by affinity chro- matography. Quantitative initial velocity and endpoint versions of the assay in solution are

Dawn T. Bravo; David O. Harris; Stanley M. Parsons

2004-01-01

12

[Gamma-hydroxybutyric acid (GHB) dependence and the GHB withdrawal syndrome: diagnosis and treatment].  

PubMed

Gamma-hydroxybutyric acid (GHB) is a neurotransmitter that occurs naturally in the brain and is increasingly being used as a 'party drug' because of its relaxing and euphoria-inducing effects. GHB has a limited medical use in the treatment of narcolepsy. GHB-intoxications occur often in non-medical use, and generally result in a coma of short duration. GHB use several times a day can lead to tolerance and dependence. After sudden cessation or reduction of intensive GHB use, a severe withdrawal syndrome may occur with symptoms varying from tremor, anxiety and agitation to autonomic instability, hallucinations and delirium. Treatment of the GHB withdrawal syndrome consists of supportive care and benzodiazepines, often in high doses. The controlled detoxification of GHB using pharmaceutical GHB in an adjusted dose is currently being investigated in the Netherlands. There is no literature concerning the treatment of patients following GHB intoxication or after detoxification. PMID:21040601

van Noorden, Martijn S; Kamal, Rama; de Jong, Cor A J; Vergouwen, A C M Ton; Zitman, Frans G

2010-01-01

13

Gamma Hydroxybutyrate (GHB) and Gamma Butyrolactone (GBL) Withdrawal: Five Case Studies  

Microsoft Academic Search

There is little medical information available about gamma- hydroxybutyrate (GHB) or gamma-butyrolactone (GBL) dependence or withdrawal. In this study the authors treated and reviewed multiple cases of GHB and GBL withdrawal in high-dose users. Five patients during nine hospitalizations were treated for GHB or GBL withdrawal. The authors describe a spectrum of GHB or GBL withdrawal from mild to severe

Charles H. McDaniel; Karen A. Miotto

2001-01-01

14

Gamma hydroxybutyric acid (GHB) concentrations in humans and factors affecting endogenous production  

Microsoft Academic Search

The endogenous nature of the drug of abuse gamma hydroxybutyric acid (GHB) has caused various interpretative problems for toxicologists. In order to obtain data for the presence of endogenous GHB in humans and to investigate any factors that may affect this, a volunteer study was undertaken. The GHB concentrations in 119 urine specimens from GHB-free subjects and 25 urine specimens

Simon P Elliott

2003-01-01

15

Effects of gamma-hydroxybutyric acid (GHB) in opioid-dependent patients  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB) is a GABA metabolite used clinically for sleep induction. The abuse liability of GHB is controversial. As part of a study of the effect of GHB pretreatment on naloxone-precipitated opiate withdrawal, eight opioid-stabilized subjects received a balanced, randomized, double-blind sequence of oral placebo, GHB 15 mg\\/kg and 30 mg\\/kg. GHB had no consistent physiological effects. After GHB

Marc I. Rosen; H. Rowland Pearsall; Scott W. Woods; Thomas R. Kosten

1997-01-01

16

Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem ®): Differences in characteristics and misuse  

Microsoft Academic Search

There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical sodium oxybate. Gamma-hydroxybutyrate sodium and sodium oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem® (sodium oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes.

Lawrence P. Carter; Daniel Pardi; Jane Gorsline; Roland R. Griffiths

2009-01-01

17

GHB-induced delirium: a case report and review of the literature of gamma hydroxybutyric acid.  

PubMed

We describe what we believe is the first psychiatric hospitalization due to GHB-induced delirium reported in the medical literature. We examine the use of the substance gamma hydroxybutyric acid (GHB) and describe the clinical findings in a patient who presented to an acute inpatient psychiatric unit with a chief complaint of feeling suicidal and a 1-year history of GHB use. A review of the literature and GHB's availability through the Internet are discussed. PMID:9513637

Hernandez, M; McDaniel, C H; Costanza, C D; Hernandez, O J

1998-02-01

18

Involvement of gamma-hydroxybutyrate (GHB) and GABA-B receptors in the acute behavioral effects of GHB in baboons  

Microsoft Academic Search

Rationale: Gamma-hydroxybutyrate (GHB) is used for the treatment of narcolepsy, but it is also a drug of abuse. The behavioral pharmacology of GHB is not well defined. Objectives: The current study was conducted to characterize the behavioral effects of a range of GHB doses in baboons (N=4) and to evaluate whether a GABA-B re- ceptor antagonist and a GHB receptor

Amy K. Goodwin; Wolfgang Froestl; Elise M. Weerts

2005-01-01

19

Gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) withdrawal: five case studies.  

PubMed

There is little medical information available about gamma-hydroxybutyrate (GHB) or gamma-butyrolactone (GBL) dependence or withdrawal. In this study the authors treated and reviewed multiple cases of GHB and GBL withdrawal in high-dose users. Five patients during nine hospitalizations were treated for GHB or GBL withdrawal. The authors describe a spectrum of GHB or GBL withdrawal from mild to severe and discuss medications used for treatment. They conclude that patients with GHB or GBL withdrawal may present with agitated psychosis, delirium, and autonomic instability. In this sample, relapse to GHB or GBL use occurred soon after treatment of withdrawal. PMID:11476261

McDaniel, C H; Miotto, K A

2001-01-01

20

Gamma Hydroxybutyric Acid (GHB) for the Treatment of Alcohol Dependence: A Review  

PubMed Central

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter ?-aminobutyric acid. Clinical trials have demonstrated that 50–100 mg/kg of GHB fractioned into three or six daily doses is able to suppress alcohol withdrawal symptoms and facilitates the maintenance of abstinence from alcohol. These studies have also shown that GHB craving episodes are a very limited phenomenon (about 10–15%). Thus, physicians with access should consider the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction.

Caputo, Fabio; Vignoli, Teo; Maremmani, Icro; Bernardi, Mauro; Zoli, Giorgio

2009-01-01

21

GC–MS determination of gamma-hydroxybutyric acid (GHB) in blood  

Microsoft Academic Search

A sensitive and specific gas chromatography–mass spectrometer (GC–MS) method using selective ion monitoring (SIM) has been developed for the quantification of gamma-hydroxybutyric acid (GHB) in blood. This method uses liquid–liquid extraction and disilyl-derivatization, without conversion to the gamma-butyrolactone (GBL), followed by GC–MS analysis using GHB-d6 as the internal standard. The method was linear from 0.1 to 20mg\\/dl, and the limit

Albert A. Elian

2001-01-01

22

Determination of endogenous gamma-hydroxybutyric acid (GHB) levels in antemortem urine and blood  

Microsoft Academic Search

Gamma-hydroxybutyric acid’s (GHB’s) natural presence in the body has made the interpretation of its levels a challenging task for the forensic toxicologist. This study was designed to measure endogenous GHB levels in antemortem urine and blood samples. The range detected in urine was from 34 to 575?g\\/dl and in blood from 17 to 151?g\\/dl. The results indicate that the concentration

Albert A. Elian

2002-01-01

23

Effects of gamma-hydroxybutyric acid (GHB) in opioid-dependent patients.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a GABA metabolite used clinically for sleep induction. The abuse liability of GHB is controversial. As part of a study of the effect of GHB pretreatment on naloxone-precipitated opiate withdrawal, eight opioid-stabilized subjects received a balanced, randomized, double-blind sequence of oral placebo, GHB 15 mg/kg and 30 mg/kg. GHB had no consistent physiological effects. After GHB and prior to naloxone, subjects rated "sluggish," "spaced," "carefree," and "good-mood" higher after GHB 30 mg/kg than after placebo. Subjects identified the 30 mg/kg dose as most similar to placebo (n = 3), benzodiazepine (n = 2), opiate (n = 2), and alcohol (n = 1). PMID:9258859

Rosen, M I; Pearsall, H R; Woods, S W; Kosten, T R

1997-01-01

24

Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem): differences in characteristics and misuse.  

PubMed

There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical sodium oxybate. Gamma-hydroxybutyrate sodium and sodium oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem (sodium oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes. This review highlights important differences between illicit GHB and sodium oxybate with regard to their relative abuse liability, which includes the likelihood and consequences of abuse. Data are summarized from the scientific literature; from national surveillance systems in the U.S., Europe, and Australia (for illicit GHB); and from clinical trials and post-marketing surveillance with sodium oxybate (Xyrem). In the U.S., the prevalence of illicit GHB use, abuse, intoxication, and overdose has declined from 2000, the year that GHB was scheduled, to the present and is lower than that of most other licit and illicit drugs. Abuse and misuse of the pharmaceutical product, sodium oxybate, has been rare over the 5 years since its introduction to the market, which is likely due in part to the risk management program associated with this product. Differences in the accessibility, purity, dosing, and misuse of illicit GHB and sodium oxybate suggest that risks associated with illicit GHB are greater than those associated with the pharmaceutical product sodium oxybate. PMID:19493637

Carter, Lawrence P; Pardi, Daniel; Gorsline, Jane; Griffiths, Roland R

2009-09-01

25

Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse  

PubMed Central

There are distinct differences in the accessibility, purity, dosing, and misuse associated with illicit gamma-hydroxybutyrate (GHB) compared to pharmaceutical sodium oxybate. Gamma-hydroxybutyrate sodium and sodium oxybate are the chemical and drug names, respectively, for the pharmaceutical product Xyrem® (sodium oxybate) oral solution. However, the acronym GHB is also used to refer to illicit formulations that are used for non-medical purposes. This review highlights important differences between illicit GHB and sodium oxybate with regard to their relative abuse liability, which includes the likelihood and consequences of abuse. Data are summarized from the scientific literature; from national surveillance systems in the U.S., Europe, and Australia (for illicit GHB); and from clinical trials and post-marketing surveillance with sodium oxybate (Xyrem). In the U.S., the prevalence of illicit GHB use, abuse, intoxication, and overdose has declined from 2000, the year that GHB was scheduled, to the present and is lower than that of most other licit and illicit drugs. Abuse and misuse of the pharmaceutical product, sodium oxybate, has been rare over the 5 years since its introduction to the market, which is likely due in part to the risk management program associated with this product. Differences in the accessibility, purity, dosing, and misuse of illicit GHB and sodium oxybate suggest that risks associated with illicit GHB are greater than those associated with the pharmaceutical product sodium oxybate.

Carter, Lawrence P.; Pardi, Daniel; Gorsline, Jane; Griffiths, Roland R.

2009-01-01

26

Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.  

PubMed

Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB-GLUC and a deuterated analogue for chromatography were synthesized. Liquid chromatography and tandem mass spectrometry were used for targeted analysis in anonymous clinical urine samples (n = 50). GHB-GLUC was found in concentrations ranging from 0.11 to 5.0 µg/mL (mean: 1.3 ± 1.2 µg/mL). Thus far, this is the first report of a GHB glucuronide detected in biological samples. Given that glucuronides generally have longer half-life values than their corresponding free drugs, GHB-GLUC should theoretically be a biomarker of GHB intoxication. It is also proposed that the hitherto unexplained reports of elevated GHB concentrations in some biological samples, which has caused the setting of a relatively high cutoff value (10 µg/mL), represent total GHB measurements (sum of free GHB and actively chemically hydrolyzed GHB-GLUC). To address these challenges, the present study must be followed by comprehensive pharmacokinetic and stability studies after the controlled administration of GHB. PMID:23612681

Petersen, Ida Nymann; Tortzen, Christian; Kristensen, Jesper Langgaard; Pedersen, Daniel Sejer; Breindahl, Torben

2013-06-01

27

[Variety of symptoms after drug use of gamma-hydroxybutyric acid (GHB)].  

PubMed

Gamma-hydroxybutyric acid (GHB, "liquid ecstasy") and its legal prodrugs gamma-butyrolactone and 1,4-butanediol are gaining importance as recreational drugs in Germany. Because of the wide availability of GHB and its prodrugs physicians are increasingly being confronted with cases of intoxication. The effect of GHB intoxication is comparable with those of alcohol and/or benzodiazepines. Likewise, symptoms of withdrawal may occur. In this review, we summarise current data regarding the history, pharmacodynamics and pharmacokinetics of the drug as well as the relevant symptoms of intoxication or withdrawal as they pertain to neurology and psychiatry. PMID:21154180

Galldiks, N; Kadow, I; Bechdolf, A; Fink, G R; Klosterkötter, J; Kuhn, J

2011-01-01

28

The presence of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic and non-alcoholic beverages.  

PubMed

Gamma-hydroxybutyric acid (GHB) and its precursor gamma-butyrolactone (GBL) are regularly implicated in instances of surreptitious drug administration, particularly in beverages (so-called "spiked drinks"). In order to assist in the interpretation of cases where analysis of the actual beverage is required, over 50 beverages purchased in the UK were analysed for the presence of GHB and GBL. It was found that naturally occurring GHB and GBL were detected in those beverages involving the fermentation of white and particularly red grapes. No GHB or GBL was detected in other drinks such as beer, juice, spirits or liqueurs. GHB/GBL was detected in red wine vermouth (8.2 mg/L), sherry (9.7 mg/L), port (GBL), red wine (4.1-21.4 mg/L) and white wine (<3-9.6 mg/L). The presence of GHB/GBL did not appear to be influenced by the alcohol content or the pH of the beverage. In addition, the concentration in wines did not appear to be related to the geographical origin of the grape type. This is believed to be the first published data concerning the endogenous presence of GHB and GBL in the beverages described. PMID:15939164

Elliott, Simon; Burgess, Victoria

2005-07-16

29

Use, function, and subjective experiences of gamma-hydroxybutyrate (GHB)  

Microsoft Academic Search

Self-reported use of ?-hydroxybutyrate (GHB) among clubbers has increased over the last decade, and is often reported in the scientific literature in association with negative events such as amnesia, overdose, and use in drug facilitated sexual assault. However, there has been relatively little work investigating the phenomenology of GHB intoxication, and the reasons underlying use. In this study, 189 individuals

Harry R. Sumnall; Kerry Woolfall; Sara Edwards; Jon C. Cole; Caryl M. Beynon

2008-01-01

30

Are the effects of gamma-hydroxybutyrate (GHB) treatment partly physiological in alcohol dependence?  

PubMed

It has been hypothesized that the therapeutic effects of Gamma-hydroxybutyrate (GHB) in alcohol dependence could be related to ethanol-mimicking action of the drug and that GHB could reduce alcohol craving, intake and withdrawal by acting as a "substitute" of the alcohol in the central nervous system. Nevertheless, alcohol being the strongest trigger of craving and intake, it is difficult to ascribe reduction of craving and intake to ethanol-mimicking activity of GHB. I have recently proposed that alcohol/substance dependence could result from a GHB-deficiency-related dysphoric syndrome in which alcohol/substances would be sought to "substitute" for insufficient GHB effect. GHB is the sole identified naturally occurring gamma-aminobutyric acid B (GABA (B)) receptor agonist. Here, I propose that exogenous GHB might in fact "substitute" for deficient endogeneous GHB and represent true substitutive treatment for GHB-deficiency. And that baclofen and GHB could both compensate for deficient effect of the physiological GABA (B) receptor agonist(s). PMID:18293241

Ameisen, Olivier

2008-01-01

31

A Web-Based Study of Gamma Hydroxybutyrate (GHB): Patterns, Experiences, and Functions of Use  

PubMed Central

GHB (gamma hydroxybutyrate) was developed as a general anesthetic. Due to dosing difficulty and side effects, regular use was discontinued. Medical uses include treating sleep and alcohol disorders. In the 1990s, it was promoted as a supplement and taken to improve mood and sex. GHB and its analogs (gamma butyrolactone and butanediol) were widely available until federal regulations were put into effect with mounting evidence of adverse events. This survey (N = 61) study was conducted to assess patterns, experiences, and functions of use. Much of what is understood regarding GHB treatment is based on hospital case studies for overdose and withdrawal. Not enough is known about prevention, reducing use and associated problems, or relapse. We know little about specific drug effect expectancies, triggers, coping skills, and consequences of use (positive/negative). While the drug treatment literature has a wealth of information to draw upon, GHB-specific information may greatly assist relapse prevention.

Stein, LAR; Lebeau, Rebecca; Clair, Mary; Martin, Rosemarie; Bryant, Monte; Storti, Susan; Monti, Peter

2011-01-01

32

Gamma-Hydroxybutyric Acid (GHB) Withdrawal: A Case Report  

Microsoft Academic Search

GHB is an increasingly popular drug of abuse that can be associated in select cases with growing dependence and a severe withdrawal syndrome. While benzodiazepines are recommended for treatment of the withdrawal syndrome, some cases have been described as benzodiazepine-resistant. The authors describe treatment of such a case, which was unsuccessfully treated initially with benzodiazepines, then successfully treated with adjuvant

W. R. Murray Bennett; Lawrence G. Wilson; Peter P. Roy-Byrne

2007-01-01

33

Intravenous self-administration of gamma-hydroxybutyrate (GHB) in baboons  

PubMed Central

Background Abuse of gamma-hydroxybutyrate (GHB) poses a public health concern. In previous studies, intravenous (IV) self-administration of GHB doses up to 10 mg/kg was not maintained in non-human primates under limited-access conditions, which was inconsistent with the usual good correspondence between drugs abused by humans and those self-injected by laboratory animals. Methods Self-administration of GHB was studied in 10 baboons using procedures standard for our laboratory to assess drug abuse liability. Each self-injection depended on completion of 120 or 160 lever responses. Sessions ran continuously; a 3-h timeout limited the number of injections per 24 h to 8. Self-injection was established at 6–8 injections/day with cocaine (0.32 mg/kg/injection) prior to substitution of each GHB dose (3.2–178 mg/kg/injection) or vehicle for 15 days. Food pellets were available 24 h/day. Results GHB maintained significantly greater numbers of injections when compared to vehicle in 6 of the 9 baboons that completed GHB evaluations that included 32 mg/kg/injection or higher. The baboons that self-administered GHB at high rates were ones for which GHB was the first drug each had tested under the 24-hr/day cocaine baseline procedure. Self-injection of the highest doses of GHB decreased food-maintained responding. Conclusions High-dose GHB can function as a reinforcer in non-human primates under 24-h access, but self-administration history may be important. The findings are consistent with the demonstrated abuse liability of GHB in humans, and remove GHB as an exception to the typical good correspondence between those drugs abused by humans and those self-administered by nonhuman primates.

Goodwin, Amy K.; Kaminski, Barbara J.; Griffiths, Roland R.; Ator, Nancy A.; Weerts, Elise M.

2010-01-01

34

Symptoms and signs in interpreting Gamma-hydroxybutyrate (GHB) intoxication - an explorative study  

PubMed Central

Background Acute poisoning with gamma-hydroxybutyrate (GHB) has been a serious medical and social problem in different parts of the world including Sweden. GHB is a drug of abuse which acts primarily as central nervous system (CNS) depressants. GHB has serious toxicity, although many young users do not recognise GHB as a dangerous drug. The aim of this pilot study was to explore how symptoms with risk of failure in vital functions would be valued among professionals that encounter GHB intoxication in the emergency phase. Methods A web-based survey focusing on the assessment of vital clinical signs for possible GHB intoxication using a numeric scale was carried out during April and May 2011. The participants, n 105, are all professionals who encounter GHB intoxicated in the emergency phase, but have different levels of training in GHB intoxication, mainly Registered Nurses (RNs) in southwest Sweden, employed in pre-hospital or emergency departments at somatic and most psychiatric health care facilities, as well as police officers who in their work come into contact with drug users. Responses in the survey were scored according to risk of GHB intoxication with serious failure of vital functions. The score value was then referred to a so-called evidence based priority (EBP) scale and analysed using descriptive statistics and Fisher's exact test. Results Cardiac arrest, coma, hypoxia, general convulsions, slow respiratory and heart rate and pale skin are symptoms with the highest risk of serious failure in vital physical functions and were predominantly recognised as such. Conclusion Despite the professionals' different levels of training in GHB intoxication, all of them were relatively well aware of and in accordance regarding the most risky symptoms. The interpretation score for the less risky symptoms and signs of GHB intoxication varied depending on their degree of training. The results should be viewed cautiously, as the size of the professional groups and their general knowledge of critical symptoms of GHB poisoning varied.

2014-01-01

35

Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication.  

PubMed

The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication. PMID:7782758

Ferrara, S D; Tedeschi, L; Frison, G; Rossi, A

1995-05-01

36

Effects of combining ethanol (EtOH) with gamma-hydroxybutyrate (GHB) on the discriminative stimulus, locomotor, and motor-impairing functions of GHB in mice  

Microsoft Academic Search

Rationale  Gamma-hydroxybutyrate (GHB) is a drug of abuse that is often coabused with ethanol (EtOH) and has been implicated as a date\\u000a rape agent in conjunction with EtOH. Much information is lacking regarding the manner in which GHB interacts with EtOH.\\u000a \\u000a \\u000a \\u000a Objective  This study was designed to further characterize the behavioral effects of GHB alone and in combination with EtOH in male

Charles D. Cook; Laura Biddlestone; Andrew Coop; Patrick M. Beardsley

2006-01-01

37

Determination of gamma-hydroxybutyrate (GHB) in biological specimens by simultaneous extraction and chemical derivatization followed by GC-MS  

Microsoft Academic Search

Urine and chicken liver fortified with gamma-hydroxybutyrate (GHB) were pretreated with in-situ liquid-liquid extraction\\/chemical derivatization (LLE-ChD) or in-situ solid-phase extraction\\/chemical derivatization (SPE-ChD) followed by gas chromatography-mass spectrometry (GC-MS). GHB as its N,O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA) derivative was recovered from urine in 23.7 % through the LLE-ChD procedure, in contrast to 60.7 % via the SPE-ChD counterpart. In the selective ion monitoring (SIM)

Sheng-Meng Wang; Yun-Seng Giang; Min-Jen Lu; Tsung-Li Kuo

38

Coma and respiratory depression following the ingestion of GHB and its precursors: Three cases 1 1 Selected Topics: Toxicology is coordinated by Kenneth Kulig, MD, of Denver, Colorado  

Microsoft Academic Search

Gamma hydroxybutyrate (GHB) is a product of the metabolism of both gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Gamma hydroxybutyrate (GHB) is an illegal agent that causes central nervous system depression. Chemical precursors of GHB, such as GBL and 1,4-BD, have been available for purchase from many health food stores and Internet websites for mood-enhancement, sleep-induction, and stimulation of growth hormone

Marianne Ingels; Cyrus Rangan; Joseph Bellezzo; Richard F Clark

2000-01-01

39

A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol  

Microsoft Academic Search

We describe a case of withdrawal from the gamma hydroxybutyric acid (GHB) precursors gamma butyrolactone and 1,4-butanediol. Symptoms included visual hallucinations, tachycardia, tremor, nystagmus, and diaphoresis. Administration of benzodiazepines and phenobarbital successfully treated the withdrawal symptoms. As predicted from the metabolism of gamma butyrolactone and 1,4-butanediol to GHB, the symptoms were nearly identical to those reported from GHB withdrawal. Because

Aaron B Schneir; Binh T Ly; Richard F Clark

2001-01-01

40

Gamma-hydroxybutyrate (GHB) induces cognitive deficits and affects GABAB receptors and IGF-1 receptors in male rats.  

PubMed

In recent years, the abuse of the club drug gamma-hydroxybutyrate (GHB) has become increasingly popular among adolescents. The drug induces euphoria but can also result in sedation, anaesthesia as well as short-term amnesia. In addition, the abuse of GHB causes cognitive impairments and the mechanism by which GHB induces these impairments is not clarified. The present study investigates the impact of GHB treatment on spatial learning and memory using a water maze (WM) test in rats. Furthermore, the behavioural data is combined with an autoradiographic analysis of the GABAB and the IGF-1 receptor systems. The results demonstrate that the animals administered with GHB display an impaired performance in the WM test as compared to controls. In addition, significant alterations in GABAB and IGF-1 receptor density as well as GABAB receptor functionality, were observed in several brain regions associated with cognitive functions e.g. hippocampus. To conclude, our findings suggest that GHB treatment can affect spatial learning and memory, and that this outcome at least to some extent is likely to involve both GABAB and IGF-1 receptors. PMID:24786330

Johansson, Jenny; Grönbladh, Alfhild; Hallberg, Mathias

2014-08-01

41

Gamma-hydroxybutyric acid  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB; liquid ecstasy, sodium oxybate) is a drug of abuse which is increasingly used recreationally and has been implicated in cases of ‘drug rape’. GHB-intoxicated patients may appear sedated or may show paradoxical agitation. After ingestion of a toxic amount of GHB, rapid onset of respiratory depression and deep coma may occur, resolving spontaneously within 24 hours with

Ruben Thanacoody

2007-01-01

42

Enzyme and receptor antagonists for preventing toxicity from the gamma-hydroxybutyric acid precursor 1,4-butanediol in CD-1 mice.  

PubMed

1,4-Butanediol (1,4-BD), the diol alcohol precursor of gamma-hydroxybutyric acid (GHB), undergoes in vivo enzymatic biotransformation to GHB by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. The subsequent metabolite, GHB, is pharmacologically active at GABA(B) and GHB receptors. GHB can be metabolized in vivo to gamma-aminobutyric acid (GABA) and trans-4-hydroxycrotonic acid (T-HCA), which are also pharmacologically active at GABA(B) receptors and GHB receptors, respectively. Therefore, we speculate that 1,4-BD overdose toxicity can be prevented or attenuated with the ADH enzyme inhibitor 4-methylpyrazole (4-MP) as well as with CGP-35348 and NCS-382, novel high-affinity receptor antagonists of GABA(B) receptors and GHB receptors, respectively. In our murine model of acute 1,4-BD overdose, pretreatment of CD-1 mice with 4-MP significantly attenuated increases in blood GHB concentrations and prevented loss of the righting reflex and failure of the rotarod test. Also, pretreatment with CGP-35348 and its combination with NCS-382 significantly decreased the duration of failure for the rotarod test and the percentage of animals failing the rotarod test, respectively. However, pretreatment of CD-1 mice with NCS-382 alone produced prolonged failure of the rotarod test, an unexpected synergistic effect with 1,4-BD and presumably GHB, which has not previously been demonstrated. PMID:12105121

Quang, Lawrence S; Desai, Malhar C; Kraner, James C; Shannon, Michael W; Woolf, Alan D; Maher, Timothy J

2002-06-01

43

Spontaneous and precipitated withdrawal after chronic intragastric administration of gamma-hydroxybutyrate (GHB) in baboons  

Microsoft Academic Search

Rationale: ?-Hydroxybuyrate (GHB) is a cur- rent drug of abuse that may produce physical dependence. Objectives: The present study characterized the behavior- al effects of chronic GHB in baboons (n=4), and evaluated whether signs of withdrawal occurred (1) after adminis- tration of the GABA-B antagonist CGP36742 during chronic GHB administration (precipitated withdrawal) and (2) following discontinuation of chronic GHB administra-

Elise M. Weerts; Amy K. Goodwin; Roland R. Griffiths; P. Rand Brown; Wolfgang Froestl; Cornelis Jakobs; K. Michael Gibson

2005-01-01

44

Comparative study of equimolar doses of gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) on catalepsy after acute and chronic administration.  

PubMed

Gamma-hydroxybutyrate (GHB), and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) are known drugs of abuse. The ability of acute and chronic administration of equimolar doses of GHB (200mg/kg), 1,4-BD (174mg/kg) and GBL (166mg/kg) to produce catalepsy in male Swiss Webster mice was examined. GHB, 1,4-BD, GBL produced catalepsy when injected acutely. Drug treatment was then continued for 14days. Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with naïve mice. Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve (AUC) of catalepsy versus time (min-sec) on days 6 (678±254), 14 (272±247), which were less than those on day 1 (1923±269). However, less tolerance was seen from GBL or 1,4-BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1. In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1,4-BD and GBL shared only some of the in vivo effects of GHB. The rate of metabolic conversion of 1,4-BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs. PMID:23104245

Towiwat, Pasarapa; Phattanarudee, Siripan; Maher, Timothy J

2013-01-01

45

Pretreatment of CD-1 mice with 4-methylpyrazole blocks toxicity from the gamma-hydroxybutyrate precursor, 1,4-butanediol.  

PubMed

1,4-Butanediol (1,4-BD) is the dihydroxy precursor of gamma-hydroxybutyrate (GHB), a popular recreational drug that has been banned by the United States Food and Drug Administration (FDA) and controlled as a federal schedule I drug. 1,4-BD is enzymatically converted in vivo to GHB by alcohol dehydrogenase (ADH), and overdoses can result in coma, severe respiratory depression, bradycardia, hypothermia, seizures, and death. Presently, there is no antidote. We pretreated CD-1 mice with the ADH antagonist, 4-methylpyrazole (4-MP), to determine if blocking ADH can prevent or decrease toxicity from 1,4-BD overdose. Pretreatment with 4-MP increased the Toxic Dose-50 (TD(50)) of 1,4-BD for the righting reflex from 585 mg/kg (95% CI, 484-707 mg/kg) in control mice to 5,550 mg/kg (95% CI, 5,353-5,756 mg/kg) in pretreated mice. Pretreatment with 4-MP also increased the TD(50) of 1,4-BD for the rotarod test from 163 mg/kg (95% CI, 136-196 mg/kg) in control mice to 4,900 mg/kg (95% CI, 4,812-4,989 mg/kg) in pretreated mice. Pretreatment with 4-MP significantly decreased the toxicity of 1,4-BD in CD-1 mice, presumably by inhibiting its ADH biotransformation to GHB. 4-MP warrants further investigation as a potential antidote for this increasingly abused drug. PMID:12074936

Quang, L S; Shannon, M W; Woolf, A D; Desai, M C; Maher, T J

2002-07-01

46

Gamma-hydroxybutyric acid (GHB) measurement by GC-MS in blood, urine and gastric contents, following an acute intoxication in Belgium.  

PubMed

Gamma-hydroxybutyrate (GHB, sodium oxybate) is a compound related to neuromodulator gamma-aminobutyric acid (GABA), emerging as a recreational drug of abuse and as a rape drug. GHB-related emergencies have dramatically increased in the 1990s, but a decrease is observed since 2000. We describe the case of an acute GHB intoxication in a 28-year-old male who fell unconscious after ingestion of a mouthful of an unknown beverage, and required medical support for 2 days. A cocaine abuse was also detected by preliminary toxicological screening, but the clinical presentation was not typical of cocaine intoxication. A simple liquid-liquid extraction was used for quantitation of GHB, followed by disilyl-derivatization and analysis in selective ion monitoring (SIM) mode by gas chromatography-mass spectrometry (GC-MS), using GHB-d6 as internal standard. High concentrations of GHB were detected in urine (3020 mg/L) and gastric contents (71487 mg/L) at admission. After a 6-hours delay, GHB was still present in urine at 2324 mg/L and in blood at 43 mg/L. The clinical symptoms of cocaine intoxication were diminished by GHB consumption, and the cerebral scan was modified. Attention must thus be paid to acute intoxications with surprising clinical symptoms, and GHB has probably to be added to the preliminary toxicological screening. Data available regarding GHB are briefly reviewed, and our results are compared with previously published reports of non-fatal GHB intoxication. PMID:18714853

Bodson, Q; Denooz, R; Serpe, P; Charlier, C

2008-01-01

47

Designing a gamma hydroxybutyrate (GHB) structured telephone-administered survey instrument  

Microsoft Academic Search

Introduction  As part of a larger study assessing the covariates and outcomes of GHB use, we developed a telephone-survey instrument for\\u000a hospitalized GHB exposed patients identified through poison control center surveillance and for self-identified GHB users\\u000a recruited from the general public.\\u000a \\u000a \\u000a \\u000a Methods  We used an iterative review process with an interdisciplinary team, including pharmacists, a physician, and a medical anthropologist.\\u000a In designing

Jo E. Dyer; Ilene B. Anderson; Susan Y. Kim; Judith C. Barker; Paul D. Blanc

2007-01-01

48

Identification of the date-rape drug GHB and its precursor GBL by Raman spectroscopy.  

PubMed

Gamma hydroxybutyric acid (GHB), also known as 'liquid ecstasy', has recently become associated with drug-facilitated sexual assaults, known colloquially as 'date rape', due to the ability of the drug to cause loss of consciousness. The drug is commonly found 'spiked' into alcoholic beverages, as alcohol increases its sedative effects. Gamma hydroxybutyric acid and the corresponding lactone gamma-butyrolactone (GBL) will reach an equilibrium in solution which favours the lactone in basic conditions and GHB in acidic conditions (less than pH 4). Therefore, we have studied both GHB and GBL, as a mildly acidic beverage 'spiked' with GHB will contain both GHB and GBL. We report the analysis of GHB as a sodium salt and GBL, its precursor, using bench-top and portable Raman spectroscopy. It has been demonstrated that we are able to detect GHB and GBL in a variety of containers including colourless and amber glass vials, plastic vials and polythene bags. We have also demonstrated the ability to detect both GBL and GHB in a range of liquid matrices simulating 'spiked' beverages. PMID:20355156

Brewster, Victoria L; Edwards, Howell G M; Hargreaves, Michael D; Munshi, Tasnim

2009-01-01

49

Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in different populations of treated alcoholics: an open comparative study.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT. PMID:18635689

Caputo, F; Francini, S; Stoppo, M; Lorenzini, F; Vignoli, T; Del Re, A; Comaschi, C; Leggio, L; Addolorato, G; Zoli, G; Bernardi, M

2009-11-01

50

The gamma-hydroxybutyrate signalling system in brain: organization and functional implications.  

PubMed

gamma-Hydroxybutyrate is a metabolite of GABA which is synthesized and accumulated by neurons in brain. This substance is present in micromolar quantities in all brain regions investigated as well as in several peripheral organs. Neuronal depolarization releases gamma-hydroxybutyrate into the extracellular space in a Ca(2+)-dependent manner. Gamma-hydroxybutyrate high-affinity receptors are present only in neurons, with a restricted specific distribution in the hippocampus, cortex and dopaminergic structures of rat brain (the striatum in general, olfactory bulbs and tubercles, frontal cortex, dopaminergic nuclei A9, A10 and A12). Stimulation of these receptors with low amounts of gamma-hydroxybutyrate induces in general hyperpolarizations in dopaminergic structures with a reduction of dopamine release. However, in the hippocampus and the frontal cortex, it seems that gamma-hydroxybutyrate induces depolarization with an accumulation of cGMP and an increase in inositol phosphate turnover. Some of the electrophysiological effects of GHB are blocked by NCS-382, a gamma-hydroxybutyrate receptor antagonist while some others are strongly attenuated by GABAB receptors antagonists. Gamma-hydroxybutyrate penetrates freely into the brain when administered intravenously or intraperitoneally. This is a unique situation for a molecule with signalling properties in the brain. Thus, the gamma-hydroxybutyrate concentration in brain easily can be increased more than 100 times. Under these conditions, gamma-hydroxybutyrate receptors are saturated and probably desensitized and down-regulated. It is unlikely that GABAB receptors could be stimulated directly by GHB. Most probably, GABA is released in part under the control of GHB receptors in specific pathways expressing GABAB receptors. Alternatively, GABAB receptors might be specifically stimulated by the GABA formed via the metabolism of gamma-hydroxybutyrate in brain. In animals and man, these GHBergic and GABAergic potentiations induce dopaminergic hyperactivity (which follows the first phase of dopaminergic terminal hyperpolarization), a strong sedation with anaesthesia and some EEG changes with epileptic spikes. It is presumed that, under pathological conditions (hepatic failure, alcoholic intoxication, succinic semialdehyde dehydrogenase defects), the rate of GHB synthesis or degradation in the peripheral organ is modified and induces increased GHB levels which could interfere with the normal brain mechanisms. This pathological status could benefit from treatments with gamma-hydroxybutyric and/or GABAB receptors antagonists. Nevertheless, the regulating properties of the endogenous gamma-hydroxybutyrate system on the dopaminergic pathways are a cause for the recent interest in synthetic ligands acting specifically at gamma-hydroxybutyrate receptors and devoid of any role as metabolic precursor of GABA in brain. PMID:9089792

Maitre, M

1997-02-01

51

The gamma-hydroxybutyrate withdrawal syndrome.  

PubMed

gamma-Hydroxybutyrate (GHB) is endogenous inhibitory transmitter that, when administered in pharmacological doses, has sedative-hypnotic properties. It is used in anaesthesia for the treatment of narcolepsy/catalepsy and in alcohol/opioid detoxification treatment regimens. Based on its purported anabolic effects, GHB use became established among bodybuilders. As the euphorigenic effects of GHB became publicised, attendees at dance clubs and rave parties began to use it alone or in combination with other psychoactive drugs. Following the ban of GHB in 1990, several precursor products (e.g. gamma-butyrolactone, butanediol) became widely used as replacement drugs until their ultimate proscription from lawful use in 2000. GHB and its precursors, like most sedative-hypnotic agents, can induce tolerance and produce dependence. Although many GHB users will experience a mild withdrawal syndrome upon drug discontinuation, those with chronic heavy GHB use can experience severe withdrawal. This syndrome clinically resembles the withdrawal syndrome noted from alcohol and other sedative-hypnotic drugs (e.g. benzodiazepines). Distinct clinical features of GHB withdrawal are its relatively mild and brief autonomic instability with prolonged psychotic symptoms. Patients with fulminant GHB withdrawal require aggressive treatment with cross-tolerant sedative hypnotics, such as benzodiazepines. PMID:15298492

Tarabar, Asim F; Nelson, Lewis S

2004-01-01

52

Characterization of the Pharmacokinetic and Pharmacodynamic Interaction between GammaHydroxybutyrate and Ethanol in the Rat  

Microsoft Academic Search

It has been reported that ethanol enhances the hypnotic effect of gamma-hydroxybutyrate (GHB). In order to clarify the nature of this interaction we studied the pharmacokinetics and pharmaco- dynamics of combinations of GHB and ethanol in rats. Intraperi- toneal injections of the GHB precursor gamma-butyrolactone (300 mg\\/kg) together with ethanol (3000 mg\\/kg) (n 4) resulted in a longer \\

Diederik K. Van Sassenbroeck; Peter De Paepe; Frans M. Belpaire; Walter A. Buylaert

2003-01-01

53

[Qualitative and quantitative gamma-hydroxybutyrate analysis].  

PubMed

Gamma-hydroxybutyrate (GHB) is a naturally occurring compound present in the brain and peripheral tissues of mammals. It is a minor metabolite and precursor of gamma-aminobutyric acid (GABA). Just as GABA, GHB is believed to play a role in neurotransmission. GHB was first synthesized in vitro in 1960, when it revealed depressive and hypnotic effects on the central nervous system. In 1960s it was used as an anaesthetic and later as an alternative to anabolic steroids, in order to enhance muscle growth. However, after it was shown that it caused strong physical dependence and severe side effects, GHB was banned. For the last fifteen years, GHB has been abused for its intoxicating effects such as euphoria, reduced inhibitions and sedation. Illicitly it is available as white powder or as clear liquid. Paradoxically GHB can easily be manufactured from its precursor gamma-butyrolactone (GBL), which has not yet been banned. Because of many car accidents and criminal acts in which it is involved, GHB has become an important object of forensic laboratory analysis. This paper describes gas and liquid chromatography, infrared spectroscopy, microscopy, colourimetry and nuclear magnetic resonance as methods for detection and quantification of GHB in urine and illicit products. PMID:17265679

Petek, Maja Jelena; Vrdoljak, Ana Luci?

2006-12-01

54

Behavioral effects of gamma-hydroxybutyrate, its precursor gamma-butyrolactone, and GABA(B) receptor agonists: time course and differential antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348).  

PubMed

Gamma-hydroxybutyrate (GHB) is used therapeutically and recreationally. The mechanism by which GHB produces its therapeutic and recreational effects is not entirely clear, although GABA(B) receptors seem to play an important role. This role could be complex, because there are indications that different GABA(B) receptor mechanisms mediate the effects of GHB and the prototypical GABA(B) receptor agonist baclofen. To further explore possible differences in underlying GABA(B) receptor mechanisms, the present study examined the effects of GHB and baclofen on operant responding and their antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). Pigeons were trained to peck a key for access to food during response periods that started at different times after the beginning of the session. In these pigeons, GHB, its precursor gamma-butyrolactone (GBL), and the GABA(B) receptor agonists baclofen and 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF97541) decreased the rate of responding in a dose- and time-dependent manner. CGP35348 shifted the dose-response curve of each agonist to the right, but the magnitude of the shift differed among the agonists. Schild analysis yielded a pA(2) value of CGP35348 to antagonize GHB and GBL [i.e., 3.9 (3.7-4.2)] that was different (P = 0.0011) from the pA(2) value to antagonize baclofen and SKF97541 [i.e., 4.5 (4.4-4.7)]. This finding is further evidence that the GABA(B) receptor mechanisms mediating the effects of GHB and prototypical GABA(B) receptor agonists are not identical. A better understanding of the similarities and differences between these mechanisms, and their involvement in the therapeutic effects of GHB and baclofen, could lead to more effective medications with fewer adverse effects. PMID:19564487

Koek, Wouter; Mercer, Susan L; Coop, Andrew; France, Charles P

2009-09-01

55

Various Seizure Activities Following gamma-Hydroxybutyrate.  

National Technical Information Service (NTIS)

The studies demonstrate that 0.7-1.0 gm/kg of gamma-hydroxybutyrate (GHB) induces 2 1/2 c/s electrical epileptiform activity which progresses to spiking with short polyphasic bursts followed by electrical silence. Spontaneous and induced myoclonic jerks a...

W. D. Winters C. E. Spooner

1965-01-01

56

From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid.  

PubMed

gamma-Hydroxybutyric acid (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and is formed primarily from the precursor gamma-aminobutyric acid (GABA). The properties of GHB suggest that it has a neuromodulatory role in the brain and has the ability to induce several pharmacological and behavioral effects. GHB has been used clinically as an anesthetic and to treat alcoholism and narcolepsy. Furthermore, GHB has emerged recently as a major recreational drug of abuse. GHB appears to have dual mechanisms of action in the brain. Biochemical data suggest that the intrinsic neurobiological activity of GHB might be mediated through the GHB receptor, which is separate and distinct from the GABA(B) receptor. However, many of the pharmacological and clinical effects of exogenously administered GHB, including the properties of addiction, tolerance, withdrawal and intoxication, are probably mediated via the GABA(B) receptor, where GHB might act both directly as a partial agonist and indirectly through GHB-derived GABA. PMID:14723976

Wong, C Guin Ting; Gibson, K Michael; Snead, O Carter

2004-01-01

57

[Life threatening symptoms of withdrawal of gamma-hydroxybutyrate].  

PubMed

Acute psychosis and extreme agitation brought about by gamma-hydroxybutyrate GHB withdrawal can be life-threatening. In order to prevent states of excitement accompanied by aggression and somatic complications it is advisable to intervene by administering strong sedatives. It is argued that GHB should be tapered off as an alternative treatment for fixation and high doses of benzodiazepines. PMID:20544599

Veerman, S R T; Dijkstra, H N; Liefting-Kluft, I

2010-01-01

58

Discrimination of gamma-hydroxybutyrate and ethanol administered separately and as a mixture in rats  

Microsoft Academic Search

The physiological effects of gamma-hydroxybutyrate (GHB) are complex and not yet clearly defined. GHB has been labeled as a recreational drug and is reported to be frequently coabused with ethanol (ETH). Other studies have yielded discrepant results as to the interaction between GHB and ETH. Thus, the present study investigated extensively the discriminative stimulus of GHB and ETH and a

Brian R. Metcalf; Jeanne M. Stahl; Joseph D. Allen; Dedra R. Woolfolk; Paul L. Soto

2001-01-01

59

Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate.  

PubMed

gamma-Hydroxybutyrate (GHB) is a GABA-active CNS depressant, commonly used as a drug of abuse. In the early 1990s, the US Drug Enforcement Administration (DEA) warned against the use of GHB and restricted its sale. This diminished availability of GHB caused a shift toward GHB analogues such as gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) as precursors and surrogates. Both GBL and 1,4-BD are metabolically converted to GHB. Furthermore, GBL is commonly used as a starting material for chemical conversion to GHB. As such, the clinical presentation and management of GBL and 1,4-BD intoxication shares a great deal of common ground with that for GHB. This similarity exists not only for acute intoxication but also for withdrawal in those patients with a history of extended high-dose abuse. This review examines the history of GHB analogue abuse as well as the clinical presentation and management of acute intoxication and withdrawal associated with abuse of these compounds. PMID:15298490

Palmer, Robert B

2004-01-01

60

The role of GABAB receptors in the discriminative stimulus effects of gamma-hydroxybutyrate in rats: time course and antagonism studies.  

PubMed

gamma-Hydroxybutyrate (GHB) is a neurotransmitter in brain and an emerging drug of abuse, although its mechanism of action is poorly understood. This study characterized the role of GABA(A), GABA(B), and other receptors in the discriminative stimulus effects of GHB. Eight rats reliably discriminated 200 mg/kg GHB from saline after a median of 35 (range: 23-41) training sessions. GHB, a metabolic precursor 1,4-butanediol (1,4-BDL), and the GABA(B) agonist (+/-)baclofen all occasioned greater than 83% responding on the GHB lever. The onset of action was similar for GHB and 1,4-BDL; however, 1,4-BDL exhibited a longer duration of action than GHB. The GHB precursor gamma-butyrolactone, the benzodiazepine diazepam, the neuroactive steroid pregnanolone, the opioid agonist morphine, and the N-methyl-d-aspartate antagonist ketamine elicited substantial GHB-appropriate responding, although none occasioned greater than 66% drug-lever responding. The barbiturate pentobarbital and the GABA(A) receptor agonist muscimol did not occasion greater than 17% drug-lever responding at any dose tested. The benzodiazepine antagonist flumazenil attenuated GHB-lever responding occasioned by diazepam, but not GHB. The GABA(B) receptor antagonist CGP 35348 antagonized GHB-lever responding occasioned by baclofen or GHB. Small doses of the purported GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) attenuated partially the effects of GHB, whereas larger doses of NCS-382 alone occasioned partial GHB-lever responding. These results implicate GABA(B) mechanisms in the discriminative stimulus effects of GHB and further suggest that the effects of 1,4-BDL under these conditions result from its conversion to GHB. That NCS-382 shares effects with GHB could explain the lack of antagonism reported for NCS-382 in some studies. PMID:12606639

Carter, Lawrence P; Flores, Lauren R; Wu, Huifang; Chen, Weibin; Unzeitig, Andrew W; Coop, Andy; France, Charles P

2003-05-01

61

Baclofen and GammaHydroxybutyrate Withdrawal  

Microsoft Academic Search

Introduction  Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies\\u000a suggest strongly that treatment with GABAB agonists, such as baclofen, will be a more effective strategy.\\u000a \\u000a \\u000a \\u000a Methods  A case report from the medical intensive care unit (ICU) of the university tertiary care hospital.\\u000a \\u000a \\u000a \\u000a Results  A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB

Jennifer L. LeTourneau; Daniel S. Hagg; Stephen M. Smith

2008-01-01

62

Safety and tolerability of gamma-hydroxybutyric acid in the treatment of alcohol-dependent patients  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB) has been in clinical use in Italy since 1991 for treatment of alcohol dependence. Results of phase III and phase IV studies have shown that the drug is effective and well tolerated in the treatment of alcohol withdrawal syndrome and in reducing alcohol consumption and alcohol craving. Pharmacosurveillance indicates that abuse of gamma-hydroxybutyric acid is a limited

Franco Beghè; Maria Teresa Carpanini

2000-01-01

63

Production of gamma-hydroxybutyric acid in postmortem liver increases with time after death.  

