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1

Gamma-Hydroxybutyrate (GHB)  

MedlinePLUS

MENU Return to Web version Club Drug Use | Gamma-Hydroxybutyrate (GHB) What is GHB? Gamma-hydroxybutyrate (GHB) is an illegal drug that is ... fX bombs Cherry meth Easy lay Everclear Firewater Gamma G Georgia homeboy GHB G.H. revitalizer Gib ...

2

Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic precursor, gamma-butyrolactone (GBL) in rats  

Microsoft Academic Search

Rationale  Gamma-hydroxybutyrate (GHB) is becoming an increasingly popular drug of abuse. Metabolic precursors of GHB, gamma-butyrolactone\\u000a (GBL) and 1,4-butanediol (BDL), are commercially available industrial solvents that may also present potential health risks.\\u000a Relatively little is known about the neurobehavioral effects of GHB and its precursors.\\u000a \\u000a \\u000a \\u000a Objective  The aim of the present investigation was to characterize the discriminative stimulus effects of GHB and

Lisa E. Baker; Timothy J. Van Tilburg; Andrew E. Brandt; Alan Poling

2005-01-01

3

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

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

GHB - Gamma-Hydroxybutyric Acid  

MedlinePLUS

... comes in a liquid or as a white powder that is dissolved in water, juice, or alcohol. In liquid form, GHB is clear and colorless and slightly salty in taste. Street Names G, Georgia Home Boy, Goop, Grievous ... in a beverage • White powder normally dissolved in a liquid How does it ...

7

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

8

Preference for Gamma-Hydroxybutyrate (GHB) in Current Users  

ERIC Educational Resources Information Center

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…

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

2012-01-01

9

Driving under the influence of gamma-hydroxybutyrate (GHB)  

Microsoft Academic Search

We used an in-house forensic toxicology database (TOXBASE) to evaluate the occurrences of gamma-hydroxybutyrate (GHB) in blood\\u000a samples from people arrested in Sweden for driving under the influence of drugs (DUID) between 1998 and 2007. Age, gender,\\u000a and concentrations of GHB in blood were compared and contrasted when GHB was the only drug present and when it occurred along\\u000a with

Alan Wayne Jones; Anita Holmgren; Fredrik C. Kugelberg

2008-01-01

10

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. PMID:19198808

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

2009-01-01

11

EXPERIENCES OF GAMMA HYDROXYBUTYRATE (GHB) INGESTION: A FOCUS GROUP STUDY  

PubMed Central

GHB (gamma hydroxybutyrate) is a significant new drug of abuse added to the United States Controlled Substance Act in 2000. The majority of the published literature on GHB consists of clinical case reports, mainly from emergency departments, and a collection of laboratory-based studies, focused mainly on anesthesia. While comments about the various experiences and behaviors of human users are often included in such studies or reports, these aspects of GHB are only just beginning to be systematically investigated or detailed. Reported here are data from a qualitative study using focus group methods on the consumption habits, experiences, and beliefs of GHB users. A total of 51 people, 30 men and 21 women, mean age of 31.1±7.6 years (range 18 – 52 years), who report having used GHB for an average of 4.3±2.5 years (range 1–11 years), were interviewed in 10 separate groups held in 2004. This paper discusses broadly the general experience of the GHB ‘high,’ major perceived benefits including sexual responses to the drug, perceived risks and dangers of ingestion, co-ingestion, and various contexts of use. The paper concludes with a discussion of the implications drawn from this information for clinicians treating patients who use GHB. PMID:17703706

Barker, Judith C.; Harris, Shana L.; Dyer, Jo E.

2008-01-01

12

BEHAVIORAL EFFECTS OF GAMMA-HYDROXYBUTYRATE (GHB) IN HUMANS  

PubMed Central

Despite the therapeutic use and abuse potential of gamma-hydroxybutyrate (GHB or Xyrem), relatively few studies have examined the behavioral effects of GHB in humans under controlled laboratory conditions. Thus, this eight-session study examined in 10 non substance-abusing volunteers the behavioral effects of GHB at each of the following doses: 0, 0.32, 0.56, 0.75, 1.0, 1.8, 2.4, 3.2 g/70 kg, p.o.. Order of dose testing was random, except that the first two participants received active doses in ascending order and 2.4 g/70 kg was always tested before 3.2 g/70 kg. Prior to drug administration and at several post-drug time points, self-report, observer-report, physiological, and psychomotor performance measures were obtained. Analyses based on area under the curve showed that GHB produced dose-related increases in subjective ratings of sedative-like, stimulant-like, positive mood, and dissociative effects, but no changes in psychomotor performance measures or blood pressure. Analyses based on peak effects generally showed dose-related increases in ratings indicating sedative-like, dissociative, and drug liking, although some measures showed U-shaped dose-related changes. These initial findings suggest that GHB at doses of 0.32–3.2 g/70 kg produces dissociative, sedating and some stimulant-like effects in humans without a history of sedative abuse. PMID:20526195

Oliveto, Alison; Gentry, W. Brooks; Pruzinsky, Rhonda; Gonsai, Kishorchandra; Kosten, Thomas R.; Martell, Bridget; Poling, James