PubMed

Gamma-hydroxybutyric (GHB) acid, which is becoming popular as a drug of abuse, was shown by means of gas chromatography-mass spectrometry (GC-MS) to increase in mouse liver with time after death. The amount detected was 0.8 +/- 1.0 microg/g at 3 h after death, 4.7 +/- 1.5 microg/g at 24 h, and 8.8 +/- 0.8 microg/g at 72 h. Furthermore, GHB was detected in samples from deceased persons, at concentrations of 2.6-12.0 microg/g in liver, 0.4-7.3 microg/ml in blood, and 0-2.6 microg/ml in urine, but was not detected in the blood and urine of living persons. Although 1,4-butanediol has been suggested to be a precursor of GHB produced after death, 1,4-butanediol was not detected in any of our samples. Additionally, succinate semialdehyde arising from gamma-aminobutyric acid (GABA) transamination to GHB was also barely detectable in any of our samples. This study supports previous reports that GHB is a product of postmortem decomposition. Production of GHB increases with time after death in postmortem liver; since we were unable to identify endogenous 1,4-butanediol and succinate semialdehyde in our samples, the pathway of GHB production after death remains unclear. PMID:11888704

Sakurada, Koichi; Kobayashi, Masahiko; Iwase, Hirotaro; Yoshino, Mineo; Mukoyama, Harutaka; Takatori, Takehiko; Yoshida, Ken-ichi

2002-03-28

64

Cardiovascular responses elicited by intragastric administration of BDL and GHB.  

PubMed

Gamma-hydroxybutyrate (GHB) and its metabolic precursor, 1,4-butanediol (BDL), are widely used recreational drugs. Although most commonly described as CNS depressants, GHB and BDL elicit significant sympathomimetic cardiovascular responses [increases in mean arterial pressure (MAP) and heart rate] when administered parenterally. Given that humans most commonly ingest both drugs orally, we examined the dose-response relationships for intragastrically administered GHB and BDL on MAP and heart rate in conscious rats using radiotelemetry. The intragastric administration of GHB increased MAP. BDL increased both MAP and heart rate and was approximately 10-fold more potent as a cardiovascular stimulant than GHB when administered intragastrically. Pretreatment with ethanol prevented the lethality of BDL. These data indicate that 1) both GHB and BDL produce cardiovascular responses when administered intragastrically and 2) BDL is more potent and potentially more dangerous than GHB when administered via this route. PMID:18702013

Hicks, Alissa R; Varner, Kurt J

2008-01-01

65

Discriminative stimulus effects of gamma-hydroxybutyrate: role of training dose.  

PubMed

gamma-Hydroxybutyrate (GHB) is a drug of abuse with actions at GHB and GABA receptors. This study examined whether the relative importance of GABA(A), GABA(B), and GHB receptors in the discriminative stimulus effects of GHB depends on the training dose. In comparison with a previous 100 mg/kg GHB-saline discrimination, pigeons were trained to discriminate either 178 or 56 mg/kg GHB from saline. Increasing the training dose shifted the GHB gradient to the right, and decreasing it shifted the gradient to the left. Similar shifts occurred with the GHB precursor gamma-butyrolactone, which substituted for GHB, and with the GABA(B) agonists baclofen and 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF97541) and the benzodiazepine diazepam, each of which produced at most 54 to 68% GHB-appropriate responding. The benzodiazepine antagonist flumazenil, the benzodiazepine inverse agonist ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]-benzodiazepine-3-carboxylate (Ro 15-4513), and the GHB receptor antagonist (2E)-5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) produced a maximum of 66 to 97% GHB-appropriate responding in animals discriminating 56 or 100 mg/kg GHB and a maximum of 1 to 49% in animals discriminating 178 mg/kg. NCS-382 did not attenuate the effects of GHB. The GABA(B) antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348) blocked GHB at all training doses. The results suggest that increasing the training dose of GHB increases the pharmacological selectivity of its discriminative stimulus effects. At a high training dose, diazepam-insensitive GABA(A) receptors, for which flumazenil and Ro 15-4513 have affinity, may no longer be involved. Diazepam-sensitive GABA(A) receptors and GABA(B) receptors appear to play a similar role at all training doses. There was no evidence for GHB receptor involvement. PMID:16330491

Koek, Wouter; Chen, Weibin; Mercer, Susan L; Coop, Andrew; France, Charles P

2006-04-01

66

Successful management of prolonged gamma-hydroxybutyrate and alcohol withdrawal.  

PubMed

A 27-year-old man was admitted with tremulousness, diaphoresis, tachypnea (28 breaths/min), full-body rigidity, irritability, paranoia, and auditory and visual hallucinations 2 days after stopping long-term gamma-hydroxybutyrate (GHB) and 8 hours after stopping alcohol intake. He received intravenous fluids and tapering dosages of lorazepam to control agitation and rigidity, and recovered with no significant sequelae after 8 days. Abrupt cessation of GHB after high-dosage abuse can precipitate a clinically significant withdrawal syndrome. Lorazepam should be considered for treatment of GHB withdrawal. Concomitant alcohol abuse may mask early GHB withdrawal symptoms and exacerbate withdrawal. PMID:11213862

Bowles, T M; Sommi, R W; Amiri, M

2001-02-01

67

An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results.  

PubMed

Abuse of gamma-hydroxybutyric acid (GHB) has been known since the early 1990's, but is not as widespread as the consumption of other illegal drugs. However, the number of severe intoxications with fatal outcomes is comparatively high; not the least of which is brought about by the consumption of the currently legal precursor substances gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). In regards to previous assumptions, addiction to GHB or its analogues can occur with severe symptoms of withdrawal. Moreover, GHB can be used for drug-facilitated sexual assaults. Its pharmacological effects are generated mainly by interaction with both GABA(B) and GHB receptors, as well as its influence on other transmitter systems in the human brain. Numerous analytical methods for determining GHB using chromatographic techniques were published in recent years, and an enzymatic screening method was established. However, the short window of GHB detection in blood or urine due to its rapid metabolism is a challenge. Furthermore, despite several studies addressing this problem, evaluation of analytical results can be difficult: GHB is a metabolite of GABA (gamma-aminobutyric acid); a differentiation between endogenous and exogenous concentrations has to be made. Apart from this, in samples with a longer storage interval and especially in postmortem specimens, higher levels can be measured due to GHB generation during this postmortem interval or storage time. PMID:21381220

Andresen, H; Aydin, B E; Mueller, A; Iwersen-Bergmann, S

2011-09-01

68

GC/MS profiling of gamma-hydroxybutyrate and precursors in various animal tissues using automatic solid-phase extraction. Preliminary investigations of its potential interest in postmortem interval determination.  

PubMed

To quantify gamma-hydroxybutyrate (GHB) and its physiological metabolites, gamma-aminobutyric acid (GABA), 1,4-butanediol (1,4-BD), and gamma-butyrolactone (GBL) in various animal tissues (kidney, muscle, heart, liver, blood, brain cortex, thalamus, hypothalamus, hippocampus, or pons), an original gas chromatographic/mass spectrometric method with a automated solid-phase extraction by Oasis MCX cartridges on a Gilson Aspec Xli was developed. Using such apparatus allowed the limit of detection (LOD) of target compounds to be significantly lowered (LOD: 0.027, 0.025, and 5.7 microg/mL for GHB, 1,4-BD, and GABA, respectively, in 200 microL or microg of sample). After validation of each analytical step, the satisfactory performances of the apparatus in conjunction with the rapidity and ease of the extraction step make it suitable for simultaneous assay of GHB, 1,4-BD, GBL, and GABA. The method was used to test the correlation between GHB levels in tissues obtained at different times after death of male Sprague-Dawley rats and the postmortem interval. Preliminary results show a linear increase of GHB levels in relation to time of death in thoracic blood and central nervous system of animals kept at 15 and 20 degrees C. PMID:15732918

Richard, Damien; Ling, Bing; Authier, Nicolas; Faict, Thierry W; Eschalier, Alain; Coudoré, François

2005-03-01

69

Experimental absence seizures: potential role of gamma-hydroxybutyric acid and GABAB receptors.  

PubMed

We have investigated whether the pathogenesis of spontaneous generalized non-convulsive seizures in rats with genetic absence epilepsy is due to an increase in the brain levels of gamma-hydroxybutyric acid (GHB) or in the rate of its synthesis. Concentrations of GHB or of its precursor gamma-butyrolactone (GBL) were measured with a new GC/MS technique which allows the simultaneous assessment of GHB and GBL. The rate of GHB synthesis was estimated from the increase in GHB levels after inhibition of its catabolism with valproate. The results of this study do not indicate significant differences in GHB or GBL levels, or in their rates of synthesis in rats showing spike-and-wave discharges (SWD) as compared to rats without SWD. Binding data indicate that GHB, but not GBL, has a selective, although weak affinity for GABAB receptors (IC50 = 150 microM). Similar IC50 values were observed in membranes prepared from rats showing SWD and from control rats. The average GHB brain levels of 2.12 +/- 0.23 nmol/g measured in the cortex and of 4.28 +/- 0.90 nmol/g in the thalamus are much lower than the concentrations necessary to occupy a major part of the GABAB receptors. It is unlikely that local accumulations of GHB reach concentrations 30-70-fold higher than the average brain levels. After injection of 3.5 mmol/kg GBL, a dose sufficient to induce SWD, brain concentrations reach 240 +/- 31 nmol/g (Snead, 1991) and GHB could thus stimulate the GABAB receptor. Like the selective and potent GABAB receptor agonist R(-)-baclofen, GHB causes a dose-related decrease in cerebellar cGMP. This decrease and the increase in SWD caused by R(-)-baclofen were completely blocked by the selective and potent GABAB receptor antagonist CGP 35348, whereas only the increase in the duration of SWD induced by GHB was totally antagonized by CGP 35348. The decrease in cerebellar cGMP levels elicited by GHB was only partially antagonized by CGP 35348. These findings suggest that all effects of R(-)-baclofen are mediated by the GABAB receptor, whereas only the induction of SWD by GHB is dependent on GABAB receptor mediation, the decrease in cGMP being only partially so. Taken together with the observations of Marescaux et al. (1992), these results indicate that GABAB receptors are of primary importance in experimental absence epilepsy and that GABAB receptor antagonists may represent a new class of anti-absence drugs. PMID:1324978

Bernasconi, R; Lauber, J; Marescaux, C; Vergnes, M; Martin, P; Rubio, V; Leonhardt, T; Reymann, N; Bittiger, H

1992-01-01

70

[Effects of gamma-hydroxybutyrate on monoamine metabolism and protein synthesis after transient global cerebral ischemia].  

PubMed

The effects of gamma-hydroxybutyrate (GHB) on 1) monoamine metabolism, and 2) protein synthesis were examined in a gerbil stroke model. The monoamine metabolism was studied by occluding bilateral common carotid arteries for 15 minutes followed by GHB administered intravenously 3 hours later. Tissue monoamine concentration was examined up to 8 hours after recirculation. Three hours after GHB administration, dopamine (DA) had increased to almost twice that of the non-treated group, whereas homovanillic acid, a metabolite of DA, did not show any significant difference. These results may mean that GHB will facilitate DA synthesis but that it has no influence on its release. Therefore, a DA-mediated increase in cerebral blood flow in the cerebral cortex cannot be expected. Tryptophan, a precursor of 5-hydroxytryptamine (5HT), started to increase just after recirculation reaching a level of over four times that of the control value at 2 to 3 hours, and then starting to decrease in the non-treated group. This decline in tryptophan was markedly facilitated by GHB administration within 1 hour. On the other hand, 5HT administration within 1 hour. On the other hand, 5HT increased only very slightly in the cerebral cortex 1 hour after GHB administration, the change ratio being 1/30 of tryptophan. It can therefore be speculated, that the decrease in tryptophan brought about by GHB administration is due to the improvement in disturbed protein synthesis rather than to stimulation of 5HT synthesis. Protein synthesis was studied by administering GHB 2 minutes prior to a 5-minute temporal common carotid artery occlusion. Ninety minutes after recirculation animals were given a single dose of 14C-leucine and further 60 minutes were allowed to pass before sacrifice. Autoradiographs of the GHB-treated group were compared with those of the non-treated group. With GHB pretreatment, autoradiographs showed an increased uptake of 14C-leucine in at least the hippocampus, thalamus, and hypothalamus, and in two out of three animals, there was diffusely increased uptake. Thus, it is speculated that GHB is effective in improving the protein synthesis in the postischemic period. The favorable function of GHB during cerebral ischemia is regarded by many to be prevention of energy failure by reducing cerebral metabolism. On the other hand, the results derived from the present study suggest that GHB may improve protein synthesis in the postischemic period. Thus, we suggest that GHB is useful if given at the acute stage of cerebral ischemia such as during internal carotid artery or middle cerebral artery occlusion. PMID:1407358

Ueki, Y

1992-09-01

71

[Gamma-hydroxybutyrate--an endogenous substance and an intoxicant].  

PubMed

Gamma-hydroxybutyrate (GHB), a compound found in the mammalian brain, meets many criteria of a neurotransmitter. Experimentally, GHB has been used as a model for petit mal epilepsy; clinically it has been used as a general anaesthetic, to treat certain sleep disorders and alcoholism. Lately GHB has been abused for its euphoric, sedative and anabolic effects. Coma and seizures following abuse of GHB have been reported, but dependency has received little attention. Adverse effects of GHB include seizure activity and a withdrawal syndrome characterised by insomnia, anxiety and tremor. The present paper reviews the neuropharmacology, potential therapeutic uses and acute adverse effects of GHB, together with a presentation of three cases. PMID:9889613

Hovda, K E; Liberg, J P; Nordby, G; Jacobsen, D

1998-11-20

72

Characterization of the pharmacokinetic and pharmacodynamic interaction between gamma-hydroxybutyrate and ethanol in the rat.  

PubMed

It has been reported that ethanol enhances the hypnotic effect of gamma-hydroxybutyrate (GHB). In order to clarify the nature of this interaction we studied the pharmacokinetics and pharmacodynamics of combinations of GHB and ethanol in rats. Intraperitoneal injections of the GHB precursor gamma-butyrolactone (300 mg/kg) together with ethanol (3000 mg/kg) (n = 4) resulted in a longer "sleeping time" than the sum of the individual times (n = 8). Pharmacokinetic analysis of GHB concentrations with a two-compartment model with Michaelis-Menten (M-M) elimination in rats receiving a bolus of GHB (400 mg/kg, i.v.) in addition to steady-state ethanol concentrations (300-3000 microg/ml) (n = 12) or saline (n = 15) showed no marked differences in the area under the curve. The nature of the pharmacodynamic interaction was studied using isobolographs and an interaction model for the loss of the startle and righting reflex and a reaction to a painful tail clamp in rats receiving combinations of steady state concentrations of ethanol (1000-3000 microg/ml) and GHB (200-1400 microg/ml). For the righting reflex, synergy was observed at high ethanol concentrations (>2000 microg/ml) and additivity at lower concentrations. For the startle reflex, it was antagonistic at ethanol concentrations below 1000 microg/ml, and additivity was seen at higher concentrations. For the tail clamp reaction, a slight but significant antagonism was found at all combined concentrations. It is concluded that ethanol prolongs the sleeping time induced by GHB in the rat, which may not be due to a pharmacokinetic interaction. Pharmacodynamic interactions between GHB and ethanol in the rat occur, and the nature varies with the reflex studied and the concentration of ethanol used. PMID:12700396

Van Sassenbroeck, Diederik K; De Paepe, Peter; Belpaire, Frans M; Buylaert, Walter A

2003-06-01

73

Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal.  

PubMed

Gamma-hydroxybutyric acid (GHB) is gaining popularity as a drug of abuse. Reports of toxicity and lethality associated with GHB use have increased. This survey study was designed to identify patterns of GHB use, its effects, and withdrawal syndrome. A survey inquiring about the effects of GHB was administered to 42 users. The results showed that GHB was used to increased feelings of euphoria, relaxation, and sexuality. Adverse effects occurred more frequently in daily users and polydrug users than in occasional GHB users. Loss of consciousness was reported by 66%, overdose by 28%, and amnesia by 13% of participants during GHB use and by 45% after GHB use. Three daily users developed a withdrawal syndrome that presented with anxiety, agitation, tremor, and delirium. Participants described GHB intoxication as having similarities to sedative-hypnotic or alcohol intoxication. Regular use has been shown to produce tolerance and dependence. Participants dependent on GHB reported using multiple daily doses around the clock. High frequency users appeared at the greatest risk for developing withdrawal delirium and psychosis after abrupt discontinuation of GHB use. PMID:11579621

Miotto, K; Darakjian, J; Basch, J; Murray, S; Zogg, J; Rawson, R

2001-01-01

74

Gamma-hydroxybutyric acid for treatment of opiate withdrawal syndrome.  

PubMed

In a double-blind placebo-controlled trial, gamma-hydroxybutyric acid (GHB) (25 mg/kg orally) suppressed most of the withdrawal symptomatology in 14 heroin addicts and 13 methadone-maintained subjects. The GHB effect was prompt (within 15 minutes) and persisted for between 2 and 3 hours. Subsequently, the same patients received GHB in an open study every 2 to 4 hours for the first 2 days and 4 to 6 hours for the following 6 days: most abstinence signs and symptoms remained suppressed and patients reported felling well. Urine analysis failed to detect any presence of opiate metabolites. No withdrawal symptomatology recurred after 8 days of treatment when GHB was suspended, and patients were challenged with an intravenous injection of 0.4 mg naloxone. The results indicate that GHB may be useful in the management of opiate withdrawal. PMID:8397726

Gallimberti, L; Cibin, M; Pagnin, P; Sabbion, R; Pani, P P; Pirastu, R; Ferrara, S D; Gessa, G L

1993-08-01

75

Severe gamma-hydroxybutyrate withdrawal: a case report and literature review  

Microsoft Academic Search

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient’s symptoms, negative polypharmacy history, and negative

Kathryn Craig; Hernan F Gomez; John L McManus; Theodore C Bania

2000-01-01

76

Tolerance to the hypnotic and electroencephalographic effect of gamma-hydroxybutyrate in the rat: pharmacokinetic and pharmacodynamic aspects.  

PubMed

Tolerance to gamma-hydroxybutyrate (GHB) has been suggested in illicit users and has been described for the hypnotic effect in the rat. The aim of this study was to investigate whether tolerance is also observed for the EEG effect, and whether the EEG can give insight into the pharmacodynamic aspects of GHB tolerance. In three series of experiments, rats were pre-treated with either the GHB precursor gamma-butyrolactone (GBL) or saline intraperitoneally twice daily. In the first series, a reduction in sleeping time was observed in the GBL pre-treated rats compared with controls. In the second series, a fast infusion of GHB (300 mg kg(-1) over 5 min) was given after 10 days pre-treatment. The GHB plasma concentration-time curves showed a slightly faster decrease in GHB concentration in the GBL pre-treated rats, suggesting a small induction of the GHB metabolism (V(max) = 2882 +/- 457 microg min(-1) kg(-1) vs 2205 +/- 315 microg min(-1) kg(-1), P < 0.01). In contrast to controls, GBL pre-treated rats did not lose righting reflex. In the third series, a slow infusion of 480 mg kg(-1) h(-1) was given after 7 days pre-treatment, which allowed fitting a sigmoid E(max) model to the EEG amplitude versus GHB plasma concentration curve. This showed reduced end-organ sensitivity to GHB in the GBL pre-treated rats (EC50 (concentration required to obtain 50% depression of the baseline effect) = 653+/- 183 microg mL(-1) vs 323 +/- 68 microg mL(-1), P < 0.001). In conclusion, chronic pre-treatment with gamma-butyrolactone in the rat results in a reduced sleeping time and this tolerance is reflected by the EEG. This can mainly be explained by reduced end-organ sensitivity. PMID:12831503

Van Sassenbroeck, Diederik K; De Paepe, Peter; Belpaire, Frans M; Boon, Paul A; Buylaert, Walter A

2003-05-01

77

Gamma-hydroxybutyrate withdrawal syndrome: dangerous but not well-known.  

PubMed

Gamma-hydroxybutyrate (GHB) is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a 'club drug.' Withdrawal symptoms after cessation of GHB use are common and depend on the intensity of use. However, GHB withdrawal syndrome and delirium are unfamiliar to most psychiatrists, probably due to the fact that neither textbooks nor guidelines cover the subject. The GHB withdrawal syndrome may have a fulminant course that progresses to delirium. In those severe cases, admission to a general hospital and involvement of a psychiatrist become necessary. We present two cases of severe GHB withdrawal delirium, provide an overview of the literature and conclude with treatment recommendations. PMID:19555805

van Noorden, Martijn S; van Dongen, Lieselotte C A M; Zitman, Frans G; Vergouwen, Ton A C M

2009-01-01

78

Contribution of GABA A and GABA B Receptors to the Discriminative Stimulus Produced by Gamma-Hydroxybutyric Acid  

Microsoft Academic Search

The present study examined the involvement of GABAA and GABAB receptors in the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Rats were trained to discriminate either 300 or 700 mg\\/kg GHB IG from water using a T-maze, food-reinforced drug-discrimination procedure. The direct GABAB agonist, baclofen, substituted completely for both training doses of GHB; its potency to substitute for GHB increased

Carla Lobina; Roberta Agabio; Roberta Reali; Gian Luigi Gessa; Giancarlo Colombo

1999-01-01

79

Chronic gamma-hydroxybutyric-acid use followed by gamma-hydroxybutyric-acid withdrawal mimic schizophrenia: a case report  

PubMed Central

Introduction Gamma-hydroxybutyric-acid is a potentially addictive drug known for its use in “rave” parties. Users have described heightened sexual drive, sensuality and emotional warmth. Its euphoric, sedative and anxiolytic-like properties are also sought by frequent users. Abrupt gamma-hydroxybutyric-acid withdrawal can rapidly cause tremor, autonomic dysfunction and anxiety, and may later culminate in severe confusion, delirium, auditory, visual or tactile hallucinations, or even death. Case presentation A 23-year-old woman presented to the emergency room with paranoid delusions and auditory hallucinations. Her psychiatric history included two brief psychotic episodes induced by amphetamines and marijuana. In the last six months, she had demonstrated bizarre behaviour, had been more isolated and apathetic, and unable to take care of daily chores. The patient reported occasional use of gamma-hydroxybutyric-acid, but her initial accounts of drug use were contradictory. Since the toxicology urine screen was negative, a schizophrenic disorder was initially suspected and an antipsychotic medication was prescribed. A few hours after her admission, signs of autonomic dysfunction (tachycardia and hypertension) appeared, lasting 24 hours. Severe agitation and confusion were also present. Restraints and a cumulative dose of 7 mg lorazepam were used to stabilize her. The confusion resolved in less than 72 hours. The patient then revealed that she had been using gamma-hydroxybutyric-acid daily for the last six months as self-medication to treat insomnia and anxiety, before stopping it abruptly 24 hours prior to her visit. Conclusions In our opinion, this original case illustrates the importance of considering gamma-hydroxybutyric-acid withdrawal delirium in the differential diagnosis of a first-break psychosis. In this case, the effects of chronic GHB use were incorrectly identified as the negative symptoms of schizophrenia prodrome. Likewise, severe gamma-hydroxybutyric-acid withdrawal syndrome was initially mistaken for acute positive symptoms of schizophrenia, until autonomic dysfunction manifested itself more clearly.

Constantinides, Prometheas

2009-01-01

80

The Clinical Development of ?-Hydroxybutyrate (GHB)  

Microsoft Academic Search

The discovery of gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable neurotransmitter. In the United States, reports of anabolic effects lead to its misuse among body builders during the 1980's

Gregory P. Wedin; Carl S. Hornfeldt; Lisa M. Ylitalo

2006-01-01

81

GHB use among gay and bisexual men  

Microsoft Academic Search

The recreational use of gamma-hydroxybutyrate (GHB) has been relatively understudied, despite its popularity in gay communities. We examined the use of GHB in a sample of 450 club drug using gay and bisexual men. Of these, 29% indicated use of the substance in the recent past. GHB users were similar to those in the sample who reported no use along

Perry N. Halkitis; Joseph J. Palamar

2006-01-01

82

Severe gamma-hydroxybutyrate withdrawal: a case report and literature review.  

PubMed

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient's symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated. PMID:10645841

Craig, K; Gomez, H F; McManus, J L; Bania, T C

2000-01-01

83

Self-medication with gamma-hydroxybutyrate to reduce alcohol intake.  

PubMed

We describe a 52-year-old man who self-medicated with gamma-hydroxybutyrate (GHB), a widely available illicit substance, to obtain a decrease in ethanol consumption. He successfully reduced his ethanol intake over a 3-month period, but he was unable to sustain abstinence. Although case reports on the use of GHB to induce euphoria have been published, this is the first report of GHB self-medication to facilitate ethanol abstinence. This report highlights the importance of considering GHB self-medication not only for euphoric and mood altering effects, but also as a potential treatment for ethanol intake reduction. PMID:12190234

Glisson, James K; Norton, John

2002-08-01

84

Clinical efficacy of gamma-hydroxybutyric acid in treatment of opiate withdrawal.  

PubMed

This paper describes the role of gamma-hydroxybutyric acid (GHB) in the treatment of opiate withdrawal syndrome. In the two patients described, after having abruptly withdrawn from long-term methadone treatment, GHB was orally administered (each dose given every 4-6 h) for 8-9 days. The GHB showed both a high efficacy (some mild and transient symptoms attributable to opiate withdrawal were observed, but only in the first days of therapy) and a good tolerability (no clinical phenomena interpreted as GHB side effects were found). These results could be of interest in improving the pharmacological treatment of drug addiction. PMID:7803523

Gallimberti, L; Schifano, F; Forza, G; Miconi, L; Ferrara, S D

1994-01-01

85

Within-patient variability in clinical presentation of gamma-hydroxybutyrate withdrawal: a case report.  

PubMed

The emergence of gamma-hydroxybutyrate (GHB) dependence in the UK is described, with specific reference to a case study of serial episodes of GHB withdrawal. Symptoms are broadly similar to those for alcohol withdrawal, and rapid deterioration into delirium is common in severe dependence. This case report reflects the variability in clinical presentation of GHB withdrawal and response to treatment, even within the same patient. It is concluded that GHB withdrawal requires vigorous clinical management, preferably on an elective basis, in an inpatient setting if dependence is severe. PMID:15990433

Glasper, Anthony; McDonough, Michael; Bearn, Jenny

2005-01-01

86

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1.

P. Palatini; L. Tedeschi; G. Frison; R. Padrini; R. Zordan; R. Orlando; L. Gallimberti; G. L. Gessa; S. D. Ferrara

1993-01-01

87

A Neurophysiological Comparison of alpha-Chloralose with gamma-Hydroxybutyrate in Cats.  

National Technical Information Service (NTIS)

The purpose of the paper is to identify and compare the various EEG and behavioral states induced by 15-65 mg/kg alpha-chloralose and 400-600 mg/kg gamma-hydroxybutyrate (GHB) in cats with chronically implanted electrodes. Observations were performed on E...

W. D. Winters C. E. Spooner

1965-01-01

88

Rewarding properties of gamma-hydroxybutyric acid: an evaluation through place preference paradigm  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB), a putative neurotransmitter or neuromodulator found in the mammalian brain, has been successfully\\u000a used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. In the present study we used a conditioned\\u000a place preference (CPP) paradigm to investigate whether GHB possesses rewarding properties in rats. In order to exclude possible\\u000a artifacts due to experimental design, we

Maria Cristina Martellotta; Liana Fattore; Gregorio Cossu; W. Fratta

1997-01-01

89

GHB use among Australians: characteristics, use patterns and associated harm  

Microsoft Academic Search

The aim of this study was to examine the characteristics of gamma-hydroxybutyrate (GHB) users, their GHB and other drug use patterns, and the harms associated with GHB use. Seventy-six GHB users were recruited and administered a structured interview on GHB use and related harms. GHB users appeared to be a stable, highly educated and well-functioning group. They had had extensive

Louisa Degenhardt; Shane Darke; Paul Dillon

2002-01-01

90

Two cases of severe gamma-hydroxybutyrate withdrawal delirium on a psychiatric unit: recommendations for management.  

PubMed

Many psychiatric professionals are unfamiliar with gamma-hydroxybutyrate (GHB), an increasingly popular drug of abuse. GHB withdrawal can lead to psychosis and agitation, and patients may present to psychiatric facilities for treatment. Withdrawal may progress to delirium, with the potential for severe or even fatal medical complications. Therefore, it is imperative for psychiatric professionals to understand how to treat these patients. In this article, we describe two cases of severe GHB withdrawal syndrome that were treated in our inpatient psychiatric unit. These are among the most severe cases reported. Pertinent literature is reviewed and suggestions for treatment are discussed. PMID:12765217

Rosenberg, Mark H; Deerfield, Laurie J; Baruch, Edward M

2003-05-01

91

GHB: An Important Pharmacologic and Clinical Update  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) intoxica- tion is a significant cause of morbidity and mortality in patients taking the drug for recreational purposes. Due to the recent increase in emergency room visits, hospi- tal admissions, and deaths, it has become necessary to re-examine the pharmacology, pharmacokinetics, phar- macodynamics, clinical manifestations, and potential adverse effects associated with GHB use. We present an important pharmacologic

Michael S. Okun; Lisa A. Boothby; Richard B. Bartfield; Paul L. Doering

2001-01-01

92

[Properties allowing the attribution to gamma-hydroxybutyrate the quality of neurotransmitter in the central nervous system].  

PubMed

gamma-Hydroxybutyrate (GHB) fulfills the main criteria of a neurotransmitter: it is unevenly distributed in C.N.S.; it is synthesized from succinic semi-aldehyde by a specific semi-aldehyde succinic reductase localized in neurons, in some dendrites and synaptic terminals; GHB is released by tissue slice depolarization, this release being reduced by 50-60% in a Ca++ free medium. Tetrodotoxin and verapamil strongly inhibited the depolarization evoked-release; high affinity heterogenously distributed binding sites for gamma-hydroxybutyrate exist in the brain. This binding does not require Na+. The bound gamma-hydroxybutyric acid is not displaceable by GABA or GABA agonists. Binding sites are enriched in the synaptosomal fraction; after micro-iontophoretic application, GHB exerts a depressant action on nigral and neocortical cells which is resistant to the presence of bicuculline methiodide. In neuronal cultures, GHB causes a hyperpolarization similar to that produced by GABA; high affinity uptake system for GHB exists both in purified plasma membrane vesicles and in brain tissue slices. This uptake is dependent on an Na+ gradient and is inhibited by ouabaïn and dinitrophenol; GABA does not modify GHB uptake by rat brain slices; GABA derived GHB has a turnover time almost three times faster than that of whole brain serotonin, 6-8 times as rapid as that of whole brain dopamine and 13-19 times as rapid as that of whole brain norepinephrine. PMID:6145513

Maitre, M; Mandel, P

1984-01-01

93

GHB Abuse Trends and Use in Drug-Facilitated Sexual Assault: Implications for Prevention.  

ERIC Educational Resources Information Center

Gamma-hydroxybutyric acid (GHB) has become increasingly popular on the campuses of American colleges and universities. In this paper, the characteristics of GHB and the effects of both voluntary and involuntary abuse are described. Further, implications for prevention efforts related to involuntary GHB ingestion and GHB-facilitated rape are…

Hensley, Laura

2003-01-01

94

Symmetrical generalization between the discriminative stimulus effects of gamma-hydroxybutyric acid and ethanol: Occurrence within narrow dose ranges  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB) has been shown to reduce ethanol consumption and suppress ethanol withdrawal syndrome both in laboratory animals and humans. The present study was designed to assess the similarity between the discriminative stimulus effects, or subjective feelings, of GHB and ethanol using a T-maze, food-reinforced drug discrimination procedure. Three groups of rats were trained to discriminate ethanol (1.0 or

Giancarlo Colombo; Roberta Agabio; Carla Lobina; Roberta Reali; Fabio Fadda; Gian Luigi Gessa

1995-01-01

95

The inkjet cleaner "Hurricane"--another GhB recipe.  

PubMed

Gamma hydroxybutyrate (GHB) is widey used as a sexual enhancement drug, a euphoriant, muscle building agent, a sleep aid, a weight loss agent, and as a date rapeagent. Precursor ingredients such as gammabutyrolactone (GBL) and GHB recipes are available, especially via the Internet. This is a report of an organic inkjet cleaner containing a GHB precursor 1,4-butanediol and butylenegycol. A 26-y-o male fell unconscious during work being unresponsive, with constricted pupils, and convulsing, he did not respond to naloxone. A bottle labeled "Hurricane" was found in his pocket. Five h later the patient awoke and was subsequently discharged with all vitals normal. The patient had recently purchased "Hurricane" as a sleep aid and to treat his panic attacks. It is an organic product with active ingredients similar to ink jet cleaner, the key ingredient being 1,4butanediol, which is metabolized to GHB. In spite of legislative changes restricting GHB, the precursors remain available and continue a public health threat. PMID:15587253

Yambo, C M; McFee, R B; Caraccio, T R; McGuigan, M

2004-12-01

96

GABAA receptor function in the gamma-hydroxybutyrate model of generalized absence seizures.  

PubMed

gamma-Hydroxybutyric acid (GHB) produces absence-like seizures when given to animals. One of the distinguishing characteristics of experimental generalized absence seizures is that they are exacerbated by GABAA agonists. Therefore, the hypothesis that GHB-induced absence seizures result from an interaction between GHB and the GABAA receptor complex was tested. The effect of GHB on the function of various components of the GABAA receptor complex in the cortex of the rat, was determined in a series of in vitro experiments. Similar studies were carried out at various times following systemic administration of the prodrug of GHB, gamma-butyrolactone (GBL) and changes in the GABAA receptor were correlated with electrographic and behavioral changes. gamma-Hydroxybutyric acid had no effect on the binding of [3H]muscimol, [3H]flunitrazepam and [35S]t-butylbicyclophosphorothionate (TBPS) or on the uptake of 36Cl- into synaptoneurosomes in the in vitro studies. Nor were changes observed after the administration of GBL before the onset of GHB-induced absence seizures. However, at the onset of GHB-induced spike wave discharge, there was a significant (P < 0.04) decrease in the binding of [35S]TBPS, associated with a significant decrease in muscimol-stimulated uptake of 36Cl- with no other biochemical change. One minute after onset of GHB-induced absence seizure, a significant (P < 0.05) increase in the binding of [3H]muscimol was noted. Ten minutes later the decrease in muscimol-stimulated uptake of 36Cl- had normalized, while the changes in binding of [3H]muscimol and [35S]TBPS persisted. Because GABAA function remained unchanged in the in vitro studies, as well as prior to the onset of GHB-induced absence seizures in the in vivo experiments, these studies do not support the hypothesis that GHB interacts directly with the GABAA receptor complex to produce absence-like seizures. PMID:8388552

Snead, O C; Liu, C C

1993-04-01

97

[GHB withdrawal delirium].  

PubMed

A 35-year-old man had been using high doses of gamma-hydroxybutyrate (GHB) for many years. He had been trying to cut down on use of this drug for 2 months. He was admitted to the hospital suffering from a withdrawal delirium accompanied by hallucinations and agitation. Use of GHB is increasing in the Netherlands. Along with serious intoxication and dependency, the possibility of withdrawal symptoms should also be taken into consideration. Administration of high doses of benzodiazepines is an effective treatment for these withdrawal symptoms. PMID:20132572

Stijnenbosch, Petra J E; Zuketto, Cassandra; Beijaert, Pieter J; Maat, Anneliek

2010-01-01

98

Determination of gamma-hydroxybutyric acid in human urine by capillary electrophoresis with indirect UV detection and confirmation with electrospray ionization ion-trap mass spectrometry.  

PubMed

Gamma-hydroxybutyric acid (GHB), a minor metabolite or precursor of gamma-aminobutyric acid (GABA), acts as a neurotransmitter/neuromodulator via binding to GABA receptors and to specific presynaptic GHB receptors. Based upon the stimulatory effects, GHB is widely abused. Thus, there is great interest in monitoring GHB in body fluids and tissues. We have developed an assay for urinary GHB that is based upon liquid-liquid extraction and capillary zone electrophoresis (CZE) with indirect UV absorption detection. The background electrolyte is composed of 4 mM nicotinic acid (compound for indirect detection), 3 mM spermine (reversal of electroosmosis) and histidine (added to reach a pH of 6.2). Having a 50 microm I.D. capillary of 40 cm effective length, 1-octanesulfonic acid as internal standard, solute detection at 214 nm and a diluted urine with a conductivity of 2.4 mS/cm, GHB concentrations > or = 2 microg/ml can be detected. Limit of detection (LOD) and limit of quantitation (LOQ) were determined to be dependent on urine concentration and varied between 2-24 and 5-60 microg/ml, respectively. Data obtained suggest that LOD and LOQ (both in microg/ml) can be estimated with the relationships 0.83 kappa and 2.1 kappa, respectively, where kappa is the conductivity of the urine in mS/cm. The assay was successfully applied to urines collected after administration of 25 mg sodium GHB/kg body mass. Negative electrospray ionization ion-trap tandem mass spectrometry was used to confirm the presence of GHB in the urinary extract via selected reaction monitoring of the m/z 103.1-->m/z 85.1 precursor-product ion transition. Independent of urine concentration, this approach meets the urinary cut-off level of 10 microg/ml that is required for recognition of the presence of exogenous GHB. Furthermore, data obtained with injection of plain or diluted urine indicate that CZE could be used to rapidly recognize GHB amounts (in microg/ml) that are > or = 4 kappa. PMID:12685588

Baldacci, Andrea; Theurillat, Regula; Caslavska, Jitka; Pardubská, Helena; Brenneisen, Rudolf; Thormann, Wolfgang

2003-03-21

99

Simultaneous determination of GHB and EtG in hair using GCMS/MS.  

PubMed

A gas chromatographic tandem mass spectrometric (GCMS/MS) method for simultaneously determining trace concentrations of gamma-hydroxybutyrate (GHB) and ethyl glucuronide (EtG) in hair has been developed. Multiple reaction monitoring (MRM) was used to detect precursor and product ions of GHB, (233 and 147) and EtG (261 and 143) following anion exchange solid phase extraction and derivatization with N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA). Deuterated standards of GHB and EtG were used as internal standards. The assay produced excellent linearity (r(2) > 0.99) and sensitivity. The lower limit of quantitation (LLOQ) was 10 pg/mg for EtG assuming a 20 mg hair sample. The method has been used to investigate cases of suspected drug facilitated assault as well as being used to identify heavy alcohol consumption in a group of volunteers. PMID:21500364

Paul, R; Tsanaclis, L; Kingston, R; Berry, A; Guwy, A

2011-04-01

100

Acute poisoning from gamma-hydroxybutyrate in California.  

PubMed Central

We report a series of 5 representative patients in California who experienced adverse reactions from the illicitly marketed substance gamma-hydroxybutyrate (GHB). The drug is a putative neurotransmitter marketed as a growth hormone releaser for bodybuilders. The most commonly reported symptoms included abrupt drowsiness, dizziness, and a "high". Other effects were headache, nausea, vomiting, myoclonic jerking, and short-term coma. There have been no reported deaths. If product use is discontinued, full recovery with no long-term side effects is universal. No clear dose-response effect was observed; this may be attributable to differences in susceptibility, wide variations in doses taken by the same person, or the coingestion of other substances. Case interviews confirm that, despite being banned by the US Food and Drug Administration, GHB is still widely available in the underground drug market. Athletes and bodybuilders may take drugs for which there are claims of improved performance or body image. Physicians should be alert for signs of GHB poisoning in emergency department and clinic patients.

Chin, M. Y.; Kreutzer, R. A.; Dyer, J. E.

1992-01-01

101

A qualitative analysis of GHB use among gay men: Reasons for use despite potential adverse outcomes  

Microsoft Academic Search

This paper examines the use of gamma-hydroxybutyrate (GHB) among a sample of gay men in New York City, who identify GHB as their most frequently used club drug. The sample was drawn from a larger longitudinal investigation of club drug using men. Thematic analysis yielded findings regarding perceived stigma for GHB use, tolerance of potential adverse side effects, and reasons

Joseph J. Palamar; Perry N. Halkitis

2006-01-01

102

GHB Depresses Fast Excitatory and Inhibitory Synaptic Transmission via GABAB Receptors in Mouse Neocortical Neurons  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) is a drug of abuse which induces sedation and euphoria. However, overdoses can severely depress the level of consciousness or can be fatal especially when combined with other substances. Studies have suggested that the GHB-effects are mediated via actions on thalamocortical pathways and local neocortical circuits, although the effect of GHB at the level of single neocortical neurons

Kimmo Jensen; Istvan Mody

2001-01-01

103

GHB: a new and novel drug of abuse  

Microsoft Academic Search

There has been increasing attention in the United States to problems of abuse of gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts of the world as well. In vitro and animal research show that, while GHB shares some properties with abused central nervous system depressant drugs, it has unique aspects of its pharmacology as well, including actions at

Katherine L. Nicholson; Robert L. Balster

2001-01-01

104

[Gamma-hydroxybutyric acid--significance for anesthesia and intensive care medicine?].  

PubMed

Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was first introduced in clinical anaesthetic practice more than 30 years ago. Although GHB induced a reliable state of sedation and anaesthesia without depressing either respiratory or cardiocirculatory parameters or liver and kidney function, the drug was nearly displaced from clinical practice because of its prolonged duration of action. The results of recent clinical studies indicate a re-evaluation of GHB in emergency and critical care medicine. GHB is regarded as a natural neuronal transmitter with circuits which synthesise, accumulate and release GHB. Specific binding sites have also been demonstrated and identified. GHB is completely metabolized in the liver to the natural substrates carbon dioxide and water without accumulation in central or peripheral tissues. The reduction of energy metabolism and its possible properties as an "oxygen radical scavenger" may be of therapeutic benefit if tissues are exposed to hypoxia or reperfusion. Therefore, the application of GHB seems to be of advantage in states of traumatic brain injury with cerebral oedema or ischaemic lesions of brain or extraneural tissues. In hypovolaemic states or in patients with impaired cardiovascular function, the pressure effects of GHB may be beneficial for the prevention of tissue damage and may improve survival in the case of cardiocirculatory resuscitation. In the intensive care unit, GHB might be a favourable alternative to established sedative agents. Occurrence of side effects such as tolerance and withdrawal syndromes after the application of sedative drugs, an impaired metabolism with the accumulation of metabolites in the case of liver or kidney dysfunction as well as an insufficient regulation of natural sleep may be diminished by the application of GHB. The results of various clinical studies also suggest that GHB may be useful in the treatment of alcohol and opiate withdrawal syndrome. However, further studies are necessary to specify the proposed indications of GHB in anaesthesiology and critical care medicine. PMID:8562713

Kleinschmidt, S; Mertzlufft, F

1995-11-01

105

Effects of 1,4-butanediol administration on oxidative stress in rat brain: study of the neurotoxicity of gamma-hydroxybutyric acid in vivo.  

PubMed

gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased in the neurometabolic-inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity or due to intoxication. SSADH deficiency is biochemically characterized by increased concentrations of GHB in tissues, cerebrospinal fluid, blood and urine of affected patients. Clinical manifestations are variable and include retardation of mental, motor, and language development along with other neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown. The precursor of GHB, 1,4-butanediol (1,4-BD) has been used to study the mechanisms of in vivo GHB neurotoxicity. Therefore, in the present work, the effect of acute administration of 20 or 120 mg/Kg 1,4-BD was investigated on various parameters of oxidative stress, such as spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), sulfhydryl and protein carbonyl contents, as well as the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in homogenates from cerebral cortex of 14-day-old Wistar rats. Acute administration of 120 mg/Kg 1,4-BD significantly increased spontaneous chemiluminescence and TBA-RS levels, while TAR measurement was markedly diminished, whereas injection of a lower dose (20 mg/Kg) did not change the parameters examined. Other parameters of oxidative stress evaluated were not affected by administration of 1,4-BD. These results indicate that 1,4-BD induces in vivo oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals intoxicated by GHB or its prodrugs (gamma-butyrolactone or 1,4-BD). PMID:19296210

Sgaravatti, Angela M; Magnusson, Alessandra S; Oliveira, Amanda S; Mescka, Caroline P; Zanin, Fernanda; Sgarbi, Mirian B; Pederzolli, Carolina D; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir; Dutra-Filho, Carlos S

2009-06-01

106

Symmetrical generalization between the discriminative stimulus effects of gamma-hydroxybutyric acid and ethanol: occurrence within narrow dose ranges.  

PubMed

Gamma-hydroxybutyric acid (GHB) has been shown to reduce ethanol consumption and suppress ethanol withdrawal syndrome both in laboratory animals and humans. The present study was designed to assess the similarity between the discriminative stimulus effects, or subjective feelings, of GHB and ethanol using a T-maze, food-reinforced drug discrimination procedure. Three groups of rats were trained to discriminate ethanol (1.0 or 2.0 g/kg; p.o.) or GHB (300 mg/kg; p.o.) from water. In the 1.0 g/kg ethanol-trained rats, substitution for ethanol was an inverted U-shape function of GHB dose, with only 300 mg/kg GHB resulting in complete substitution for ethanol. No dose of GHB elicited selection of ethanol-appropriate arm higher than 10% in the 2.0 g/kg ethanol-trained group. In the 300 mg/kg GHB-trained rats, complete substitution for GHB occurred only at the dose of 1.0 g/kg ethanol. Doses of ethanol lower or higher than 1.0 g/kg did not substitute for GHB. The results of the present study indicate that symmetrical generalization between ethanol and GHB occurred within narrow dose ranges. They are discussed in terms of common neurotransmitter systems involved in the mediation of GHB and ethanol effects. PMID:7878101

Colombo, G; Agabio, R; Lobina, C; Reali, R; Fadda, F; Gessa, G L

1995-01-01

107

gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness.  

PubMed

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence. PMID:17140279

Pardi, Daniel; Black, Jed

2006-01-01

108

Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam.  

PubMed

In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics. PMID:17613965

Nava, Felice; Premi, Stefania; Manzato, Ezio; Campagnola, Wally; Lucchini, Alfio; Gessa, Gian Luigi

2007-01-01

109

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.  

PubMed Central

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

Ferrara, S D; Zotti, S; Tedeschi, L; Frison, G; Castagna, F; Gallimberti, L; Gessa, G L; Palatini, P

1992-01-01

110

Gamma-hydroxybutyrate in urine and serum: additional data supporting current cut-off recommendations.  

PubMed

Besides the use of Gamma-Hydroxybutyrate (GHB) as a recreational drug, use of GHB as an agent in drug-facilitated crime should also be considered. In these cases, there is often a delay of several hours from the incident to collection of the samples. As GHB has a very short plasma half-life, the window of detection is small and in the majority of these specimens, levels of GHB are low. Because GHB is naturally occurring in humans, discrimination between endogenous and exogenous GHB is complicated, particularly in those samples with low concentrations. In this study, endogenous GHB levels of 50 serum and 50 urine samples were determined by GC-MS after conversion to trimethyl-silyl-derivatives. Concentrations in serum ranged from 0.62 to 3.24 mg/L (mean=1.14 mg/L; median=0.97 mg/L) and from 0.64 to 4.20mg/L (mean=1.21 mg/L; median=0.96 mg/L) in urine. Based on this substantial data, the current suggested lower cut-off of 4 mg/L in ante mortem serum samples could be confirmed. For urine, we propose the lower cut-off of 6 mg/L instead of 10mg/L to avoid false negative interpretation. PMID:20418032

Andresen, H; Sprys, N; Schmoldt, A; Mueller, A; Iwersen-Bergmann, S

2010-07-15

111

Analysis of Electrical Brain Waves in Neurotoxicology: Gamma-Hydroxybutyrate  

PubMed Central

Advances in computer technology have allowed quantification of the electroencephalogram (EEG) and expansion of quantitative EEG (qEEG) analysis in neurophysiology, as well as clinical neurology, with great success. Among the variety of techniques in this field, frequency (spectral) analysis using Fast Fourier Transforms (FFT) provides a sensitive tool for time-course studies of different compounds acting on particular neurotransmitter systems. Studies presented here include Electrocorticogram (ECoG) analysis following exposure to a glutamic acid analogue - domoic acid (DOM), psychoactive indole alkaloid - ibogaine, as well as cocaine and gamma-hydroxybutyrate (GHB). The ECoG was recorded in conscious rats via a tether and swivel system. The EEG signal frequency analysis revealed an association between slow-wave EEG activity delta and theta and the type of behavioral seizures following DOM administration. Analyses of power spectra obtained in rats exposed to cocaine alone or after pretreatment with ibogaine indicated the contribution of the serotonergic system in ibogaine mediated response to cocaine (increased power in alpha1 band). Ibogaine also lowered the threshold for cocaine-induced electrographic seizures (increased power in the low-frequency bands, delta and theta). Daily intraperitoneal administration of cocaine for two weeks was associated with a reduction in slow-wave ECoG activity 24 hrs following the last injection when compared with controls. Similar decreased cortical activity in low-frequency bands observed in chronic cocaine users has been associated with reduced metabolic activity in the frontal cortex. The FFT analyses of power spectra relative to baseline indicated a significant energy increase over all except beta2 frequency bands following exposure to 400 and 800 mg/kg GHB. The EEG alterations detected in rats following exposure to GHB resemble absence seizures observed in human petit mal epilepsy. Spectral analysis of the EEG signals combined with behavioral observations may prove to be a useful approach in studying chronic exposure to drugs of abuse and treatment of drug dependence.

Binienda, Z.K; Beaudoin, M.A; Thorn, B.T; Ali, S.F

2011-01-01

112

Determination of GHB and its precursors (GBL and 1,4-BD) in dietary supplements through the synthesis of their isotopologues and analysis by GC-MS method.  

PubMed

Gamma-hydroxybutyric acid (GHB) and its "pro-drugs", gamma-butyrolactone (GBL) and 1,4 butanediol (1,4-BD), are drugs of abuse with depressant effects on the central nervous system. Many analytical methods have been proposed for the quantitative determination of these compounds mainly in biological matrices but only few have been addressed to dietary supplements and foods. Facile synthesis of the GBL and 1,4-BD isotopologues are available by "one pot" Ru-catalyzed homogeneous deuteration of dicarboxylic acids. In this work we propose a new method for determination of GHB, GBL and 1,4-BD in commercially available dietary supplements, based on isotope dilution mass spectrometry (ID-MS). The procedure involves a simple extraction of sample with acidic acetonitrile and direct analysis by GC-ID-MS method without any purification or derivatization. Indeed, the proposed method takes advantage of the complete conversion of GHB (free acid or its salts) to GBL, allowing the quantification of GHB and its pro-drugs. Five levels for each calibration curve have been prepared by diluting working solutions of the analytes to obtain concentrations ranging from 1 to 20mg/mL. The validation procedures have shown an accuracy between 88% and 99% and a precision between 7.3% and 2.9% of each analyte in the sample matrix. Positive ions chemical ionization (PICI) have been employed to preserve the information on molecular ions and to improve specificity and sensitivity of quantitative determination. PMID:23245230

Rosi, Luca; Frediani, Piero; Bartolucci, Gianluca

2013-02-23

113

GHB: Forensic examination of a dangerous recreational drug by FTIR spectroscopy  

NASA Astrophysics Data System (ADS)

Gamma-hydroxybutyric acid (GHB) is an illegal drug that has been abused for its intoxicating effects. However, GHB can also produce harmful physiological effects ranging from mild (nausea, drowsiness) to severe (coma, death). Because GHB is often produced by clandestine manufacture, its concentration, purity, and final form can be variable. Therefore, the analysis of suspected GHB samples using FTIR spectroscopy requires a variety of sample preparations and accessories, based on the sample matrix.

Kindig, J. P.; Ellis, L. E.; Brueggemeyer, T. W.; Satzger, R. D.

1998-06-01

114

Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures.  

PubMed

The efficacy of gamma-hydroxybutyrate (GHB) versus placebo for treating narcolepsy was evaluated in 20 patients with narcolepsy, 10 men and 10 women, using a double-blind counterbalanced crossover design. Each patient completed a daily sleep-wake log and questionnaire during a 14-day baseline, a 29-day placebo period, a 29-day GHB period (50 mg GHB/kg/night given 25 mg/kg h.s. and 25 mg/kg 3 hr later), and a 6-day washout period after each treatment. Cataplexy frequency was significantly lower during GHB treatment than during placebo treatment (p = 0.022). Compared to baseline values, the number of cataplexy attacks per day declined by 52% and 69% during GHB treatment weeks 1 and 4, respectively. The number of subjective arousals from sleep was less with GHB than with placebo (p = 0.035), and the number of sleep attacks was not significantly different during GHB versus placebo treatment. GHB did not have a significant effect on subjective estimates of sleep onset latency, total sleep time, Stanford Sleepiness Scale ratings at morning wake-up, methylphenidate usage, or the number of naps per day. The results indicate that GHB is efficacious for reducing the frequency of cataplexy attacks and subjective nocturnal arousals in patients with narcolepsy within the first 4 weeks of treatment. PMID:2669980

Scrima, L; Hartman, P G; Johnson, F H; Hiller, F C

1989-08-01

115

Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats.  

PubMed

gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures. PMID:1436382

Banerjee, P K; Snead, O C

1992-10-01

116

Gamma-hydroxybutyrate withdrawal syndrome: a case report  

PubMed Central

Introduction To raise awareness among health care workers of the risk of withdrawal symptoms after longstanding and intense abuse of gamma-hydroxybutyric acid. Case presentation A 23 year old Caucasian woman presented with gamma-hydroxybutyric addiction and withdrawal syndrome. The symptoms of gamma-hydroxybutyric withdrawal in this patient initially went unrecognized, upon which her situation deteriorated in such a way that she needed to be admitted to the Intensive Care Unit for airway protection and mechanical ventilation. Treatment with high doses of benzodiazepines led to liberation of the ventilator and further recovery. Conclusion Withdrawal symptoms of gamma-hydroxybutyric addiction are often not well recognized and the responsible physicians at Emergency Department, Intensive Care Unit and the Psychiatry ward need better understanding of diagnose and treatment. Gamma-hydroxybutyric acid withdrawal is potentially life threatening and its management may require a multidisciplinary approach. Early recognition of gamma-hydroxybutyric acid withdrawal may lead to better management of these patients.

2009-01-01

117

The epidemiology of GHB and ketamine use in an Australian household survey  

Microsoft Academic Search

BackgroundThere have been apparent increases in recent years in the illicit use of ketamine and gamma-hydroxybutyrate (GHB), but to date there has been no examination of the epidemiology of use in the general population. This paper provides the first such Australian data on the patterns and correlates of GHB and ketamine use.

Louisa Degenhardt; Matthew Dunn

2008-01-01

118

Weekly gamma-hydroxybutyrate exposure sensitizes locomotor hyperactivity to low-dose 3,4-methylenedioxymethamphetamine in rats.  

PubMed

Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with gamma-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 degrees C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA. PMID:19893336

van Nieuwenhuijzen, P S; Li, K M; Hunt, G E; McGregor, I S

2009-01-01

119

Gamma-Hydroxybutyrate inhibits excitatory postsynaptic potentials in rat hippocampal slices.  

PubMed

Gamma-Hydroxybutyrate (GHB) has been shown to mimic different central actions of ethanol, to suppress alcohol withdrawal syndrome, and to reduce alcohol consumption both in rats and in humans. The aim of the present study was to determine if GHB shared with alcohol the ability to inhibit glutamate action at both NMDA and AMPA/kainate receptors. The NMDA or the AMPA/kainate receptors-mediated postsynaptic potentials were evoked in CA1 pyramidal neurons by stimulation of Schaffer-collateral commissural fibers in the presence of CGP 35348, bicuculline to block the GABA(B) and GABA(A) receptors, and 10 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX) or 30 microM DL-2-amino-5-phosphonovalerate (d-APV) to block AMPA/kainate or NMDA receptors, respectively. GHB (600 microM) produced a depression of both NMDA and AMPA/kainate receptors-mediated excitatory postsynaptic potentials with recovery on washout. The GHB receptors antagonist, NCS-382, at the concentration of 500 microM had no effect per se on these responses but prevented the depressant effect of GHB (600 microM) on the NMDA and AMPA/kainate-mediated responses. In the paired-pulse experiments, GHB (600 microM) depressed the amplitude of the first and the second evoked AMPA/kainate excitatory postsynaptic potentials, and significantly increased the paired-pulse facilitation (PPF). These results suggest that GHB inhibits excitatory synaptic transmission at Schaffer-collateral commissural-pyramidal neurons synapses by decreasing the probability of release of glutamate. PMID:10513569

Berton, F; Brancucci, A; Beghè, F; Cammalleri, M; Demuro, A; Francesconi, W; Gessa, G L

1999-09-10

120

The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study.  

PubMed

The effects of gamma-hydroxybutyrate (GHB: 25 mg/kg h.s. and 3 h later) vs. placebo on objectively evaluated nighttime sleep and daytime sleepiness in narcolepsy were evaluated in a double-blind, counterbalanced crossover design. Twenty narcolepsy patients were given an overnight polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT) at baseline and on the 1st and 29th days of GHB and placebo treatment. The overnight PSGs indicated that the narcolepsy patients had the following significant results during GHB versus placebo treatment: decreased stage 1 (p = 0.012), increased stage 3 (p = 0.008), increased delta (stage 3 and 4 combined) sleep (p = 0.049), fewer stage shifts (p = 0.002), and fewer awakenings (p = 0.006). Minutes of wakefulness were significantly increased only for the last 2 h of the 8 h sleep period on GHB versus placebo (p = 0.019), which is beyond the time of GHB's direct influence. The MSLTs indicated that the narcolepsy patients had a marginally increased sleep latency mean during GHB versus placebo treatment (p = 0.074) and significantly increased total stage 0 (wakefulness) on day 29 of GHB versus day 29 of placebo treatment (p = 0.038). Female narcolepsy patients had significantly fewer naps with REM sleep (REM naps) on day 29 of GHB vs. day 29 of placebo treatment (p = 0.020). The therapeutic effect of GHB in narcolepsy patients, i.e., decreases cataplexy, appears to be due to its improving nocturnal sleep quality, since its half-life is only 1.5 to 2 h. It is conjectured that GHB, an endogenous neurochemical, may be a sleep neurotransmitter or neuromodulator, since GHB rapidly induces sleep, and increases sleep continuity and delta sleep without suppressing REM sleep in both normals and narcolepsy patients. PMID:2281247

Scrima, L; Hartman, P G; Johnson, F H; Thomas, E E; Hiller, F C

1990-12-01

121

Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens  

PubMed Central

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca2+ transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca2+ dynamics evoked by GHB suggested that Ca2+ was released from internal stores. Similarly to SUC, the GHB response was also characterized by an effective concentration of 50??M. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca2+ signal remained in mice lacking GABAB receptor type 1 subunit in the presence and absence of the N-Methyl-d-Aspartate (NMDA) receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV), indicating action mechanisms independent of the GABAB or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252, and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca2+ signaling in astrocytic networks.

Molnar, Tunde; Heja, Laszlo; Emri, Zsuzsa; Simon, Agnes; Nyitrai, Gabriella; Pal, Ildiko; Kardos, Julianna

2011-01-01

122

Determination of GHB in urine and serum by LC\\/MS using a simple one-step derivative  

Microsoft Academic Search

A sensitive and specific method for the determination of gamma-hydroxybutyric acid (GHB) in urine and serum is described. Prior to quantification by LC\\/MS in a Pauli-type ion trap, the molecule is converted by a fast and simple one-step procedure into its n-butyl ester derivative. Hexa-deutero GHB has been used as internal standard.

Eckhard Kaufmann; Andreas Alt

2007-01-01

123

Design and structure-activity relationship analysis of ligands of gamma-hydroxybutyric acid receptors.  

PubMed

With the use of [3H]gamma-hydroxybutyric acid, binding experiments allowed the screening of new compounds as ligands of gamma-hydroxybutyric acid receptors. Starting from the acid-alcohol gamma-hydroxybutyric acid structure, structure-activity relation analysis and lead optimization highlighted gamma-hydroxybutyric acid derivatives with significantly increased affinities, when compared with the affinity of gamma-hydroxybutyric acid. Further pharmacological studies with the use of gamma-hydroxybutyric acid derivatives allowed the characterization of the first competitive antagonist acting at gamma-hydroxybutyric acid receptors (NCS 382). PMID:10869864

Bourguignon, J J; Schmitt, M; Didier, B

2000-04-01

124

Analysis of GHB and 4-methyl-GHB in postmortem matrices after long-term storage.  

PubMed

Postmortem heart blood, peripheral blood, vitreous humor, urine, and bile specimens from 26 autopsy cases were analyzed for the presence of gamma-hydroxybutyric acid (GHB) and gamma-methyl gamma-hydroxybutyric acid (4-Me-GHB) after long-term freezer storage. Cases were selected for which exogenous GHB, gamma-butyrolactone (GBL), gamma valerolactone (GVL), or 1,4-butanediol use was not suspected. One documented positive GHB case subjected to the same storage conditions was also evaluated for comparison. Specimens did not contain any preservatives or additives except heart blood, which contained sodium fluoride (2% w/v). The results of the analysis for GHB in vitreous humor (n = 26) demonstrated, with one exception, concentrations below the limit of detection for the method (5 mg/L). In the exception case, the value was determined to be 7 mg/L. Documented cases of GHB positive fatalities showed vitreous humor concentrations (n = 6) that exceeded this range by a factor of 12 or more. There was no apparent relationship between storage times and GHB concentrations. The data developed in this study demonstrate a postmortem endogenous range for GHB in vitreous humor that is less than or equal to 7 mg/L. Studies of the stored GHB-positive case demonstrated no significant change in concentration over the time period studied. None of the specimens analyzed in this study contained detectable amounts of 4-Me-GHB. This would support the contention that when 4-Me-GHB is detected, it is most likely due to the exogenous consumption of GVL. PMID:15808012

Marinetti, Laureen J; Isenschmid, Daniel S; Hepler, Bradford R; Kanluen, Sawait

2005-01-01

125

Gamma hydroxybutyrate--a coma inducing recreational drug.  

PubMed Central

The effects of gamma hydroxybutyrate, a coma inducing recreational drug, are described and illustrated by case reports of five patients presenting to accident and emergency (A&E). All had depressed levels of consciousness. There was strong circumstantial evidence of gamma hydroxybutyrate ingestion in all cases, and laboratory evidence in two. All recovered and supportive treatment. gamma Hydroxybutyrate has become a fashionable recreational drug. The majority of people who have ingested it will recover spontaneously without long term sequelae but its toxic effects may be dramatic while they last, particularly when it is taken with other drugs or alcohol. Images Figure 3 Figure 1

Ryan, J M; Stell, I

1997-01-01

126

Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal.  

PubMed

The aim of this double-blind, comparative study was to assess the efficacy and safety of gamma-hydroxybutyrate (GHB) in ameliorating the symptoms of alcohol withdrawal. Newly admitted alcohol-dependent patients (n = 98) were randomized to receive either clomethiazole 1000 mg daily (CLO group) (n = 33), or 50 mg GHB/kg body wt (n = 33) or 100 mg GHB/kg body wt (n = 32). This dose was administered for 5 days, halved on day 6, and on days 7 and 8 only placebo was given. As CLO is available as capsules and GHB as syrup, a double-dummy method was used to try to ensure blindness. The groups were matched in terms of baseline demographic and alcohol-related variables. There was no difference between the three treatments in ratings of alcohol withdrawal symptoms nor requests for additional medication. After tapering off the active medication, there was no increase in withdrawal symptoms, indicating that physical tolerance did not develop to either GHB or CLO within the 5-day treatment period. The most frequently reported side-effect of GHB was transient vertigo, particularly after the evening double dose. PMID:11825860

Nimmerrichter, Amanda A; Walter, Henriette; Gutierrez-Lobos, Karin E; Lesch, Otto M

2002-01-01

127

Chemical composition and structure of the microcrystals formed between silver(I) and gamma-hydroxybutyric acid and gamma-hydroxyvaleric acid.  

PubMed

This study examined microcrystals formed by silver with gamma-hydroxybutyric acid (GHB) and gamma-hydroxyvaleric acid (GHV), the five-carbon analog of GHB, in the presence of silver, copper, and lanthanide nitrates. Distinct microcrystals formed with silver (+1) and lanthanum (+3) ions but not with the copper (+2) ions. The crystals formed with GHB were distinctly different than those formed with GHV and in all cases, the drug microcrystals were easily distinguishable from reagent crystals. X-ray diffraction analysis provided definitive structure for the microcrystals. The morphological differences between the silver-GHB and silver-GHV crystals were characterized using simple measurements such as size and angles provided by image recognition software. The utility of the test for casework was demonstrated using spiked beverage samples. PMID:16882223

Bell, Suzanne C; Oldfield, Lucy S; Shakleya, Diaa M; Petersen, Jeffrey L; Mercer, Jennifer W

2006-07-01

128

Simultaneous analysis of gamma-hydroxybutyric acid, gamma-butyrolactone, and 1,4-butanediol by micellar electrokinetic chromatography.  

PubMed

A micellar electrokinetic chromatography (MEKC) method was optimised for simultaneous analysis of gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (BD). Best conditions for separation and baseline stability were achieved using a carrier electrolyte comprising 30.0mM sodium barbital and 150.0mM sodium dodecyl sulphate (SDS) at pH 10.2. Calibration functions were linear, giving correlation coefficients (r(2)) >0.998 for the three target compounds. Limits of detection (LOD) defined as three times the noise, were 5.1mg/l, 0.34 and 0.25g/l for GHB, GBL and BD, respectively. The repeatability of migration times and peak areas, expressed as the R.S.D. (n = 9) was better than 0.41 and 3.05%, respectively. Some casework samples were analysed using the optimised conditions. PMID:11909651

Dahlén, Johan; Vriesman, Thyrsa

2002-02-18

129

Quantitation of Gamma-Hydroxybutyric Acid in Dried Blood Spots: Feasibility Assessment for Newborn Screening of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency  

PubMed Central

Objective SSADH deficiency, the most prevalent autosomal recessive disorder of GABA degradation, is characterized by elevated gamma-hydroxybutyric acid (GHB). Neurological outcomes may be improved with early intervention and anticipatory guidance. Morbidity has been compounded by complications, e.g. hypotonia, in undiagnosed infants with otherwise routine childhood illnesses. We report pilot methodology on the feasibility of newborn screening for SSADH deficiency. Method Dried blood spot (DBS) cards from patients affected with SSADH deficiency were compared with 2831 archival DBS cards for gamma-hydroxybutyric acid content. Following extraction with methanol, GHB in DBS was separated and analyzed using ultra high-performance liquid chromatography tandem mass spectrometry. Results Methodology was validated to meet satisfactory accuracy and reproducibility criteria, including intra-day and inter-day validation. Archival refrigerated dried blood spots samples of babies, infants and children (N=2831) were screened for GHB, yielding a mean +/- S.D. of 8 ± 5 nM (99.9 %-tile 63 nM) (Min 0.0 Max 78 nM). The measured mean and median concentrations in blood spots derived from seven SSADH deficient patients were 1182 nM and 699 nM respectively (Min 124, Max 4851nM). Conclusions GHB concentration in all 2831 dried blood spot cards was well below the lowest concentration of affected children. These data provide proof-of-principle for screening methodology to detect SSADH deficiency with applicability to newborn screening and earlier diagnosis.

Forni, Sabrina; Pearl, Phillip L.; Gibson, K. Michael; Yu, Yuezhou; Sweetman, Lawrence

2013-01-01

130

Determination of gamma-hydroxybutyric acid in biological fluids by using capillary electrophoresis with indirect detection.  

PubMed

gamma-Hydroxybutyric acid (GHB) is a central nervous system (CNS) depressant and hypnotic which, in recent times, has shown an increasing abuse either as recreational drug (due to its euphoric effects and ability to reduce inhibitions) or as doping agent (enhancer of muscle growth). Analogues of GHB, namely gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), share its biological activity and are rapidly converted in vivo into GHB. At present, GHB and analogues are placed in the Schedules of Controlled Substances. Numerous intoxications in GHB abusers have been reported with depressive effects, seizures, coma and possibly death. The purpose of the present work was the development of a rapid analytical method based on capillary zone electrophoresis for the direct determination of GHB in human urine and serum at potentially toxic concentrations. Analytical conditions were as follows. Capillary: length 40 cm (to detector), 75 microm i.d.; buffer: 5.0 mM Na(2)HPO(4), 15 mM sodium barbital adjusted to pH 12 with 1.0 M NaOH; voltage: 25 kV at 23 degrees C; indirect UV detection at 214 nm; injection by application of 0.5 psi for 5 s. alpha-Hydroxyisobutyric acid was used as internal standard (IS). Sample pretreatment was limited to 1:8 dilution. Under these conditions, the sensitivity was approximately 3.0 microg/ml (signal-to-noise ratio >3). Calibration curves prepared in water, urine and serum were linear over concentration ranges 25-500 microg/ml with R(2)>/=0.998. Analytical precision was fairly good with R.S.D.<0.60% (including intraday and day-to-day tests). Quantitative precision in both intraday and day-to-day experiments was also very satisfactory with R.S.D.GHB determination of biological fluids, which could be important for screening purposes in clinical and forensic toxicology. PMID:14698260

Bortolotti, Federica; De Paoli, Giorgia; Gottardo, Rossella; Trattene, Maristella; Tagliaro, Franco

2004-02-01

131

Temporal differences in gamma-hydroxybutyrate overdoses involving injecting drug users versus recreational drug users in Helsinki: a retrospective study  

PubMed Central

Background Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have been profiled as 'party drugs' used mainly at dance parties and in nightclubs on weekend nights. The purpose of this study was to examine the frequency of injecting drug use among GHB/GBL overdose patients and whether there are temporal differences in the occurrence of GHB/GBL overdoses of injecting drug and recreational drug users. Methods In this retrospective study, the ambulance and hospital records of suspected GHB- and GBL overdose patients treated by the Helsinki Emergency Medical Service from January 1st 2006 to December 31st 2007 were reviewed. According to the temporal occurrence of the overdose, patients were divided in two groups. In group A, the overdose occurred on a Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. Group B consisted of overdoses occurring on outside this time frame. Results Group A consisted of 39 patient contacts and the remaining 61 patient contacts were in group B. There were statistically significant differences between the two groups in (group A vs. B, respectively): history of injecting drug abuse (33% vs. 59%, p = 0.012), reported polydrug and ethanol use (80% vs. 62%, p = 0.028), the location where the patients were encountered (private or public indoors or outdoors, 10%, 41%, 41% vs. 25%, 18%, 53%, p = 0.019) and how the knowledge of GHB/GBL use was obtained (reported by patient/bystanders or clinical suspicion, 72%, 28% vs. 85%, 10%, p = 0.023). Practically all (99%) patients were transported to emergency department after prehospital care. Conclusion There appears to be at least two distinct groups of GHB/GBL users. Injecting drug users represent the majority of GHB/GBL overdose patients outside weekend nights.

2012-01-01

132

Concurrent use of methamphetamine, MDMA, LSD, ketamine, GHB, and flunitrazepam among American youths  

Microsoft Academic Search

BackgroundThe magnitude and the characteristics of the use of methamphetamine, MDMA (Ecstasy), LSD (d-lysergic acid diethylamide), ketamine, GHB (gamma-hydroxybutyrate), and flunitrazepam (Rohypnol) were examined in a probability sample of the U.S. civilian population that included multiethnic urban, suburban, and rural youths aged 16–23 (N=19,084).

Li-Tzy Wu; William E. Schlenger; Deborah M. Galvin

2006-01-01

133

Quantitative analysis of gamma-hydroxybutyrate at endogenous concentrations in hair using liquid chromatography tandem mass spectrometry.  

PubMed

A method capable of quantifying endogenous concentrations of gamma-hydroxybutyrate (GHB) in human head hair was developed and validated using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Hair was digested under alkaline conditions, and GHB was isolated using liquid-liquid extraction. LC/MS/MS was performed using atmospheric pressure chemical ionization in the negative mode, multiple reaction monitoring, and deuterated internal standard (GHB-D(6)). Linearity was observed between 0.1 and 100 ng/mg GHB (R(2) = 1.000). The limits of detection and quantitation in human hair were 0.2 and 0.4 ng/mg, respectively. Accuracy at 2 ng/mg and 10 ng/mg was determined to be 97% and 94%, and intra-assay CVs at these concentrations were 5.2% and 7.4% (n = 4). Beta-hydroxybutyrate (BHB), alpha-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol did not produce an interference, and there was negligible ion suppression or enhancement from the matrix. PMID:20141559

Stout, Phillip A; Simons, Kelsie D; Kerrigan, Sarah

2010-03-01

134

Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats.  

PubMed

In unanesthetized rats the intravenous (i.v.) administration of gamma-hydroxybutyric acid (GHB) at the doses of 50-400 mg/kg produced a dose-related stimulation (10-56%) of the firing rate of dopaminergic (DA) neurons in the pars compacta of the substantia nigra. Doses of 1000 and 1500 mg/kg inhibited the firing rate almost completely. In unanesthetized rats the intraperitoneal injection of GHB at the dose of 750 mg/kg produced a brief initial stimulation (23%) followed by a modest reduction in the firing rate (29%). On the other hand, in chloral hydrate-anesthetized rats the i.v. administration of GHB at cumulative doses of up to 200 mg/kg failed to modify the firing rate of DA neurons, while a cumulative dose of 400 mg/kg suppressed neuronal firing. The results indicate that sub-anesthetic doses of GHB stimulate the firing rate of DA neurons in unanesthetized rats. PMID:1814536

Diana, M; Mereu, G; Mura, A; Fadda, F; Passino, N; Gessa, G

1991-12-01

135

Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review.  

PubMed

1,4-butanediol (1,4-BD) is an industrial solvent that is metabolized to gamma-hydroxybutyrate (GHB), a gamma-aminobutyric acid agonist and central nervous system depressant. GHB and its analogues are popular drugs of abuse. Withdrawal from these agents is characterized by autonomic instability and altered mental status. We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis. In addition, we conducted a systematic review of the English literature pertaining to withdrawal from GHB, 1,4-BD and gamma-butyrolactone (GBL). Data collected from source articles included last use prior to symptom onset, clinical features on presentation, duration of symptoms and outcome. Twenty-seven studies with 57 episodes of withdrawal were included. Thirty-six cases (63%) involved GHB, 3 cases (5%) involved 1,4-BD and 18 (32%) involved GBL. The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred. Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome. PMID:18226321

Wojtowicz, Jeremy M; Yarema, Mark C; Wax, Paul M

2008-01-01

136

Effect of gamma-hydroxybutyrate on keratinocytes proliferation: A preliminary prospective controlled study in severe burn patients  

PubMed Central

Background: Hypermetabolism and hyposomatotropism related to severe burns lead to impaired wound healing. Growth hormone (GH) boosts wound healing notably following stimulation of the production of insulin-like growth factor-1 (IGF1), a mitogen factor for keratinocytes. Gamma-hydroxybutyrate (GHB) stimulates endogenous GH secretion. Aim: To assess effects of GHB sedation on keratinocytes proliferation (based on immunohistochemical techniques). Design: Monocentric, prospective, controlled trial. Materials and Methods: Patients (aging 18-65 years, burn surface area >30%, expected to be sedated for at least one month) were alternately allocated, at the 5th day following injury, in three groups according to the intravenous GHB dose administered for 21 days: Evening bolus of 50 mg/kg (Group B), continuous infusion at the rate of 10 mg/kg/h (Group C), or absence of GHB (Group P). They all received local standard cares. Immunohistochemistry (Ki67/MIB-1, Ulex europaeus agglutinin-1 and Mac 387 antibodies) was performed at D21 on adjacent unburned skin sample for assessing any keratinocyte activation. Serum IGF1 levels were measured at initiation and completion of the protocol. Statistical Analysis: Categorical variables were compared with Chi-square test. Comparisons of medians were made using Kruskal-Wallis test. Post hoc analyses were performed using Mann-Whitney test with Bonferroni correction for multiple comparisons. A P < 0.05 was considered to be statistically significant. Results: A total of 14 patients completed the study (Group B: n = 5, Group C: n = 5, Group P: n = 4). Continuous administration of GHB was associated with a significant higher Ki67 immunolabeling at D21 (P = 0.049) and with a significant higher increase in the IGF1 concentrations at D21 (P = 0.024). No adverse effects were disclosed. Conclusions: Our preliminary data support a positive effect of GHB on keratinocyte proliferation and are encouraging enough to warrant large prospective studies.

Rousseau, Anne-Francoise; Bargues, Laurent; Bever, Herve Le; Vest, Philippe; Cavalier, Etienne; Ledoux, Didier; Pierard, Gerald E.; Damas, Pierre

2014-01-01

137

Gamma-hydroxybutyrate: an overview of the pros and cons for it being a neurotransmitter and/or a useful therapeutic agent.  

PubMed

Gamma-hydroxybutyrate (GHB) is a catabolite in brain of gamma-aminobutyrate (GABA) and is also found in nonneuronal tissues. It is present in the brain at about one thousandth of the concentration of its parent compound. High affinity and specific uptake, and energy dependent transport systems for GHB have been described in brain in addition to a class of high affinity binding sites, functional at a rather unphysiologically low pH. Administration of large doses of GHB to animals and man leads to sedation, and at the highest doses, anaesthesia. These effects are prominent when GHB brain levels are over one hundred-fold the endogenous levels. In some animals, GHB administration also induces an electroencephalographic and behavioural changes resembling that of human petit mal epilepsy. GHB has been used in man as an anaesthetic adjuvant. GHB lowers cerebral energy requirements and may play a neuroprotective role. Administered GHB profoundly effects the cerebral dopaminergic system by a mechanism which remains to be unravelled. GHB has been tested with success on alcoholic patients where it attenuates the withdrawal syndrome. It is indicated here that in this situation, it may owe its effect by acting as a pro-drug of the neurotransmitter GABA into which it can be transformed. As administration of GHB, a GABAB receptor agonist and a natural opioid peptide all elicit similar abnormal EEG phenomena, it may be suggested that they are acting via a common pathway. The petit mal epileptic effects of GHB might be ascribed to its direct, or indirect agonist properties after transformation to a pool of GABA at the GABAB receptor or via interactions at its own binding sites linked to a similar series of biochemical events. Some anticonvulsant drugs, the opiate antagonist naloxone and a synthetic structural GHB analogue antagonise certain behavioural effects of GHB administration. It is postulated that GHB exerts some of its effects via transformation to GABA pools, and that substances which inhibit this process antagonise its effects by blocking GABA formation. GHB has been proposed as a neurotransmitter, although straightforward evidence for this role is lacking. Evidence for and against GHB, as a neurotransmitter, is reviewed here together with a discussion of its potential as a therapeutically useful drug. PMID:7914688

Cash, C D

1994-01-01

138

A novel method for GHB detection in urine and its application in drug-facilitated sexual assaults  

Microsoft Academic Search

A confirmation procedure for the identification and quantification of gamma-hydroxybutyric acid (GHB) in urine is presented. This method is unique in that it does not involve the conversion of GHB to the gamma-butyrolactone (GBL). The urine samples were extracted using ethyl acetate, evaporated and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS), and analyzed by gas chromatography–mass spectrometry. Quantification was

Albert A Elian

2000-01-01

139

The possible influence of micro-organisms and putrefaction in the production of GHB in post-mortem biological fluid  

Microsoft Academic Search

In recent years, the post-mortem production of the drug of abuse gamma-hydroxybutyric acid (GHB) in biological fluids (e.g. blood and urine) has caused various interpretative problems for toxicologists. Previously, other researchers have shown certain microbial species (Pseudomonas spp. and Clostridium aminobutyricum) possess the necessary enzymes to convert GABA to GHB.A preliminary investigation involving putrefied post-mortem blood indicated there was no

Simon Elliott; Pauline Lowe; Amanda Symonds

2004-01-01

140

Gamma-hydroxybutyric acid and alcohol-related syndromes  

Microsoft Academic Search

We report on the effectiveness and safety of gamma-hydroxybutyric acid in the therapy of overt alcohol withdrawal syndromes, their prevention, and the prevention of relapses in formerly detoxified alcoholics. We studied 321 patients (236 men, 85 women), divided into two open-study groups for the treatment and prevention of alcohol withdrawal syndromes and one double-blind study group to evaluate the effects

M. Moncini; E. Masini; F. Gambassi; P. F. Mannaioni

2000-01-01

141

GHB acid: A rage or reprive.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs. PMID:24350046

Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

2013-10-01

142

GHB acid: A rage or reprive  

PubMed Central

Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

2013-01-01

143

Testing for GHB in hair by GC/MS/MS after a single exposure. Application to document sexual assault.  

PubMed

Gamma-hydroxybutyric acid, or GHB, is a substance naturally present within mammal species. Properties of neurotransmitter or neuromodulator are generally given to this substance. GHB is therapeutically used as an anesthetic, but can be used for criminal offenses (date-rape drug). It appears that the window of detection of GHB is very short in both blood and urine, and therefore its presence is very difficult to prove after a rape case. In order to document single exposure, we investigated the use of hair. Hair was collected one month after the allegated event in order to sample the corresponding period after regular growing. After rapid (2 min) decontamination with dichloromethane, the hair shaft was cut into 3-mm segments. They were overnight incubated in 0.01 N NaOH in the presence of GHB-d6, followed by neutralization and extraction in ethyl acetate under acidic conditions. GHB (precursor ion m/z 233, product ions m/z 147 and 148) was tested by GC/MS/MS (Finnigan TSQ 700) after derivatization with BSTFA + 1% TMCS. Physiological concentrations (n = 24) were in the range 0.5 to 12.0 ng/mg, with no influence due to hair color. No variation of concentrations was observed along the hair shaft in controlled subjects, except for the proximal segment, due to an incorporation through sweat. This demonstrates that endogenous levels for each single subject are constant during hair growth. A controlled human administration of 25 mg/kg to a volunteer demonstrated that a single exposure to GHB is detectable in hair after segmentation. In a case of rape under influence, a clear increase of the corresponding segment (about 2.4 ng/mg) in time was observed, in comparison with the other segments (0.6 to 0.8 ng/mg). This study demonstrates that a single exposure to GHB in a case of sexual assault can be documented by hair analysis when collected about one month after the crime. PMID:12570228

Kintz, Pascal; Cirimele, Vincent; Jamey, Carole; Ludes, Bertrand

2003-01-01

144

Unusually high concentrations in a fatal GHB case.  

PubMed

The first case in France involving a fatal overdose resulting from the ingestion of gamma-hydroxybutyrate (GHB) is presented. GHB was tested by gas chromatography-mass spectrometry (GC-MS) after precipitation. Briefly, 20 microL of body fluids (blood, bile, urine, gastric contents, or vitreous humor) was pipetted in a glass tube, followed by 20 microL GHB-d6 and 45 microL acetonitrile. After vortex mixing and centrifuging, the supernatant was collected and evaporated to dryness. The residue was derivatized with BSTFA with 1% TMCS for 20 min at 70 degrees C. After injection on a 30-m HP5 MS capillary column, GHB (m/z 233, 204, and 147) and GHB-d6 (m/z 239) were identified by MS. GHB was also tested in pubic hair after incubation in 0.01 N NaOH, neutralization, acidification, extraction in ethyl acetate and derivatization with MTBSTFA, using GC-MS-MS. GHB was positive in all the tested specimens, with the following concentrations 2937, 33,727, 1800, and 2856 mg/L in femoral blood, urine, bile, and vitreous humor, respectively. This seems to be the highest blood concentration ever observed. Postmortem redistribution appears weak, as the concentration in cardiac blood was 3385 mg/L (cardiac blood/femoral blood ratio of 1.15). Oral route was suggested with GHB at 7.08 g in 100 mL of gastric contents. Pubic hair analysis clearly indicated chronic GHB abuse, with concentrations along the shaft in the range 19.4 to 25.0 ng/mg (in comparison with physiological concentrations < 2 ng/mg). Methylenedioxymethamphetamine was present in femoral blood at 144 ng/mL. These results are consistent with an acute fatal overdose of GHB. PMID:16168184

Kintz, Pascal; Villain, Marion; Pélissier, Anne-Laure; Cirimele, Vincent; Leonetti, Georges

2005-09-01

145

[GHB, GBL and butanediol poisonings--a serious problem in Western Sweden].  

PubMed

Acute poisoning with GHB (Gamma-hydroxybutyrate, Gamma-hydroxybutyric acid) has been an increasing medical and social problem during the last decade in Sweden, especially on the west coast. The number of poisonings decreased in the beginning of this millennium but has again increased during the last years. At the same time the number of seizures by the police has increased similarly as well as the number of drug-related deaths. During 2004 the number of GHB-abuse related deaths in western Sweden was seven, approximately the same figures as for heroin. Two other substances which are transformed to GHB in the human body, GBL (gamma-butyrolactone) and 1,4-butanediol, have during the last years presented themselves among the same users as for GHB. Since GBL and butanediol are not classified as illicit drugs the possibilities for the police force to intervene and capture the drugs are severely restricted. Intoxication by GBL and butanediol has shown to be as dangerous as intoxication by GHB. Acute intoxications and abuse of these drugs is still a serious medical and social problem. A legal classification of GBL and butanediol as narcotics appears to be medically motivated. PMID:16342543

Knudsen, Kai; Greter, Joachim; Verdicchio, Mario; Cederquist, Thomas

146

Gamma-hydrobutyric acid (GHB) and its chemical modifications: a review of the GHBergic system.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance with function of an inhibitory neurotransmitter in the central nervous system in mammals. GHB can be used as a medicine in narcolepsy (Xyrem) and for general anesthesia (sodium oxybate). It is also a popular drug of abuse, causing coma, addiction and severe withdrawal syndrome, and, therefore, demanding thorough studies on the GHBergic system and expanded research on toxicology of this compound. The aim of this review is to present the proved and some suggested mechanisms of its action from pharmacological point of view, which may help to properly treat intoxication or other pathological states caused by GHB ingestion. Some new GHB derivatives studied for analogous action and their present use are also described. PMID:15047976

Waszkielewicz, Anna; Bojarski, Jacek

2004-01-01

147

Gamma-hydroxybutyric acid in the treatment of alcohol and heroin dependence  

Microsoft Academic Search

We briefly review two double-blind, placebo-controlled surveys conducted in this laboratory with the aim of evaluating the efficacy of gamma-hydroxybutyric acid in the treatment of alcohol withdrawal syndrome as well as alcohol craving and consumption in alcoholics. In the first study, acute administration of 50 mg\\/kg gamma-hydroxybutyric acid, a nonhypnotic dose in alcoholic patients, resulted in a rapid and significant

Luigi Gallimberti; Maurizio Raffaele Spella; Carlo Alberto Soncini; Gian Luigi Gessa

2000-01-01

148

Comparative abuse liability of GHB and ethanol in humans.  

PubMed

Gamma-hydroxybutyric acid (GHB; sodium oxybate) is approved for narcolepsy symptom treatment, and it is also abused. This study compared the participant-rated, observer-rated effects, motor/cognitive, physiological, and reinforcing effects of GHB and ethanol in participants with histories of sedative (including alcohol) abuse. Fourteen participants lived on a residential unit for ?1 month. Sessions were conducted Monday through Friday. Measures were taken before and repeatedly up to 24 hours after drug administration. Participants were administered GHB (1, 2, 4, 6, 8, and 10 g/70 kg), ethanol (12, 24, 48, 72, 96, and 120 g/70 kg), or placebo in a double-blind, within-subjects design. For safety, GHB and ethanol were administered in an ascending dose sequence, with placebos and both drugs intermixed across sessions. The sequence for each drug was stopped if significant impairment or intolerable effects occurred. Only 9 and 10 participants received the full dose range for GHB and ethanol, respectively. The highest doses of GHB and ethanol showed onset within 30 minutes, with peak effects at 60 minutes. GHB effects dissipated between 4 and 6 hours, whereas ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, postsession measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, most likely as a result of the delayed aversive ethanol effects (e.g., headache). PMID:23421353

Johnson, Matthew W; Griffiths, Roland R

2013-04-01

149

Detection of gamma-hydroxybutyrate in hair: validation of GC-MS and LC-MS/MS methods and application to a real case.  

PubMed

A gas chromatography-mass spectrometry (GC-MS) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method were validated for quantifying endogenous and exogenous hair concentrations of gamma-hydroxybutyrate (GHB). The GC-MS method is based on overnight extraction of 25 mg hair in NaOH at 56 °C, liquid/liquid extraction in ethylacetate and trimethylsylil derivatization; analysis is by electron ionization and single ion monitoring of three ions. The LC-MS/MS method entails a rapid digestion of 25 mg hair with NaOH at 75 °C for 40 min, liquid/liquid extraction in ethylacetate and reconstitution of the extract in the LC mobile phase; negative ion electrospray ionization and multiple reaction monitoring (MRM) analysis are employed for the LC-MS/MS detection. In both cases, GHB-d6 is used as an internal standard. The endogenous amount in "blank" hair are estimated by the standard addition method. Limits of detection are 0.4 and 0.5 ng/mg for GC-MS and LC-MS/MS respectively, while the limit of quantification (LOQ) is 0.6 ng/mg for both methods; the GC-MS method proved to be linear in the range 1-50 ng/mg whereas linearity was demonstrated from 0.6 to 50 ng/mg for the LC-MS/MS; imprecision and inaccuracy were always lower than 23% for quality controls samples. The two methods were applied to a real case of a man addicted to GHB; the drug concentration in segments from 17 cm hair strand well correlated with self-reported use of GHB in different periods of his life. Performances of the two methods were similar. PMID:22884787

Bertol, Elisabetta; Argo, Antonina; Procaccianti, Paolo; Vaiano, Fabio; Di Milia, Maria Grazia; Furlanetto, Sandra; Mari, Francesco

2012-11-01

150

Spinal anaesthesia with gamma hydroxybutyrate. A study in a rat model.  

PubMed

Gamma hydroxybutyric acid, a central inhibitory neurotransmitter and a cerebral metabolite of gamma-aminobutyric acid, is present in high concentrations in the mammalian hypothalamus and basal ganglia. Its sodium salt gamma hydroxybutyrate has been effectively used as an intravenous anaesthetic agent, and as an oral sedative, and in the management of the alcohol withdrawal syndrome. In an animal model, using 72 Wistar strain rats allocated to one of six groups of 12 animals each, with implanted lumbar intrathecal catheters, we examined whether gamma hydroxybutyrate, 20% 40 microL (32 mg kg-1) administered alone or combined with fentanyl, gamma hydroxybutyrate 20% 20 microL (16 mg kg-1), fentanyl 0.005% 20 microL (4 mg kg-1) as an intrathecal bolus, provides intraoperative anaesthesia, comparable with that produced by intrathecal lignocaine. We demonstrated that gamma hydroxybutyrate, given by an intrathecal bolus in the rat model, produced reversible segmental antinociception, together with muscular relaxation of the abdominal wall and rear limbs. This is accompanied by moderate sedation without haemodynamic or respiratory depression. This agent may thus be promising for use as a spinal anaesthetic drug. PMID:10390669

Chanimov, M; Bahar, M; Cohen, M L; Brenner, R; Koifman, I; Grinshpon, Y

1999-05-01

151

Determination of ?-hydroxybutyrate (GHB), ?-hydroxybutyrate (BHB), pregabalin, 1,4-butane-diol (1,4BD) and ?-butyrolactone (GBL) in whole blood and urine samples by UPLC-MSMS.  

PubMed

The demand of high throughput methods for the determination of gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butane-diol (1,4BD) as well as for pregabalin is increasing. Here we present two analytical methods using ultra-high pressure liquid chromatography (UPLC) and tandem mass spectrometric (MS/MS) detection for the determination of GHB, beta-hydroxybutyrate (BHB), pregabalin, 1,4BD and GBL in whole blood and urine. Using the 96-well formate, the whole blood method is a simple high-throughput method suitable for screening of large sample amounts. With an easy sample preparation for urine including only dilution and filtration of the sample, the method is suitable for fast screening of urine samples. Both methods showed acceptable linearity, acceptable limits of detection, and limits of quantification. The within-day and between-day precisions of all analytes were lower than 10% RSD. The analytes were extracted from matrices with recoveries near 100%, and no major matrix effects were observed. Both methods have been used as routine screening analyses of whole blood and urine samples since January 2010. PMID:22226469

Dahl, Sandra Rinne; Olsen, Kirsten Midtbøen; Strand, Dag Helge

2012-02-15

152

Target Analysis of GHB, GBL, 1.4BD and GVL in Whole Blood and Urine by LC\\/MS\\/MS and Application to a Forensic Case  

Microsoft Academic Search

A LC\\/MS\\/MS application for identification and quantification of gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), 1.4-butanediol (1.4-BD) and gamma-valerolactone (GVL) in biological samples from forensic cases is developed. Sample preparation is a simple protein precipitation (whole blood) or dilution (urine). Chromatographic separation is achieved on a Zorbax SB C18 column and detection by a tandem mass spectrometer in MRM mode. The linear range

Sys Stybe Johansen; Charlotte Norup Windberg

153

Gamma-hydroxybutyric acid Efficacy, potential abuse, and dependence in the treatment of alcohol addiction  

Microsoft Academic Search

The main objective in alcoholism therapy is to achieve and maintain abstinence and to prevent relapse. Pharmacotherapy may be necessary in treating persons who are not helped by group or psychosocial support alone. Among the substances experimented with in the past few years, gamma-hydroxybutyric acid has been effective in preventing alcohol withdrawal syndrome and in inducing a reduction in craving

Giovanni Addolorato; Fabio Caputo; Esmeralda Capristo; G. Francesco Stefanini; Giovanni Gasbarrini

2000-01-01

154

GC-MS Analysis of [gamma]-Hydroxybutyric Acid Analogs: A Forensic Chemistry Experiment  

ERIC Educational Resources Information Center

An upper-division forensic chemistry experiment is described. It involves using glycolic acid and sodium glycolate as analogs of [gamma]-hydroxybutyric acid and its sodium salt. The experiment shows the use of silylation in GC-MS analysis and gives students the opportunity to work with a commonly used silylating reagent,…

Henck, Colin; Nally, Luke

2007-01-01

155

Gamma-hydroxybutyric aciduria: A biochemist’s education from a heritable disorder of GABA metabolism  

Microsoft Academic Search

In keeping with the theme of the 41st Annual Symposium (Metabolic Encephalopathies), the current report provides an overview of a quarter century of research investigating a rare inborn error of GABA metabolism, succinic semialdehyde dehydrogenase (SSADH) deficiency (also referred to as gamma-hydroxybutyric aciduria). The clinical phenotype, treatment challenges, pathomechanistic concepts, as well as metabolic, enzymatic and molecular characteristics, of the

K. M. Gibson

2005-01-01

156

Acute toxicity and withdrawal syndromes related to ?-hydroxybutyrate (GHB) and its analogues ?-butyrolactone (GBL) and 1,4-butanediol (1,4-BD).  