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

Self-administration of gamma-hydroxybutyric acid (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 gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse. Objective Given the reports of abuse, and the ease at which GBL and 1,4-BD may be obtained, we investigated the reinforcing of GBL (n=5) and 1,4-BD (n=4) in baboons using IV self-administration procedures. Methods Sessions ran 24 h/day. Each injection was contingent upon completion of a fixed number (120 or 160) of lever responses. A 3-h timeout period followed each injection, limiting the total number of injections to 8/day. Self-administration was first established with cocaine (0.32 mg/kg/injection). GBL (10–130.0 mg/kg/injection), 1,4-BD (10–100 mg/kg/injection) or vehicle were substituted for cocaine at least 15 days. Food pellets were available ad libitum 24 h/day and were contingent upon completion of 10 lever responses. Results GBL (32–100 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in 4 of 5 baboons and mean rates of injection were high (>6 per day) in 3 baboons and moderate in the fourth baboon (4–6 per day). 1,4-BD (78–130 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in only 2 out of 4 baboons and rates were moderate to high in both baboons. Self-injection of these doses of GBL and 1,4-BD generally inhibited food-maintained responding. Conclusions GBL and 1,4-BD have abuse liability. Given that GBL and 1,4-BD are self-administered, are easier to obtain than GHB, and are detected in seized samples, additional legal control measures of these GHB pro-drugs may be needed. PMID:22945514

Goodwin, Amy K.; Kaminski, Barbara J.; Weerts, Elise M.

2012-01-01

17

Driving under the influence of gamma-hydroxybutyrate (GHB).  

PubMed

We used an in-house forensic toxicology database (TOXBASE) to evaluate the occurrences of gamma-hydroxybutyrate (GHB) in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID) between 1998 and 2007. Age, gender, and concentrations of GHB in blood were compared and contrasted when GHB was the only drug present and when it occurred along with other drugs. GHB was determined in blood by gas chromatography (GC) after conversion to gamma-butyrolactone (GBL) and analysis of the latter with a flame ionization detector. The cut-off concentration of GHB in blood for reporting a positive result was 8 mg/l, which served as limit of quantitation. The mean and median GHB concentrations were 89 mg/l and 82 mg/l, respectively (2(1/2) and 97(1/2) percentiles 12 and 220 mg/l) in 548 arrested drivers. These individuals were predominantly men (95%) with an average age of 26 +/- 5.5 years (range 15-50 years) and women (5%) were several years older with an average age of 32 +/- 8.0 years (range 19-47). There were 102 individuals (29%) who were arrested more than once with GHB in blood (average approximately 3 times per person) and one as many as 10 times. GHB was the only psychoactive substance detected in 215 cases (39%) at mean and median blood-concentrations of 91 mg/l and 83 mg/l, respectively. These concentrations were not significantly different from poly-drug users. A weak but statistically significant correlation existed between the concentration of GHB in blood and the person's age (N = 548, r = 0.135, P < 0.01). The signs of drug influence noted by arresting police officers included sedation, agitation, unsteady gait, slurred speech, irrational behavior, jerky body movements, dilated pupils, and spitting. The blood concentrations reported here are probably appreciably less than at time of driving (30-90 min earlier) owing to the short elimination half-life of GHB (t ((1/2)) = 30-40 min). PMID:19291440

Jones, Alan Wayne; Holmgren, Anita; Kugelberg, Fredrik C

2008-01-01

18

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

19

Gamma-hydroxybutyrate (GHB): a scoping review of pharmacology, toxicology, motives for use, and user groups.  

PubMed

Gamma hydroxybutyrate (GHB) is a central nervous system depressant with euphoric and relaxant effects. Documentation of GHB prevalence and the underreporting of abuse remains problematic, given the availability of GHB and its precursors ?-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) and the ease of synthesis from kits available on the Internet. The continued abuse of and dependence on GHB, and associated fatalities, present an on-going public health problem. As the drug GHB remains an underresearched topic, a scoping review was chosen as a technique to map the available literature into a descriptive summarized account. PRISMA was used to assist in data retrieval, with subsequent data charting into three key themes (pharmacology and toxicology, outcomes, and user groups). Administered orally, GHB is dose-dependent and popular for certain uses (therapeutic, body enhancement, sexual assault) and amongst user sub groups (recreational party drug users, homosexual men). Despite the low prevalence of use in comparison to other club drugs, rising abuse of the drug is associated with dependence, withdrawal, acute toxicity, and fatal overdose. Clinical diagnosis and treatment is complicated by the co-ingestion of alcohol and other drugs. Limitations of the scoping review and potential for further research and harm reduction initiatives are discussed. PMID:25052883

Brennan, Rebekah; Van Hout, Marie Claire

2014-01-01

20

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

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

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. PMID:19493637

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

2009-01-01

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

The extraction and infrared identification of gamma-hydroxybutyric acid (GHB) from aqueous solutions.  