PubMed

Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues gamma-butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues. PMID:21548140

Wood, David M; Brailsford, Alan D; Dargan, Paul I

2011-01-01

157

Screening and confirmation methods for GHB determination in biological fluids.  

PubMed

The purpose of this review is to provide a comprehensive overview of reported methods for screening and confirmation of the low-molecular-weight compound and drug of abuse gamma-hydroxybutyric acid (GHB) in biological fluids. The polarity of the compound, its endogenous presence, its rapid metabolism after ingestion, and its instability during storage (de novo formation and interconversion between GHB and its lactone form gamma-butyrolactone) are challenges for the analyst and for interpretation of a positive result. First, possible screening procedures for GHB are discussed, including colorimetric, enzymatic, and chromatography-based procedures. Confirmation methods for clinical and forensic cases mostly involve gas chromatography (coupled to mass spectrometry), although liquid chromatography and capillary zone electrophoresis have also been used. Before injection, sample-preparation techniques include (a combination of) liquid-liquid, solid-phase, or headspace extraction, and chemical modification of the polar compound. Also simple "dilute-and-shoot" may be sufficient for urine or serum. Advantages, limitations, and trends are discussed. PMID:24500753

Ingels, Ann-Sofie M E; Wille, Sarah M R; Samyn, Nele; Lambert, Willy E; Stove, Christophe P

2014-06-01

158

Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain  

Microsoft Academic Search

Two parent clones of a -hydroxybu- tyrate (GHB) receptor, C12K32 and GHBh1, were isolated from a human frontal cortex cDNA library. The two clones differ by a deleted cytosine in C12K32. CHO cells transfected with either C12K32 or GHBh1 responded positively to submicromolar GHB stimula- tion. However, unlike C12K32, GHBh1 desensitizes rapidly on application of low concentrations of GHB. GHB

Christian Andriamampandry; Omar Taleb; Veronique Kemmel; Jean-Paul Humbert; Dominique Aunis; Michel Maitre

2007-01-01

159

Effects of sustained gamma-hydroxybutyrate treatments on spontaneous and evoked firing activity of locus coeruleus norepinephrine neurons  

Microsoft Academic Search

BackgroundGamma-hydroxybutyrate is currently used to promote nighttime sleep in the treatment of narcolepsy; however, it is also a drug of abuse (“Liquid Ecstacy”) associated with a withdrawal syndrome with anxiety features. Of interest, the activity of locus coeruleus neurons is a reflective index of these above mentioned behavioral states.

Steven T Szabo; Mark S Gold; Bruce A Goldberger; Pierre Blier

2004-01-01

160

Antiabsence seizure activity of specific GABAB and gamma-Hydroxybutyric acid receptor antagonists.  

PubMed

Hydroxybutyric acid (GHB) is a naturally occurring compound that has the ability to induce generalized absence seizures possibly by GABAB-receptor-mediated mechanisms. The object of these experiments was to examine the effectiveness of a range of specific GABAB-receptor agonists and antagonists of varying specificity, as well as the specific GHB-receptor antagonist NCS 382, in two experimental animal models of generalized absence seizures: one in which the seizures are induced by GHB and the other in which the seizures are induced by administration of low-dose (20-mg/kg) pentylenetetrazole. All specific GABAB-receptor antagonists as well as the specific GHB-receptor antagonist produced blockade of experimental absence seizures in both models; pretreatment with GABAB-receptor agonists resulted in generalized absence status epilepticus lasting for hours. These data confirm the concept that specific GABAB-receptor antagonist activity confers antiabsence seizure activity, suggest that the same holds for specific GHB-receptor antagonists, and raise the possibility that both GHB- and GABAB-antagonist drugs have the potential to be useful therapeutic agents in generalized absence seizures. PMID:8848463

Snead, O C

1996-01-01

161

The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms.  

PubMed

Sodium oxybate (gamma-hydroxybutyrate; GHB) has demonstrated efficacy for the treatment of narcolepsy. However, there are reports of withdrawal following chronic abuse of illicit GHB which involve escalating both doses and dosing frequency. The present trial afforded an opportunity to test the hypothesis that chronic daily therapeutic dosing of sodium oxybate in narcoleptics does not cause withdrawal following abrupt cessation. Fifty-five narcoleptic patients, taking sodium oxybate (dose range 3-9 gm/night) for 7-44 months (mean 21 months), were randomized into a 2-week double-blind period: 29 patients received placebo and 26 continued to receive sodium oxybate. During this 2-week trial period, the following symptoms were reported in patients receiving placebo (N): anxiety (2), dizziness (1), insomnia (1) and somnolence (1). While these symptoms may represent possible symptoms of mild GHB withdrawal, they are also highly consistent with the returning symptoms of narcolepsy. We conclude there is minimal evidence of withdrawal symptoms following abrupt cessation of chronic sodium oxybate dosing in the therapeutic range. PMID:12733850

2003-01-01

162

Glycoconjugated hypocrellin: photosensitized generation of free radicals (O2*-, *OH, and GHB*-) and singlet oxygen (1O2).  

PubMed

To improve water solubility and specific affinity for malignant tumors, glycoconjugated hypocrellin B (GHB) has been synthesized. Illumination of deoxygenated DMSO solution containing GHB generates a strong electron paramagnetic resonance (EPR) signal. The EPR signal is assigned to the semiquinone anion radical of GHB (GHB*-) based on a series of experimental results. Spectrophotometric measurements show that the absorption bands at 645 nm and 502 nm (pH 8.0) or 505 nm (pH 11.0) arise from the semiquinone anion radical (GHB*-) and hydroquinone (GHBH2) of GHB, respectively. GHBH2 is readily formed via the decay of GHB*- in water-contained solution. The increase of pH value of the reaction media promotes this process. When oxygen is present, superoxide anion radical (O2*-) is formed, via the electron transfer from GHB*-, the precursor, to ground state molecular oxygen. Hydroxyl radical can be readily detected by DMPO spin trapping when aerobic aqueous solution containing GHB is irradiated. As compared with the parent compound, hypocrellin B (HB), the efficiency of O2* and *OH generation by GHB photosensitization is enhanced significantly. Singlet oxygen (1O2) can be produced via the energy transfer from triplet GHB to ground state oxygen molecules, with a decreased quantum yield, i.e., 0.19. These findings suggest that the new GHB possesses an enhanced type I process and a decreased type II process as compared with hypocrellin B. PMID:10443937

Yuying, H; Jingyi, A; Lijin, J

1999-07-01

163

Management of Gamma-Butyrolactone Dependence with Assisted Self-Administration of GBL  

PubMed Central

Gamma-hydroxybutyric acid (GHB) and its liquid precursor gamma-butyrolactone (GBL) have become increasingly popular beyond the clubbing culture resulting in daily consumption and dependence in the broader population. This case report illustrates the challenges of managing GHB-withdrawal and a possibly superior future approach of its management by titration and tapering of the addictive agent.

Meyer, Rafael; Jenewein, Josef

2014-01-01

164

Cloning of a rat brain succinic semialdehyde reductase involved in the synthesis of the neuromodulator gamma-hydroxybutyrate.  

PubMed Central

The gamma-hydroxybutyrate biosynthetic enzyme succinic semialdehyde reductase (SSR) was purified to homogeneity from rat brain. Peptides were generated by tryptic cleavage and sequenced. PCR primers were designed from the amino acid sequences of two of the peptides showing a similarity (75-85%) to a mitochondrial aldehyde dehydrogenase. A PCR-amplified DNA fragment was generated from recombinant plasmids prepared by a mass excision procedure from a rat hippocampal cDNA library and used as a probe to screen this cDNA library. One cDNA of 1341 bp had an open reading frame encoding a protein of 447 residues with a deduced molecular mass of 47967 Da. The enzyme was expressed in Escherichia coli. Immunoblotting analysis revealed the existence of a protein with the same electrophoretic mobility as the SSR purified from rat brain and with an estimated molecular mass of 45 kDa. Northern blot experiments showed that this enzyme was not expressed in the kidney or in the liver. In the brain tissue, a single but rather broad band was labelled under high stringency conditions, suggesting the presence of more than one messenger species coding for SSR. Hybridization in situ performed on brain tissue slices showed specific labelling of the hippocampus, the upper cortex layer, the thalamus, the substantia nigra, the cerebellum, the pons medulla and the olfactory tract. The recombinant enzyme showed catalytic properties similar to those of the SSR purified from rat brain, particularly in regard to its substrate affinities and Ki for inhibition by phthalaldehydic acid. Valproic acid did not inhibit the cloned SSR. This enzyme had 20-35% identity in highly conserved regions involved in NADPH binding with four other proteins belonging to the aldo-oxo reductase family.

Andriamampandry, C; Siffert, J C; Schmitt, M; Garnier, J M; Staub, A; Muller, C; Gobaille, S; Mark, J; Maitre, M

1998-01-01

165

Behavioral analyses of GHB: Receptor mechanisms  

Microsoft Academic Search

GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss

Lawrence P. Carter; Wouter Koek; Charles P. France

2009-01-01

166

76 FR 17968 - Manufacturer of Controlled Substances; Notice of Registration  

Federal Register 2010, 2011, 2012, 2013

...registered as a bulk manufacturer of Gamma Hydroxybutyric Acid (GHB) (2010), a basic class of controlled substance listed in...The company plans to manufacture Gamma Hydroxybutyric Acid (GHB) [[Page 17969

2011-03-31

167

75 FR 53719 - Manufacturer of Controlled Substances; Notice of Application  

Federal Register 2010, 2011, 2012, 2013

...registered as a bulk manufacturer of Gamma Hydroxybutyric Acid (GHB) (2010), a basic class of controlled substance listed in...The company plans to manufacture Gamma Hydroxybutyric Acid (GHB) (2010) in bulk active pharmaceutical ingredient (API)...

2010-09-01

168

3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone  

SciTech Connect

An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg el-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP. 34 references, 4 figures.

Vayer, P.; Gobaille, S.; Mandel, P.; Maitre, M.

1987-08-03

169

Ethanol withdrawal-induced up-regulation of the alpha2 subunit of the GABAA receptor and its prevention by diazepam or gamma-hydroxybutyric acid.  

PubMed

The gamma-aminobutyric acid type A (GABA(A)) receptor is an important pharmacological target of ethanol. The effect of ethanol withdrawal on the expression of the alpha(2) subunit of this receptor was examined with rat cerebellar granule cells in primary culture. Long-term exposure of these cells to ethanol (100 mM, 5 days) did not affect the abundance of the mRNA for the alpha(2) subunit, as revealed by an RNase protection assay. In contrast, subsequent ethanol withdrawal for 3 h induced a marked increase in the amount of this mRNA (2.6-fold) as well as in that of the encoded polypeptide (2.2-fold), the latter revealed by immunoblot analysis. Exposure of the cells to gamma-hydroxybutyric acid (100 mM) during ethanol withdrawal prevented the increase in the amounts of both the alpha(2) mRNA and polypeptide, whereas similar treatment with diazepam (10 microM) blocked the increase in the abundance of the alpha(2) polypeptide but not that in the amount of the alpha(2) mRNA. The effect of gamma-hydroxybutyric acid was not blocked by the competitive GABA(B) receptor antagonist SCH 50911(10 microM). Given that the alpha(2) subunit of the GABA(A) receptor mediates the anxiolytic action of benzodiazepines, its up-regulation during discontinuation of long-term ethanol exposure might be relevant to the therapeutic efficacy of these drugs in the treatment of anxiety associated with ethanol withdrawal. PMID:14741402

Follesa, Paolo; Biggio, Francesca; Mancuso, Luisa; Cabras, Stefano; Caria, Stefania; Gorini, Giorgio; Manca, Annalisa; Orru, Alessandro; Biggio, Giovanni

2004-01-01

170

Effect of storage temperature on endogenous GHB levels in urine  

Microsoft Academic Search

Because ?-hydroxybutyrate (GHB) is an endogenous substance present in the body and is rapidly eliminated after ingestion, toxicologists investigating drug-facilitated sexual assault cases are often asked to differentiate between endogenous and exogenous levels of GHB in urine samples.This study was designed to determine the effects of storage temperature on endogenous GHB levels in urine. Specifically, it was designed to ascertain

Marc A LeBeau; Mark L Miller; Barry Levine

2001-01-01

171

Chronic intragastric administration of gamma-butyrolactone produces physical dependence in baboons  

Microsoft Academic Search

Rationale  Abuse of gamma-hydroxybutyrate (GHB) and its precursors is a public health concern. Gamma-butyrolactone (GBL) is found in commercially available products and, when ingested, is metabolized to GHB.Objective  The goal was to evaluate the physical dependence potential and behavioral effects of GBL.Methods  Vehicle and then GBL were administered continuously (24 h per da\\u0009y) in baboons (Papio anubis, n=5) via intragastric catheters. GBL dosing

Amy K. Goodwin; Roland R. Griffiths; P. Rand Brown; Wolfgang Froestl; Cornelis Jakobs; K. Michael Gibson; Elise M. Weerts

2006-01-01

172

A validated GC-MS procedure for fast, simple, and cost-effective quantification of glycols and GHB in human plasma and their identification in urine and plasma developed for emergency toxicology.  

PubMed

Methods developed for use in emergency toxicology have to be fast and simple. Additionally, such methods should be multi-analyte procedures because they allow monitoring of analytes of different drug classes in one single body sample. This is important because often only a limited amount of sample is available and the results have to be reported as fast as possible. Therefore, we describe the improvement of an existing method published by van Hee at al. The new method is fast and simple and designed for the simultaneous determination of ethylene glycol, 1,2-propylene glycol, lactic acid, glycolic acid, gamma-hydroxybutyric acid (GHB), diethylene glycol, triethylene glycol, and tetraethylene glycol in human plasma or urine. A 50-?L aliquot of sample was deproteinized and 20 ?l of the diluted specimen were derivatized using bis-N,O-trimethylsilyl trifluoroacetamide and the catalyst dimethylformamide. After microwave-assisted derivatization, an aliquot was injected into the gas chromatograph and analyzed with electron ionization mass spectrometry in selective ion monitoring mode. All compounds are separated within 12 min and detected with a limit of quantification of 0.05 and 0.01 g/L for glycols and GHB, respectively. Calibration was linear from 0.05 to 1.0 g/L for glycols and 0.01 to 0.2 g/L for GHB. Validation criteria were shown to be in the required limits with exception of lactic acid. Average analysis time from starting sample preparation until quantitative plasma results of approximately 35 min was achieved. This turnaround time is considered most appropriate for emergency cases. PMID:21336790

Meyer, Markus R; Weber, Armin A; Maurer, Hans H

2011-04-01

173

The pharmacology of gamma valerolactone (GVL) as compared to gamma hydroxybutyrate (GHB), gamma butyrolactone (GBL), 1,4 butanediol (1,4 BD), ethanol (EtOH) and baclofen (BAC) in the rat  

Microsoft Academic Search

The recent emergence of diet aid products containing gamma valerolactone (GVL) is a cause for concern. Although GVL is approved by the Food and Drug Administration (FDA), the FDA approved “dose” of GVL is tens of thousands of times lower than that which is currently recommended in the diet aid products. Little is known about the pharmacological effects of high

Laureen J Marinetti

2003-01-01

174

Reconstructors: Nothing To Rave About - Episode 2. Students learn about gas chromatography/mass spectrometry, gamma hydroxybutyrate (GHB), methylenedioxymethamphetamine and how ecstasy and other club drugs act on the nervous system  

NSDL National Science Digital Library

In Nothing To Rave About Episode 2, students are asked to uncover why there has been a dramatic increase in the number of teens admitted to the emergency room after partying at a local dance club. During their investigation, they learn how ecstasy and other club drugs act on the nervous system. Also available in Spanish.

Learning, Center F.

2011-09-28

175

Long-Term ?-Hydroxybutyric Acid (GHB) and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics  

PubMed Central

Leading Italian studies support the use of ?-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

Maremmani, Angelo Giovanni Icro; Pani, Pier Paolo; Rovai, Luca; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

2011-01-01

176

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB  

Microsoft Academic Search

Although preclinical studies suggest that GHB has low likelihood for abuse, case reports indicate that GHB is abused. This study evaluated the relative abuse liability of GHB in 14 volunteers with histories of drug abuse. Psychomotor, subjective, and cognitive effects of a broad range of GHB doses (2–18 g\\/70 kg), up to a dose that produced severe behavioral impairment in

Lawrence P Carter; Brian D Richards; Miriam Z Mintzer; Roland R Griffiths

2006-01-01

177

Forensic cases involving the use of GHB in The Netherlands  

Microsoft Academic Search

In this study, forensic cases involving the use of Gamma Hydroxy Butyric acid (GHB) from the second half of 1999 through the second half of 2001 in The Netherlands (blood >5mg\\/l and urine >10mg\\/l) are described. GHB was analysed by GC–MS after lactone formation and using GHB-d6 as internal standard. The results are divided into three groups: cases of chemical

Ingrid J. Bosman; Klaas J. Lusthof

2003-01-01

178

Determination of gamma-hydroxybutyric acid in biofluids using a one-step procedure with "in-vial" derivatization and headspace-trap gas chromatography-mass spectrometry.  

PubMed

A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to determine GHB, a low molecular weight compound and drug of abuse, in various biological fluids. Combining this relatively novel and fully automated headspace technique with "in-vial" methylation of GHB allowed for a straightforward approach. One single method could be used for all biofluids (urine, plasma, serum, whole blood or lyzed blood), requiring only 100?l of sample. Moreover, our approach involves mere addition of all reagents and sample into one vial. Following optimization of headspace conditions and trap settings, validation was performed. Although sample preparation only consists of the addition of salt and derivatization reagents directly to a 100?l-sample in a HS-vial, adequate method sensitivity and selectivity was obtained. Calibration curves ranged from 5 to 150?g/ml GHB for urine, from 2 to 150?g/ml for plasma, and from 3.5 to 200?g/ml for whole blood. Acceptable precision and accuracy (<13% bias and imprecision) were seen for all quality controls (QC's) (LLOQ-level, low, medium, high), including for the supplementary serum- and lyzed blood-based QC's, using calibration curves prepared in plasma or whole blood, respectively. Incurred sample reanalysis demonstrated assay reproducibility, while cross-validation with another GC-MS method demonstrated that our method is a valuable alternative for GHB determination in toxicological samples, with the advantage of requiring only 100?l and minimal hands-on time, as sample preparation is easy and injection automated. PMID:23664352

Ingels, Ann-Sofie M E; Neels, Hugo; Lambert, Willy E; Stove, Christophe P

2013-06-28

179

?-Hydroxybutyrate (GHB)-Induced Respiratory Depression: Combined Receptor-Transporter Inhibition Therapy for Treatment in GHB Overdose  

PubMed Central

Overdose of ?-hydroxybutyrate (GHB) frequently causes respiratory depression, occasionally resulting in death; however, little is known about the dose-response relationship or effects of potential overdose treatment strategies on GHB-induced respiratory depression. In these studies, the parameters of respiratory rate, tidal volume, and minute volume were measured using whole-body plethysmography in rats administered GHB. Intravenous doses of 200, 600, and 1500 mg/kg were administered to assess the dose-dependent effects of GHB on respiration. To determine the receptors involved in GHB-induced respiratory depression, a specific GABAB receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABAA receptor antagonist, bicuculline, were administered before GHB. The potential therapeutic strategies of receptor inhibition and monocarboxylate transporter (MCT) inhibition were assessed by inhibitor administration 5 min after GHB. The primary effect of GHB on respiration was a dose-dependent decrease in respiratory rate, accompanied by an increase in tidal volume, resulting in little change in minute volume. Pretreatment with 150 mg/kg SCH50911 completely prevented the decrease in respiratory rate, indicating agonism at GABAB receptors to be primarily responsible for GHB-induced respiratory depression. Administration of 50 mg/kg SCH50911 after GHB completely reversed the decrease in respiratory rate; lower doses had partial effects. Administration of the MCT inhibitor l-lactate increased GHB renal and total clearance, also improving respiratory rate. Administration of 5 mg/kg SCH50911 plus l-lactate further improved respiratory rate compared with the same dose of either agent alone, indicating that GABAB and MCT inhibitors, alone and in combination, represent potential treatment options for GHB-induced respiratory depression.

Morse, Bridget L.; Vijay, Nisha

2012-01-01

180

?-Hydroxybutyrate (GHB)-induced respiratory depression: combined receptor-transporter inhibition therapy for treatment in GHB overdose.  

PubMed

Overdose of ?-hydroxybutyrate (GHB) frequently causes respiratory depression, occasionally resulting in death; however, little is known about the dose-response relationship or effects of potential overdose treatment strategies on GHB-induced respiratory depression. In these studies, the parameters of respiratory rate, tidal volume, and minute volume were measured using whole-body plethysmography in rats administered GHB. Intravenous doses of 200, 600, and 1500 mg/kg were administered to assess the dose-dependent effects of GHB on respiration. To determine the receptors involved in GHB-induced respiratory depression, a specific GABA(B) receptor antagonist, (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), and a specific GABA(A) receptor antagonist, bicuculline, were administered before GHB. The potential therapeutic strategies of receptor inhibition and monocarboxylate transporter (MCT) inhibition were assessed by inhibitor administration 5 min after GHB. The primary effect of GHB on respiration was a dose-dependent decrease in respiratory rate, accompanied by an increase in tidal volume, resulting in little change in minute volume. Pretreatment with 150 mg/kg SCH50911 completely prevented the decrease in respiratory rate, indicating agonism at GABA(B) receptors to be primarily responsible for GHB-induced respiratory depression. Administration of 50 mg/kg SCH50911 after GHB completely reversed the decrease in respiratory rate; lower doses had partial effects. Administration of the MCT inhibitor l-lactate increased GHB renal and total clearance, also improving respiratory rate. Administration of 5 mg/kg SCH50911 plus l-lactate further improved respiratory rate compared with the same dose of either agent alone, indicating that GABA(B) and MCT inhibitors, alone and in combination, represent potential treatment options for GHB-induced respiratory depression. PMID:22561075

Morse, Bridget L; Vijay, Nisha; Morris, Marilyn E

2012-08-01

181

What You Need to Know about Drugs: GHB  

MedlinePLUS

... About Drugs: GHB KidsHealth > Kids > Puberty & Growing Up > Drugs, Alcohol & Smoking > What You Need to Know About Drugs: ... THIS TOPIC What You Need to Know About Drugs Alcohol Dealing With Peer Pressure Contact Us Print Additional ...

182

Blockade of the discriminative stimulus effects of ?-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS382  

Microsoft Academic Search

The present study was designed to assess the ability of the newly synthetized, selective ?-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700

Giancarlo Colombo; Roberta Agabio; Jacques Bourguignon; Fabio Fadda; Carla Lobina; Michel Maitre; Roberta Reali; Martine Schmitt; Gian Luigi Gessa

1995-01-01

183

Development of a fluorescent sensor for illicit date rape drug GHB.  

PubMed

The first fluorescent sensor (GHB Orange) for date rape drug GHB was developed. It exhibits the fluorescence quenching property for GHB and allows its detection in various drinks. The interaction mechanism was elucidated as intramolecular charge transfer induced by a hydrogen bond. This discovery will help in solving the drug facilitated sexual assault problems. PMID:24492471

Zhai, Duanting; Tan, Yong Qiao Elton; Xu, Wang; Chang, Young-Tae

2014-03-18

184

Reconsidering GHB: orphan drug or new model antidepressant?  

PubMed

For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. PMID:21926421

Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Wetter, Thomas C

2012-05-01

185

EEG-Veränderungen unter Sedierung mit ?-Hydroxybuttersäure (GHB)  

Microsoft Academic Search

Zusammenfassung  \\u000a \\u000a \\u000a Gamma-Hydroxybuttersäure (GHB) als zentraler Neurotransmitter wird zur Sedierung in der Intensivmedizin eingesetzt. Trotz\\u000a insgesamt sehr günstigen pharmakologischen Profils wurde seine Eignung in Frage gestellt, da es beim Tier in sehr hoher Dosierung\\u000a Krampfpotentiale auslösen kann und in dieser Absicht sogar als Modellsubstanz für die Absenzen-typische Attacke dient. Nach\\u000a eigenen positiven Erfahrungen mit GHB im klinischen Einsatz wurde bei 31

E. Entholzner; L. Mielke; R. Pichlmeier; F. Weber; H. Schneck

1995-01-01

186

?-Hydroxybutyric acid (GHB) is not an agonist of extrasynaptic GABAA receptors.  

PubMed

?-Hydroxybutyric acid (GHB) is an endogenous compound and a drug used clinically to treat the symptoms of narcolepsy. GHB is known to be an agonist of GABAB receptors with millimolar affinity, but also binds with much higher affinity to another site, known as the GHB receptor. While a body of evidence has shown that GHB does not bind to GABAA receptors widely, recent evidence has suggested that the GHB receptor is in fact on extrasynaptic ?4?1? GABAA receptors, where GHB acts as an agonist with an EC50 of 140 nM. We investigated three neuronal cell types that express a tonic GABAA receptor current mediated by extrasynaptic receptors: ventrobasal (VB) thalamic neurons, dentate gyrus granule cells and striatal medium spiny neurons. Using whole-cell voltage clamp in brain slices, we found no evidence that GHB (10 µM) induced any GABAA receptor mediated current in these cell types, nor that it modulated inhibitory synaptic currents. Furthermore, a high concentration of GHB (3 mM) was able to produce a GABAB receptor mediated current, but did not induce any other currents. These results suggest either that GHB is not a high affinity agonist at native ?4?1? receptors, or that these receptors do not exist in classical areas associated with extrasynaptic currents. PMID:24244421

Connelly, William M; Errington, Adam C; Crunelli, Vincenzo

2013-01-01

187

Possible long-term effects of ?-hydroxybutyric acid (GHB) due to neurotoxicity and overdose.  

PubMed

In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory. PMID:22342779

van Amsterdam, Jan G C; Brunt, Tibor M; McMaster, Minni T B; Niesink, Raymond J M

2012-04-01

188

?-Hydroxybutyric Acid (GHB) Is Not an Agonist of Extrasynaptic GABAA Receptors  

PubMed Central

?-Hydroxybutyric acid (GHB) is an endogenous compound and a drug used clinically to treat the symptoms of narcolepsy. GHB is known to be an agonist of GABAB receptors with millimolar affinity, but also binds with much higher affinity to another site, known as the GHB receptor. While a body of evidence has shown that GHB does not bind to GABAA receptors widely, recent evidence has suggested that the GHB receptor is in fact on extrasynaptic ?4?1? GABAA receptors, where GHB acts as an agonist with an EC50 of 140 nM. We investigated three neuronal cell types that express a tonic GABAA receptor current mediated by extrasynaptic receptors: ventrobasal (VB) thalamic neurons, dentate gyrus granule cells and striatal medium spiny neurons. Using whole-cell voltage clamp in brain slices, we found no evidence that GHB (10 µM) induced any GABAA receptor mediated current in these cell types, nor that it modulated inhibitory synaptic currents. Furthermore, a high concentration of GHB (3 mM) was able to produce a GABAB receptor mediated current, but did not induce any other currents. These results suggest either that GHB is not a high affinity agonist at native ?4?1? receptors, or that these receptors do not exist in classical areas associated with extrasynaptic currents.

Connelly, William M.; Errington, Adam C.; Crunelli, Vincenzo

2013-01-01

189

Regulation of ?-aminobutyric acid (GABA) release in cerebral cortex in the ?-hydroxybutyric acid (GHB) model of absence seizures in rat  

Microsoft Academic Search

?-Hydroxybutyric acid (GHB) has the ability to induce absence seizures. The precise way in which GHB causes seizures remains unclear, but GABAB- and\\/or GHB-mediated presynaptic mechanisms within thalamocortical circuitry may play a role. In the present study, we determined the basal and K+-evoked release of GABA and glutamate in the superficial laminae of frontal cortex during GHB-induced absence seizures. Our

R. Q Hu; P. K Banerjee; O. C Snead III

2000-01-01

190

Gammahydroxybutyrate withdrawal syndrome: dangerous but not well-known  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) is an endogenous inhibitory neurotransmitter and anesthetic agent that is being abused as a ‘club drug.’ Withdrawal symptoms after cessation of GHB use are common and depend on the intensity of use. However, GHB withdrawal syndrome and delirium are unfamiliar to most psychiatrists, probably due to the fact that neither textbooks nor guidelines cover the subject. The GHB

Martijn S. van Noorden; Lieselotte C. A. M. van Dongen; Frans G. Zitman

2009-01-01

191

Verve and Jolt: deadly new Internet drugs.  

PubMed

As regulatory agencies have increased restrictions on the sale and marketing of gamma-hydroxybutyrate (GHB), they have been frustrated by the appearance of precursor molecules such as gamma-butyrolactone (GBL) that have become widely available over the Internet. These dangerous precursors are vigorously marketed to adolescents and young adults as dietary supplements that increase muscle mass and enhance sexual performance with seductive names such as Verve and Jolt, both easily recognizable teen icons. We present the case of an adolescent who ingested both of these GBL products 2 weeks apart, resulting in life-threatening respiratory depression and emergent intubation on both occasions. The GBL toxidrome, necessary acute interventions, and public health implications are reviewed. We urge all health care providers to report similar cases immediately to the FDA MedWatch system. Gamma-butyrolactone, gamma-hydroxybutyrate, respiratory insufficiency, central nervous system depressants, substance abuse. PMID:11015528

Winickoff, J P; Houck, C S; Rothman, E L; Bauchner, H

2000-10-01

192

?4?? GABAA receptors are high-affinity targets for ?-hydroxybutyric acid (GHB)  

PubMed Central

?-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both physiological and pharmacological actions. However, the mechanistic links between these lines of data are unknown. To identify molecular targets for specific GHB high-affinity binding, we undertook photolinking studies combined with proteomic analyses and identified several GABAA receptor subunits as possible candidates. A subsequent functional screening of various recombinant GABAA receptors in Xenopus laevis oocytes using the two-electrode voltage clamp technique showed GHB to be a partial agonist at ???- but not ???-receptors, proving that the ?-subunit is essential for potency and efficacy. GHB showed preference for ?4 over ?(1,2,6)-subunits and preferably activated ?4?1? (EC50 = 140 nM) over ?4?(2/3)? (EC50 = 8.41/1.03 mM). Introduction of a mutation, ?4F71L, in ?4?1(?)-receptors completely abolished GHB but not GABA function, indicating nonidentical binding sites. Radioligand binding studies using the specific GHB radioligand [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid showed a 39% reduction (P = 0.0056) in the number of binding sites in ?4 KO brain tissue compared with WT controls, corroborating the direct involvement of the ?4-subunit in high-affinity GHB binding. Our data link specific GHB forebrain binding sites with ?4-containing GABAA receptors and postulate a role for extrasynaptic ?4?-containing GABAA receptors in GHB pharmacology and physiology. This finding will aid in elucidating the molecular mechanisms behind the proposed function of GHB as a neurotransmitter and its unique therapeutic effects in narcolepsy and alcoholism.

Absalom, Nathan; Eghorn, Laura F.; Villumsen, Inge S.; Karim, Nasiara; Bay, Tina; Olsen, Jesper V.; Knudsen, Gitte M.; Brauner-Osborne, Hans; Fr?lund, Bente; Clausen, Rasmus P.; Chebib, Mary; Wellendorph, Petrine

2012-01-01

193

Urinary endogenous concentrations of GHB and its isomers in healthy humans and diabetics  

Microsoft Academic Search

Urinary endogenous concentrations of ?-hydroxybutyric acid (GHB), ?-hydroxybutyric acid (AHB) and ?-hydroxybutyric acid (BHB) have been investigated for both healthy humans and diabetics by using a newly optimized GC–MS procedure. The endogenous concentrations in healthy volunteers’ urine ranged 0.16–2.14?g\\/ml for GHB, 0.10–2.68?g\\/ml for AHB and 8.51–34.7?g\\/ml for BHB. In diabetics, the concentrations ranged 0.17–3.03?g\\/ml for GHB, 0.14–124?g\\/ml for AHB and

Noriaki Shima; Akihiro Miki; Tooru Kamata; Munehiro Katagi; Hitoshi Tsuchihashi

2005-01-01

194

Uptake of gamma-valerolactone--detection of gamma-hydroxyvaleric acid in human urine samples.  

PubMed

Gamma-valerolactone (GVL) is reported to be a substance that can be used as a legal substitute for gamma-hydroxybutyric acid (GHB), which is currently a controlled substance in several countries. Unlike gamma-butyrolactone and 1,4-butanediol, GVL is not metabolized to GHB, which causes the effects after uptake of these two chemicals. In the case of GVL, the lactone ring is split to gamma-hydroxyvaleric acid (GHV or 4-methyl-GHB) by a lactonase. Because of its affinity for the GHB receptor, GHV reveals similar effects to GHB, although it is less potent. Intoxications with GVL, or its use as a date rape drug, are conceivable. Despite these facts, there are no publications in the literature regarding detections of GHV in human samples. This study reports three cases, including five urine samples, in which GHV could be detected in concentrations between 3 and 5.8 mg/L. In one of these cases, a drug-facilitated sexual assault (DFSA) was assumed; four of these samples were from two people suspected of abusing GHB. The results indicate that GVL is used as an alternative to GHB and its precursors and should be taken seriously. GVL or GHV should be included in toxicological analysis, particularly in DFSA cases. More information is needed regarding the pharmacokinetics of GVL/GHV for the meaningful interpretation of positive or negative results. PMID:23486087

Andresen-Streichert, H; Jungen, H; Gehl, A; Müller, A; Iwersen-Bergmann, S

2013-05-01

195

Gammahydroxybutyrate withdrawal syndrome  

Microsoft Academic Search

Study Objective: Gamma-hydroxybutyrate (GHB) withdrawal syndrome is increasingly encountered in emergency departments among patients presenting for health care after discontinuing frequent GHB use. This report describes the characteristics, course, and symptoms of this syndrome. Methods: A retrospective review of poison center records identified 7 consecutive cases in which patients reporting excessive GHB use were admitted for symptoms consistent with a

Jo Ellen Dyer; Brett Roth; Bruce A. Hyma

2001-01-01

196

Gammahydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) is both a therapeutic agent and a recreative drug. It has sedative, anxiolytic and euphoric effects. These effects are believed to be due to GHB-induced potentiation of cerebral GABAergic and dopaminergic activities, but the serotonergic system might also be involved. In this study, we examine the effects of pharmacological doses of GHB on the serotonergic activity in rat

Serge Gobaille; Carmen Schleef; Viviane Hechler; Sandrine Viry; Dominique Aunis; Michel Maitre

2002-01-01

197

Relation of the [ 3H]?-hydroxybutyric acid (ghb) binding site to the ?-aminobutyric acid b (gaba b) receptor in rat brain  

Microsoft Academic Search

Hydroxybutyric acid (GHB) is a naturally occurring compound that has the ability to induce generalized absence seizures when given to animals. GHB has been hypothesized to induce this effect via the postsynaptic ?-aminobutyric acidB (GABAB) receptor. We sought to test this hypothesis by examining the affinity of GABAB agonists and antagonists for the [3H]GHB binding site, the affinity of GHB

O. Carter Snead

1996-01-01

198

Behavioral Effects of ?-Hydroxybutyrate, Its Precursor ?-Butyrolactone, and GABAB Receptor Agonists: Time Course and Differential Antagonism by the GABAB Receptor Antagonist 3-Aminopropyl(diethoxymethyl)phosphinic Acid (CGP35348)  

PubMed Central

?-Hydroxybutyrate (GHB) is used therapeutically and recreationally. The mechanism by which GHB produces its therapeutic and recreational effects is not entirely clear, although GABAB receptors seem to play an important role. This role could be complex, because there are indications that different GABAB receptor mechanisms mediate the effects of GHB and the prototypical GABAB receptor agonist baclofen. To further explore possible differences in underlying GABAB receptor mechanisms, the present study examined the effects of GHB and baclofen on operant responding and their antagonism by the GABAB receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). Pigeons were trained to peck a key for access to food during response periods that started at different times after the beginning of the session. In these pigeons, GHB, its precursor ?-butyrolactone (GBL), and the GABAB receptor agonists baclofen and 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF97541) decreased the rate of responding in a dose- and time-dependent manner. CGP35348 shifted the dose-response curve of each agonist to the right, but the magnitude of the shift differed among the agonists. Schild analysis yielded a pA2 value of CGP35348 to antagonize GHB and GBL [i.e., 3.9 (3.7–4.2)] that was different (P = 0.0011) from the pA2 value to antagonize baclofen and SKF97541 [i.e., 4.5 (4.4–4.7)]. This finding is further evidence that the GABAB receptor mechanisms mediating the effects of GHB and prototypical GABAB receptor agonists are not identical. A better understanding of the similarities and differences between these mechanisms, and their involvement in the therapeutic effects of GHB and baclofen, could lead to more effective medications with fewer adverse effects.

Koek, Wouter; Mercer, Susan L.; Coop, Andrew; France, Charles P.

2009-01-01

199

Restless legs syndrome in narcolepsy: a side effect of sodium oxybate?  

PubMed

Gamma-hydroxybutyrate (GHB) has re-emerged as a major treatment for narcolepsy. As dopaminergic transmission is clearly involved in the pathophysiology of restless legs syndrome (RLS), and GHB reduces dopamine release, one may hypothesize that RLS may occur in narcolepsy in the presence of GHB. We report a case of narcolepsy with a severe occurrence of typical RLS with GHB, symptoms never previously experienced by the subject and reversible after withdrawal. PMID:17275405

Abril, Beatriz; Carlander, Bertrand; Touchon, Jacques; Dauvilliers, Yves

2007-03-01

200

Residual social, memory and oxytocin-related changes in rats following repeated exposure to ?-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination  

Microsoft Academic Search

Rationale  There has been little investigation of the possible lasting adverse effects of ?-hydroxybutyrate (GHB).\\u000a \\u000a \\u000a \\u000a Objectives  This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting\\u000a changes in brain monoamines and oxytocin-related gene expression.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Rats received daily intraperitoneal injections of GHB (500 mg\\/kg), methylenedioxymethamphetamine (MDMA; 5 mg\\/kg) or their\\u000a combination (GHB\\/MDMA) over ten consecutive

Petra S. van Nieuwenhuijzen; Leonora E. Long; Glenn E. Hunt; Jonathon C. Arnold; Iain S. McGregor

2010-01-01

201

Gamma-Hydroxybuttersäure: Neurotransmitter, Sedativum und Droge  

Microsoft Academic Search

Summary. Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was first intro- duced in clinical anaesthesic practice more than 40 years ago. The drug was nearly forced from clinical practice be- cause of its prolonged and variable duration of action. The results of recent clinical studies indicate a re-evaluation of GHB in various clinical fields. In the

2005-01-01

202

New synthesis and tritium labeling of a selective ligand for studying high-affinity ?-hydroxybutyrate (GHB) binding sites.  

PubMed

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [(3)H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [(3)H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Vogensen, Stine B; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H F; Clausen, Rasmus P

2013-10-24

203

Pharmacokinetics of GHB and detection window in serum and urine after single uptake of a low dose of GBL - an experiment with two volunteers.  

PubMed

During the last few years ?-hydroxybutyric acid (GHB) and ?-butyrolactone (GBL) have attracted much interest as recreational drugs and knock-out drops in drug-facilitated sexual assaults. This experiment aims at getting an insight into the pharmacokinetics of GHB after intake of GBL. Therefore Two volunteers took a single dose of 1.5?ml GBL, which had been spiked to a soft drink. Assuming that GBL was completely metabolized to GHB, the corresponding amount of GHB was 2.1?g. Blood and urine samples were collected 5?h and 24?h after ingestion, respectively. Additionally, hair samples (head hair and beard hair) were taken within four to five weeks after intake of GBL. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after protein precipitation with acetonitrile. The following observations were made: spiked to a soft drink, GBL, which tastes very bitter, formed a liquid layer at the bottom of the glass, only disappearing when stirring. Both volunteers reported weak central effects after approximately 15?min, which disappeared completely half an hour later. Maximum concentrations of GHB in serum were measured after 20 min (95?µg/ml and 106?µg/ml). Already after 4-5?h the GHB concentrations in serum decreased below 1?µg/ml. In urine maximum GHB concentrations (140?µg/ml and 120?µg/ml) were measured after 1-2?h, and decreased to less than 1?µg/ml within 8-10?h. The ratio of GHB in serum versus blood was 1.2 and 1.6. PMID:23733593

Schröck, Alexandra; Hari, Yvonne; König, Stefan; Auwärter, Volker; Schürch, Stefan; Weinmann, Wolfgang

2014-04-01

204

Survey and assessment of the actual state of routine measurement of glycohaemoglobin\\/GHb by commercial methods: warning to the users and the providers  

Microsoft Academic Search

As the clinical availability of glycohaemoglobin\\/GHb measurement increases, so does the need for comparable and accurate values among different laboratories and different methods. At least there should be comparability, i.e., commutability or feasibility of providing comparable results from different assays in different laboratories. A clinical joint study on insulin therapy, a survey of the actual inter-laboratory differences in GHb measurement

Tadao Hoshine; Mikiko Okahashi; Hiroko Arai

1997-01-01

205

Placement of gamma-butyrolactone in List I of the Controlled Substances Act (21 U.S.C. 802(34)). Drug Enforcement Administration, Justice. Final rule.  

PubMed

Public Law 106-172, signed into law on February 18, 2000, and known as the "Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 1999," amends section 102(34) of the Controlled Substances Act as amended (CSA) by designating gamma-butyrolactone (GBL), the precursor to gamma-hydroxybutyric acid (GHB), as a List I chemical. Reflecting this change in stature, the Drug Enforcement Administration (DEA) is amending its regulation to reflect the status of GBL as a List I chemical subject to the requirements of the CSA and its regulations. Establishment of a threshold for GBL will be the subject of a separate rulemaking. Therefore, unless and until a threshold is established, any distribution of GBL is a regulated transaction as described by 21 CFR 1300.02(b)(28). All handlers of GBL must comply with the CSA regulatory requirements pertaining to List I chemicals as described in the body of this document. PMID:11010670

2000-04-24

206

A novel quadruplex real-time PCR method for simultaneous detection of Cry2Ae and two genetically modified cotton events (GHB119 and T304-40)  

PubMed Central

Background To date, over 150 genetically modified (GM) crops are widely cultivated. To comply with regulations developed for genetically modified organisms (GMOs), including labeling policies, many detection methods for GMO identification and quantification have been developed. Results To detect the entrance and exit of unauthorized GM crop events in China, we developed a novel quadruplex real-time PCR method for simultaneous detection and quantification of GM cotton events GHB119 and T304-40 in cotton-derived products (based on the 5?-flanking sequence) and the insect-resistance gene Cry2Ae. The limit of detection was 10 copies for GHB119 and Cry2Ae and 25 copies for T304-40. The limit of quantification was 25 copies for GHB119 and Cry2Ae and 50 copies for T304-40. Moreover, low bias and acceptable standard deviation and relative standard deviation values were obtained in quantification analysis of six blind samples containing different GHB119 and T304-40 ingredients. Conclusions The developed quadruplex quantitative method could be used for quantitative detection of two GM cotton events (GHB119 and T304-40) and Cry2Ae gene ingredient in cotton derived products.

2014-01-01

207

Trends in the use of alcohol and other drugs in cases of sexual assault  

Microsoft Academic Search

Recent media coverage has raised awareness of the involvement of drugs, both licit and illicit, in the crime of 'date' or 'acquaintance' rape. The term 'date rape drug' has been coined and has been used to label a few specific drugs because of their alleged properties. These include flunitrazepam (Rohypnol), gamma hydroxybutyrate (GHB) and ketamine. Concerns over reports of flunitrazepam

Ian Hindmarch; Rüdiger Brinkmann

1999-01-01

208

Pentobarbital for severe gamma-butyrolactone withdrawal  

Microsoft Academic Search

Study Objective: Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have become popular drugs of abuse. Acute overdose with either agent results in a well-recognized syndrome of central nervous system and respiratory depression. Recently, a withdrawal syndrome has been described for GHB. We report a severe form of GBL withdrawal, characterized by delirium, psychosis, autonomic instability, and resistance to benzodiazepine therapy. Methods: We

Marco L. A. Sivilotti; Michael J. Burns; Cynthia K. Aaron; Michael J. Greenberg

2001-01-01

209

Gamma-hydroxy butyric acid: Neurotransmitter, sedative and party drug  

Microsoft Academic Search

Summary Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was first introduced in clinical anaesthesic practice more than 40 years ago. The drug was nearly forced from clinical practice because of its prolonged and variable duration of action. The results of recent clinical studies indicate a re-evaluation of GHB in various clinical fields. In the intensive care unit,

Sascha Meyer; Stefan Kleinschmidt; Sven Gottschling; Ludwig Gortner; Matthias Strittmatter

2005-01-01

210

Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling.  

PubMed

Succinic semialdehyde dehydrogenase (SSADH) catalyzes the NADP-dependent oxidation of succinic semialdehyde to succinate, the final step of the GABA shunt pathway. SSADH deficiency in humans is associated with excessive elevation of GABA and gamma-hydroxybutyrate (GHB). Recent studies of SSADH-null mice show that elevated GABA and GHB are accompanied by reduced glutamine, a known precursor of the neurotransmitters glutamate and GABA. In this study, cerebral metabolism was investigated in urethane-anesthetized SSADH-null and wild-type 17-day-old mice by intraperitoneal infusion of [1,6-(13)C(2)]glucose or [2-(13)C]acetate for different periods. Cortical extracts were prepared and measured using high-resolution (1)H-[(13)C] NMR spectroscopy. Compared with wild-type, levels of GABA, GHB, aspartate, and alanine were significantly higher in SSADH-null cortex, whereas glutamate, glutamine, and taurine were lower. (13)C Labeling from [1,6-(13)C(2)]glucose, which is metabolized in neurons and glia, was significantly lower (expressed as mumol of (13)C incorporated per gram of brain tissue) for glutamate-(C4,C3), glutamine-C4, succinate-(C3/2), and aspartate-C3 in SSADH-null cortex, whereas Ala-C3 was higher and GABA-C2 unchanged. (13)C Labeling from [2-(13)C]acetate, a glial substrate, was lower mainly in glutamine-C4 and glutamate-(C4,C3). GHB was labeled by both substrates in SSADH-null mice consistent with GABA as precursor. Our findings indicate that SSADH deficiency is associated with major alterations in glutamate and glutamine metabolism in glia and neurons with surprisingly lesser effects on GABA synthesis. PMID:17854388

Chowdhury, G M I; Gupta, M; Gibson, K M; Patel, A B; Behar, K L

2007-12-01

211

Comparison of the actions of gamma-butyrolactone and 1,4-butanediol in Swiss-Webster mice.  

PubMed

The abuse of gamma-hydroxybutyrate (GHB) and two of its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are recognized as a public health concern. Here, we report dose-response and time-course analyses for effects of GBL and 1,4-BD on locomotor activity and body temperature in Swiss-Webster mice. Locomotor activity was measured for 2 h following a single injection of one of four doses of each agent plus a saline vehicle control. At 50 mg/kg, GBL produced an initial depression of locomotor activity which was followed by stimulation of locomotor activity. In contrast, 1,4-BD at 50 mg/kg stimulated locomotor activity without producing any depression of activity. At higher doses, GBL produced primarily a dose-dependent decrease in locomotor activity that returned to baseline within 50 min. In contrast, 1,4-BD produced an initial depression which was followed by stimulation of activity. Body temperature was measured rectally across a 2.5-h time course following injection with either agent. Both drugs produced hypothermia with peak effects occurring at 20 and 30 min for both drugs for the lower and higher dose, respectively. At 150 mg/kg, GBL produced a greater hypothermic response; however, no differences in hypothermic response were observed at 100 mg/kg. These studies demonstrate that the precursor drugs to GHB have some differential actions from each other. PMID:15099915

de Fiebre, Christopher M; de Fiebre, Nancy Ellen C; Coleman, Scott L; Forster, Michael J

2004-04-01

212

Monochromatic precursor starts  

NASA Astrophysics Data System (ADS)

Whistler precursors are discrete emissions that precede two-hop whistlers, starting shortly after the one-hop delay. More evidence is presented that the precursor and associated whistler propagate through the same duct, and observations of a new type of precursor are presented. This new precursor has a monochromatic precursor start (MPS) which may or may not trigger a riser. Although MPS's may be emissions entrained by power line radiation (PLR), phase analysis of the starting frequencies shows that they are not simply related to harmonics of the power line frequencies in the two conjugate regions (50 Hz in New Zealand, 60 Hz in Alaska). If the MPS is due to entrainment by PLR, then previous theories of precursor generation need not be discarded. Forward triggering of a precursor at a power line harmonic by a hybrid whistler may occur.

Rietveld, M. T.

1980-05-01

213

Quantitative autoradiographic analysis of the new radioligand [ 3H](2 E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[ a][7]annulen-6-ylidene) ethanoic acid ([ 3H]NCS382) at ?-hydroxybutyric acid (GHB) binding sites in rat brain  

Microsoft Academic Search

(2E)-(5-Hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid (NCS-382) is an antagonist for ?-hydroxybutyric acid (GHB) at GHB receptor sites. Advantages of using [3H]NCS-382 over [3H]GHB in radioligand binding studies are that unlike GHB, NCS-382 does not appear to bind to, activate, or interfere with the functioning of GABAB or GABAA receptors, either directly or indirectly. Herein we establish a protocol for use of [3H]NCS-382

Georgianna G. Gould; Ashok K. Mehta; Alan Frazer; Maharaj K. Ticku

2003-01-01

214

Simultaneous determination of ?-Hydroxybutyrate (GHB) and its analogues (GBL, 1.4-BD, GVL) in whole blood and urine by liquid chromatography coupled to tandem mass spectrometry.  

PubMed

A simple liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for simultaneous identification and quantification of ?-hydroxybutyrate (GHB), ?-butyrolactone (GBL), 1.4-butanediol (1.4-BD), and ?-valerolactone (GVL) in whole blood from forensic cases. The sample preparation of whole blood involved protein precipitation by acidic methanol. Urine samples were diluted and evaluated in relation to a control at the cutoff concentration. Hexadeutero GHB (GHB-d(6)) was used as the internal standard. Separation was achieved by reversed-phase chromatography, and detection was by MS-MS in MRM mode. The linear range for all compounds was from 1.0 to 100 mg/kg in whole blood with a limit of quantification of about 1 mg/kg. The method was validated with regards to selectivity, recovery, accuracy and precision, and stability. The method is currently applied to investigations on suspected drug-facilitated sexual assaults, driving under the influence of drugs, and general intoxication with these substances. PMID:21219697

Johansen, Sys Stybe; Windberg, Charlotte Norup

2011-01-01

215

Polyimide Precursor Solid Residuum  

NASA Technical Reports Server (NTRS)

A polyimide precursor solid residuum is an admixture of an aromatic dianhydride or derivative thereof and an aromatic diamine or derivative thereof plus a complexing agent, which is complexed with the admixture by hydrogen bonding. The polyimide precursor solid residuum is effectively employed in the preparation of polyimide foam and the fabrication of polyimide foam structures.

Weiser, Erik S. (Inventor); St.Clair, Terry L. (Inventor); Echigo, Yoshiaki (Inventor); Kaneshiro, Hisayasu (Inventor)

2001-01-01

216

Precursors to Lymphoproliferative Malignancies  

PubMed Central

We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy.

Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

2013-01-01

217

Potential of IRMS technology for tracing gamma-butyrolactone (GBL).  

PubMed

Popularity of gamma-hydroxybutyric acid (GHB) is fairly stable among drug users, while the consumption of its chemical precursor, gamma-butyrolactone (GBL), is a growing phenomenon. Although conventional analytical methods allow to detect this substance in various matrices, linking a trace and a source is still a difficult challenge. However, as several synthesis pathways and chemical precursors exist for the production of GBL, its carbon isotopic signature may vary extensively. For that purpose, a method has been developed to determine the carbon isotopes content of GBL by means of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). The delta(13)C-values of 19 bulk samples purchased worldwide were in the range from -23.1 to -45.8 per thousand (SD<0.3 per thousand). Furthermore, testing on the purification of GBL by distillation has not been found to be consistent with such a large range of delta(13)C-values, which are likely to result from the isotopic composition of the organic precursors used to produce GBL together with the kinetic isotope effect associated with the synthesis routes. Finally, inter- and intra-variability measurements of the delta(13)C-values demonstrated the high potential of IRMS for discriminating between seizures of GBL and for source determination. PMID:20056363

Marclay, François; Pazos, Diego; Delémont, Olivier; Esseiva, Pierre; Saudan, Christophe

2010-05-20

218

An Interstellar Precursor Mission.  

National Technical Information Service (NTIS)

A mission out of the planetary system, with launch about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern char...

C. Ivie H. N. Norton J. C. Lewis L. D. Jaffe R. Lipes

1977-01-01

219

Wilson loops as precursors  

NASA Astrophysics Data System (ADS)

There is substantial evidence that string theory on AdS5×S5 is a holographic theory in which the number of degrees of freedom scales as the area of the boundary in Planck units. Precisely how the theory can describe bulk physics using only surface degrees of freedom is not well understood. A particularly paradoxical situation involves an event deep in the interior of the bulk space. The event must be recorded in the (Schrödinger picture) state vector of the boundary theory long before a signal, such as a gravitational wave, can propagate from the event to the boundary. In a previous paper with Polchinski, we argued that the ``precursor'' operators which carry information stored in the wave during the time when it vanishes in a neighborhood of the boundary are necessarily non-local. In this paper we argue that the precursors cannot be products of local gauge invariant operators such as the energy momentum tensor. In fact gauge theories have a class of intrinsically non-local operators which cannot be built from local gauge invariant objects. These are the Wilson loops. We show that the precursors can be identified with Wilson loops whose spatial size is dictated by the UV-IR connection.

Susskind, Leonard; Toumbas, Nicolaos

2000-02-01

220

The EM Earthquake Precursor  

NASA Astrophysics Data System (ADS)

Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After the 1989 Loma Prieta Earthquake, American earthquake investigators predetermined magnetometer use and a minimum earthquake magnitude necessary for EM detection. This action was set in motion, due to the extensive damage incurred and public outrage concerning earthquake forecasting; however, the magnetometers employed, grounded or buried, are completely subject to static and electric fields and have yet to correlate to an identifiable precursor. Secondly, there is neither a networked array for finding any epicentral locations, nor have there been any attempts to find even one. This methodology needs dismissal, because it is overly complicated, subject to continuous change, and provides no response time. As for the minimum magnitude threshold, which was set at M5, this is simply higher than what modern technological advances have gained. Detection can now be achieved at approximately M1, which greatly improves forecasting chances. A propagating precursor has now been detected in both the field and laboratory. Field antenna testing conducted outside the NE Texas town of Timpson in February, 2013, detected three strong EM sources along with numerous weaker signals. The antenna had mobility, and observations were noted for recurrence, duration, and frequency response. Next, two directional techniques were employed, resulting in three mapped, potential epicenters. The remaining, weaker signals presented similar directionality results to more epicentral locations. In addition, the directional results of the Timpson field tests lead to the design and construction of a third prototype antenna. In a laboratory setting, experiments were created to fail igneous rock types within a custom-designed Faraday Cage. An antenna emplaced within the cage detected EM emissions, which were both reproducible and distinct, and the laboratory results paralleled field results. With a viable system and continuous monitoring, a fracture cycle could be established and observed in real-time. Sequentially, field data would be reviewed quickly for assessment; thus, leading to a much improved earthquake forecasting capability. The EM precursor determined by this method may surpass all prior precursor claims, and the general public will finally receive long overdue forecasting.

Jones, K. B., II; Saxton, P. T.

2013-12-01

221

[Precursors of breast cancer].  

PubMed

It has become apparent that estrogen receptor (ER) -?positive and -?negative breast lesions are completely distinct diseases. Precursors of low-grade breast cancer are low-grade premalignant lesions, usually ER and progesterone receptor (PR) positive and HER2 negative. On the other hand, precursors of high-grade breast cancer are high-grade premalignant lesions, usually ER and PR negative and HER2 positive. Lobular neoplasia (LN) and ductal carcinoma in situ (DCIS) are important from the clinical point of view. LN increases the risk of bilateral breast cancer. This is why the recommendation for the treatment of LN is very different -? from just following?up up to bilateral mastectomy. The complete surgical excision of the lesion with negative margins is the usual treatment of DCIS. Several big randomized clinical trials showed the benefit of adjuvant radiotherapy (RT). Some of them suppose that there is a group of patients who do not need adjuvant treatment. The benefit of adjuvant tamoxifen is clear only for patients with ER positive disease. The UK/?ANZ study showed the benefit of tamoxifen only in patients without RT. PMID:24325156

Petráková, K

2013-01-01

222

Precursors of prostate cancer.  

PubMed

High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115,000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10 years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer. PMID:22212075

Bostwick, David G; Cheng, Liang

2012-01-01

223

Identified EM Earthquake Precursors  

NASA Astrophysics Data System (ADS)

Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After a number of custom rock experiments, two hypotheses were formed which could answer the EM wave model. The first hypothesis concerned a sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio transmission. Electron flow along fracture surfaces was determined to be inadequate in creating strong EM fields, because rock has a very high electrical resistance making it a high quality insulator. Penetrative flow could not be corroborated as well, because it was discovered that rock was absorbing and confining electrons to a very thin skin depth. Radio wave transmission and detection worked with every single test administered. This hypothesis was reviewed for propagating, long-wave generation with sufficient amplitude, and the capability of penetrating solid rock. Additionally, fracture spaces, either air or ion-filled, can facilitate this concept from great depths and allow for surficial detection. A few propagating precursor signals have been detected in the field occurring with associated phases using custom-built loop antennae. Field testing was conducted in Southern California from 2006-2011, and outside the NE Texas town of Timpson in February, 2013. The antennae have mobility and observations were noted for recurrence, duration, and frequency response. At the Southern California field sites, one loop antenna was positioned for omni-directional reception and also detected a strong First Schumann Resonance; however, additional Schumann Resonances were absent. At the Timpson, TX field sites, loop antennae were positioned for directional reception, due to earthquake-induced, hydraulic fracturing activity currently conducted by the oil and gas industry. Two strong signals, one moderately strong signal, and approximately 6-8 weaker signals were detected in the immediate vicinity. The three stronger signals were mapped by a biangulation technique, followed by a triangulation technique for confirmation. This was the first antenna mapping technique ever performed for determining possible earthquake epicenters. Six and a half months later, Timpson experienced two M4 (M4.1 and M4.3) earthquakes on September 2, 2013 followed by a M2.4 earthquake three days later, all occurring at a depth of five kilometers. The Timpson earthquake activity now has a cyclical rate and a forecast was given to the proper authorities. As a result, the Southern California and Timpson, TX field results led to an improved design and construction of a third prototype antenna. With a loop antenna array, a viable communication system, and continuous monitoring, a full fracture cycle can be established and observed in real-time. In addition, field data could be reviewed quickly for assessment and lead to a much more improved earthquake forecasting capability. The EM precursors determined by this method appear to surpass all prior precursor claims, and the general public will finally receive long overdue forecasting.

Jones, Kenneth, II; Saxton, Patrick

2014-05-01

224

An interstellar precursor mission  

NASA Technical Reports Server (NTRS)

A mission out of the planetary system, with launch about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern characteristics of the heliopause, the interstellar medium, stellar distances (by parallax measurements), low energy cosmic rays, interplanetary gas distribution, and mass of the solar system. Secondary objectives include investigation of Pluto. Candidate science instruments are suggested. Individual spacecraft systems for the mission were considered, technology requirements and problem areas noted, and a number of recommendations made for technology study and advanced development. The most critical technology needs include attainment of 50-yr spacecraft lifetime and development of a long-life NEP system.

Jaffe, L. D.; Ivie, C.; Lewis, J. C.; Lipes, R. G.; Norton, H. N.; Stearns, J. W.; Stimpson, L.; Weissman, P.

1977-01-01

225

GABAB receptor activation exacerbates spontaneous spike-and-wave discharges in DBA/2J mice.  

PubMed

Rich evidence has highlighted that stimulation of gamma-amino-butyric acid (GABA)(B) receptors increases the occurrence of spike-and-wave discharges (SWDs), the electroencephalographic (EEG) landmark of absence epilepsy (AE). Recent findings suggest that the outcomes of GABA(B) activation in vivo are contingent on the chemical characteristics of the agonist. In particular, the endogenous ligand gamma-hydroxybutyrate (GHB) and its precursor gamma-butyro-lactone (GBL) have been shown to elicit different effects than the prototypical GABA(B) agonist baclofen. In view of these premises, the present study was aimed at the characterization of the effects of baclofen (0.5-10 mg/kg, i.p.) and GBL (5-100 mg/kg, i.p.) on the spontaneous SWDs and locomotor activity of DBA/2J mice. While both baclofen and GBL dose-dependently increased SWDs episodes, high doses of the latter (100 mg/kg, i.p.) reduced the occurrence of these phenomena and increased the number of isolated spikes. Interestingly, both compounds elicited a dose-dependent reduction of locomotor activity, in comparison with their vehicle-treated controls. The GABA(B) selective antagonist, SCH50911 (50 mg/kg, i.p.), reversed the changes in SWD occurrence and locomotion induced by baclofen and GBL, but failed to elicit intrinsic effects on either paradigm. These results indicate that GABA(B) receptor signaling might exert differential effects on SWDs in DBA/2J mice. PMID:20233662

Bortolato, Marco; Frau, Roberto; Orrù, Marco; Fà, Mauro; Dessì, Christian; Puligheddu, Monica; Barberini, Luigi; Pillolla, Giuliano; Polizzi, Lorenzo; Santoni, Federico; Mereu, Giampaolo; Marrosu, Francesco

2010-05-01

226

On the reliability of precursors  

NASA Astrophysics Data System (ADS)

The systematic study of a proposed earthquake precursor involves many choices in accommodating the hypothesis to the data base, as exemplified in the work of Mantovani et al. The reliability of the precursor is determined by testing the hypothesis against a different, usually subsequent, set of data.

Rhoades, D. A.; Evison, F. F.

1989-12-01

227

Protamine 2 precursors and processing.  

PubMed

Protamine 2 (P2) is synthesised as a precursor protein (pre-P2) which by proteolysis is processed to generate the mature components of the protamine 2 family of proteins (HP2, HP3 and HP4). In infertile patients, abnormal processing of the protamine 2 precursors has been suggested by the detection of an increased presence of precursor forms. However, the presence of small detectable amounts of precursor proteins has been demonstrated also in normal sperm samples, although the variation of pre-P2 in individual human sperm cells had not yet been explored. In the present manuscript we perform a mini-review describing what is known about protamine 2 precursors and P2 processing. In addition, we by immunofluorescence demonstrate the existence of a marked variation in the presence and abundance of pre-P2 in individual sperm cells. PMID:21443491

de Mateo, Sara; Ramos, Liliana; de Boer, Peter; Meistrich, Marvin; Oliva, Rafael

2011-08-01

228

PRECURSOR FLARES IN OJ 287  

SciTech Connect

We have studied three most recent precursor flares in the light curve of the blazar OJ 287 while invoking the presence of a precessing binary black hole in the system to explain the nature of these flares. Precursor flare timings from the historical light curves are compared with theoretical predictions from our model that incorporate effects of an accretion disk and post-Newtonian description for the binary black hole orbit. We find that the precursor flares coincide with the secondary black hole descending toward the accretion disk of the primary black hole from the observed side, with a mean z-component of approximately z{sub c} = 4000 AU. We use this model of precursor flares to predict that precursor flare of similar nature should happen around 2020.96 before the next major outburst in 2022.

Pihajoki, P.; Berdyugin, A.; Lindfors, E.; Reinthal, R.; Sillanpaeae, A.; Takalo, L. [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Piikkioe (Finland)] [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Piikkioe (Finland); Valtonen, M.; Nilsson, K. [Finnish Centre for Astronomy with ESO, University of Turku, FI-21500 Piikkioe (Finland)] [Finnish Centre for Astronomy with ESO, University of Turku, FI-21500 Piikkioe (Finland); Zola, S.; Koziel-Wierzbowska, D. [Astronomical Observatory, Jagiellonian University, ul. Orla 171, PL-30-244 Krakow (Poland)] [Astronomical Observatory, Jagiellonian University, ul. Orla 171, PL-30-244 Krakow (Poland); Liakos, A. [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR 157 84 Zografos, Athens, Hellas (Greece)] [Department of Astrophysics, Astronomy and Mechanics, University of Athens, GR 157 84 Zografos, Athens, Hellas (Greece); Drozdz, M.; Winiarski, M.; Ogloza, W. [Mount Suhora Observatory, Pedagogical University, ul. Podchorazych 2, PL-30-084 Krakow (Poland)] [Mount Suhora Observatory, Pedagogical University, ul. Podchorazych 2, PL-30-084 Krakow (Poland); Provencal, J. [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States)] [Department of Physics and Astronomy, University of Delaware, Newark, DE 19716 (United States); Santangelo, M. M. M. [O.A.C. Osservatorio Astronomico di Capannori, Via di Valle, I-55060 Vorno, Capannori (Italy)] [O.A.C. Osservatorio Astronomico di Capannori, Via di Valle, I-55060 Vorno, Capannori (Italy); Salo, H. [Department of Physical Sciences, University of Oulu, P.O. Box 3000, FI-90014 University of Oulu (Finland)] [Department of Physical Sciences, University of Oulu, P.O. Box 3000, FI-90014 University of Oulu (Finland); Chandra, S.; Ganesh, S.; Baliyan, K. S., E-mail: popiha@utu.fi [Astronomy and Astrophysics Division, Physical Research Laboratory, Ahmedabad 380009 (India); and others

2013-02-10

229

An interstellar precursor mission  

NASA Technical Reports Server (NTRS)

A mission out of the planetary system, launched about the year 2000, could provide valuable scientific data as well as test some of the technology for a later mission to another star. Primary scientific objectives for the precursor mission concern characteristics of the heliopause, the interstellar medium, stellar distances (by parallax measurements), low-energy cosmic rays, interplanetary gas distribution, and the mass of the solar system. Secondary objectives include investigation of Pluto. The mission should extend to 400-1000 AU from the sun. A heliocentric hyperbolic escape velocity of 50-100 km/sec or more is needed to attain this distance within a reasonable mission duration (20-50 years). The trajectory should be toward the incoming interstellar gas. For a year 2000 launch, a Pluto encounter and orbiter can be included. A second mission targeted parallel to the solar axis would also be worthwhile. The mission duration is 20 years, with an extended mission to a total of 50 years. A system using one or two stages of nuclear electric propulsion (NEP) was selected as a possible baseline. The most promising alternatives are ultralight solar sails or laser sailing, with the lasers in earth orbit, for example. The NEP baseline design allows the option of carrying a Pluto orbiter as a daughter spacecraft.

Jaffe, L. D.; Ivie, C.; Lewis, J. C.; Lipes, R.; Norton, H. N.; Stearns, J. W.; Stimpson, L. D.; Weissman, P.

1980-01-01

230

Removing Trihalomethane Precursors by Coagulation.  

National Technical Information Service (NTIS)

The removal of trihalomethane precursors by coagulation was studied with low turbidity, low alkalinity waters containing high levels of aquatic humic matter. Jar tests were conducted with synthetic and natural waters using alum, high-molecular-weight poly...

R. E. Hubel J. K. Edzwald

1987-01-01

231

Preparation of superconductor precursor powders  

DOEpatents

A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

Bhattacharya, Raghunath (Littleton, CO)

1998-01-01

232

Trending analysis of precursor events.  

National Technical Information Service (NTIS)

The Accident Sequence Precursor (ASP) Program of United States Nuclear Regulatory Commission (U.S.NRC) identifies and categorizes operational events at nuclear power plants in terms of the potential for core damage. The ASP analysis has been performed on ...

N. Watanabe

1998-01-01

233

Precursor control of neurotransmitter synthesis.  

PubMed

Studies performed during the past decade have shown that the rates at which certain neurons produce and release their neurotransmitters can be affected by precursor availability, and thus by the changes in plasma composition that occur after ingestion of the precursors in purified form or as constituents of foods. Thus, tryptophan administration or a plasma ratio of tryptophan to other large neutral amino acids, thereby raising brain tryptophan levels, increasing the substrate saturation of tryptophan hydroxylase, and accelerating the synthesis and release of serotonin. Tyrosine administration or a high-protein meal similarly elevates brain tyrosine and can accelerate catecholamine synthesis in the CNS and sympathoadrenal cells, while the consumption of lecithin or choline increases brain choline levels and neuronal acetylcholine synthesis. The physiologic and biochemical mechanisms that must exist in order for nutrient consumption to affect neurotransmitte synthesis have been characterized and include: 1) the lack of significant feedback control of plasma levels of the precursor; 2) the lack of a real "bloodbrain barrier" for the precursor, i.e. the ability of the plasma level of the precursor to control its influx into, or efflux from, the CNS; 3) the existence of a low-affinity (and thus unsaturated) transport system mediating the flux of the precursor between blood and brain; 4) low-affinity kinetics for the enzyme that initiates the conversion of the precursor to the transmitter; and, 5) the lack of end-product inhibition of the enzyme, in vivo, by its ultimate product, the neurotransmitter. The extent to which neurotransmitter synthesis in any particular aminergic neuron happens to be affected by changes in the availability of its precursor probably varies directly with the neuron's firing frequency. This relationship allows precursor administration to produce selective physiologic effects by enhancing neurotransmitter release from some but not all of the neurons potentially capable of utilizing the precursor for this purpose. It also allows the investigator to predict when administering the precursor might be useful for amplifying a physiologic process, or for treating a pathologic state. (for example, tyrosine administration raises blood pressure in hypotensive rats, lowers it in hypertensive animals, and has little effect on blood pressure in normotensive animals; the elevation in blood pressure probably reflects enhanced catecholamine release from sympathoadrenal cells, while the reduction in hypertensive animals probably results from increased catecholamine release within the brain-stem.) Such predictions are now being tested clinically in many institution. Available evidence suggests that lecithin or cholie administration can diminish the frequency of abnormal movements in patients with tardive dyskinesia... PMID:6115400

Wurtman, R J; Hefti, F; Melamed, E

1980-12-01

234

Precursor decay in several aluminas  

NASA Astrophysics Data System (ADS)

Plate impact experiments were performed on three ceramics with alumina content varying from 88 to 99.9% using a 50 mm single stage gas gun. Tiles of ceramic with thicknesses varying from 2 to 12 mm were impacted above their Hugoniot Elastic Limits (HELs) and the rate dependent strength was investigated by monitoring the variation in amplitude of the elastic precursor with propagation distance. Stress levels in the target were recorded using manganin stress transducers and a 1 GS s-1 storage oscilloscope. All grades of alumina were found to exhibit some elastic precursor decay indicating strain rate sensitivity.

Murray, N. H.; Bourne, N. K.; Rosenberg, Z.

1996-05-01

235

Precursors of Hypertension: A Review  

PubMed Central

Recent advances in hypertension therapy have been remarkable; however, much less is known about those precursors that facilitate preventive and early intervention measures. This review of the literature indicates that relevant precursors are early elevated casual systolic blood pressures, positive family history, and obesity in females. Additional predisposing or enhancing factors point to high sodium ingestion, heavy smoking, and high socioecologic stress. Evidence for a high-risk hypertensive personality is not conclusive. There is a paucity of longitudinal data on hypertension in the black population.

Thomas, John; Neser, William B.; Thomas, Johniene; Semenya, Kofi; Green, Donald R.

1983-01-01

236

Robotic Lunar Precursors to Apollo  

NASA Astrophysics Data System (ADS)

In four short years (1964-1968) lunar science boomed, driven by NASA's three series of small robotic spacecraft: Ranger, Surveyor and Lunar Orbiter. These started their programmatic lives as remote laboratories, then were repurposed as "precursors" to the Apollo missions.

Bugos, G. E.; Boyd, J. W.

2008-07-01

237

Preparation of superconductor precursor powders  

DOEpatents

A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic and/or reduced particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of all metals in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products. 7 figs.

Bhattacharya, R.

1998-08-04

238

Preparation of superconductor precursor powders  

DOEpatents

A process for the preparation of a precursor metallic powder composition for use in the subsequent formation of a superconductor. The process comprises the steps of providing an electrodeposition bath comprising an electrolyte medium and a cathode substrate electrode, and providing to the bath one or more soluble salts of one or more respective metals, such as nitrate salts of thallium, barium, calcium, and copper, which are capable of exhibiting superconductor properties upon subsequent appropriate treatment. The bath is continually energized to cause the metallic particles formed at the electrode to drop as a powder from the electrode into the bath, and this powder, which is a precursor powder for superconductor production, is recovered from the bath for subsequent treatment. The process permits direct inclusion of thallium in the preparation of the precursor powder, and yields an amorphous product mixed on an atomic scale to thereby impart inherent high reactivity. Superconductors which can be formed from the precursor powder include pellet and powder-in-tube products.

Bhattacharya, Raghunath (Littleton, CO); Blaugher, Richard D. (Evergreen, CO)

1995-01-01

239

On the infrasonic precursor generation  

NASA Astrophysics Data System (ADS)

High-intensity atmospheric events such as cyclones and thunderstorms produce strong atmospheric perturbations, accompanied by infrasonic generation, detectable at a large distance from the source. These infrasonic signals can serve as a precursor of these intense atmospheric events. Infrasonic generation can be instigated in a variety of ways in the presence of unstable flow. It can be developed in a layer with a negative temperature gradient, unstable with respect to convection processes. Two regimes can be separated: a) below-threshold regime, which is the instability of a motionless layer heated from below, b) above-threshold regime, which connected to instability of convection flow. Both are considered in the present paper to consider conditions of precursor generation.

Naugolnykh, K. A.

2011-12-01

240

Polymeric precursors to refractory metal borides  

Microsoft Academic Search

Polymeric precursors to zirconium and hafnium diboride are described. Initial studies concentrated on carbothermal\\/borothermal reduction of metal alkoxides; however, improved results were obtained from oxide free-precursors prepared from the metal borohydride and borazine. The metal borides are obtained in good chemical and ceramic yield upon pyrolysis, and the polymeric precursors obtained through the reaction of borazine with the metal borohydride

S. T. Schwab; C. A. Stewart; K. W. Dudeck; S. M. Kozmina; J. D. Katz; B. Bartram; E. J. Wuchina; W. J. Kroenke; G. Courtin

2004-01-01

241

The Interrelationships of Mathematical Precursors in Kindergarten  

ERIC Educational Resources Information Center

This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors

Cirino, Paul T.

2011-01-01

242

PRECURSORS OF SHORT GAMMA-RAY BURSTS  

SciTech Connect

We carried out a systematic search of precursors on the sample of short gamma-ray bursts (GRBs) observed by Swift. We found that {approx}8%-10% of short GRBs display such early episodes of emission. One burst (GRB 090510) shows two precursor events, the former {approx}13 s and the latter {approx}0.5 s before the GRB. We did not find any substantial difference between the precursor and the main GRB emission, and between short GRBs with and without precursors. We discuss possible mechanisms to reproduce the observed precursor emission within the scenario of compact object mergers. The implications of our results on quantum gravity constraints are also discussed.

Troja, E.; Gehrels, N. [NASA, Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Rosswog, S. [School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen (Germany)

2010-11-10

243

New Worlds Observer Precursor Mission  

NASA Astrophysics Data System (ADS)

The New Worlds Observer architecture uses an external occulter to extinguish the on-axis light from a star and a separate telescope to collect the light from objects around that star, such as planets and debris disks. The separation of the starlight suppression capability from the photon collection capability makes the New Worlds Observer architecture very flexible. This paper describes NWO concepts ranging from low-cost precursor missions to Terrestrial Planet Finding (TPF) missions, and provides a path that extends beyond TPF to Planet-Imager and LifeFinder. Low cost precursor missions could be launched on a Minotaur using a small(~10 meter) occulter to work with a small(~0.5 m), telescope. Intermediate precursor missions could be accomplished by launching a larger occulter as a secondary payload to work with existing telescopes such as SOFIA or JWST. The former may allow direct detection of known giant planets, while the latter has the potential to discover Exo-Earths. A full TPF mission would consists of a large occulter working with a dedicated telescope; this can potentially find many terrestrial planets, as well as perform a host of ancillary astronomy investigations such as imaging debris disks and characterizing atmospheres of Jovian planets, as well as making general astrophysics observations. By utilizing the in space servicing capabilities that may be developed for the Exploration program, the lifetime of these occulters may be greatly extended by refueling and repair. In the future, larger occulters (>100 m) could be assembled on orbit. Thus, when coupled with a large telescope, the NWO architecture provides a path towards Lifefinder. NWO is a flexible architecture that allows scalability on all levels to suit the budget available for Exo-Planet Missions.

Lillie, C. F.; Lo, A. S.; Dailey, D.; Glassman, T. M.

2007-06-01

244

[Comparative study of permeability of derivatives of gamma-aminobutyric and gamma-hydroxybutyric acids through hemato-encephalic barrier].  

PubMed

The authors studied the permeability of the blood-brain barrier (CEB) to two nootropics: calcium ketogomopantothenate (KRA-Ca), a GABA derivative, and and calcium salt of oxybutyrate (OB-Ca), a derivative of GOBA. It was established that both preparations penetrate the CEB easily and are found in the brain at different intervals after their administration. However, essential differences in the distribution constant of these drugs were disclosed: KPA-Ca permeated the CEB more intensively and was accumulated in larger amounts in the late-term intervals. PMID:9460601

Nasybullina, N M; Zherdev, V P; Gunar, V I; Kopelevich, V M; Kozlova, G S

1997-01-01

245

Mechanistic investigation of soot precursors  

SciTech Connect

Fuels with low H/C ratios are particularly prone to soot production during combustion; aromatic species generally (but not universally) do so more readily than aliphatics. It is now well recognized that soot is not a singular material. Besides characterizing the variety of soots with respect to composition, volatile content, and structure, extensive efforts have been devoted to determining conditions which promote the development of soot in flames and in internal combustion engines. In this report our objectives are: A. To call attention to the differences and the conceptual similarities between the sooting process and a kinetic model for nucleation/condensation. B. List the types of precursors required for sooting, and the underlying experimental basis. C. Present a minimal set of reactions, with rate constants, which model the observed time evolution of condensed molecular structures (soot precursors). This list must incorporate a repetitive growth cycle for continued condensation. As a minimum, the model must semiquantitatively reproduce observed delay times for the onset of condensation. D. Present qualitative spectral data which support C.

Bauer, S.H.; Jeffers, P.M.

1988-01-01

246

Annealing of aromatic polyimide precursors  

NASA Technical Reports Server (NTRS)

A study has been made of the thermal behavior of polyimide precursors: an isomeric pair of crystals of the complex formed by p-phenylenediamine with the separated isomers of the di-isopropyl ester of pyromellitic acid. Specimens of this material were isothermally annealed in the temperature range 120 C to 170 C for periods of time up to 1 week. Although this temperature range is well below that customarily used for imidizations, the working hypothesis was that it would be more likely that a polymer embodying at least part of the precursor structure could be formed if the molecular motion was minimized to that actually required for the formation of the imide linkage. The progress of the annealing was followed by: infrared spectroscopy, differential thermal analysis, powder X-ray diffraction, and thermal gravimetric analysis. Single crystal X-ray analysis of the meta monomer yields a structure of chains of alternating acid and base and suggests that this monomer is amenable to polymerization with a minimum of geometrical disruption.

Wakelyn, N. T.

1975-01-01

247

Epidemiology of recreational drug toxicity in a nightclub environment.  

PubMed

Data on 173 individuals with recreational drug toxicity requiring "medical" assistance in a large urban nightclub was collected from September 2007 to January 2008. Clubbers required assistance following use of a variety of recreational drugs, particularly gamma-hydroxybutyrate (GHB), gammabutyrolactone (GBL), and ketamine. The majority of individuals were not first-time recreational drug users, and a significant proportion have recurrent recreational drug toxicity requiring assistance. Limitations related to data collection are discussed. Further studies are needed to investigate the use brief interventions in those with problem recreational drug use within the nightclub environment. PMID:19938928

Wood, David M; Nicolaou, Michelle; Dargan, Paul I

2009-01-01

248

Intermolecular Interactions between Eosin Y and Caffeine Using 1H-NMR Spectroscopy  

PubMed Central

DETECHIP has been used in testing analytes including caffeine, cocaine, and tetrahydrocannabinol (THC) from marijuana, as well as date rape and club drugs such as flunitrazepam, gamma-hydroxybutyric acid (GHB), and methamphetamine. This study investigates the intermolecular interaction between DETECHIP sensor eosin Y (DC1) and the analyte (caffeine) that is responsible for the fluorescence and color changes observed in the actual array. Using 1H-NMR, 1H-COSY, and 1H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed.

Okuom, Macduff O.; Wilson, Mark V.; Jackson, Abby; Holmes, Andrea E.

2014-01-01

249

STIMULATED PLATELETS RELEASE AMYLOID ?-PROTEIN PRECURSOR  

PubMed Central

Human platelets can be stimulated by thrombin or ionomycin to secrete soluble truncated amyloid ?–protein precursor and particulate membrane fragments which contain C-terminal and N-terminal immunoreactive amyloid ?–protein precursor. This suggests a possible circulating source of ?–protein in serum which may play a role in the formation of amyloid deposits. The release of soluble amyloid ?-protein precursor could be involved in normal platelet physiology.

Galasko, Douglas; Shapiro, I. Paul; Saitoh, Tsunao

2014-01-01

250

Fullerene polymers from solid precursors  

SciTech Connect

One of the many speculations that quickly followed on the heels of the Kraetschmer-Huffman process for producing large quantities of C[sub 60] buckminsterfullerene was the possibility of stitching the molecules together to create a linear chain polymer, a [open quotes]pearl necklace[close quotes] of buckyballs. In addition to being chemically elegant and intrinsically beautiful, such a material might be expected to exhibit interesting electronic and nonlinear optical properties. Traditional solution-phase routes to fullerene polymerization have thus far resulted only in mixtures of incompletely characterized species with a high degree of cross-linking. This article reviews experiments that show that this goal might be achieved by starting from a fullerene solid precursor.

Fischer, J.E. (Univ. of Pennsylvania, Philadelphia, PA (United States) National Institute of Standards and Technology, Gaithersburg, MD (United States))

1994-06-10

251

Molecular and polymeric ceramic precursors  

SciTech Connect

The development of new methods for the production of complex materials is one of the most important problems in modern solid state chemistry and materials science. This project is attempting to apply the synthetic principles which have evolved in inorganic and organometallic chemistry to the production of technologically important non-oxide ceramics, such as boron nitride, boron carbide and metal borides. Recent work has now resulted in the production of new polymer systems, including poly(B-vinylborazine), polyvinylpentaborane and polyborazylene, that have proven to be high yield precursors to boron-based ceramic materials. Current work is now directed toward the synthesis of new types of molecular and polymeric boron-containing species and an exploration of the solid state properties of the ceramics that have been produced in these studies.

Sneddon, L.G.

1992-06-01

252

Molecular and polymeric ceramic precursors  

SciTech Connect

The development of new methods for the production of complex materials is one of the most important problems in modern solid state chemistry and materials science. This project is attempting to apply the synthetic principles which have evolved inorganic and organometallic chemistry to the production of technologically important non-oxide ceramics, such as boron nitride, boron carbide and metal borides. Our recent work has now resulted in the production of new polymer systems, including poly(B-vinylborazine), polyvinylpentaborane and polyborazylene, that have proven to be high yield precursors to boron-based ceramic materials. Current work is now directed toward the synthesis of new types of molecular and polymeric boron-containing species and on exploration of the solid state properties of the ceramics that have been produced in these studies.

Sneddon, L.G.

1991-08-01

253

1995 Accident Sequence Precursor (ASP) Program results  

SciTech Connect

The Accident Sequence Precursor (ASP) Program involves the systematic review and evaluation of operational events that have occurred at light-water reactors to identify and categorize precursors to potential severe core damage accident sequences. The results of the ASP Program are published in an annual report. The most recent report, which contains the precursors for 1995, is NUREG/CR-4674, Volume 23, Precursors to Potential Severe Core Damage Accidents: 1995, A Status Report, published in April 1997. This article provides an overview of the ASP review and evaluation process and a summary of the results for 1995.

Muhlheim, M.D.; Belles, R.J.; Cletcher, J.W.; Copinger, D.A. [Oak Ridge National Lab., TN (United States); O`Reilly, P.D. [Nuclear Regulatory Commission, Washington, DC (United States); Dolan, B.W.; Minarick, J.W. [Science Applications International Corp., Oak Ridge, TN (United States)

1997-01-01

254

PLT Powders from Water Soluble Precursors.  

National Technical Information Service (NTIS)

Non aqueous solutions of PLT precursors are likely to hydrolyze resulting in large particles, which will influence the qualities of the PLT film. Water soluble precursors of PLT are prepared from modified Ti metal salts that are insensible to moisture. Th...

W. G. Liu L. Zhang Y. Xi

1994-01-01

255

The Interrelationships of Mathematical Precursors in Kindergarten  

PubMed Central

This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 Kindergarteners via latent variable techniques, and the contribution of precursors from each domain was established for small sums addition. Results showed a five factor structure for the quantity precursors with the major distinction between nonsymbolic and symbolic tasks. The overall model demonstrated good fit, and strong predictive power (R2 = 55%) for addition number combinations. Linguistic and spatial attention domains showed indirect relationships with outcomes, with their effects mediated by symbolic quantity measures. These results have implications for the measurement of mathematical precursors, and yield promise for predicting future math performance.

Cirino, Paul T.

2011-01-01

256

Method of texturing a superconductive oxide precursor  

DOEpatents

A method of forming a textured superconductor wire includes constraining an elongated superconductor precursor between two constraining elongated members placed in contact therewith on opposite sides of the superconductor precursor, and passing the superconductor precursor with the two constraining members through flat rolls to form the textured superconductor wire. The method includes selecting desired cross-sectional shape and size constraining members to control the width of the formed superconductor wire. A textured superconductor wire formed by the method of the invention has regular-shaped, curved sides and is free of flashing. A rolling assembly for single-pass rolling of the elongated precursor superconductor includes two rolls, two constraining members, and a fixture for feeding the precursor superconductor and the constraining members between the rolls. In alternate embodiments of the invention, the rolls can have machined regions which will contact only the elongated constraining members and affect the lateral deformation and movement of those members during the rolling process.

DeMoranville, Kenneth L. (Jefferson, MA); Li, Qi (Marlborough, MA); Antaya, Peter D. (Sutton, MA); Christopherson, Craig J. (Worcester, MA); Riley, Jr., Gilbert N. (Marlborough, MA); Seuntjens, Jeffrey M. (Bangau, SG)

1999-01-01

257

Do double 'SS precursors' mean double discontinuities?  

NASA Astrophysics Data System (ADS)

Stacks of SS precursors have been widely used in the past two decades to investigate the existence and characteristics of upper mantle discontinuities on a global scale as well as in several regional cases. Here, we present observations of SS precursors from an Mb 6.7 earthquake recorded at the US Transportable Array in 2010. In this particular case, the S660S precursors on the transverse component are strong enough to be identified on individual seismograms across the array without any stacking procedures. Two S660S precursors are observed, seeming to suggest double discontinuities around 660 km depth in the bounce point region. Through careful analysis of 1-D and 3-D synthetic seismograms, we however discover that, although they have arrival times and slownesses that are very close to the theoretical values of SS precursors, the apparent 'double precursors' are artefacts because of mantle heterogeneity in the upper mantle near the receivers away from the bounce point region. This suggests that caution must be taken about appropriate azimuthal coverage at the SS bounce point, before interpreting double SS or PP precursors in terms of complex mineralogical transitions.

Zheng, Zhao; Romanowicz, Barbara

2012-12-01

258

Neural precursors of delayed insight.  

PubMed

The solution of a problem left unresolved in the evening can sometimes pop into mind as a sudden insight after a night of sleep in the following morning. Although favorable effects of sleep on insightful behavior have been experimentally confirmed, the neural mechanisms determining this delayed insight remain unknown. Here, using fMRI, we characterize the neural precursors of delayed insight in the number reduction task (NRT), in which a hidden task structure can be learned implicitly, but can also be recognized explicitly in an insightful process, allowing immediate qualitative improvement in task performance. Normal volunteers practiced the NRT during two fMRI sessions (training and retest), taking place 12 hours apart after a night of sleep. After this delay, half of the subjects gained insight into the hidden task structure ("solvers," S), whereas the other half did not ("nonsolvers," NS). Already at training, solvers and nonsolvers differed in their cerebral responses associated with implicit learning. In future solvers, responses were observed in the superior frontal sulcus, posterior parietal cortex, and the insula, three areas mediating controlled processes and supporting early learning and novice performance. In contrast, implicit learning was related to significant responses in the hippocampus in nonsolvers. Moreover, the hippocampus was functionally coupled with the basal ganglia in nonsolvers and with the superior frontal sulcus in solvers, thus potentially biasing participants' strategy towards implicit or controlled processes of memory encoding, respectively. Furthermore, in solvers but not in nonsolvers, response patterns were further transformed overnight, with enhanced responses in ventral medial prefrontal cortex, an area previously implicated in the consolidation of declarative memory. During retest in solvers, before they gain insight into the hidden rule, significant responses were observed in the same medial prefrontal area. After insight, a distributed set of parietal and frontal areas is recruited among which information concerning the hidden rule can be shared in a so-called global workspace. PMID:20666600

Darsaud, Annabelle; Wagner, Ullrich; Balteau, Evelyne; Desseilles, Martin; Sterpenich, Virginie; Vandewalle, Gilles; Albouy, Geneviève; Dang-Vu, Thanh; Collette, Fabienne; Boly, Melanie; Schabus, Manuel; Degueldre, Christian; Luxen, Andre; Maquet, Pierre

2011-08-01

259

21 CFR 1308.47 - Control of immediate precursors.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Control of immediate precursors. 1308.47 Section 1308.47 ...§ 1308.47 Control of immediate precursors. Pursuant to section 201... an order controlling an immediate precursor. The order shall designate the...

2010-04-01

260

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Reporting on precursor chemical substances. 766.38 Section...Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances....

2010-07-01

261

21 CFR 1308.47 - Control of immediate precursors.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 false Control of immediate precursors. 1308.47 Section 1308.47 ...§ 1308.47 Control of immediate precursors. Pursuant to section 201... an order controlling an immediate precursor. The order shall designate the...

2009-04-01

262

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2010 CFR

... 2009-07-01 false Reporting on precursor chemical substances. 766.38 Section...Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances....

2009-07-01

263

Explorations Precursor Robotic Missions (xPRM)  

NASA Video Gallery

Jay Jenkins delivers a presentation from the Exploration Precursor Robotic Missions (xPRM) study team on May 25, 2010, at the NASA Exploration Enterprise Workshop held in Galveston, TX. The purpose...

264

Random catecholaminergic differentiation of mesencephalic neural precursors.  

PubMed

We investigated how several factors influence the catecholaminergic phenotype establishment from embryonic mesencephalic neural precursors in culture. Using a semiquantitative RT-PCR procedure we found no significant effect of several growth factors or conditioned media on tyrosine hydroxylase (TH) mRNA levels. Nevertheless, neural precursor cells expanded by epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) showed the ability to express TH mRNA. Subcultures of EGF expanded neural precursor cells expressed TH mRNA, but not all individual secondary colonies obtained had this characteristic. Preferential dopaminergic differentiation was observed in our culture conditions. Our results suggest that EGF stimulates the proliferation of neural precursor cells that have the potential but differentiate randomly to catecholaminergic cells. PMID:8747161

Santa-Olalla, J; Covarrubias, L

1995-11-27

265

Biochemical Removal of HAP Precursors From Coal  

SciTech Connect

This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

Olson, G.; Tucker, L.; Richards, J.

1997-07-01

266

Chemical Precursor Routes to Ceramic Nanocylinders.  

National Technical Information Service (NTIS)

The objective this AFOSR sponsored project was to design and synthesize new processable chemical precursors to nonoxide ceramics that allow the formation of the ceramics in nano-structured forms. These studies demonstrated that the use of a suitably desig...

L. G. Sneddon

2003-01-01

267

Psychosis in the context of sodium oxybate therapy.  

PubMed

Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses. PMID:22171207

Langford, Jody; Gross, William L

2011-12-15

268

Psychosis in the Context of Sodium Oxybate Therapy  

PubMed Central

Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses. Citation: Langford J; Gross WL. Psychosis in the context of sodium oxybate therapy. J Clin Sleep Med 2011;7(6):665-666.

Langford, Jody; Gross, William L.

2011-01-01

269

Hydridosiloxanes as precursors to ceramic products  

DOEpatents

A method is provided for preparing ceramic precursors from hydridosiloxane starting materials and then pyrolyzing these precursors to give rise to silicious ceramic materials. Si-H bonds present in the hydridosiloxane starting materials are catalytically activated, and the activated hydrogen atoms may then be replaced with nonhydrogen substituents. These preceramic materials are pyrolyzed in a selected atmosphere to give the desired ceramic product. Ceramic products which may be prepared by this technique include silica, silicon oxynitride, silicon carbide, metal silicates, and mullite.

Blum, Y.D.; Johnson, S.M.; Gusman, M.I.

1997-06-03

270

Hydridosiloxanes as precursors to ceramic products  

DOEpatents

A method is provided for preparing ceramic precursors from hydridosiloxane starting materials and then pyrolyzing these precursors to give rise to silicious ceramic materials. Si--H bonds present in the hydridosiloxane starting materials are catalytically activated, and the activated hydrogen atoms may then be replaced with nonhydrogen substituents. These preceramic materials are pyrolyzed in a selected atmosphere to give the desired ceramic product. Ceramic products which may be prepared by this technique include silica, silicon oxynitride, silicon carbide, metal silicates, and mullite.

Blum, Yigal D. (San Jose, CA); Johnson, Sylvia M. (Piedmont, CA); Gusman, Michael I. (Palo Alto, CA)

1997-01-01

271

Optical Precursor of a Single Photon  

SciTech Connect

We report the direct observation of optical precursors of heralded single photons with step- and square-modulated wave packets passing through cold atoms. Using electromagnetically induced transparency and the slow-light effect, we separate the single-photon precursor, which always travels at the speed of light in vacuum, from its delayed main wave packet. In the two-level superluminal medium, our result suggests that the causality holds for a single photon.

Zhang Shanchao; Chen, J. F.; Liu, Chang; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang [Department of Physics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

2011-06-17

272

Optical precursor of a single photon.  

PubMed

We report the direct observation of optical precursors of heralded single photons with step- and square-modulated wave packets passing through cold atoms. Using electromagnetically induced transparency and the slow-light effect, we separate the single-photon precursor, which always travels at the speed of light in vacuum, from its delayed main wave packet. In the two-level superluminal medium, our result suggests that the causality holds for a single photon. PMID:21770570

Zhang, Shanchao; Chen, J F; Liu, Chang; Loy, M M T; Wong, G K L; Du, Shengwang

2011-06-17

273

Mechanism(s) regulating inhibition of thymidylate synthase and growth by gamma-L-glutaminyl-4-hydroxy-3-iodobenzene, a novel melanin precursor, in melanogenic melanoma cells.  

PubMed

A proposed mechanism for the melanoma specific activity of phenolic amines is based upon the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. In this study, we synthesized an iodinated analog of gamma-L-glutaminyl-4-hydroxybenzene (GHB) with increased antimelanoma activity in both human and murine melanoma cell lines. GHB and gamma-L-glutaminyl-4-hydroxy-3-iodobenzene (I-GHB) were shown to be substrates for both mammalian and mushroom tyrosinase. Glutathione, a cellular antioxidant, inhibited tyrosinase mediated formation of gamma-L-glutaminyl-3,4-benzoquinone (GBQ) from GHB, inhibited melanin production, and blocked the inhibition of the enzyme thymidylate synthase by oxidized GHB. Buthionine sulfoximine (BSO) depletion of cellular glutathione enhanced the growth inhibitory activity and the inhibition of in situ thymidylate synthase by phenolic amines in melanoma cells. GHB and I-GHB were shown to be approximately 5- and 10-fold more cytotoxic, respectively, in highly metastatic B16-BL6 cells than in weakly metastatic B16-F1 cells with approximately equal tyrosinase activity. B16-BL6 cells had approximately 20-fold higher gamma-glutamyltranspeptidase (gamma-GTPase) activity than B16-F1 cells which suggested the possible involvement of this enzyme in the activation of the cytotoxicity of the phenolic amines. 4-Aminophenol, a product of gamma-GTPase reaction with GHB, was a substrate for tyrosinase and a potent inhibitor of in situ thymidylate synthase activity in melanogenic cells. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone mediated mechanism of phenolic amine cytotoxicity may be uniquely important and the cellular antioxidant glutathione essential in the detoxification of these quinone-generated intermediates. PMID:8435097

Prezioso, J A; Damodaran, K M; Wang, N; Bloomer, W D

1993-01-26

274

From the street to the brain: neurobiology of the recreational drug ?-hydroxybutyric acid  

Microsoft Academic Search

?-Hydroxybutyric acid (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and is formed primarily from the precursor ?-aminobutyric acid (GABA). The properties of GHB suggest that it has a neuromodulatory role in the brain and has the ability to induce several pharmacological and behavioral effects. GHB has been used clinically as an anesthetic and to

C. Guin Ting Wong; K. Michael Gibson; O. Carter Snead

2004-01-01

275

Investigating ``Precursor Flows'' in Solar Flares  

NASA Astrophysics Data System (ADS)

Despite some measure of theoretical and predictive success of the electron-heated model of solar flares, observations of low levels of soft X-ray emission prior to the detection of hard X-rays in most flares present a problem for the paradigm, since it suggests some sort of ``preheating'' of the chromospheric plasma before electron acceleration. Particularly troublesome are assertions that plasma flows have been observed prior to hard X-ray emission, because they imply significant and rapid energy input by some agent without leaving a (currently) detectable hard X-ray signature. Given this challenge to a prevailing paradigm, it is imperative to investigate more comprehensively the existence of ``precursor flows'' manifested in the asymmetry of X-ray spectral lines. In this paper, we examine a sample of 50 disk-center flares observed by the Yohkoh Bragg Crystal Spectrometer (BCS) between 1991 and 1993, and determine with the velocity differential emission measure the extent to which ``precursor flows'' occur. We explore specifically the possibility that these ``precursor flows'' are only apparent, arising from the existence of more than one emission region on the solar disk. The spatial separation between regions could cause the emission to be registered by the detector in a wavelength bin that is shifted relative to the line's nominal location, giving rise to line asymmetries. In our sample, we find that only five flares manifest ``precursor flows,'' three of which can be explained definitively by the presence of other active regions. It also appears plausible that the remaining two events can be explained in terms of such spatial effects, although the evidence is more circumstantial. We conclude, therefore, that one can reasonably question the existence of ``precursor flows'' in our sample and that the observations to date cannot contribute decisively to the electron versus proton debate. These results are contrasted with those of Plunkett & Simnett, who identified 14 precursor events in a sample of 35 flares and hence concluded, without further analysis, that protons, rather than electrons, must be the primary energy carriers in flares. Our paper's sample included eight of Plunkett & Simnett's 14 precursor events, and yet our analysis, which employed substantially different methods, identified only one of these eight as a ``precursor'' event. The remaining seven were either troubled by BCS data dropout or failed to exceed the 10% threshold required to classify a flare as a``precursor'' event.

Newton, Elizabeth K.

1997-07-01

276

Germanium nanowire synthesis using solid precursors  

NASA Astrophysics Data System (ADS)

We report on the synthesis of single crystalline, high aspect ratio germanium (Ge) nanowires (NWs) by vapor transport method using three different solid powder precursors. Investigated precursors were either powder like germanium or powder mixtures like germanium dioxide with carbon and germanium iodide with germanium. As-grown NWs were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD) and X-Ray photoelectron spectroscopy (XPS) to obtain structural information. The effect of temperature and pressure on the diameter and morphology of the NWs were determined. Both pressure and temperature were found to increase the diameter of the NWs independent of precursor type. Growth direction of the NWs was found to be the same while clear differences in the morphology and surrounding oxide layer thickness were observed with different precursors. Oxide layer removal via hydrobromic acid treatment was also realized. Results provided in this paper allow the basis for optimizing the synthesis of Ge NWs using solid precursors.

Aksoy, Burcu; Kalay, Yunus Eren; Unalan, Husnu Emrah

2014-04-01

277

76 FR 77016 - Controlled Substances: Final Adjusted Aggregate Production Quotas for 2011  

Federal Register 2010, 2011, 2012, 2013

...fentanyl, gamma hydroxybutyric acid, hydrocodone, meperidine, methadone...diphenoxylate, gamma hydroxybutyric acid, meperidine, and pentobarbital required...expressed in grams of anhydrous acid or base, as...

2011-12-09

278

Imaging Hematopoietic Precursor Division in Real Time  

PubMed Central

SUMMARY Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.

Wu, Mingfu; Kwon, Hyog Young; Rattis, Frederique; Blum, Jordan; Zhao, Chen; Ashkenazi, Rina; Jackson, Trachette L.; Gaiano, Nicholas; Oliver, Tim; Reya, Tannishtha

2008-01-01

279

[Update on colorectal cancer precursor lesions].  

PubMed

The adenoma-carcinoma sequence is currently well established, and therefore, the potential for adenomas to progress to colorectal cancer (CRC). In the last decade, there has been a change in the paradigm that considered these lesions as the only precursors of CRC and nowadays serrated polyps are also considered to have the potential for malignant transformation. The studies presented this year at the congress of the American Gastroenterological Association provide important information to improve the characterization of CRC precursor lesions, especially as regards their detection, prevalence and treatment and surveillance strategies. Notable among these studies were those focussing on evaluating the epidemiological characteristics of serrated polyps and those attempting to improve the quality of colonoscopy -with the ultimate aim of achieving greater detection of these precursor lesions- by evaluating colon cleansing, the polyp detection rate, withdrawal times, the use of endoscopic caps, narrow band imaging, high-definition endoscopy and, lastly, adequate endoscopic surveillance. PMID:23018012

Moreira, Leticia

2012-09-01

280

Precursors Prior to Type IIn Supernova Explosions are Common: Precursor Rates, Properties, and Correlations  

NASA Astrophysics Data System (ADS)

There is a growing number of Type IIn supernovae (SNe) which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to poorly charted phenomena in the final stages of stellar evolution. By coadding Palomar Transient Factory (PTF) images taken prior to the explosion, here we present a search for precursors in a sample of 16 Type IIn SNe. We find five SNe IIn that likely have at least one possible precursor event (PTF 10bjb, SN 2010mc, PTF 10weh, SN 2011ht, and PTF 12cxj), three of which are reported here for the first time. For each SN we calculate the control time. We find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, >50% of SNe IIn have at least one pre-explosion outburst that is brighter than 3 × 107 L ? taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely >~ 1 yr–1, and fainter precursors are possibly even more common. Ignoring the two weakest precursors in our sample, the precursors rate we find is still on the order of one per year. We also find possible correlations between the integrated luminosity of the precursor and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material.

Ofek, Eran O.; Sullivan, Mark; Shaviv, Nir J.; Steinbok, Aviram; Arcavi, Iair; Gal-Yam, Avishay; Tal, David; Kulkarni, Shrinivas R.; Nugent, Peter E.; Ben-Ami, Sagi; Kasliwal, Mansi M.; Cenko, S. Bradley; Laher, Russ; Surace, Jason; Bloom, Joshua S.; Filippenko, Alexei V.; Silverman, Jeffrey M.; Yaron, Ofer

2014-07-01

281

Color tuning of black for electrochromic polymers using precursor blends.  

PubMed

We demonstrate a facile controlling of the optical and colorimetric properties of a donor-acceptor conjugated polymer simply by varying the mix ratio of two precursors in a precursor blend. The conversion of a precursor blend results in an entirely new donor-acceptor polymer, distinct from the conjugated polymer of each precursor. Careful optimization of the mix ratio of two precursors results in a black electrochromic polymer. PMID:23628884

Lee, Ki-Ryong; Sotzing, Gregory A

2013-06-01

282

Precursor shocks and cosmic ray acceleration  

NASA Astrophysics Data System (ADS)

Cosmic ray acceleration takes place in shocks of relativistic jets in Active Galactic Nuclei (AGN). The diffusive or stochastic acceleration are believed to be the main responsible mechanisms. Additionally, it is known that the back-reaction of accelerated cosmic rays in shock fronts in astrophysical environments, may lead to the formation of a precursor shock with a length scale which corresponds to the diffusive scale of the energetic particles. In this work we will investigate the properties of relativistic, parallel and perpendicular precursor shocks, via numerical test-particle simulations, allowing diffusive and stochastic acceleration.

Meli, A.

2013-02-01

283

High-Solids Polyimide Precursor Solutions  

NASA Technical Reports Server (NTRS)

The invention is a highly concentrated stable solution of polymide precursors (monometers) having a solids content ranging from about 80 to 98 percent by weight in lower aliphatic alcohols i.e. methyl and/or ethylalcohol. the concentrated polyimide precursos solution comparisons effective amounts of at least one aromatic diamine, at least one aromatic dianhydride, and a monofunctional endcap including monoamines, monoanhydrides and lower alkyl esters of said monoanhydrides. These concentrated polyimide precursor solutions are particularly useful for the preparation of fibrous prepregs and composites for use in structural materials for military and civil applications.

Chuang, Chun-Hua (Inventor)

2004-01-01

284

Polymeric precursors for fibers and matrices  

NASA Technical Reports Server (NTRS)

Candidate polymeric precursors for ceramic fiber and matrix processing are discussed, with a view to the advantages and disadvantages of this approach relative to existing alternatives. The properties of ceramic products thus derived are noted to strongly depend on the molecular weight and structure of the starting polymer; in particular, the ceramic's composition and morphology are dependent on the character and extent of crosslinking, as well as on the path of pyrolysis. While large and complex structural ceramic components may ultimately be obtainable by these means, the polymer-precursor method is still in its developmental infancy.

Hurwitz, Frances I.

1992-01-01

285

The immediate precursors of binary planetary nebulae  

NASA Astrophysics Data System (ADS)

By observing the number of red giants almost filling their Roche lobes in binary systems relative to the number of single red giants, we can predict the numbers of planetary nebulae (PNe) produced by binary interaction relative to the numbers of PNe produced by single stars or wide binaries. When we have both radial velocity and light curves, we can derive the masses of these binary PN precursor stars. In this paper we discuss our recent work on the precursors of binary planetary nebulae in the LMC.

Wood, P.; Nie, J. D.; Nicholls, C. P.

2014-04-01

286

School Violence: Prevalence, Precursors, and Prevention.  

ERIC Educational Resources Information Center

Reviews types of school violence students confront, including a frequent precursor thereto: bullying. Discusses positive and negative aspects of current approach to school violence prevention such as surveillance, zero-tolerance policies, anti-bullying programs. Describes components of model school violence-prevention program. (Contains 38…

Juvonen, Jaanna

2002-01-01

287

2-Arylacetic anhydrides as ammonium enolate precursors.  

PubMed

Readily prepared 2-arylacetic anhydrides act as convenient ammonium enolate precursors in isothiourea (HBTM-2.1)-mediated catalytic asymmetric intermolecular Michael addition-lactonisation processes, giving diverse synthetic building blocks in good yield with high diastereo- and enantiocontrol (up to 98?:?2 dr and >99% ee). PMID:24292454

Morrill, Louis C; Ledingham, Lyndsay A; Couturier, Jean-Philippe; Bickel, Jasmine; Harper, Andrew D; Fallan, Charlene; Smith, Andrew D

2014-01-28

288

The Stability of Cosmic Ray Precursors  

NASA Astrophysics Data System (ADS)

I consider the stability of cosmic ray precursors near shocks propagating in a high-? plasma. It is shown that the interplay between cosmic ray effects and the classical firehose and mirror instabilities lead to a more vigorous instability. Consequences for cosmic ray acceleration are discussed.

Achterberg, A.

2013-01-01

289

Superconductor precursor mixtures made by precipitation method  

DOEpatents

Method and apparatus for preparing highly pure homogeneous precursor powder mixtures for metal oxide superconductive ceramics. The mixes are prepared by instantaneous precipitation from stoichiometric solutions of metal salts such as nitrates at controlled pH's within the 9 to 12 range, by addition of solutions of non-complexing pyrolyzable cations, such as alkyammonium and carbonate ions.

Bunker, Bruce C. (Albuquerque, NM); Lamppa, Diana L. (Albuquerque, NM); Voigt, James A. (Albuquerque, NM)

1989-01-01

290

Biochemical Removal of HAP Precursors from Coal  

SciTech Connect

Column biooxidation tests with Kentucky coal confirmed results of earlier shake flask tests showing significant removal from the coal of arsenic, selenium, cobalt, manganese, nickel and cadmium. Rates of pyrite biooxidation in Kentucky coal were only slightly more than half the rates found previously for Indiana and Pittsburgh coals. Removal of pyrite from Pittsburgh coal by ferric ion oxidation slows markedly as ferrous ions accumulate in solution, requiring maintenance of high redox potentials in processes designed for removal of pyrite and hazardous air pollutant (HAP) precursors by circulation of ferric solutions through coal. The pyrite oxidation rates obtained in these tests were used by Unifield Engineering to support the conceptual designs for alternative pyrite and HAP precursor bioleaching processes for the phase 2 pilot plant. Thermophilic microorganisms were tested to determine if mercury could be mobilized from coal under elevated growth temperatures. There was no evidence for mercury removal from coal under these conditions. However, the activity of the organisms may have liberated mercury physically. It is also possible that the organisms dissolved mercury and it readsorbed to the clay preferentially. Both of these possibilities are undergoing further testing. The Idaho National Engineering and Environmental Laboratory?s (INEEL) slurry column reactor was operated and several batches of feed coal, product coal, waste solids and leach solutions were submitted to LBL for HAP precursor analysis. Results to date indicate significant removal of mercury, arsenic and other HAP precursors in the combined physical-biological process.

Gregory J. Olson

1997-05-12

291

Detection of Chemical Precursors of Explosives  

NASA Technical Reports Server (NTRS)

Certain selected chemicals associated with terrorist activities are too unstable to be prepared in final form. These chemicals are often prepared as precursor components, to be combined at a time immediately preceding the detonation. One example is a liquid explosive, which usually requires an oxidizer, an energy source, and a chemical or physical mechanism to combine the other components. Detection of the oxidizer (e.g. H2O2) or the energy source (e.g., nitromethane) is often possible, but must be performed in a short time interval (e.g., 5 15 seconds) and in an environment with a very small concentration (e.g.,1 100 ppm), because the target chemical(s) is carried in a sealed container. These needs are met by this invention, which provides a system and associated method for detecting one or more chemical precursors (components) of a multi-component explosive compound. Different carbon nanotubes (CNTs) are loaded (by doping, impregnation, coating, or other functionalization process) for detecting of different chemical substances that are the chemical precursors, respectively, if these precursors are present in a gas to which the CNTs are exposed. After exposure to the gas, a measured electrical parameter (e.g. voltage or current that correlate to impedance, conductivity, capacitance, inductance, etc.) changes with time and concentration in a predictable manner if a selected chemical precursor is present, and will approach an asymptotic value promptly after exposure to the precursor. The measured voltage or current are compared with one or more sequences of their reference values for one or more known target precursor molecules, and a most probable concentration value is estimated for each one, two, or more target molecules. An error value is computed, based on differences of voltage or current for the measured and reference values, using the most probable concentration values. Where the error value is less than a threshold, the system concludes that the target molecule is likely. Presence of one, two, or more target molecules in the gas can be sensed from a single set of measurements.

Li, Jing

2012-01-01

292

Treatment of disinfection by-product precursors.  

PubMed

Formation of harmful disinfection by-products (DBPs), of which trihalomethanes (THMs) and haloacetic acids (HAAs) are the major groups, can be controlled by removal of natural organic matter (NOM) before disinfection. In the literature, removal of precursors is variable, even with the same treatment. The treatment of DBP precursors and NOM was examined with the intention of outlining precursor removal strategies for various water types. Freundlich adsorption parameters and hydroxyl rate constants were collated from the literature to link treatability by activated carbon and advanced oxidation processes (AOPs), respectively, to physico-chemical properties. Whereas hydroxyl rate constants did not correlate meaningfully with any property, a moderate correlation was found between Freundlich parameters and log K(ow), indicating activated carbon will preferentially adsorb hydrophobic NOM. Humic components of NOM are effectively removed by coagulation, and, where they are the principal precursor source, coagulation may be sufficient to control DBPs. Where humic species remaining post-coagulation retain significant DBP formation potential (DBPFP), activated carbon is deemed a suitable process selection. Anion exchange is an effective treatment for transphilic species, known for high carboxylic acid functionality, and consequently is recommended for carboxylic acid precursors. Amino acids have been linked to HAA formation and are important constituents of algal organic matter. Amino acids are predicted to be effectively removed by biotreatment and nanofiltration. Carbohydrates have been found to reach 50% of NOM in river waters. If the carbohydrates were to pose a barrier to successful DBP control, additional treatment stages such as nanofiltration are likely to be required to reduce their occurrence. PMID:21473265

Bond, T; Goslan, E H; Parsons, S A; Jefferson, B

2011-01-01

293

Crystallization trends of precursor pyroxene in ordinary chondrites: Implications for igneous origin of precursor  

NASA Technical Reports Server (NTRS)

Various observations suggest that the precursor of the fine fragments and the relict pyroxene was formed by an igneous process in a grandparent body of the chondrite. Furthermore, the fact that the precursors appear as fragments in the matrix as well as relicts in the chondrule suggests a shock origin for the chondrite by collision of two or more bodies, which had already to some extent undergone igneous differentiation.

Fujita, T.; Kitamura, M.

1994-01-01

294

Electromagnetic Whistler Precursors at Supercritical Interplanetary Shocks  

NASA Technical Reports Server (NTRS)

We present observations of electromagnetic precursor waves, identified as whistler mode waves, at supercritical interplanetary shocks using the Wind search coil magnetometer. The precursors propagate obliquely with respect to the local magnetic field, shock normal vector, solar wind velocity, and they are not phase standing structures. All are right-hand polarized with respect to the magnetic field (spacecraft frame), and all but one are right-hand polarized with respect to the shock normal vector in the normal incidence frame. Particle distributions show signatures of specularly reflected gyrating ions, which may be a source of free energy for the observed modes. In one event, we simultaneously observe perpendicular ion heating and parallel electron acceleration, consistent with wave heating/acceleration due to these waves.

Wilson, L. B., III

2012-01-01

295

[Presentation of the Lunar Precursor Robotics Program  

NASA Technical Reports Server (NTRS)

The Lunar Precursor Robotics Program (LPRP) is the host program for the Exploration Systems Mission Directorate's (ESMD) lunar robotic precursor missions to the Moon. The program includes two missions, the Lunar Reconnaissance Orbiter (LRO), and the Lunar CRater Observation and Sensing Satellite (LCROSS). Both missions will provide the required lunar information to support development and operations of those systems required for Human lunar return. LPRP is developing a lunar mapping plan, Called the Lunar Mapping and Modeling Project, to create the capability to archive and present all data from LRO, LCROSS, historical lunar missions, and international lunar missions for future mission planning and operations. LPRP is also developing its educational and public outreach activities for the Vision for Space Exploration's first missions. LPRP is working closely with the Science Mission Directorate as their lunar activities come into focus.

Lavoie, Anthony R.

2008-01-01

296

Observations of Electromagnetic Whistler Precursors at Supercritical Interplanetary Shocks.  

National Technical Information Service (NTIS)

We present observations of electromagnetic precursor waves, identified as whistler mode waves, at supercritical interplanetary shocks using the Wind search coil magnetometer. The precursors propagate obliquely with respect to the local magnetic field, sho...

A. Breneman A. Koval A. Szabo B. A. Maruca C. A. Cattell J. C. Kasper K. Goetz K. Kersten L. B. Wilson M. Pulupa P. J. Kellogg

2012-01-01

297

Precursors to radiopharmaceutical agents for tissue imaging  

DOEpatents

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Srivastava, Prem C. (Oak Ridge, TN); Knapp, Jr., Furn F. (Oak Ridge, TN)

1988-01-01

298

Nuclear Export of MicroRNA Precursors  

Microsoft Academic Search

MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically,

Elsebet Lund; Stephan Güttinger; Angelo Calado; James E. Dahlberg; Ulrike Kutay

2004-01-01

299

UF with pretreatment for removing DBP precursors  

Microsoft Academic Search

Although ultrafiltration (UF) is an efficient disinfection process, it is relatively ineffective because of its high-molecular-weight cutoff for removing the natural organic matter that contributes to disinfection by-product (DBP) formation. A pilot study was conducted to evaluate the efficacy of powdered activated carbon (PAC) as a UF pretreatment to provide enhanced removal of trihalomethane and haloacetic acid precursors. PAC addition

Joseph G. Jacangelo; Jean-Michel Laîné; Edward W. Cummings; Samer S. Adham

1995-01-01

300

Human neural precursor cells – an in vitro characterization  

Microsoft Academic Search

We have compared the properties of human neural precursors isolated from fetal tissue with progenitor and precursor cells identified from rodent fetal tissue and human excretory\\/secretory (ES) cells. We have identified multipotent human neuroepithelial precursor cells (hNEPs) that are fibroblast growth factor dependent, grow in adherent culture, and differentiate into neurons, astrocytes, and oligodendrocytes in mass and clonal cultures. A

Margot Mayer-Proschel; Ying Liu; Haipeng Xue; Yuanyuan Wu; Melissa K. Carpenter; Mahendra S. Rao

2002-01-01

301

Precursor Warhead Attachment for an Anti-Armor Rocket.  

National Technical Information Service (NTIS)

A precursor warhead for a high-explosive, anti-armor (HEAA) warhead is provided. The precursor warhead is a cylindrically-shaped attachment adapted for a friction fit over the nose cone of existing HEAA warheads. The precursor warhead has an instantaneous...

L. E. Crabtree

1998-01-01

302

Carbon fibers: precursor systems, processing, structure, and properties.  

PubMed

This Review gives an overview of precursor systems, their processing, and the final precursor-dependent structure of carbon fibers (CFs) including new developments in precursor systems for low-cost CFs. The following CF precursor systems are discussed: poly(acrylonitrile)-based copolymers, pitch, cellulose, lignin, poly(ethylene), and new synthetic polymeric precursors for high-end CFs. In addition, structure-property relationships and the different models for describing both the structure and morphology of CFs will be presented. PMID:24668878

Frank, Erik; Steudle, Lisa M; Ingildeev, Denis; Spörl, Johanna M; Buchmeiser, Michael R

2014-05-19

303

The Mars 2001 Athena Precursor Experiment (APEX)  

NASA Technical Reports Server (NTRS)

The Athena Precursor Experiment (APEX) is a suite of scientific instruments for the Mars Surveyor Program 2001 (MSP'01) lander. The major elements of the APEX pay load are: (1) Pancam/Mini-TES, a combined stereo color imager and mid-infrared point spectrometer. (2) An Alpha-Proton-X-Ray Spectrometer (APXS) for in-situ elemental analysis. (3) A Mossbauer Spectrometer for in-situ determination of the mineralogy of Fe-bearing rocks and soils. (4) A Magnet Array that can separate magnetic soil particles from non-magnetic ones.

Squyres, S. W.; Arvidson, R.; Bell, J. F., III; Carr, M.; Christensen, P.; DesMarais, D.; dUston, C.; Economou, T.; Gorevan, S.; Klingelhoefer, G.

1999-01-01

304

Osteogenic precursor cells in reparative osteogenesis  

SciTech Connect

The authors aim to discover osteogenic precursor cells in chinchilla rabbits appearing in the medullary cavity after removal of bone marrow. For this purpose the authors modified a model of medullary curettage. Pieces of tissue for electron-microscope autoradiography were incubated in medium with /sup 3/H-thymidine. To discover the proliferative properties of cells of the regenerating bone marrow tissue, an electron-microscopic autoradiographic investigation was carried out. It was found that DNA synthesis took place mainly in undifferentiated cells, endothelial cells, and differentiated cells.

Mikhailova, L.N.; Pal'tsyn, A.A.

1986-11-01

305

Earthquake precursors in magnetically conjugated ionosphere regions  

NASA Astrophysics Data System (ADS)

It is known that the highly conducting geomagnetic field flux tube and quasitrapped energetic particles provide strong electrodynamic coupling between magnetically conjugated regions in the ionosphere. Such a connection is likely to cause ionospheric disturbances before a pending earthquake not only over the epicentral zone but also in the opposite hemisphere. Data from the INTERCOSMOS-18 and ALOUETTE satellites were analyzed from this point of view. Earthquake precursors in magnetically-conjugated ionosphere regions were found in very low frequency (VLF) emission and F2 -peak parameters.

Ruzhin, Yu. Ya.; Larkina, V. I.; Depueva, A. Kh.

306

Amyloid precursor protein and neural development.  

PubMed

Interest in the amyloid precursor protein (APP) has increased in recent years due to its involvement in Alzheimer's disease. Since its molecular cloning, significant genetic and biochemical work has focused on the role of APP in the pathogenesis of this disease. Thus far, however, these studies have failed to deliver successful therapies. This suggests that understanding the basic biology of APP and its physiological role during development might be a crucial missing link for a better comprehension of Alzheimer's disease. Here, we present an overview of some of the key studies performed in various model organisms that have revealed roles for APP at different stages of neuronal development. PMID:24961795

Nicolas, Maya; Hassan, Bassem A

2014-07-01

307

Solar-cycle precursors and predictions  

NASA Astrophysics Data System (ADS)

The sunspot number data during the past 400 years indicates that both the profile and the amplitude of the solar cycle have large variations. Some precursors of the solar cycle were identified aiming to predict the solar cycle. The polar field and the geomagnetic index are two precursors which are received the most attention. The geomagnetic variations during the solar minima are potentially caused by the solar polar field by the connection of the solar open flux. The robust prediction skill of the polar field indicates that the memory of the dynamo process is less than 11 yrs based on the frame of the Babcock-Leighton flux transport dynamo. One possible reason to get the short magnetic memory is the high magnetic diffusivity in the convective zone. Our recent studies show that the radial downward pumping is another possible reason. Based upon the mechanism, we well simulate the cycle irregularities during RGO time period. This opens the possibility to set up a standard dynamo based model to predict the solar cycle. In the end, the no correlation between the polar field and the preceding cycle strength due to two nonlinearities involved in the sunspot emergence will be stressed.

Jiang, Jie

2013-07-01

308

Diagenesis and catagenesis of marine kerogen precursors  

SciTech Connect

The approaches used were (1) investigations of marine kerogen precursors in a natural environment, e.g., in reefal carbonate sediments (in Puerto Rico and Belize) and (2) laboratory modeling of the condensation of marine kerogen precursors, i.e., amino acids and sugars and subsequent formation and reactions of melanoidin polymers. The organic facies model of a reef environment was developed from the analysis of (1) total organic carbon, (2) visual protokerogen types, (3) Rock-Eval indices and (4) sedimentological considerations. Rates of melanoidin formation, incorporation of amino acid and glucose into the melanoidin polymers and their attendant decrease in the melanoidin solutions were evaluated. The observed pattern was that of initially rapid loss of biomonomers from the melanoidin solutions and concomitant formation of melanoidin polymers. The rate of incorporation of amino acids into the polymers is related partly to glucose concentration and partly to the type of amino acid. The racemization rates of amino acids were also investigated. During the course of melanoidin formation the original amino acid abundances and stereochemistry are redistributed during simulated diagenesis. This may have implications for natural environments where diagenesis may obscure the original depositional signal and complicate geochronological studies. Catagenetic evolution of both synthetic geopolymer (lysine, histidine, arginine, glucose - melanoidin) and natural geopolymers (Belizian organic matter) was simulated using hydrous pyrolysis.

Rafalska-Bloch, J.

1987-01-01

309

Gamma butyrolactone (GBL) and gamma valerolactone (GVL): similarities and differences in their effects on the acoustic startle reflex and the conditioned enhancement of startle in the rat.  

PubMed

Gamma butyrolactone (GBL) is metabolized to gamma hydroxybutyrate (GHB) in the body. GHB is a DEA Schedule 1 compound; GBL is a DEA List 1 chemical. Gamma valerolactone (GVL) is the 4-methyl analog of GBL; GVL is metabolized to 4-methyl-GHB; GVL is NOT metabolized to GBL or GHB. The effects of GBL (18.75-150 mg/kg), GVL (200-1600 mg/kg) or vehicle on the acoustic startle reflex (ASR), and the classically-conditioned enhancement of startle, the Startle Anticipated Potentiation of Startle (SAPS) response were studied in male rats. Both compounds produced a dose-dependent reduction of ASR, with GBL 5-7 times more potent than GVL. In contrast, GBL treatment significantly reduced SAPS at doses that exerted only moderate effects on ASR, whereas GVL exerted little or no effect on the SAPS, except at doses that produced pronounced reductions in Noise Alone ASR. In a second experiment, rats were tested for Noise Alone ASR behavior following treatment with a single mid-range dose of GBL (75 mg/kg), GVL (400mg/kg) or vehicle; immediately following startle testing the animals were sacrificed and their brains and blood were collected for determination of GHB, 4-methyl-GHB, GBL and GVL. GHB was found in measurable concentrations in all of the blood specimens and 6 (of 8) of the brain specimens from the GBL-treated subjects. 4-Methyl-GHB was found in measurable concentrations in all of the blood and brain specimens of the GVL-treated subjects; the change in startle amplitude was inversely correlated to the brain concentrations of these compounds. These findings confirm the differences in the metabolic fate of GBL and GVL as pro-drugs for the formation of GHB and 4-methyl-GHB, respectively. Moreover, the dissimilarity in effect profile for GBL and GVL on ASR versus SAPS behaviors suggests that different receptor(s) may be involved in mediating these behavioral effects. PMID:22349589

Marinetti, Laureen J; Leavell, Bonita J; Jones, Calleen M; Hepler, Bradford R; Isenschmid, Daniel S; Commissaris, Randall L

2012-06-01

310

Chondrule synthesis using fine-grained precursors  

NASA Astrophysics Data System (ADS)

High temperature petrologic experiments have been used in order to reproduce the textures of chondrules, which are rounded to irregularly shaped ferromagnesion silicate objects. Such experiments shed light on the conditions that existed and mechanisms that operated in the early solar nebula, as natural chondrules are believed to have formed there due to some type of heating event. The exact nature of this heating event and the conditions that existed at the time of the formation of the solar nebula are not completely understood. Chondrules, which are believed to be composed of some of the oldest remnants of the solar system, nebular condensates, are the basic components of chondrites. Chondrites comprise ˜82% of all meteorites. Despite years of petrographic examination and experimental petrology, the thermal history of chondrules still remains uncertain. Natural chondrules exhibit a variety of different textures ranging from glassy, barred, porphyritic, microporphyritc to protoporphyritc. Petrologic experiments in a muffle tube furnace under controlled fugacity conditions using type IAB bulk composition analogs have been successful in reproducing each of these textures in the laboratory. Charges are prepared, heated, water quenched, mounted, polished and photographed using back-scattered electron imagery. Subsequent analysis provides numerical data, which can then be used to calculate the nominal grain size of the olivine crystals in each charge. Porphyritic chondrules are the most abundant in nature by far and any model for chondrule formation must be capable of producing porphyritic textures. To reproduce this texture in the laboratory, however, seems to require a very narrow range of maximum temperature and soak time parameters even when using a variety of different types of fine-grained and agglomerated olivine precursor material. Experiments undertaken in this study bring into question some of the basic assumptions of various classical models of chondrule formation, which call for fine-grained precursors (nebular condensates) being processed by a single heating event. In light of these findings, models for chondrule formation that incorporate mechanisms for the recycling of fine-grained precursor material appear to be more favorable.

Fox, George Ernest

2002-11-01

311

Study of tectonic earthquake precursors by geodetic methods  

SciTech Connect

Deformations of the Earth's surface which can be revealed by geodetic methods are among the most reliable earthquake precursors. A brief list is presented of geodetic leveling methods which have revealed the precursors of several earthquakes. To confirm the accuracy of determination of precursors of earthquakes based on the results of repeated leveling in epicenter zones and observations at Alma-Ata, the magnitudes of 7 earthquakes which occurred in northern Tien Shan during measurement of tectonic precursors were calculated and compared to valves based on seismologic measurements. The agreement found is satisfactory. A scientifically well-founded program of tectonic movements by geodetic methods in the northern Tien Shan has thus established the presence of tectonic precursors of earthquakes, determined the distances over which they are manifested and shown the possiblity of using the results of geodetic measurements in combiantion with geophysical and seismologic data to estimate the possible time of appearance of earthquake precursors.

Sigalov, V.M.

1985-02-01

312

Thermal Stability of Jet Fuels: Kinetics of Forming Deposit Precursors  

NASA Technical Reports Server (NTRS)

The focus of this study was on the autoxidation kinetics of deposit precursor formation in jet fuels. The objectives were: (1) to demonstrate that laser-induced fluorescence is a viable kinetic tool for measuring rates of deposit precursor formation in jet fuels; (2) to determine global rate expressions for the formation of thermal deposit precursors in jet fuels; and (3) to better understand the chemical mechanism of thermal stability. The fuels were isothermally stressed in small glass ampules in the 120 to 180 C range. Concentrations of deposit precursor, hydroperoxide and oxygen consumption were measured over time in the thermally stressed fuels. Deposit precursors were measured using laser-induced fluorescence (LIF), hydroperoxides using a spectrophotometric technique, and oxygen consumption by the pressure loss in the ampule. The expressions, I.P. = 1.278 x 10(exp -11)exp(28,517.9/RT) and R(sub dp) = 2.382 x 10(exp 17)exp(-34,369.2/RT) for the induction period, I.P. and rate of deposit precursor formation R(sub dp), were determined for Jet A fuel. The results of the study support a new theory of deposit formation in jet fuels, which suggest that acid catalyzed ionic reactions compete with free radical reactions to form deposit precursors. The results indicate that deposit precursors form only when aromatics are present in the fuel. Traces of sulfur reduce the rate of autoxidation but increase the yield of deposit precursor. Free radical chemistry is responsible for hydroperoxide formation and the oxidation of sulfur compounds to sulfonic acids. Phenols are then formed by the acid catalyzed decomposition of benzylic hydroperoxides, and deposit precursors are produced by the reaction of phenols with aldehydes, which forms a polymer similar to Bakelite. Deposit precursors appear to have a phenolic resin-like structure because the LIF spectra of the deposit precursors were similar to that of phenolic resin dissolved in TAM.

Naegeli, David W.

1997-01-01

313

Mars MetNet Precursor Mission Status  

NASA Astrophysics Data System (ADS)

We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

2013-09-01

314

Silsesquioxanes as precursors to ceramic composites  

NASA Technical Reports Server (NTRS)

Silsesquioxanes having the general structure RSiO sub 1.5, where R = methyl, propyl, or phenyl, melt flow at 70 to 100 C. Above 100 C, free -OH groups condense. At 225 C further crosslinking occurs, and the materials form thermosets. Pyrolysis, with accompanying loss of volatiles, takes place at nominally 525 C. At higher temperatures, the R group serves as an internal carbon soruce for carbo-thermal reduction to SiC accompanied by the evolution of CO. By blending silsesquioxanes with varying R groups, both the melt rheology and composition of the fired ceramic can be controlled. Fibers can be spun from the melt which are stable in argon in 1400 C. The silsesquioxanes also were used as matrix precursors for Nicalon and alpha-SiC platelet reinforced composites.

Hurwitz, Frances I.; Hyatt, Lizbeth H.; Gorecki, Joy; Damore, Lisa

1987-01-01

315

Silsesquioxanes as precursors to ceramic composites  

NASA Technical Reports Server (NTRS)

Silsesquioxanes having the general structure RSiO(1.5), where R = methyl, propyl, or phenyl, melt flow at 70 to 100 C. Above 100 C, free OH groups condense. At 225 C further crosslinking occurs, and the materials form thermosets. Pyrolysis, with accompanying loss of volatiles, takes place at nominally 525 C. At higher temperatures, the R group serves as an internal carbon source for carbo-thermal reduction to SiC accompanied by the evolution of CO. By blending silsesquioxanes with varying R groups, both the melt rheology and composition of the fired ceramic can be controlled. Fibers can be spun from the melt which are stable in argon in 1400 C. The silsesquioxanes also were used as matrix precursors for Nicalon and alpha-SiC platelet reinforced composites.

Hurwitz, F. I.; Hyatt, L.; Gorecki, J.; D'Amore, L.

1987-01-01

316

Filler/ Polycarbosilane Systems as CMC Matrix Precursors  

NASA Technical Reports Server (NTRS)

Pyrolytic conversion of polymeric precursors to ceramics is accompanied by loss of volatiles and large volume changes. Infiltration of a low viscosity polymer into a fiber preform will fill small spaces within fiber tows by capillary forces, but create large matrix cracks within large, intertow areas. One approach to minimizing shrinkage and reducing the number of required infiltration cycles is to use particulate fillers. In this study, Starfire allylhydridopolycarbosilane (AHPCS) was blended with a silicon carbide powder, with and without dispersant, using shear mixing. The polymer and polymer/particle interactions were characterized using nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and rheometry. Polymer/particulate slurries and suspensions were used to infiltrate a figidized preform of an eight ply five harness satin CG Nicalon fiber having a dual layer BN/SiC interface coating, and the resulting composites characterized by optical and scanning electron microscopy.

Hurwitz, Frances I.

1998-01-01

317

Design of Aerosol Coating Reactors: Precursor Injection  

PubMed Central

Particles are coated with thin shells to facilitate their processing and incorporation into liquid or solid matrixes without altering core particle properties (coloristic, magnetic, etc.). Here, computational fluid and particle dynamics are combined to investigate the geometry of an aerosol reactor for continuous coating of freshly-made titanium dioxide core nanoparticles with nanothin silica shells by injection of hexamethyldisiloxane (HMDSO) vapor downstream of TiO2 particle formation. The focus is on the influence of HMDSO vapor jet number and direction in terms of azimuth and inclination jet angles on process temperature and coated particle characteristics (shell thickness and fraction of uncoated particles). Rapid and homogeneous mixing of core particle aerosol and coating precursor vapor facilitates synthesis of core-shell nanoparticles with uniform shell thickness and high coating efficiency (minimal uncoated core and free coating particles).

Buesser, Beat; Pratsinis, Sotiris E.

2013-01-01

318

Molecular imaging in myeloma precursor disease.  

PubMed

Multiple myeloma (MM) is consistently preceded by its pre-malignant states, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). By definition, precursor conditions do not exhibit end-organ disease (anemia, hypercalcemia, renal failure, skeletal lytic lesions, or a combination of these). However, new imaging methods are demonstrating that some patients in the MGUS or SMM category are exhibiting early signs of MM. Although MGUS/SMM patients are currently defined as low-risk versus high-risk based on clinical markers, we currently lack the ability to predict the individual patient's risk of progression from MGUS/SMM to MM. Given that the presence of gross lytic bone lesions is a hallmark of MM, it is reasonable to believe that less severe bone changes defined by more sensitive imaging may be predictive of MM progression. Indeed, since bone disease is such an essential aspect of MM, imaging techniques directed at the detection of early bone lesions, have the potential to become increasingly more useful in the setting of MGUS/SMM. Current guidelines for the radiological assessment of MM still recommend the traditional skeletal survey, although its limitations are well documented, especially in early phases of the disease when radiographs can significantly underestimate the extent of bone lesions and bone marrow involvement. Newer, more advanced imaging modalities, with higher sensitivities, including whole-body low-dose computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are being employed. Also various imaging techniques have been used to provide an assessment of bone involvement and identify extra-osseous disease. This review emphasizes the current state of the art and emerging imaging methods, which may help to better define high-risk versus low-risk MGUS/SMM. Ultimately, improved imaging could allow more tailored clinical management, and, most likely play an important role in the development of future treatment strategies for high-risk precursor disease. PMID:21232655

Mena, Esther; Choyke, Peter; Tan, Esther; Landgren, Ola; Kurdziel, Karen

2011-01-01

319

Club Drugs (GHB, Ketamine, and Rohypnol)  

MedlinePLUS

... were added to the study. For the latest data visit: High School and Youth Trends . ** “Lifetime” refers to use ... Intertwined Epidemics Understanding Drug Abuse and Addiction Survey Data Drug-Related Hospital Emergency Room Visits High School and Youth Trends Nationwide Trends Treatment Statistics ...

320

Hydrodeoxygenation of coal using organometallic catalyst precursors  

NASA Astrophysics Data System (ADS)

The objective of this dissertation was to determine the desirability of organometallic compounds for the hydrodeoxygenation (HDO) of coal during liquefaction. The primary focus of this study was the removal of phenol-like compounds from coal liquids for the production of a thermally stable jet fuel. Investigation of the HDO ability of an organometallic compound containing both cobalt and molybdenum (CoMo-T2) was achieved using a combination of model compound and coal experiments. Model compounds were chosen representing four oxygen functional groups present in a range of coals. Electron density and bond order calculations were performed for anthrone, dinaphthyl ether, xanthene, di-t-butylmethylphenol, and some of their derivatives to ascertain a potential order of hydrogenolysis and hydrogenation reactivity for these compounds. The four model compounds were then reacted with CoMo-T2, as well as ammonium tetrathiomolybdate (ATTM). Products of reaction were grouped as compounds that had undergone deoxygenation, those that had aromatic rings reduced, those that were products of both reaction pathways, and those produced through other routes. ATTM had an affinity for both reaction types. Its reaction order for the four model compounds with respect to deoxygenated compounds was the same as that estimated from electron density calculations for hydrogenolysis reactivity. CoMo-T2 appeared to show a preference toward hydrogenation, although deoxygenated products were still achieved in similar, or greater, yields, for almost all the model compounds. The reactivity order achieved for the four compounds with CoMo-T2 was similar to that estimated from bond order calculations for hydrogenation reactivity. Three coals were selected representing a range of coal ranks and oxygen contents. DECS-26 (Wyodak), DECS-24 (Illinois #6), and DECS-23 (Pittsburgh #8) were analyzed by CPMAS 13C NMR and pyrolysis-GC-MS to determine the functional groups comprising the oxygen content of these coals. Trends within the data were similar to those reported by other authors. Based on the conclusions from both the model compound studies and the coal analysis, predictions were made of the catalyst precursors' performance in the HDO of the three selected coals. It was concluded that CoMo-T2 is a desirable catalyst precursor for the HDO of coals (particularly low-rank coals), but that an optimum set of conditions must be determined to take full advantage of its HDO ability. (Abstract shortened by UMI.)

Kirby, Stephen R.

2002-04-01

321

Synthesis of barium titanate nanopowder using polymeric precursor method  

Microsoft Academic Search

Barium titanate powder was prepared by a polymerized complex method based on the Pechini type reaction route, where barium and titanium ions were polymerized in mixed solution of citric acid, ethylene glycol, to form a transparent resin, which was used as a precursor. Barium titanate powder was formed by heat treating the polymeric precursor in air at 500–900°C. The thermal

V. Vinothini; Paramanand Singh; M. Balasubramanian

2006-01-01

322

Dopamine depletion impairs precursor cell proliferation in Parkinson disease  

Microsoft Academic Search

Cerebral dopamine depletion is the hallmark of Parkinson disease. Because dopamine modulates ontogenetic neurogenesis, depletion of dopamine might affect neural precursors in the subependymal zone and subgranular zone of the adult brain. Here we provide ultrastructural evidence showing that highly proliferative precursors in the adult subependymal zone express dopamine receptors and receive dopaminergic afferents. Experimental depletion of dopamine in rodents

Pamela Rizk; Marie P Muriel; Charles Duyckaerts; Wolfgang H Oertel; Isabelle Caille; Etienne C Hirsch; Günter U Höglinger

2004-01-01

323

TECHNICAL ASSISTANCE DOCUMENT FOR SAMPLING AND ANALYSIS OF OZONE PRECURSORS  

EPA Science Inventory

This document contains guidance and discussion on methods applicable to the proposed revisions to Title 40 Part 58 of the Code of Federal Regulations. he proposed revisions pertain to the enhanced monitoring of ozone precursors and meteorological monitoring. he precursors address...

324

Sols and mixtures of sols as precursors of unique oxides  

Microsoft Academic Search

There is considerable evidence that sols, or colloidal oxides, can play a critical role as precursors to the primary particles of crystalline or amorphous oxides. Sols have been demonstrated to be useful precursors to form microengineered catalysts when adsorbed onto geometric structures, such as monolith honeycombs, or onto macroporous supports capable of allowing entry of the sol structure into the

L. L. Murrell

1997-01-01

325

Hydrokinetic simulations of nanoscopic precursor films in rough channels  

Microsoft Academic Search

We report on simulations of capillary filling of highly wetting fluids in nanochannels with and without obstacles. We use atomistic (molecular dynamics) and hydrokinetic (lattice Boltzmann; LB) approaches which indicate clear evidence of the formation of thin precursor films, moving ahead of the main capillary front. The dynamics of the precursor films is found to obey a square-root law like

S. Chibbaro; L. Biferale; K. Binder; D. Dimitrov; F. Diotallevi; A. Milchev; S. Succi

2009-01-01

326

PAC activity vs by-product precursors in water disinfection  

Microsoft Academic Search

Disinfection by-products (DBP) are among the most significant negative side effects of drinking water treatments. Chlorinated disinfectants and organic precursors found in source waters are involved in their formation. Purpose of this study is to investigate the applicability of powdered activation carbon (PAC) to the adsorptive removal of precursors. Three different PACs provided by manufacturers have been applied to water

P. Sandrucci; G. Merlo; G. Genon; L. Meucci

1995-01-01

327

Production of activated carbon from a new precursor: Molasses  

Microsoft Academic Search

Activated carbon has been prepared from molasses, a natural precursor of vegetable origin resulting from the sugar industry in Morocco. The preparation of the activated carbon from the molasses has been carried out by impregnation of the precursor with sulfuric acid, followed by carbonization. The adsorption capacity, the BET surface area, and the pore volume of the activated carbon were

K. Legrouri; M. Ezzine; S. Ichcho; H. Hannache; R. Denoyel; R. Pailler; R. Naslain

2005-01-01

328

An Evaluation of Strengthening Precursors to Increase Preschooler Compliance  

ERIC Educational Resources Information Center

We evaluated the strategy of increasing precursors to compliance on the compliance of 2 preschool boys. Modeling and differential reinforcement were used to increase specific responses to his name being called prior to the opportunity to comply with an instruction. The precursors were stopping the ongoing activity and orienting to, making eye…

Kraus, Aaron J.; Hanley, Gregory P.; Cesana, Lori L.; Eisenberg, Danielle; Jarvie, Adam C.

2012-01-01

329

Precursors to Aggression Are Evident by 6 Months of Age  

ERIC Educational Resources Information Center

We tested the hypothesis that developmental precursors to aggression are apparent in infancy. Up to three informants rated 301 firstborn infants for early signs of anger, hitting and biting; 279 (93%) were assessed again as toddlers. Informants' ratings were validated by direct observation at both ages. The precursor behaviours were…

Hay, Dale F.; Waters, Cerith S.; Perra, Oliver; Swift, Naomi; Kairis, Victoria; Phillips, Rebecca; Jones, Roland; Goodyer, Ian; Harold, Gordon; Thapar, Anita; van Goozen, Stephanie

2014-01-01

330

Seabed Doming: a Precursor to Pockmark Formation?  

NASA Astrophysics Data System (ADS)

Since their discovery in 1960's, the frequent occurrence of pockmarks on the ocean floor and their potential as a geohazard has led researchers to seek out and understand their presence. Evidence of seabed doming in pockmarked areas, combined with upward bending of sediment layers beneath many pockmarks and mud volcanoes suggests that doming may be a possible precursor to sediment failure and pockmark formation. The ability of fluids to migrate vertically due to buoyancy is well documented, but more recent studies have shown migration pathways to become horizontal under some conditions. Sediment layering can create planes of weakness along which fluid can migrate horizontally and result in local surface layer doming. Initial experiments using thin layers of gelatin and mixtures of mud-silt-sand particles show that horizontally migrating fluid under a thin layer of sediment causes uplift and doming of the surface in the shape of a spherical cap. Continued fluid flow between layers causes tensional failure of the surface layer and release of the fluid from a focal point, resulting in a pockmark-like feature. The induced doming can be described using thin-plate bending theory for domes whose diameters are many times greater than the overlying layer thickness. From the theory, stress created in a domed seabed can be nearly two orders of magnitude larger than the pressure applied by the underlying fluid. This can allow for low relief domes to induce large tensile stresses while going undetected by most acoustical imaging methods.

Barry, M. A.; Johnson, B.

2009-05-01

331

Assimilation of NAD(+) precursors in Candida glabrata.  

PubMed

The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD(+)) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD(+). C. glabrata salvage pathways defined in this article allow NAD(+) to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss-Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD(+) via the nicotinamidase Pnc1 and the Preiss-Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD(+) sources during disseminated infection. PMID:17725566

Ma, Biao; Pan, Shih-Jung; Zupancic, Margaret L; Cormack, Brendan P

2007-10-01

332

Bacterial Cellular Materials as Precursors of Chloroform  

NASA Astrophysics Data System (ADS)

The environmental sources of chloroform and other halocarbons have been intensively investigated because their effects of stratospheric ozone destruction and environmental toxicity. It has been demonstrated that microorganisms could facilitate the biotic generation of chloroform from natural organic matters in soil, but whether the cellular materials itself also serves as an important precursor due to photo-disinfection is poorly known. Herein, seven common pure bacterial cultures (Acinetobacter junii, Aeromonas hydrophila, Bacillus cereus, Bacillus substilis, Escherichia coli, Shigella sonnei, Staphylococcus sciuri) were chlorinated to evaluate the yields of chloroform, dibromochloromethane, dichlorobromomethane, and bromoform. The effects of bromide on these chemical productions and speciations were also investigated. Results showed that, on average, 5.64-36.42 ?g-chloroform /mg-C were generated during the bacterial chlorination, in similar order of magnitude to that generated by humic acid (previously reported as 78 ?g-chloroform/mg-C). However, unlike humic acid in water chlorination, chloroform concentration did not simply increase with the total organic carbon in water mixture. In the presence of bromide, the yield of brominated species responded linearly to the bromide concentration. This study provides useful information to understand the contributions of chloroform from photodisinfection processes in coastal environments.

Wang, J.; Ng, T.; Zhang, Q.; Chow, A. T.; Wong, P.

2011-12-01

333

Robotic Precursor Missions for Mars Habitats  

NASA Technical Reports Server (NTRS)

Infrastructure support for robotic colonies, manned Mars habitat, and/or robotic exploration of planetary surfaces will need to rely on the field deployment of multiple robust robots. This support includes such tasks as the deployment and servicing of power systems and ISRU generators, construction of beaconed roadways, and the site preparation and deployment of manned habitat modules. The current level of autonomy of planetary rovers such as Sojourner will need to be greatly enhanced for these types of operations. In addition, single robotic platforms will not be capable of complicated construction scenarios. Precursor robotic missions to Mars that involve teams of multiple cooperating robots to accomplish some of these tasks is a cost effective solution to the possible long timeline necessary for the deployment of a manned habitat. Ongoing work at JPL under the Mars Outpost Program in the area of robot colonies is investigating many of the technology developments necessary for such an ambitious undertaking. Some of the issues that are being addressed include behavior-based control systems for multiple cooperating robots (CAMPOUT), development of autonomous robotic systems for the rescue/repair of trapped or disabled robots, and the design and development of robotic platforms for construction tasks such as material transport and surface clearing.

Huntsberger, Terry; Pirjanian, Paolo; Schenker, Paul S.; Trebi-Ollennu, Ashitey; Das, Hari; Joshi, Sajay

2000-01-01

334

Cystic precursors to invasive pancreatic cancer.  

PubMed

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not. PMID:21383670

Matthaei, Hanno; Schulick, Richard D; Hruban, Ralph H; Maitra, Anirban

2011-03-01

335

PRECOMBUSTION REMOVAL OF HAZARDOUS AIR POLLUTANT PRECURSORS  

SciTech Connect

In response to growing environmental concerns reflected in the 1990 Clean Air Act Amendment (CAAA), the United States Department of Energy (DOE) sponsored several research and development projects in late 1995 as part of an initiative entitled Advanced Environmental Control Technologies for Coal-Based Power Systems. The program provided cost-shared support for research and development projects that could accelerate the commercialization of affordable, high-efficiency, low-emission, coal-fueled electric generating technologies. Clean coal technologies developed under this program would serve as prototypes for later generations of technologies to be implemented in the industrial sector. In order to identify technologies with the greatest potential for commercial implementation, projects funded under Phase I of this program were subject to competitive review by DOE before being considered for continuation funding under Phase II. One of the primary topical areas identified under the DOE initiative relates to the development of improved technologies for reducing the emissions of air toxics. Previous studies have suggested that many of the potentially hazardous air pollutant precursors (HAPPs) occur as trace elements in the mineral matter of run-of-mine coals. As a result, these elements have the potential to be removed prior to combustion at the mine site by physical coal cleaning processes (i.e., coal preparation). Unfortunately, existing coal preparation plants are generally limited in their ability to remove HAPPs due to incomplete liberation of the mineral matter and high organic associations of some trace elements. In addition, existing physical coal cleaning plants are not specifically designed or optimized to ensure that high trace element rejections may be achieved.

Unknown

2000-10-09

336

Precursor Science for the Terrestrial Planet Finder  

NASA Technical Reports Server (NTRS)

This document outlines a path for the development of the field of extrasolar planet research, with a particular emphasis on the goals of the Terrestrial Planet Finder (TPF). Over the past decade, a new field of research has developed, the study of extrasolar planetary systems, driven by the discovery of massive planets around nearby stars. The planet count now stands at over 130. Are there Earth-like planets around nearby stars? Might any of those planets be conducive to the formation and maintenance of life? These arc the questions that TPF seeks to answer. TPF will be implemented as a suite of two space observatories, a 6-m class optical coronagraph, to be launched around 20 14, and a formation flying mid-infrared interferometer, to be launched sometime prior to 2020. These facilities will survey up to 165 or more nearby stars and detect planets like Earth should they be present in the 'habitable zone' around each star. With observations over a broad wavelength range, TPF will provide a robust determination of the atmospheric composition of planets to assess habitability and the presence of life. At this early stage of TPF's development, precursor observational and theoretical programs are essential to help define the mission, to aid our understanding of the planets that TPF could discover, and to characterize the stars that TPF will eventually study. This document is necessarily broad in scope because the significance of individual discoveries is greatly enhanced when viewed in thc context of the field as a whole. This document has the ambitious goal of taking us from our limited knowledge today, in 2004, to the era of TPF observations in the middle of the next decade. We must use the intervening years wisely. This document will be reviewed annually and updated as needed. The most recent edition is available online at http://tpf.jpl.nasa.gov/ or by email request to lawson@hucy.jpl.nasa.gov

Lawson, P. R. (Editor); Unwin, S. C. (Editor); Beichman, C. A. (Editor)

2004-01-01

337

Different control mechanisms of growth hormone (GH) secretion between gamma-amino- and gamma-hydroxy-butyric acid: neuroendocrine evidence in Parkinson's disease.  

PubMed

The observation that baclofen stimulates growth hormone (GH) secretion in normal men, but not in parkinsonian patients led us to test the GH releasing effect of other gamma-amino-butyric acid (GABA)ergic agents with different mechanisms of action in Parkinson's disease. For this purpose 10 normal men and 10 de novo parkinsonian patients were tested with sodium valproate (800 mg PO), gamma-hydroxybutyric acid (GHB) (25 mg/kg body weight PO) and baclofen (10 mg PO). All drugs induced a significant increment in serum GH levels in the normal controls. On the other hand, GH secretion in parkinsonian patients did not change after baclofen or sodium valproate administration, whereas it showed normal responsiveness to GHB. These data suggest that the mechanism underlying the GH response to GHB is different from that (or those) mediating sodium valproate and/or baclofen action. In addition, the former, but not the latter mechanism appears to be preserved in the parkinsonian brain. PMID:9373886

Volpi, R; Chiodera, P; Caffarra, P; Scaglioni, A; Saccani, A; Coiro, V

1997-10-01

338

Raves: a review of the culture, the drugs and the prevention of harm  

PubMed Central

Raves are all-night dance parties attended by large numbers of youth, sometimes in excess of 20,000. The rave scene, which is international in scope, is distinguished by clandestine venues, hypnotic electronic music and the liberal use of drugs such as ecstasy (3,4-methylenedioxymethamphetamine), GHB (gamma-hydroxybutyrate) and ketamine. Several rave-related deaths in Canada in 1999 alerted health authorities, parents and police to the health risks of rave attendance. Family physicians, emergency physicians and pediatricians should have some understanding of raves, the drugs and the health risks so they can effectively counsel and treat patients. The rave culture in Canada and the drugs commonly used at raves are reviewed, and strategies and initiatives for harm reduction are discussed.

Weir, E

2000-01-01

339

Methods for forming particles from single source precursors  

DOEpatents

Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

Fox, Robert V. (Idaho Falls, ID); Rodriguez, Rene G. (Pocatello, ID); Pak, Joshua (Pocatello, ID)

2011-08-23

340

Surface doping of nitrogen atoms on graphene via molecular precursor  

NASA Astrophysics Data System (ADS)

Surface doping can be a powerful way to modify the electronic properties of graphene with the unique potential to retain the excellent pristine properties of graphene. Here, we report an atomic surface doping method for graphene via dissociation of adsorbed precursor molecules of tetrafluorotetracyanoquinodimethane (F4-TCNQ) induced by hydrogen plasma treatment. Significantly, the location of the dopant N atoms can be pre-determined by the location and orientation of the F4-TCNQ molecule precursor on graphene, leading in principle to site-selective doping. Furthermore, the molecular precursor is stable under ambient conditions, satisfying an important consideration for patterning processes.

Hong, Guo; Wu, Qi-Hui; Wang, Chundong; Ren, Jianguo; Xu, Tingting; Zhang, Wenjun; Lee, Shuit-Tong

2013-02-01

341

The solution precursor plasma spray processing of nanomaterials  

NASA Astrophysics Data System (ADS)

Solution precursor plasma spray (SPPS) synthesis is a simple, single-step, and rapid technique for synthesizing nano-ceramic materials from solution precursors. This innovative method uses molecularly mixed precursors as liquids, avoiding a separate processing method for the preparation of powders and enabling the synthesis of a wide range of metal oxide powders and coatings. Also, this technique is considered to be promising for the formation of non-equilibrium phases in multi-component oxide systems. This short review provides an insight into the important aspects of SPPS, the properties obtained in comparison to conventional plasma spray, and the potential applications of the SPPS process.

Brinley, E.; Babu, K. S.; Seal, S.

2007-07-01

342

Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein.  

PubMed

Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the Alzheimer disease amyloid beta peptide (Abeta). The molecular mechanisms underlying the control of APP shedding remain little understood but are in part dependent on the low density lipoprotein receptor-related protein (LRP), which is involved in APP endocytosis. Here, we show that the APP homolog APLP1 (amyloid precursor-like protein 1) influences APP shedding. In human embryonic kidney 293 cells expression of APLP1 strongly activated APP shedding by alpha-secretase and slightly reduced beta-secretase cleavage. As revealed by domain deletion analysis, the increase in APP shedding required the NPTY amino acid motif within the cytoplasmic domain of APLP1. This motif is conserved in APP and is essential for the endocytosis of APP and APLP1. Unrelated membrane proteins containing similar endocytic motifs did not affect APP shedding, showing that the increase in APP shedding was specific to APLP1. In LRP-deficient cells APLP1 no longer induced APP shedding, suggesting that in wild-type cells APLP1 interferes with the LRP-dependent endocytosis of APP and there by increases APP alpha-cleavage. In fact, an antibody uptake assay revealed that expression of APLP1 reduced the rate of APP endocytosis. In summary, our study provides a novel mechanism for APP shedding, in which APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage. PMID:16344553

Neumann, Stephanie; Schöbel, Susanne; Jäger, Sebastian; Trautwein, Anna; Haass, Christian; Pietrzik, Claus U; Lichtenthaler, Stefan F

2006-03-17

343

40 CFR 141.135 - Treatment technique for control of disinfection byproduct (DBP) precursors.  

Code of Federal Regulations, 2010 CFR

...control of disinfection byproduct (DBP) precursors. 141.135 Section 141.135 ...Byproducts, and Disinfection Byproduct Precursors § 141.135 Treatment technique...control of disinfection byproduct (DBP) precursors. (a) Applicability....

2010-07-01

344

40 CFR 141.135 - Treatment technique for control of disinfection byproduct (DBP) precursors.  

Code of Federal Regulations, 2010 CFR

...control of disinfection byproduct (DBP) precursors.] 40 PROTECTION OF ENVIRONMENT...control of disinfection byproduct (DBP) precursors. (a) Applicability. (1...Treatment technique requirements for DBP precursors. The Administrator identifies the...

2009-07-01

345

Biological Indicators in Studies of Earthquake Precursors  

NASA Astrophysics Data System (ADS)

Time series of data on variations in the electric activity (EA) of four species of weakly electric fish Gnathonemus leopoldianus and moving activity (MA) of two cat-fishes Hoplosternum thoracatum and two groups of Columbian cockroaches Blaberus craniifer were analyzed. The observations were carried out in the Garm region of Tajikistan within the frameworks of the experiments aimed at searching for earthquake precursors. An automatic recording system continuously recorded EA and DA over a period of several years. Hourly means EA and MA values were processed. Approximately 100 different parameters were calculated on the basis of six initial EA and MA time series, which characterize different variations in the EA and DA structure: amplitude of the signal and fluctuations of activity, parameters of diurnal rhythms, correlated changes in the activity of various biological indicators, and others. A detailed analysis of the statistical structure of the total array of parametric time series obtained in the experiment showed that the behavior of all animals shows a strong temporal variability. All calculated parameters are unstable and subject to frequent changes. A comparison of the data obtained with seismicity allow us to make the following conclusions: (1) The structure of variations in the studied parameters is represented by flicker noise or even a more complex process with permanent changes in its characteristics. Significant statistics are required to prove the cause-and-effect relationship of the specific features of such time series with seismicity. (2) The calculation of the reconstruction statistics in the EA and MA series structure demonstrated an increase in their frequency in the last hours or a few days before the earthquake if the hypocenter distance is comparable to the source size. Sufficiently dramatic anomalies in the behavior of catfishes and cockroaches (changes in the amplitude of activity variation, distortions of diurnal rhythms, increase in the mismatch of coordination between the activity dynamics of one type of biological indicators) were observed in one case before the November 12, 1987, event at a hypocenter distance of 8 km from the observation point (i.e., the animals were located within the source zone). (3) Changes observed before the earthquakes do not have any specific features and correspond quite well to the variations permanently observed without any relation to the earthquakes. (4) The activity of individual specimens has specific features. This hampers the implication of the biological monitoring. (5) The conclusions made here should not be considered absolute or extrapolated over all cases of observation of the behavior of animals, because the animals were kept under experimental (laboratory) conditions and could be screened from the influence of the stimuli of some modalities.

Sidorin, A. Ya.; Deshcherevskii, A. V.

2012-04-01

346

Development of Supersonic Retropropulsion for a Mars Precursor Mission  

NASA Astrophysics Data System (ADS)

Supersonic Retropropulsion (SRP) is a promising EDL technology for future Mars missions. This paper summarizes the current state of SRP and recommends tasks to prepare for a Mars robotic precursor mission in the 2018-2024 timeframe.

Edquist, K. T.; Dyakonov, A. A.; Korzun, A. M.; Cianciolo, A. D.; Zarchi, K. A.; Lemke, L. G.; Bakhtian, N. M.

2012-06-01

347

REMOVAL OF TRIHALOMETHANE PRECURSORS BY DIRECT FILTRATION AND CONVENTIONAL TREATMENT  

EPA Science Inventory

This research examined direct filtration for the removal of trihalomethane (THM) precursors. Direct filtration pilot plant results were compared with the performance of two full scale conventional type water treatment plants. Two different water sources were studied - the Grasse ...

348

Antibodies to Myeloid Precursor Cells in Autoimmune Neutropenia.  

National Technical Information Service (NTIS)

Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been described in the sera of some patients with apparent autoimmune neutropenia. To further explore the prevalence and specificities of antibodies to myeloid precursor cells, we...

K. R. Hartman V. F. LaRussa S. Rothwell T. O. Atolagbe F. T. Ward

1994-01-01

349

Control of CVD precursor purity for integrated circuit manufacture  

NASA Astrophysics Data System (ADS)

Chemical vapor deposition, CVD, has assumed an increasing share of the processes utilized in the manufacture of submicron integrated circuits. In addition to the conventional CVD materials such as silicon oxide, nitride and polysilicon, an array of new materials for both dielectric and conductive material applications are in development. For films like BPSG or tungsten, convenient volatile precursor sources exist, however, in other cases temperature sensitive, lower volatility liquids and solids are utilized. The quality and consistency of these molecular precursors can have a marked impact on the film forming process. The application of SPC methodology to precursor manufacture provides an effective metric for controlling both the quality and the consistency of the precursors.

Roberts, David A.; Graf, Hans J.; Halberstadt, Michael J.

1995-09-01

350

Study of Precursor Phenomena Ahead of Ionizing Shock Waves.  

National Technical Information Service (NTIS)

Precursor densities were measured, and the following results were obtained: (1) both electrons and ions exist and the electron density is larger than ion density; (2) the electron density profile is consistent with that expected by free diffusion at rerat...

G. Kamimoto K. Teshima

1972-01-01

351

Technical Approach to Marking Explosives, Propellants, and Precursor Chemicals.  

National Technical Information Service (NTIS)

Techniques for marking or tagging explosives, propellants, and precursor chemicals-chemicals which can be used to manufacture explosives and propellants-are discussed. The history of taggant technology and the effectiveness of various techniques are discu...

R. J. Mayersak

1998-01-01

352

Removal of Trihalomethane Precursors by Direct Filtration and Conventional Treatment.  

National Technical Information Service (NTIS)

This research examined direct filtration for the removal of trihalomethane (THM) precursors. Direct filtration pilot plant results were compared with the performance of two full scale conventional type water treatment plants. Two different water sources w...

J. K. Edzwald

1984-01-01

353

Chondrule Precursors and Cooling Paths: The Sulfur Evidence.  

National Technical Information Service (NTIS)

The behavior of moderately volatile elements (Na and S) is controversial but critical in understanding chondrule precursors and heating processes. Sulfide appeared to be present in most chondrules, but S should have been vaporized during chondrule formati...

B. Zanda Y. Yu M. Bourot-denise R. H. Hewins H. C. Connolly

1994-01-01

354

Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites  

DOEpatents

An oxide superconductor composite having improved texture and durability. The oxide superconductor composite includes an oxide superconductor phase substantially surrounded with/by a noble metal matrix, the noble metal matrix comprising a metal oxide in an amount effective to form metal oxide domains that increase hardness of the composite. The composite is characterized by a degree of texture at least 10% greater than a comparable oxide superconductor composite lacking metal oxide domains. An oxide superconducting composite may be prepared by oxidizing the precursor composite under conditions effective to form solute metal oxide domains within the silver matrix and to form a precursor oxide in the precursor alloy phase; subjecting the oxidized composite to a softening anneal under conditions effective to relieve stress within the noble metal phase; and converting the oxide precursor into an oxide superconductor.

Podtburg, Eric R. (Natick, MA)

1999-01-01

355

Ab initio characterization of graphene nanoribbons and their polymer precursors  

NASA Astrophysics Data System (ADS)

Bottom-up fabrication of graphene nanoribbons (GNRs) from halogen-terminated aromatic precursors is a promising method for achieving atomically precise nanoribbons at competitive yields. GNR fabrication proceeds via the polymerization of the precursors and successive dehydrogenation. By first principles density functional theory calculations, we perform a systematic characterization of the polymeric precursors and the corresponding graphene nanoribbons in terms of structural and electronic properties, and we compute the Raman and infrared spectra. The band structure properties are examined by considering the bonding features and the partial charge densities of the structures. The physical origin of the infrared and Raman peaks is investigated in terms of the morphology and vibrational properties of the precursors and products. We show that light spectroscopy provides a unique fingerprint for each type of GNR, which may be used to monitor the quality of the final products and the kinetics of the synthesis process.

Peköz, Rengin; Feng, Xinliang; Donadio, Davide

2012-03-01

356

The Chemistry of Fuel Deposits and Their Precursors.  

National Technical Information Service (NTIS)

The objective of the work described was to determine the chemistry of deposit formation in jet turbine fuel systems. This involved the determination of the nature and method of formation of deposit precursors that should have higher molecular weights and ...

F. R. Mayo N. A. Kirshen H. Richardson R. S. Stringham

1972-01-01

357

Precursor composites for oxygen dispersion hardened silver sheathed superconductor composites  

DOEpatents

An oxide superconductor composite having improved texture and durability is disclosed. The oxide superconductor composite includes an oxide superconductor phase substantially surrounded with/by a noble metal matrix, the noble metal matrix comprising a metal oxide in an amount effective to form metal oxide domains that increase hardness of the composite. The composite is characterized by a degree of texture at least 10% greater than a comparable oxide superconductor composite lacking metal oxide domains. An oxide superconducting composite may be prepared by oxidizing the precursor composite under conditions effective to form solute metal oxide domains within the silver matrix and to form a precursor oxide in the precursor alloy phase; subjecting the oxidized composite to a softening anneal under conditions effective to relieve stress within the noble metal phase; and converting the oxide precursor into an oxide superconductor. 1 fig.

Podtburg, E.R.

1999-06-22

358

Weekend/Weekday Differences in Oxidants and Their Precursors.  

National Technical Information Service (NTIS)

Differences between weekend and weekday oxidant and oxidant precursor concentrations in the Northeastern United States are examined. Statistical tests are employed to assess whether any differences in daily maximum oxidant concentrations are significant. ...

J. Cassmassi L. Gurtowski L. Lai Y. Horie

1979-01-01

359

Shape-programmed nanofabrication: understanding the reactivity of dichalcogenide precursors.  

PubMed

Dialkyl and diaryl dichalcogenides are highly versatile and modular precursors for the synthesis of colloidal chalcogenide nanocrystals. We have used a series of commercially available dichalcogenide precursors to unveil the molecular basis for the outcome of nanocrystal preparations, more specifically, how precursor molecular structure and reactivity affect the final shape and size of II-VI semiconductor nanocrystals. Dichalcogenide precursors used were diallyl, dibenzyl, di-tert-butyl, diisopropyl, diethyl, dimethyl, and diphenyl disulfides and diethyl, dimethyl, and diphenyl diselenides. We find that the presence of two distinctively reactive C-E and E-E bonds makes the chemistry of these precursors much richer and interesting than that of other conventional precursors such as the more common phosphine chalcogenides. Computational studies (DFT) reveal that the dissociation energy of carbon-chalcogen (C-E) bonds in dichalcogenide precursors (R-E-E-R, E=S or Se) increases in the order (R): diallylprecursor reactivity, leading to progressively slower nucleation and higher selectivity for anisotropic growth, all the way from dots to pods to tetrapods. Under identical experimental conditions, we obtain CdS and CdSe nanocrystals with spherical, elongated, or tetrapodal morphology by simply varying the identity and reactivity of the dichalcogenide precursor. Interestingly, we find that precursors with strong C-E and weak E-E bond dissociation energies such as Ph-S-S-Ph serve as a ready source of thiol radicals that appear to stabilize small CdE nuclei, facilitating anisotropic growth. These CdS and CdSe nanocrystals have been characterized using structural and spectroscopic methods. An intimate understanding of how molecular structure affects the chemical reactivity of molecular precursors enables highly predictable and reproducible synthesis of colloidal nanocrystals with specific sizes, shapes, and optoelectronic properties for customized applications. PMID:23517277

Guo, Yijun; Alvarado, Samuel R; Barclay, Joshua D; Vela, Javier

2013-04-23

360

Superior thermal barrier coatings using solution precursor plasma spray  

Microsoft Academic Search

A novel process, solution precursor plasma spray (SPPS), is presented for depositing thermal barrier coatings (TBCs), in which\\u000a aqueous chemical precursors are injected into a standard direct current plasma spray system. The resulting coatings microstructure\\u000a has three unique features: (1) ultra fine splats (1 µm), (2) nanometer and micron-sized interconnected porosity, and (3) closely\\u000a spaced, through-thickness cracks. Coatings over 3

E. H. Jordan; L. Xie; M. Gell; N. P. Padture; B. Cetegen; A. Ozturk; X. Ma; J. Roth; T. D. Xiao; P. E. C. Bryant

2004-01-01

361

Robotic precursor missions to the moon and Mars  

NASA Technical Reports Server (NTRS)

NASA's Office of Exploration has determined that both the global and the more focused data sets required for the engineering development of manned lunar and Martian exploration systems call for the running of robotic precursor missions. Accounts are presented of the nature of such robotic precursor efforts, which must conduct (1) resource characterization and location, (2) site selection, and (3) fundamental scientific data acquisition tasks. Attention is given to the configurations and instrument suites of prospective robotic lander designs.

Smith, William L.

1993-01-01

362

Synthesis of boron carbide powder from polyvinyl borate precursor  

Microsoft Academic Search

Polyvinyl borate (PVBO) was prepared by the condensation of poly(vinyl alcohol) (PVA) and boric acid, and used as a precursor for boron carbide. Boron carbide powder was synthesized by the pyrolysis of the PVBO precursor in air at 600 °C for 2 h, followed by heat treatment in Ar flow at 1300 °C for 5 h, which is a relatively low temperature compared with

Ikuo Yanase; Riichi Ogawara; Hidehiko Kobayashi

2009-01-01

363

Preparation and characterization of a novel solid titania precursor  

Microsoft Academic Search

Titania (TiO2) is an important metal-oxide semiconductor and has a broad range of industrial applications in areas including pigment, photocatalysts, solar cells, ceramics, inorganic membranes, sensors, nonlinear optics and environmental purification, etc. Titania is often prepared using titania precursors. Here we report preparation of a novel solid titania precursor using a simple synthetic method, with a general chemical formula of

Yuan-Qing Li; Shao-Yun Fu; Guo Yang; Ming Li

2006-01-01

364

Improved Single-Source Precursors for Solar-Cell Absorbers  

NASA Technical Reports Server (NTRS)

Improved single-source precursor compounds have been invented for use in spray chemical vapor deposition (spray CVD) of chalcopyrite semiconductor absorber layers of thin-film cells. A "single-source precursor compound" is a single molecular compound that contains all the required elements, which when used under the spray CVD conditions, thermally decomposes to form CuIn(x)Ga(1-x)S(y)Se(2-y).

Banger, Kulbinder K.; Harris, Jerry; Hepp, Aloysius

2007-01-01

365

MetNet Precursor - Network Mission to Mars  

Microsoft Academic Search

We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The first MetNet vehicle, MetNet Precursor, slated for launch in 2011. The MetNet development work started already in 2001. The actual practical Precursor Mission development work started in January 2009

Arri-Matti Harri

2010-01-01

366

Plasma spray synthesis from precursors: Progress, issues, and considerations  

NASA Astrophysics Data System (ADS)

Precursor plasma spray synthesis is an innovative and rapid method for making functional oxide ceramic coatings by starting from solution precursors and directly producing inorganic films. This emerging method utilizes molecularly mixed precursor liquids, which essentially avoids the handling and selection of powders, opening up new avenues for developing compositionally complex functional oxide coatings. Precursor plasma spray also offers excellent opportunities for exploring the nonequilibrium phase evolution during plasma spraying of multicomponent oxides from inorganic precursors. Although there have been efforts in this area since the 1980s and early 1990s with the goal of synthesizing nanoparticles, only recently has the work progressed in the area of functional systems. At the Center for Thermal Spray Research an integrated investigative strategy has been used to explore the benefits and limits of this synthesis strategy. Water- and alcohol-based sol/solution precursors derived from various chemical synthesis methods were used as feedstocks to deposit thin/thick films of spherical and nanostructured coatings of yttrium aluminum garnet (YAG), yttrium iron garnet, lanthanum strontium manganate and Zr-substituted yttrium titanates, and compositions of Y2O3-Al2O3 and their microstructural space centered around stoichiometric YAG. A detailed discussion of the salient features of the radiofrequency induction plasma spraying approach, the results obtained in the investigations to develop various functional oxide coatings, and process issues and challenges are presented.

Ravi, B. G.; Sampath, S.; Gambino, R.; Parise, J. B.; Devi, P. S.

2006-12-01

367

Characterizing precursors to stellar clusters with Herschel  

NASA Astrophysics Data System (ADS)

Context. Despite their profound effect on the universe, the formation of massive stars and stellar clusters remains elusive. Recent advances in observing facilities and computing power have brought us closer to understanding this formation process. In the past decade, compelling evidence has emerged that suggests infrared dark clouds (IRDCs) may be precursors to stellar clusters. However, the usual method for identifying IRDCs is biased by the requirement that they are seen in absorption against background mid-IR emission, whereas dust continuum observations allow cold, dense pre-stellar-clusters to be identified anywhere. Aims: We aim to understand what dust temperatures and column densities characterize and distinguish IRDCs, to explore the population of dust continuum sources that are not IRDCs, and to roughly characterize the level of star formation activity in these dust continuum sources. Methods: We use Hi-GAL 70 to 500 ?m data to identify dust continuum sources in the ? = 30° and ? = 59° Hi-GAL science demonstration phase (SDP) fields, to characterize and subtract the Galactic cirrus emission, and perform pixel-by-pixel modified blackbody fits on cirrus-subtracted Hi-GAL sources. We utilize archival Spitzer data to indicate the level of star-forming activity in each pixel, from mid-IR-dark to mid-IR-bright. Results: We present temperature and column density maps in the Hi-GAL ? = 30° and ? = 59° SDP fields, as well as a robust algorithm for cirrus subtraction and source identification using Hi-GAL data. We report on the fraction of Hi-GAL source pixels which are mid-IR-dark, mid-IR-neutral, or mid-IR-bright in both fields. We find significant trends in column density and temperature between mid-IR-dark and mid-IR-bright pixels; mid-IR-dark pixels are about 10 K colder and have a factor of 2 higher column density on average than mid-IR-bright pixels. We find that Hi-GAL dust continuum sources span a range of evolutionary states from pre- to star-forming, and that warmer sources are associated with more star formation tracers. Additionally, there is a trend of increasing temperature with tracer type from mid-IR-dark at the coldest, to outflow/maser sources in the middle, and finally to 8 and 24 ?m bright sources at the warmest. Finally, we identify five candidate IRDC-like sources on the far-side of the Galaxy. These are cold (~20 K), high column density (N(H2) > 1022 cm-2) clouds identified with Hi-GAL which, despite bright surrounding mid-IR emission, show little to no absorption at 8 ?m. These are the first inner Galaxy far-side candidate IRDCs of which the authors are aware. Herschel in an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation by NASA.The FITS files discussed in the paper would be released publicly WITH the Hi-GAL data (on the Hi-GAL website) when the Hi-GAL data is released publicly.

Battersby, C.; Bally, J.; Ginsburg, A.; Bernard, J.-P.; Brunt, C.; Fuller, G. A.; Martin, P.; Molinari, S.; Mottram, J.; Peretto, N.; Testi, L.; Thompson, M. A.

2011-11-01

368

Predicting Solar Cycle 24 Using a Geomagnetic Precursor Pair  

NASA Astrophysics Data System (ADS)

We describe using Ap and F10.7 as a geomagnetic-precursor pair to predict the amplitude of Solar Cycle 24. The precursor is created by using F10.7 to remove the direct solar-activity component of Ap. Four peaks are seen in the precursor function during the decline of Solar Cycle 23. A recurrence index that is generated by a local correlation of Ap is then used to determine which peak is the correct precursor. The earliest peak is the most prominent but coincides with high levels of non-recurrent solar activity associated with the intense solar activity of October and November 2003. The second and third peaks coincide with some recurrent activity on the Sun and show that a weak cycle precursor closely following a period of strong solar activity may be difficult to resolve. A fourth peak, which appears in early 2008 and has recurrent activity similar to precursors of earlier solar cycles, appears to be the "true" precursor peak for Solar Cycle 24 and predicts the smallest amplitude for Solar Cycle 24. To determine the timing of peak activity it is noted that the average time between the precursor peak and the following maximum is ? 6.4 years. Hence, Solar Cycle 24 would peak during 2014. Several effects contribute to the smaller prediction when compared with other geomagnetic-precursor predictions. During Solar Cycle 23 the correlation between sunspot number and F10.7 shows that F10.7 is higher than the equivalent sunspot number over most of the cycle, implying that the sunspot number underestimates the solar-activity component described by F10.7. During 2003 the correlation between aa and Ap shows that aa is 10 % higher than the value predicted from Ap, leading to an overestimate of the aa precursor for that year. However, the most important difference is the lack of recurrent activity in the first three peaks and the presence of significant recurrent activity in the fourth. While the prediction is for an amplitude of Solar Cycle 24 of 65±20 in smoothed sunspot number, a below-average amplitude for Solar Cycle 24, with maximum at 2014.5±0.5, we conclude that Solar Cycle 24 will be no stronger than average and could be much weaker than average.

Pesnell, W. Dean

2014-06-01

369

Effects of monocarboxylate transporter inhibition on the oral toxicokinetics/toxicodynamics of ?-hydroxybutyrate and ?-butyrolactone.  

PubMed

Respiratory depression and death secondary to respiratory arrest have occurred after oral overdoses of ?-hydroxybutyrate (GHB) and its precursor ?-butyrolactone (GBL). GHB is a substrate for monocarboxylate transporters (MCTs), and increasing GHB renal clearance or decreasing GHB absorption via MCT inhibition represents a potential treatment strategy for GHB/GBL overdose. In these studies, GHB and GBL were administered in doses of 1.92, 5.77, and 14.4 mmol/kg orally with and without MCT inhibition to determine effects of this treatment strategy on the oral toxicokinetics and toxicodynamics of GHB and GBL. The competitive MCT inhibitor l-lactate was administered by intravenous infusion starting 1 hour after GHB and GBL administration. Oral administration of l-lactate and the MCT inhibitor luteolin was also evaluated. Respiratory depression was measured using plethysmography. Intravenous l-lactate, but not oral treatments, significantly increased GHB renal and/or oral clearances. At the low dose of GHB and GBL, i.v. l-lactate increased GHB renal clearance. Due to the increased contribution of renal clearance to total clearance at the moderate dose, increased renal clearance translated to an increase in oral clearance. At the highest GHB dose, oral clearance was increased without a significant change in renal clearance. The lack of effect of i.v. l-lactate on renal clearance after a high oral GHB dose suggests possible effects of i.v. l-lactate on MCT-mediated absorption. The resulting increases in oral clearance improved respiratory depression. Intravenous l-lactate also reduced mortality with the high GBL dose. These data indicate i.v. l-lactate represents a potential treatment strategy in oral overdose of GHB and GBL. PMID:23392755

Morse, Bridget L; Morris, Marilyn E

2013-04-01

370

Effects of Monocarboxylate Transporter Inhibition on the Oral Toxicokinetics/Toxicodynamics of ?-Hydroxybutyrate and ?-Butyrolactone  

PubMed Central

Respiratory depression and death secondary to respiratory arrest have occurred after oral overdoses of ?-hydroxybutyrate (GHB) and its precursor ?-butyrolactone (GBL). GHB is a substrate for monocarboxylate transporters (MCTs), and increasing GHB renal clearance or decreasing GHB absorption via MCT inhibition represents a potential treatment strategy for GHB/GBL overdose. In these studies, GHB and GBL were administered in doses of 1.92, 5.77, and 14.4 mmol/kg orally with and without MCT inhibition to determine effects of this treatment strategy on the oral toxicokinetics and toxicodynamics of GHB and GBL. The competitive MCT inhibitor l-lactate was administered by intravenous infusion starting 1 hour after GHB and GBL administration. Oral administration of l-lactate and the MCT inhibitor luteolin was also evaluated. Respiratory depression was measured using plethysmography. Intravenous l-lactate, but not oral treatments, significantly increased GHB renal and/or oral clearances. At the low dose of GHB and GBL, i.v. l-lactate increased GHB renal clearance. Due to the increased contribution of renal clearance to total clearance at the moderate dose, increased renal clearance translated to an increase in oral clearance. At the highest GHB dose, oral clearance was increased without a significant change in renal clearance. The lack of effect of i.v. l-lactate on renal clearance after a high oral GHB dose suggests possible effects of i.v. l-lactate on MCT-mediated absorption. The resulting increases in oral clearance improved respiratory depression. Intravenous l-lactate also reduced mortality with the high GBL dose. These data indicate i.v. l-lactate represents a potential treatment strategy in oral overdose of GHB and GBL.

Morse, Bridget L.

2013-01-01

371

Isolation of pheromone precursor genes of Magnaporthe grisea.  

PubMed

In heterothallic ascomycetes one mating partner serves as the source of female tissue and is fertilized with spermatia from a partner of the opposite mating type. The role of pheromone signaling in mating is thought to involve recognition of cells of the opposite mating type. We have isolated two putative pheromone precursor genes of Magnaporthe grisea. The genes are present in both mating types of the fungus but they are expressed in a mating type-specific manner. The MF1-1 gene, expressed in Mat1-1 strains, is predicted to encode a 26-amino-acid polypeptide that is processed to produce a lipopeptide pheromone. The MF2-1 gene, expressed in Mat1-2 strains, is predicted to encode a precursor polypeptide that is processed by a Kex2-like protease to yield a pheromone with striking similarity to the predicted pheromone sequence of a close relative, Cryphonectria parasitica. Expression of the M. grisea putative pheromone precursor genes was observed under defined nutritional conditions and in field isolates. This suggests that the requirement for complex media for mating and the poor fertility of field isolates may not be due to limitation of pheromone precursor gene expression. Detection of putative pheromone precursor gene mRNA in conidia suggests that pheromones may be important for the fertility of conidia acting as spermatia. PMID:10441451

Shen, W C; Bobrowicz, P; Ebbole, D J

1999-01-01

372

Time limited immunomodulatory functions of transplanted neural precursor cells.  

PubMed

Fetal neural stem/precursor cells (NPCs) possess powerful immunomodulatory properties which enable them to protect the brain from immune-mediated injury. A major issue in developing neural stem/precursor cell (NPC) therapy for chronic neuroinflammatory disorders such as multiple sclerosis is whether cells maintain their immune-regulatory properties for prolonged periods of time. Therefore, we studied time-associated changes in NPC immunomodulatory properties. We examined whether intracerebrally-transplanted NPCs are able to inhibit early versus delayed induction of autoimmune brain inflammation and whether allogeneic NPC grafts continuously inhibit host rejection responses. In two experimental designs, intraventricular fetal NPC grafts attenuated clinically and pathologically brain inflammation during early EAE relapse but failed to inhibit the disease relapse if induced at a delayed time point. In correlation, long-term cultured neural precursors lost their capacity to inhibit immune cell proliferation in vitro. Loss of NPC immune functions was associated with transition into a quiescent undifferentiated state. Also, allogeneic fetal NPC grafts elicited a strong immune reaction of T cell and microglial infiltration and were rejected from the host brain. We conclude that long-term functional changes in transplanted neural precursor cells lead to loss of their therapeutic immune-regulatory properties, and render allogeneic grafts vulnerable to immunologic rejection. Thus, the immunomodulatory effects of neural precursor cell transplantation are limited in time. PMID:23001547

Fainstein, Nina; Einstein, Ofira; Cohen, Mikhal E; Brill, Livnat; Lavon, Iris; Ben-Hur, Tamir

2013-02-01

373

A novel class of peptide pheromone precursors in ascomycetous fungi  

PubMed Central

Recently, sexual development in the heterothallic ascomycete Trichoderma reesei (anamorph of Hypocrea jecorina) has been achieved and thus initiated attempts to elucidate regulation and determinants of this process. While the ?-type pheromone of this fungus fits the consensus known from other fungi, the assumed a-type peptide pheromone precursor shows remarkably unusual characteristics: it comprises three copies of the motif (LI)GC(TS)VM thus constituting a CAAX domain at the C-terminus and two Kex2-protease sites. This structure shares characteristics of both a- and ?-type peptide pheromone precursors. Presence of hybrid-type peptide pheromone precursor 1 (hpp1) is essential for male fertility, thus indicating its functionality as a peptide pheromone precursor, while its phosphorylation site is not relevant for this process. However, sexual development in a female fertile background is not perturbed in the absence of hpp1, which rules out a higher order function in this process. Open reading frames encoding proteins with similar characteristics to HPP1 were also found in Fusarium spp., of which Fusarium solani still retains a putative a-factor-like protein, but so far in no other fungal genome available. We therefore propose the novel class of h-type (hybrid) peptide pheromone precursors with H. jecorina HPP1 as the first member of this class.

Schmoll, Monika; Seibel, Christian; Tisch, Doris; Dorrer, Marcel; Kubicek, Christian P

2010-01-01

374

Two-dimensional characterization of ELM precursors in NSTX  

NASA Astrophysics Data System (ADS)

Gas puff imaging has been used to capture the two-dimensional evolution of edge-localized mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H-L back-transitions in radio-frequency heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outwards. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05-0.2 cm-1. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the scrape-off layer (SOL) explosively with radial velocities peaking at 8 km s-1. Once in the SOL, filaments reverse their propagation direction and travel in the ion diamagnetic direction. Edge intensity fluctuations are strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n = 5-10. Quantitatively similar precursors have been observed in ohmic H-mode plasmas as well, though significantly fewer events are seen in the ohmic cases and none were observed in the near-threshold NBI H-modes studied.

Sechrest, Y.; Munsat, T.; Battaglia, D. J.; Zweben, S. J.

2012-12-01

375

Two-Dimensional Characterization of ELM Precursors in NSTX  

NASA Astrophysics Data System (ADS)

Gas Puff Imaging (GPI) has been used to capture the two-dimensional evolution of Edge Localized Mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H-L back transitions in radio frequency (RF) heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outward. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05-0.2 cm-1. Edge intensity fluctuations are strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n=5-10. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the Scrape-Off Layer (SOL) explosively with radial velocities peaking at 8 km/s. Quantitatively similar precursors have been observed in Ohmic H-mode plasmas as well, though significantly fewer events are seen in the Ohmic cases and none were observed in similar near-threshold NBI shots studied.

Sechrest, Y.; Munsat, T.; Battaglia, D. J.; Zweben, S. J.

2012-10-01

376

Hydrokinetic simulations of nanoscopic precursor films in rough channels  

NASA Astrophysics Data System (ADS)

We report on simulations of capillary filling of highly wetting fluids in nanochannels with and without obstacles. We use atomistic (molecular dynamics) and hydrokinetic (lattice Boltzmann; LB) approaches which indicate clear evidence of the formation of thin precursor films, moving ahead of the main capillary front. The dynamics of the precursor films is found to obey a square-root law like that obeyed by the main capillary front, z^2(t) \\propto t , although with a larger prefactor, which we find to take the same value for the different geometries (2D-3D) under inspection. The two methods show a quantitative agreement which indicates that the formation and propagation of thin precursors can be handled at a mesoscopic/hydrokinetic level. This can be considered as a validation of the LB method and opens the possibility of using hydrokinetic methods to explore space-time scales and complex geometries of direct experimental relevance. Then, the LB approach is used to study the fluid behaviour in a nanochannel when the precursor film encounters a square obstacle. A complete parametric analysis is performed which suggests that thin-film precursors may have an important influence on the efficiency of nanochannel-coating strategies.

Chibbaro, S.; Biferale, L.; Binder, K.; Dimitrov, D.; Diotallevi, F.; Milchev, A.; Succi, S.

2009-06-01

377

Plutonium Immobilization Project (PIP) Precursor Material Calcine Temperature  

SciTech Connect

As a result of the end of the Cold War, approximately 50 metric tons of plutonium are no longer needed and have been identified for disposition. A ceramic waste form is the chosen option for immobilization of the excess plutonium. The plutonium ceramic form then will be encased in high-level waste glass using can-in-canister technology for final disposition. The precursor materials are the non-radioactive components that are added to the plutonium feed stream to form the desired phases in the immobilization product. The precursor materials are blended and calcined prior to being mixed with the plutonium feed stream. The purpose of the calcine step is to remove any physical or chemical water retained in the precursors and convert any hydroxides or carbonates to the oxides. Initially, a temperature of 750 degrees C for a period of one hour was chosen for the calcining of the precursors. In this effort, several different calcine temperatures were investigated to evaluate the effect on initial phase formation (in the calcined precursors), thermal expansion of the pressed pellets during heating, and mineralogy and porosity of the final product.

Cozzi, A.D.

1999-07-29

378

Unconsumed precursors and couplers after formation of oxidative hair dyes.  

PubMed

Contact allergy to hair dye ingredients, especially precursors and couplers, is a well-known entity among consumers having hair colouring done at home or at a hairdresser. The aim of the present investigation was to estimate consumer exposure to some selected precursors (p-phenylenediamine, toluene-2,5-diamine) and couplers (3-aminophenol, 4-aminophenol, resorcinol) of oxidative hair dyes during and after hair dyeing. Concentrations of unconsumed precursors and couplers in 8 hair dye formulations for non-professional use were investigated, under the conditions reflecting hair dyeing. Oxidative hair dye formation in the absence of hair was investigated using 6 products, and 2 products were used for experimental hair dyeing. In both presence and absence of hair, significant amounts of unconsumed precursors and couplers remained in the hair dye formulations after final colour development. Thus, up to 1.1% p-phenylenediamine (PPD), 0.04% toluene-2,5-diamine, 0.02% 3-aminophenol and 0.02% resorcinol were found in the hair dye formulation after the required colour was developed. The consumers are thus exposed to precursors and couplers of oxidative hair dyes, both during and after hair dyeing, when the hair is washed. Furthermore, the consumers are also expected to be exposed to intermediates of oxidative hair dyes. The allergenic potential of oxidative hair dyes as well as the intermediates of these remains unknown. PMID:16930234

Rastogi, Suresh Chandra; Søsted, Heidi; Johansen, Jeanne Duus; Menné, Torkil; Bossi, Rossana

2006-08-01

379

The Research of Hydrogeological Precursors of Earthquakes in Armenia  

NASA Astrophysics Data System (ADS)

The observations of hydro-geological regime of underground waters in observed boreholes began in Armenia in 1986. Now observations are being carried out by National Seismic Service. For a long time observations were done by studying several parameters (debit, temperature, chemical and gas composition) in several deposits of carbon mineral waters of Armenia. The interpretation of materials shows that a number of strong and medium-strength earthquakes are accompanied by anomalous changes of underground water level. Regarding mineral waters, in connection with earthquakes some parameters are immediately changed: debit, temperature, chemical and gas composition. The study of hydrogeodynamic characteristics of precursors specify that the quantity of registered hydrogeodynamic precursors decreases with the increase of epicentral distance. The majority of precursors are registered up to the 200 km from epicenter. There is a tendency of gradual increase of time and amplitude of a precursor of an earthquake depending on the rise of magnitude and epicentral distance. The behaviour of hydrogeodynamic precursors depends on the angle between the faults that this or that borehole reaches; by the increase of this angle the deformation of the zone of the fault during the preparation of earthquakes is stronger, than in case of small angles.

Hakhverdyan, L.; Pashayan, R.

2013-12-01

380

Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana  

PubMed Central

Abstract Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and ?-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in ?-glutamylcysteine (?-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of ?-glutamylcysteine synthetase (GSH1) – the first enzyme of glutathione synthesis – causes a reduction of ?-EC levels and an accumulation of all other glutathione precursors within the cells.

Koffler, Barbara Eva; Maier, Romana; Zechmann, Bernd

2011-01-01

381

Anise oil as para-methoxyamphetamine (PMA) precursor.  

PubMed

These days, MDMA is one of the most popular drugs of abuse. Due to its illegality, MDMA and its chemical precursors are watched by governmental organizations in many countries. To avoid conflicts with legal instances, underground chemists have tried to market several new unregulated amphetamine analogues, such as 4-MTA. Para-methoxyamphetamine (PMA), on the other hand, is regulated by law but its precursors are easily obtained since they are cheap and unwatched. This article presents such a case, namely the large scale synthesis of PMA using anethole, a main constituent of anise oil, as precursor. Anethole has been converted to its phenyl acetone analogue via peracid oxidation, while PMA itself has been synthesized using this ketone as precursor in the Leuckart synthesis. The synthesis of PMA using anethole as starting product has been investigated applying GC/MS and GC-HSPME/MS techniques, hereby discovering new specific (4-methoxyphenol) and already identified synthesis impurities (4-methyl-5-(4-methoxyphenyl)pyrimidine, N-(beta-4-methoxyphenylisopropyl)-4-methoxybenzyl methyl ketimine, 1-(4-methoxyphenyl)-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, 1-(4-methoxyphenyl)-N-methyl-N-(2-(4-methoxyphenyl)-1-methylethyl-2-propanamine, N-(beta-4-methoxyphenylisopropyl)-4-methoxybenzaldimine). The new impurity 4-methoxyphenol is specific for the application of a peracid oxidation method where anethole is used as precursor. PMID:12742705

Waumans, Dieter; Bruneel, Noël; Tytgat, Jan

2003-04-23

382

Influence of the Precursor on Cerium Distribution over Alumina  

NASA Astrophysics Data System (ADS)

The Ce/Al2O3 catalysts were prepared with Ce(NO3)3, (NH4)2Ce(NO3)6 and with cerium acethylacetonate precursors over alumina, by impregnation and grafting, respectively. Results have shown that the CeO2 surface area of the catalysts with the nitrate precursors is very similar but much higher on the catalysts with the acethylacetonate after grafting. The reducibility of this catalyst is better than of the catalysts with the nitrate precursor. TPR results indicate a reduction of CeO2, the formation of CeAlO3 and Ce2O3. The experimental condition employed here allows to attain saturation over alumina which is probably due to steric effects of the Ce(Acet)3 molecules.

Appel, Lucia G.; Appel, Lucia G.; Eon, J. G.; Schmal, M.

1997-09-01

383

The proteolytic processing site of the precursor of lysyl oxidase.  

PubMed Central

The precise cleavage site of the N-terminal propeptide region of the precursor of lysyl oxidase has not yet been established, due to N-terminal blocking of the mature protein. Using a combination of peptide fragmentation, amino acid sequencing, time-of-flight m.s. and partial chemical unblocking procedures, it is shown that the mature form of lysyl oxidase begins at residue Asp-169 of the precursor protein (numbered according to the human sequence). The cleavage site is 28 residues to the C-terminal side of the site previously suggested on the basis of apparant molecular mass by SDS/PAGE, with the consequence that the two putative, N-linked glycosylation sites and the position of the Arg/Gln sequence polymorphism are now all in the precursor region.

Cronshaw, A D; Fothergill-Gilmore, L A; Hulmes, D J

1995-01-01

384

Development on polymeric precursor routes to produce superconducting nanoparticles  

NASA Astrophysics Data System (ADS)

The well-known polymeric precursor route is a simple and low-cost sol-gel method based on the preparation of an aqueous precursor solution of metals followed by the addition of a water-soluble polymer. This method consists of a polyesterification process between a metal chelate complex by using a hydroxycarboxylic acid and a polyhydroxy alcohol. In this work, citric acid (CA), tartaric acid (TA) and ethylenediaminetetraacetic acid (EDTA) are used as the hydroxycarboxylic acid and ethylene glycol (EG) is used as the polyhydroxy alcohol. The effects of the precursor pH solution, time and temperature of polymerization step as well as the combination of different chelating agents in order to obtain nanoscopic YBa 2Cu 3O y samples were traced.

Lisboa-Filho, P. N.; Motta, M.; Saeki, M. J.

2007-09-01

385

Elastic precursor decay in S-200F beryllium  

NASA Astrophysics Data System (ADS)

We have performed a series of plate impact experiments on vacuum hot-pressed (VHP) S-200F Be at peak shock stresses between 2.1 and 23.0 GPa to gain insight into the dynamic strength (Hugoniot elastic limit (HEL)), equation-of-state, and damage behavior of this technologically important material. In this paper we focus on our VISAR observations of the evolution of elastic precursor amplitude with Be target thickness in a series of plate impact experiments conducted in both transmission and reverse geometry. We observe monotonic decay in precursor amplitude with run distance for sample thicknesses between 4 and 8 mm and present the HEL values obtained from these experiments. We will discuss the observed precursor decay with respect to the relative roles of twinning and dislocation-mediated slip in the overall dynamic material mechanical response.

Adams, C. D.; Anderson, W. W.; Blumenthal, W. R.; Gray, G. T., III

2014-05-01

386

Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.  

PubMed

Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development. PMID:24925912

Espinosa-Medina, I; Outin, E; Picard, C A; Chettouh, Z; Dymecki, S; Consalez, G G; Coppola, E; Brunet, J-F

2014-07-01

387

Effect of precursor solution dark incubation on gold nanorods morphology  

NASA Astrophysics Data System (ADS)

Gold nanorods were synthesized in an aqueous solution of hexadecyltrimethylammonium bromide via a combination of chemical reduction and UV photoirradiation. Gold ligand complexes, present in the stock solution, are initially reduced, by ascorbic acid as mild reducing agent. The gold ions nucleation and colloid growth proceeds then by subsequent UV irradiation of the so-obtained precursor solution. We present a systematic study of the effect of incubation of the precursor solution on the dispersion state and aspect ratio of the produced nanorods. Incubation of the precursor solution allows the synthesis of higher aspect ratio nanorods with narrower size distribution compared to those obtained without incubation. We propose a mechanism for the gold nanorods formation including two stages, a nucleation and a diffusive growth. This allows us to explain the synthesis improvement as a consequence of the increase in the size of the gold ligand complexes aggregates, leading to a decrease of the nanorods growth rate.

Abdelrasoul, Gaser N.; Scotto, Marco; Cingolani, Roberto; Diaspro, Alberto; Athanassiou, Athanassia; Pignatelli, Francesca

2012-12-01

388

Whole-cell fungal transformation of precursors into dyes  

PubMed Central

Background Chemical methods of producing dyes involve extreme temperatures and unsafe toxic compounds. Application of oxidizing enzymes obtained from fungal species, for example laccase, is an alternative to chemical synthesis of dyes. Laccase can be replaced by fungal biomass acting as a whole-cell biocatalyst with properties comparable to the isolated form of the enzyme. The application of the whole-cell system simplifies the transformation process and reduces the time required for its completion. In the present work, four fungal strains with a well-known ability to produce laccase were tested for oxidation of 17 phenolic and non-phenolic precursors into stable and non-toxic dyes. Results An agar-plate screening test of the organic precursors was carried out using four fungal strains: Trametes versicolor, Fomes fomentarius, Abortiporus biennis, and Cerrena unicolor. Out of 17 precursors, nine were transformed into coloured substances in the presence of actively growing fungal mycelium. The immobilized fungal biomass catalyzed the transformation of 1 mM benzene and naphthalene derivatives in liquid cultures yielding stable and non-toxic products with good dyeing properties. The type of fungal strain had a large influence on the absorbance of the coloured products obtained after 48-hour transformation of the selected precursors, and the most effective was Fomes fomentarius (FF25). Whole-cell transformation of AHBS (3-amino-4-hydroxybenzenesulfonic acid) into a phenoxazinone dye was carried out in four different systems: in aqueous media comprising low amounts of carbon and nitrogen source, in buffer, and in distilled water. Conclusions This study demonstrated the ability of four fungal strains belonging to the ecological type of white rot fungi to transform precursors into dyes. This paper highlights the potential of fungal biomass for replacing isolated enzymes as a cheaper industrial-grade biocatalyst for the synthesis of dyes and other commercially important products. The use of immobilized fungal biomass limits free migration of cells and facilitates their reuse in a continuous system for precursor transformation.

2010-01-01

389

Precursor Exploration Missions in Kelly Lake, British Columbia- MARSLIFE project  

NASA Astrophysics Data System (ADS)

Precursor missions are an integral step in coordinated exploration between unmanned and manned systems both for terrestrial and astrobiology applications. Testing and developing the protocols for efficient, safe, and meaningful precursor missions is a key step in readiness for space exploration and is integral to the new MARSLIFE analogue research project. Here we present first-year field results from the use of an autonomous underwater vehicle (AUV) to conduct high-resolution (<1 m/pixel) geoacoustic mapping (bathymetry and backscatter) of the MARSLIFE field site. Rapid operations and quick-turn-around data-processing (within 1 - 2 days) allowed us to provide our precursor mission data in the form of digital maps to the MARSLIFE operating team for site assessment and mission planning. Precursor mapping helped identify target areas for specific operations, including ROV and Deepworker missions during the field campaign. Mission critical results from the AUV survey included morphology (micro-bathymetry), target localization, and suitability of terrain types based on slope and rugosity for different mission activities (e.g. SCUBA slope transects and water samples). The rapid acquisition and data processing turn around allowed us to provide mission critical measurements such as depth, slope, composition, and roughness to the entire exploration team. In total during the July 2010 field campaign, over 3 days of intensive AUV and ROV missions were run in Kelly Lake resulting in nearly 50 km of trackline data (side-scan sonar, swath bathymetry, color video, and water quality measurements) of the lake at sub-meter resolution in side-scan sonar and interferometric swath bathymetry resulting in precursor derived geoacoustic maps that will facilitate the safe and expedient follow-on exploration from subsequent manned missions in the next field season. During the course of the precursor AUV missions distinct patches of shallow and deep microbialites were mapped at a spatial resolution of 0.5 m/pixel providing the first detailed bathymetric charts for this alpine lake.

Trembanis, A. C.; Gutsche, J.; Nebel, S. H.

2010-12-01

390

Research of Hydro-Geological Precursors of Earthquakes in Armenia  

NASA Astrophysics Data System (ADS)

The observations of hydro-geological regime of underground waters in observed boreholes began in Armenia in 1986. Now these work is concentrated in National Seismic Service. For a long time observations are carried out studying several parameters (debit, temperature, chemical and gas composition) in several deposits of carbon mineral waters of Armenia. The interpretation of materials shows that that a number of strong and medium-strength earthquakes are accompanied by anomal changes in the level of underground waters. Regarding mineral waters, in connection with earthquakes some parameters are immediately changed: debit, temperature, chemical and gas composition. The study of hydrogeodynamic characteristics of precursors specify that the quantity of registered hydrogeodynamic precursors decreases with the increase of epicentrical distance. The majority of precursors is registered at the distance of 200 km from epicenter. There is a tendency of gradual increase of time and amplitude of a precursor of an earthquake depending on the rise of magnitude and epicentral distance. The behaviour of hydrogeodynamic precursors depends on the angle between the faults, to which this or that borehole reaches; with increase of this angle the deformation in the zone of the fault during the preparation of earthquakes is stronger, than in terms of small angles. 1. S1 2. Earthquake processes, Precursors and Forecasts 3. Garni Geophysical Observatory of the National Academy of Sciences of Armenia, 375019, Yerevan, Republic of Armenia, email: hakhleon@sci.am 4. O 5. 10808801 6. Artavazd Payment Type: select 'Purchase Order' PO Number: AGU WAIVER Billing Address: Enter Your Institution City: Enter Your City Country Code: Enter Your Country Name: Enter Your Name Phone: Enter Your Telephone Number

Pashayan, R.

2007-12-01

391

Simple Synthesis and Characterization of Several Nickel Catalytic Precursors  

NASA Astrophysics Data System (ADS)

The one-week experimental series described here is a simple way of explaining the concepts involved in the preparation of several catalytic precursors (bulk and supported over g-Al 2O3, and NiAl2O4). The supported-NiO samples are prepared by the incipient-wetness method. These experiments also introduce students to some solid-state characterization techniques: X-ray diffraction (XRD), temperature-programmed reduction (TPR), and scanning electron microscopy (SEM). The results obtained by these techniques illustrate such important concepts in heterogeneous catalysis as the relationship between the reducibility of a catalytic precursor and its interaction with a support.

Cesteros, Yolanda; Salagre, Pilar; Medina, Francisco; Sueiras, Jesus E.

2002-04-01

392

Urinary ?-hydroxybutyrate concentrations in 1126 female subjects.  

PubMed

?-Hydroxybutyrate (GHB) and its metabolic precursor ?-butyrolactone (GBL) are often implicated in cases of drug-facilitated sexual assault (DFSA), although definitive confirmation of GHB/GBL ingestion is complicated by GHB's endogenous nature and rapid elimination following ingestion. Multiple studies have attempted to establish a discriminant limit (generally 10 mg/L) above which urinary GHB concentrations can be considered consistent with GHB/GBL consumption. To supplement the currently available data, a rapid gas chromatography-mass spectrometry method was developed and validated for the analysis of GHB (following acidic conversion to GBL) and used to analyze urine samples collected from 1126 women (mean = 0.84 mg/L, median = 0.68 mg/L, range = 0.00-5.5 mg/L). GHB concentrations were shown to be independent of urinary pH (within the range 4.6-9.3), age (within the range 18-35 years), body mass index (within the range 13.8-36.3), and race. Adjusting GHB concentrations with respect to urinary specific gravity had little effect on the mean value (0.91 mg/L) and range (0.0-7.76 mg/L), although a statistically significant trend of increasing GHB concentration with specific gravity could be observed. Our results can be taken to offer further support for the 10 mg/L discriminant limit for GHB administration in antemortem urine samples. PMID:21073808

Brailsford, Alan D; Cowan, David A; Kicman, Andrew T

2010-11-01

393

Evolution and ultrastructure of the bovine spermatogonia precursor cell line  

Microsoft Academic Search

The spermatogonial stem cell line in prepubertal and adult bovine testis was studied by electron microscopy and protein gene product 9.5 immunohistochemistry. Three successive spermatogonia precursor cell configurations were observed. Small basal stem cells were found to possess a spherical shape and nuclei with two to three nucleoli. They were observed in prepubertal testes (25 and 30 weeks) and in

Karl-Heinz Wrobel; Daniela Bickel; Richard Kujat; Margit Schimmel

1995-01-01

394

SURROGATE PARAMETERS FOR MONITORING ORGANIC MATTER AND THM PRECURSORS  

EPA Science Inventory

UV absorbance at 254 nm is a good surrogate parameter for estimating the raw water concentrations of organic carbon (NPTOC--nonpurgeable total organic carbon) and THM precursors (TTHMFP--total trihalomethane formation potential). UV absorbance can be used to estimate the NPTOC an...

395

Acenes generated from precursors and their semiconducting properties.  

PubMed

Acenes are a class of aromatic hydrocarbons composed of linearly fused benzene rings. Noteworthy features of these molecules include their extended flat structure and the narrow gap between the HOMO and LUMO energy levels. However, the preparation of larger acenes, those that are larger than pentacene, has been challenging. These molecules are relatively unstable and have low solubility in typical solvents. Recently researchers have developed a new synthesis route for higher acenes using stable and soluble "precursors," which generate these structures on demand by either heating or irradiation of light. Using this method, nonsubstituted hexacene, heptacene, octacene, and nonacene were successfully prepared. In this Account, we summarize the preparation of nonsubstituted acenes from corresponding precursors, describe their physical properties, and discuss potential applications including potential usage in organic semiconductor devices. We first introduced the concept of using a precursor in the work with pentacene. Overall, we divide this methodology into two categories: masking pentacene itself with a dienophile to form a cycloadduct and the construction of higher acenes through conventional synthetic procedures. For the first category, a diverse array of dienophiles could be chosen, depending on the processing needs, especially for use in field-effect transistors (FETs). For the second category, researchers synthesized the pentacene precursor molecules using a multistep procedure. Upon proper activation, these molecules expel small fragments to generate pentacene readily. This strategy enabled the production of pentacene andunprepared higher acenes ranging from hexacene to nonacene. This new method provides a way to unravel the fascinating chemistry of higher acenes. PMID:23611137

Watanabe, Motonori; Chen, Kew-Yu; Chang, Yuan Jay; Chow, Tahsin J

2013-07-16

396

PILOT SCALE EVALUATION OF PHOTOLYTIC OZONATION FOR TRIHALOMETHANE PRECURSOR REMOVAL  

EPA Science Inventory

The use of ozone combined with ultraviolet radiation has been studied at the pilot-scale for removing trihalomethane (THM) precursors from potable water. The effects of variations in ozone dose rate, UV intensity and other parameters were first studied using a synthetic feedwater...

397

Protic ionic liquids and salts as versatile carbon precursors.  

PubMed

Instead of traditional polymer precursors and complex procedures, easily prepared and widely obtainable nitrogen-containing protic ionic liquids and salts were explored as novel, small-molecule precursors to prepare carbon materials (CMs) via direct carbonization without other treatments. Depending on the precursor structure, the resultant CMs can be readily obtained with a relative yield of up to 95.3%, a high specific surface area of up to 1380 m(2)/g, or a high N content of up to 11.1 wt%, as well as a high degree of graphitization and high conductivity (even higher than that of graphite). One of the carbons, which possesses a high surface area and a high content of pyridinic N, exhibits excellent electrocatalytic activity toward the oxygen reduction reaction in an alkaline medium, as revealed by an onset potential, half-wave potential, and kinetic current density comparable to those of commercial 20 wt% Pt/C. These low-cost and versatile precursors are expected to be important building blocks for CMs. PMID:24450770

Zhang, Shiguo; Miran, Muhammed Shah; Ikoma, Ai; Dokko, Kaoru; Watanabe, Masayoshi

2014-02-01

398

Precursors of geomagnetic storms observed by the muon detector network  

Microsoft Academic Search

We report the first systematic survey of cosmic ray precursors of geomagnetic storms. Our data set comprises the 14 ``major'' geomagnetic storms (peak Kp>=8-) identified by Gosling et al. [1990] together with 25 large storms (peak Kp>=7-) observed from 1992 through 1998. After eliminating events for which the muon detector network had poor coverage of the sunward interplanetary magnetic field

Kazuoki Munakata; John W. Bieber; Shin-ichi Yasue; Chihiro Kato; Morikazu Koyama; Shigenobu Akahane; Kazuhiko Fujimoto; Zenjiro Fujii; John E. Humble; Marcus L. Duldig

2000-01-01

399

ASSESSMENT OF NATIONAL AND REGIONAL ACID DEPOSITION PRECURSOR EMISSION TRENDS  

EPA Science Inventory

The report gives results of an analysis of national and regional acid deposition precursor emission trends, involving SOx, NOx, and VOCs. While the focus is on emissions during 1980-1985, comparisons are made (for perspective) with emission trends for 1940-1980. Study methods int...

400

Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates  

ERIC Educational Resources Information Center

Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

Benasich, April A., Ed.; Fitch, R. Holly, Ed.

2012-01-01

401

Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension  

PubMed Central

Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34+CD133+ bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34+CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-? or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process.

Asosingh, Kewal; Aldred, Micheala A.; Vasanji, Amit; Drazba, Judith; Sharp, Jacqueline; Farver, Carol; Comhair, Suzy A.A.; Xu, Weiling; Licina, Lauren; Huang, Lan; Anand-Apte, Bela; Yoder, Mervin C.; Tuder, Rubin M.; Erzurum, Serpil C.

2008-01-01

402

N-linked glycosylation selectively regulates autonomous precursor BCR function  

Microsoft Academic Search

Developing B cells express distinct classes of B cell antigen receptors (BCRs) that differ in their heavy chain (HC). Although only ?HC is expressed in early stages, ?HC-containing BCRs dominate on the surface of mature B cells. The reason for the tightly regulated expression of these receptors is poorly understood. Here we show that ?HC was specifically required for precursor

Rudolf Übelhart; Martina P Bach; Cathrin Eschbach; Thomas Wossning; Michael Reth; Hassan Jumaa

2010-01-01

403

Radiation-induced Precursors in Crystalline Energetic Composites  

NASA Astrophysics Data System (ADS)

We present new experimental evidence that demonstrates the origination of precursors of the major reaction front at SDT in PBXs, based on the results of wedge tests of the HMX/Epoxy 77/23 (wt. %) and HMX/Water composites. The precursors were spatially resolved in the modified wedge tests performed with the Multi-Channel Optical Analyzer -- MCOA by means of the simultaneous registration of the reaction radiance transmitting through the explosive bulk at the SDT and the stress field, which is induced by the reaction zone in the optical monitor. Experimental evidence, obtained at a wide variation of the HMX particle sizes (1.64 ?m < d50 < 960 ?m), point to the fact that the precursor is arisen as a result of the radiation heating due to the photon absorption, as the reaction radiation is scattered within the bulk of the crystalline explosive material. Within the precursor layer, thickness of which depends on both, temperature localization and radiation intensity in the major DRZ as well as on optical and kinetic properties (the photon absorption and further reactivity of the explosive particles), the explosive particles undergo thermal expansion, phase transformation and partial decomposition. Such a mechanism implies that the photo-excitation and energy localization due to radiation of the shock front play a crucial role in starting decomposition process.

Plaksin, I.; Rodrigues, L.; Plaksin, S.; Campos, J.; Mendes, R.; Ribeiro, J.; Gois, J.

2009-06-01

404

Synthesis and use of a trifluoromethylated azomethine ylide precursor.  

PubMed

The presence of fluorous substituents can impart a dramatic effect on the efficacy of molecules used for a range of applications in society. Here, we describe the preparation and use of a new trifluoromethylated azomethine ylide precursor, which leads to a series of fluorinated pyrrolidine, 3-pyrroline, and pyrrole building blocks. PMID:23176732

Tran, Gaël; Meier, Robin; Harris, Lawrence; Browne, Duncan L; Ley, Steven V

2012-12-21

405

Design of precursors for the CVD of inorganic thin films.  

PubMed

Applications of inorganic thin films in the electronics industry have spurred activity in the area of chemical vapor deposition (CVD). This article discusses the increasingly sophisticated design strategies for precursor complexes through a series of case studies on CVD of metal oxide and metal nitride films. PMID:17102856

McElwee-White, Lisa

2006-12-01

406

Low temperature polymeric precursor derived zinc oxide thin films  

NASA Astrophysics Data System (ADS)

Zinc oxide (ZnO) is a versatile environmentally benign II-VI direct wide band gap semiconductor with several technologically plausible applications such as transparent conducting oxide in flat panel and flexible displays. Hence, ZnO thin films have to be processed below the glass transition temperatures of polymeric substrates used in flexible displays. ZnO thin films were synthesized via aqueous polymeric precursor process by different metallic salt routes using ethylene glycol, glycerol, citric acid, and ethylene diamine tetraacetic acid (EDTA) as chelating agents. ZnO thin films, derived from ethylene glycol based polymeric precursor, exhibit flower-like morphology whereas thin films derived of other precursors illustrate crack free nanocrystalline films. ZnO thin films on sapphire substrates show an increase in preferential orientation along the (002) plane with increase in annealing temperature. The polymeric precursors have also been used in fabricating maskless patterned ZnO thin films in a single step using the commercial Maskless Mesoscale Materials Deposition (M3D(TM)) system.

Choppali, Uma

407

Monitoring precursor chemicals of methamphetamine through enantiomer profiling.  

PubMed

Smuggling of methamphetamine is affected by enforced regulation and international situation, resulting in changes of precursors and synthetic methods used. Enantiomer ratio of methamphetamine can provide information concerning its precursor and synthetic method. This information is useful for the prevention of smuggling methamphetamine and its precursor, and resultant reduction of methamphetamine abuse. In the present study, we investigated on the enantiomer ratios of 433 crystalline methamphetamine samples seized in Korea from 1994 to 2005. Excluding 17 samples of low purity, 416 samples were used for enantiomer profiling. The methamphetamine samples were derivatized with (S)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride ((S)-(+)-MTPACl), and the derivatives were analyzed by GCMS in selected ion monitoring (SIM) mode. The enantiomer ratios of the samples were calculated from the standard calibration curves of each enantiomer, both of which showed good linearity in the range of 0-1.2 microg. Most of the seizures were pure S(+)-enantiomer, but 21% (95 of 416 samples) contained R(-)-enantiomer above 1%. They began to appear from 1997, and increased continuously up to 50% in the year 2005 (55 of 111 samples). From this study, we could find out that alternative precursors have been used recently for the illicit manufacture of methamphetamine seized in Korea. PMID:17188827

Lee, Jae Sin; Yang, Wun Kyung; Han, Eun Young; Lee, Soo Yeun; Park, Yong Hoon; Lim, Mi Ae; Chung, Hee Sun; Park, Jeong Hill

2007-11-15

408

The oligodendrocyte precursor cell in health and disease  

Microsoft Academic Search

Adult oligodendrocyte precursor cells (OPCs) make up around 5–8% of the glial cell population in the CNS. Their function in the undamaged CNS is largely unknown, but their processes are in contact with nodes of Ranvier and synapses, suggesting a regulatory role at these structures. The cells divide slowly, and constitute ?70% of cells labelled following a pulse injection of

Joel M Levine; Richard Reynolds; James W Fawcett

2001-01-01

409

Process for Producing Ceramic Nitrides And Carbonitrides and Their Precursors.  

National Technical Information Service (NTIS)

A process for preparing ceramic nitrides and carbon nitrides in the form of very pure, fine particulate powder. Appropriate precursors is prepared by reaching a transition metal alkylamide with ammonia to produce a mixture of metal amide and metal imide i...

G. M. Brown L. Maya

1987-01-01

410

Process for producing ceramic nitrides and carbonitrides and their precursors  

DOEpatents

A process for preparing ceramic nitrides and carbonitrides in the form of very pure, fine particulate powder. Appropriate precursor is prepared by reacting a transition metal alkylamide with ammonia to produce a mixture of metal amide and metal imide in the form of an easily pyrolyzable precipitate.

Brown, Gilbert M. (Knoxville, TN); Maya, Leon (Oak Ridge, TN)

1988-01-01

411

Process for producing ceramic nitrides anc carbonitrides and their precursors  

DOEpatents

A process for preparing ceramic nitrides and carbon nitrides in the form of very pure, fine particulate powder. Appropriate precursors is prepared by reaching a transition metal alkylamide with ammonia to produce a mixture of metal amide and metal imide in the form of an easily pyrolyzable precipitate.

Brown, G.M.; Maya, L.

1987-02-25

412

AIMSTAR: Antimatter initiated microfusion for pre-cursor interstellar missions  

NASA Astrophysics Data System (ADS)

We address the challenge of delivering a scientific payload to 10,000 A.U. in 50 years. This mission may be viewed as a pre-cursor to later missions to Alpha Centauri and beyond. We consider a small, aneutronic nuclear fusion engine sparked by clouds of antiprotons, and describe the principle and operation of the engine and mission parameters.

Gaidos, G.; Lewis, R. A.; Meyer, K.; Schmidt, T.; Smith, G. A.

1999-05-01

413

Validation of aggregate delayed neutron spectra calculated from precursor data  

SciTech Connect

An extensive reference library of delayed neutron data has been compiled which contains fission yields and branchings, delayed neutron emission probabilities, and spectra for 271 precursors. These data have been used to calculate the aggregate behavior of delayed neutrons following a fission event in 43 fissioning systems. Least-squares techniques were used to produce fitted decay constants and abundances in the conventional six-group formalism from these calculated activity curves. A consistent set of six-group spectra have also been calculated for each of the fissioning systems. Recent measurements at the University of Lowell have produced measured energy spectra for delayed neutrons following the thermal fission (T) of {sup 235}U and {sup 239}Pu, and the fast fission (F) of {sup 238}U. These measured spectra provide data that may be used to validate the precursor data base and the fitted six-group data. This summary presents results of this validation effort. Both the individual precursor data and the six-group data have been used to calculate aggregate equilibrium spectra for {sup 235}U(T), {sup 238}U(F), and {sup 239}Pu(T) via summation techniques. The important precursors in each case are identified, and the status of their data reviewed. 8 refs., 3 figs., 3 tabs.

Brady, M. C.; England, T. R. [Oak Ridge National Lab., TN (USA); ,

1989-01-01

414

Barium strontium titanate powder obtained by polymeric precursor method  

Microsoft Academic Search

Pure barium strontium titanate powder, with Ba\\/Sr ratio of 80\\/20 was prepared by the polymeric precursor method (also called Pechini process). The powder was obtained after a calcination at 800 °C for 8 h and characterized by XRD, IR, BET and SEM. The requirements to avoid barium carbonate as a secondary phase are presented and discussed in detail.

A. Ries; A. Z. Simões; M. Cilense; M. A. Zaghete; J. A. Varela

2003-01-01

415

Barium strontium titanate powder obtained by polymeric precursor method  

SciTech Connect

Pure barium strontium titanate powder, with Ba/Sr ratio of 80/20 was prepared by the polymeric precursor method (also called Pechini process). The powder was obtained after a calcination at 800 deg. C for 8 h and characterized by XRD, IR, BET and SEM. The requirements to avoid barium carbonate as a secondary phase are presented and discussed in detail.

Ries, A.; Simoes, A.Z.; Cilense, M.; Zaghete, M.A.; Varela, J.A

2003-03-15

416

Synthesis of yttrium iron garnet precursor particles by homogeneous precipitation  

Microsoft Academic Search

Yttrium iron garnet (YIG) precursor particles were obtained by homogeneous precipitation in a nitrate salt solution by a reaction involving the thermal decomposition of urea. Chemical analysis indicated that solid phases were initially precipitated with sequential iron ion content. The precipitate formed was an amorphous mixed iron oxide phase. The complex composition and the thermal decomposition of the precipitate were

Y. S. Ahn; M. H. Han; C. O. Kim

1996-01-01

417

Lithographic printing plate precursor and lithographic printing method  

US Patent & Trademark Office Database

A lithographic printing plate precursor comprising a support and an image-recording layer containing at least one compound selected from the group consisting of a spiropyran compound and a spirooxazine compound, and an acid generator, and a lithographic printing method including a process of removing the unexposed area of the image-recording layer on a printing press.

2008-09-16

418

Descriptive and Experimental Analyses of Potential Precursors to Problem Behavior  

ERIC Educational Resources Information Center

We conducted descriptive observations of severe problem behavior for 2 individuals with autism to identify precursors to problem behavior. Several comparative probability analyses were conducted in addition to lag-sequential analyses using the descriptive data. Results of the descriptive analyses showed that the probability of the potential…

Borrero, Carrie S. W.; Borrero, John C.

2008-01-01

419

Precursors to Numeracy in Kindergartners with Specific Language Impairment  

ERIC Educational Resources Information Center

The present study investigated to what extent children with specific language impairment (SLI) differ in their early numeracy skills, when compared to normal language achieving (NLA) children. It was also explored which precursors were related to the early numeracy skills in both groups. Sixty-one children with SLI (6; 1 years) and 111 NLA…

Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

2011-01-01

420

College Student Stress: A Predictor of Eating Disorder Precursor Behaviors  

ERIC Educational Resources Information Center

Eating disorders are compulsive behaviors that can consume a person's life to the point of becoming life threatening. Previous research found stress associated with eating disorders. College can be a stressful time. If stress predicted precursor behaviors to eating disorders, then counselors would have a better chance to help students sooner. This…

Shelton, Virginia L.; Valkyrie, Karena T.

2010-01-01

421

NASA's Accident Precursor Analysis Process and the International Space Station  

NASA Technical Reports Server (NTRS)

This viewgraph presentation reviews the implementation of Accident Precursor Analysis (APA), as well as the evaluation of In-Flight Investigations (IFI) and Problem Reporting and Corrective Action (PRACA) data for the identification of unrecognized accident potentials on the International Space Station.

Groen, Frank; Lutomski, Michael

2010-01-01

422

Environment Conscious, Biomorphic Ceramics from Pine and Jelutong Wood Precursors  

NASA Technical Reports Server (NTRS)

Environment conscious, biomorphic ceramics have been fabricated from pine and jelutong wood precursors. A carbonaceous preform is produced through wood pyrolysis and subsequent infiltration with oxides (ZrO2 sols) and liquid silicon to form ceramics. These biomorphic ceramics show a wide variety of microstructures, densities, and hardness behavior that are determined by the type of wood and infiltrants selected.

Singh, Mrityunjay; Yee, Bo-Moon; Gray, Hugh R. (Technical Monitor)

2002-01-01

423

Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function  

PubMed Central

Increased osteoclastic bone resorption leads to periarticular erosions and systemic osteoporosis in RA patients. Although a great deal is known about how osteoclasts differentiate from precursors and resorb bone, the identity of an osteoclast precursor (OCP) population in vivo and its regulatory role in RA remains elusive. Here, we report the identification of a CD11b–/loLy6Chi BM population with OCP activity in vitro and in vivo. These cells, which can be distinguished from previously characterized precursors in the myeloid lineage, display features of both M1 and M2 monocytes and expand in inflammatory arthritis models. Surprisingly, in one mouse model of RA (adoptive transfer of SKG arthritis), cotransfer of OCP with SKG CD4+ T cells diminished inflammatory arthritis. Similar to monocytic myeloid-derived suppressor cells (M-MDSCs), OCPs suppressed CD4+ and CD8+ T cell proliferation in vitro through the production of NO. This study identifies a BM myeloid precursor population with osteoclastic and T cell–suppressive activity that is expanded in inflammatory arthritis. Therapeutic strategies that prevent the development of OCPs into mature bone-resorbing cells could simultaneously prevent bone resorption and generate an antiinflammatory milieu in the RA joint.

Charles, Julia F.; Hsu, Lih-Yun; Niemi, Erene C.; Weiss, Arthur; Aliprantis, Antonios O.; Nakamura, Mary C.

2012-01-01

424

Solution precursor plasma deposition of nanostructured ZnO coatings  

SciTech Connect

Highlights: {yields} The solution precursor route employed is an inexpensive process with capability to produce large scale coatings at fast rates on mass scale production. {yields} It is highly capable of developing tailorable nanostructures. {yields} This technique can be employed to spray the coatings on any kind of substrates including polymers. {yields} The ZnO coatings developed via solution precursor plasma spray process have good electrical conductivity and reflectivity properties in spite of possessing large amount of particulate boundaries, porosity and nanostructured grains. -- Abstract: Zinc oxide (ZnO) is a wide band gap semiconducting material that has various applications including optical, electronic, biomedical and corrosion protection. It is usually synthesized via processing routes, such as vapor deposition techniques, sol-gel, spray pyrolysis and thermal spray of pre-synthesized ZnO powders. Cheaper and faster synthesis techniques are of technological importance due to increased demand in alternative energy applications. Here, we report synthesis of nanostructured ZnO coatings directly from a solution precursor in a single step using plasma spray technique. Nanostructured ZnO coatings were deposited from the solution precursor prepared using zinc acetate and water/isopropanol. An axial liquid atomizer was employed in a DC plasma spray torch to create fine droplets of precursor for faster thermal treatment in the plasma plume to form ZnO. Microstructures of coatings revealed ultrafine particulate agglomerates. X-ray diffraction confirmed polycrystalline nature and hexagonal Wurtzite crystal structure of the coatings. Transmission electron microscopy studies showed fine grains in the range of 10-40 nm. Observed optical transmittance ({approx}65-80%) and reflectivity ({approx}65-70%) in the visible spectrum, and electrical resistivity (48.5-50.1 m{Omega} cm) of ZnO coatings are attributed to ultrafine particulate morphology of the coatings.

Tummala, Raghavender [Department of Mechanical Engineering, University of Michigan - Dearborn, MI 48128 (United States)] [Department of Mechanical Engineering, University of Michigan - Dearborn, MI 48128 (United States); Guduru, Ramesh K., E-mail: rkguduru@umich.edu [Department of Mechanical Engineering, University of Michigan - Dearborn, MI 48128 (United States); Mohanty, Pravansu S. [Department of Mechanical Engineering, University of Michigan - Dearborn, MI 48128 (United States)] [Department of Mechanical Engineering, University of Michigan - Dearborn, MI 48128 (United States)

2011-08-15

425

Precursors of Androctonus australis scorpion neurotoxins. Structures of precursors, processing outcomes, and expression of a functional recombinant toxin II.  

PubMed

From a cDNA library made from telsons of scorpions of the species Androctonus australis, full-length cDNAs of about 370 nucleotides encoding precursors of toxins active on mammals or on insects have been isolated using oligonucleotide probes. Sequence analysis of the cDNAs revealed that the precursors contain signal peptides of about 20 amino acid residues. In addition, precursors of toxins active on mammals have extensions at their COOH-terminal ends: Arg or Gly-Arg. The processing steps required to generate toxins from their respective precursors are thus not identical for all of them. Southern blot analysis performed at the genomic level with a cDNA encoding toxin II suggested a single copy gene having a minimum size of 2800 base pairs. Finally, in an attempt to successfully express an animal toxin, monkey kidney COS-7 cells transfected with a plasmid harboring a cDNA encoding toxin II transiently expressed a recombinant toxin having the immunological and biological properties of toxin II. PMID:2808423

Bougis, P E; Rochat, H; Smith, L A

1989-11-15

426

Precursors of Androctonus australis Scorpion Neurotoxins. Structures of Precursors, Processing Outcomes, and Expression of a Functional Recombinant Toxin II,  

National Technical Information Service (NTIS)

WE isolated full-length cDNA clones encoding Androctonu s australis scorpion neurotoxins active in mammals or insects. Sequence analysis of the cDNAs revealed that precursors of toxins contained signal peptides of about 20 amino acids. In addition, the sc...

H. Rochat L. A. Smith P. E. Bougis

1989-01-01

427

Australian lungfish neurohypophysial hormone genes encode vasotocin and [Phe2]mesotocin precursors homologous to tetrapod-type precursors  

PubMed Central

In view of the well-established role of neurohypophysial hormones in osmoregulation of terrestrial vertebrates, lungfishes are a key group for study of the molecular and functional evolution of the hypothalamo-neurohypophysial system. Here we report on the primary structure of the precursors encoding vasotocin (VT) and [Phe2]mesotocin ([Phe2]MT) of the Australian lungfish, Neoceratodus forsteri. Genomic sequence analysis and Northern blot analysis confirmed that [Phe2]MT is a native oxytocin family peptide in the Australian lungfish, although it has been reported that the lungfish neurohypophysis contains MT. The VT precursor consists of a signal peptide, VT, that is connected to a neurophysin by a Gly-Lys-Arg sequence, and a copeptin moiety that includes a Leu-rich core segment and a glycosylation site. In contrast, the [Phe2]MT precursor does not contain a copeptin moiety. These structural features of the lungfish precursors are consistent with those in tetrapods, but different from those in teleosts where both VT and isotocin precursors contain a copeptin-like moiety without a glycosylation site at the carboxyl terminals of their neurophysins. Comparison of the exon/intron organization also supports homology of the lungfish [Phe2]MT gene with tetrapod oxytocin/MT genes, rather than with teleost isotocin genes. Moreover, molecular phylogenetic analysis shows that neurohypophysial hormone genes of the lungfish are closely related to those of the toad. The present results along with previous morphological findings indicate that the hypothalamo-neurohypophysial system of the lungfish has evolved along the tetrapod lineage, whereas the teleosts form a separate lineage, both within the class Osteichthyes.

Hyodo, Susumu; Ishii, Susumu; Joss, Jean M. P.

1997-01-01

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CARBONACEOUS MATTER PRECURSORS AND METAMORPHIC CONDITIONS IN THERMALLY PROCESSED CHONDRITES  

NASA Astrophysics Data System (ADS)

Unravelling the origin of carbonaceous matter in pristine chondrites requires the understanding of the effect of post-accretion processes. In chondrites of petrologic type 3, thermal metamorphism modified to various extents the composition and structure of carbonaceous matter. Interestingly, this process controls the degree of structural order of carbonaceous matter, and clues on the thermal history of the parent body may be recovered from the physico-chemical study of carbonaceous matter. Following this framework, geothermometers based on Raman spectrometry of carbonaceous matter and covering a wide range of temperatures (100-650 °C) have been developed over recent years, both on terrestrial rocks and chondrites. While Raman data have been largely interpreted in terms of temperature, they are also the fingerprint of certain metamorphic conditions, especially in the low temperature range relevant to poorly ordered carbonaceous matter. This study investigates the Raman spectra of two series of chondritic carbonaceous matter and coal samples formed from different precursors and under different metamorphic conditions. The Raman spectra of Polyaromatic Carbonaceous Matter (PCM) from 42 chondrites and 27 coal samples, measured with visible (514 nm) and ultra-violet (244 nm) excitation wavelengths, are analyzed. The Raman spectra of low rank coals and chondrites of petrologic types 1 and 2, which contain the more disordered PCM, reflect the distinct carbon structures of their precursors. The 514 nm Raman spectra of high rank coals and chondrites of petrologic type 3 exhibit continuous and sy