PubMed

The chemical analysis of gamma-hydroxybutyric acid (GHB) in most forensic laboratories is complicated by the highly polar nature of the GHB molecule, which makes it unsuitable for direct analysis by gas chromatography (GC). Consequently, a popular analytical approach is to convert GHB into the corresponding lactone or a derivative compound that is then identified by mass spectrometry employed in conjunction with GC (GC/MS). An alternative approach is presented here where GHB may be isolated as a free acid specie from complex aqueous solutions employing a liquid-liquid extraction technique. This approach can yield a relatively pure residue of GHB that presents an infrared transmission spectrum that is sufficiently distinct for identification purposes. Infrared spectroscopy (IR) is a very popular technique that is available to most crime laboratories. The liquid-liquid extraction behavior of GHB is examined in detail and the uniqueness of the infrared spectrum is discussed. PMID:14979343

Chappell, John S; Meyn, Ashleigh W; Ngim, Kenley K

2004-01-01

26

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

27

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. PMID:21175918

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

2011-01-01

28

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. PMID:21112162

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

2010-01-01

29

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. PMID:24758357

2014-01-01

30

Gamma-hydroxybutyric acid (GHB) and the mesoaccumbens reward circuit: evidence for GABA(B) receptor-mediated effects.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid naturally occurring in the mammalian brain, which recently emerged as a major recreational drug of abuse. GHB has multiple neuronal mechanisms including activation of both the GABA(B) receptor, and a distinct GHB-specific receptor. This complex GHB-GABA(B) receptor interaction is probably responsible for the multifaceted pharmacological, behavioral and toxicological profile of GHB. Drugs of abuse exert remarkably similar effects upon reward-related circuits, in particular the mesolimbic dopaminergic system and the nucleus accumbens (NAc). We used single unit recordings in vivo from urethane-anesthetized rats to characterize the effects of GHB on evoked firing in NAc "shell" neurons and on spontaneous activity of antidromically identified dopamine (DA) cells located in the ventral tegmental area. GHB was studied in comparison with the GABA(B) receptor agonist baclofen and antagonist (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911). Additionally, we utilized a GHB analog, gamma-(p-methoxybenzil)-gamma-hydroxybutyric acid (NCS-435), devoid of GABA(B) binding properties, but with high affinity for specific GHB binding sites. In common with other drugs of abuse, GHB depressed firing in NAc neurons evoked by the stimulation of the basolateral amygdala. On DA neurons, GHB exerted heterogeneous effects, which were correlated to the baseline firing rate of the cells but led to a moderate stimulation of the DA system. All GHB actions were mediated by GABA(B) receptors, since they were blocked by SCH50911 and were not mimicked by NCS-435. Our study indicates that the electrophysiological profile of GHB is close to typical drugs of abuse: both inhibition of NAc neurons and moderate to strong stimulation of DA transmission are distinctive features of diverse classes of abused drugs. Moreover, it is concluded that addictive and rewarding properties of GHB do not necessarily involve a putative high affinity GHB receptor. PMID:15708487

Pistis, M; Muntoni, A L; Pillolla, G; Perra, S; Cignarella, G; Melis, M; Gessa, G L

2005-01-01

31

[Gamma-hydroxybutyrate (GHB) and its lactone (GBL) as psychoactive substances].  

PubMed

Gammabutyrolactone is included in the solvent such as wheel cleaners, pesticides, cosmetics, drugs. After ingestion GBL is converted to gamma-hydroxybutyrate. Both substances are classified as so called "club drugs" and their action is characterized by euphoria, sedation, and induction of retrograde amnesia of events. These activities were basis for the use of GHB and its lactone as rape pill. Acute poisoning with these compounds causes confusion, agitation, ataxia, nausea, vomiting, nystagmus, dyskinesia, hallucinations, coma, irregular breathing, hypothermia, bradycardia, hypotension, convulsions, respiratory paralysis and thus respiratory arrest. These substances carry a risk of development of physical addiction of the hard proceeding of abstinence syndrome. In the USA there is a ban on the sale and promotion of these compounds. In Poland despite the fact that GHB is a controlled substance, there is no regulation of GBL trading. The aim of this paper is to summarize current knowledge regarding the pharmacology, impact on the human body, toxicity, and the effects of chronic abuse of these substances. PMID:23243924

Krajewska, Anna; Kwiecie?-Obara, Ewelina; Szponar, Jaros?aw; Majewska, Magdalena; Ko?odziej, Ma?gorzata

2012-01-01

32

A review of pharmacology of NCS-382, a putative antagonist of gamma-hydroxybutyric acid (GHB) receptor.  

PubMed

Gamma-hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a semirigid compound structurally related to GHB, is the only compound reported to be an antagonist of the GHB receptor sites. In this article we review the in vivo and in vitro pharmacological properties of NCS-382 and its interaction with GHB and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a stereoselective ligand for GHB-binding sites, with both, the high and the low component of population, showing the same distribution of GHB receptors. Indeed, this compound did not display affinity for GABA(A), GABA(B), or any other known receptors, while conflicting data have been reported as to its selective antagonist action at GHB receptor. Only a few studies have shown that NCS-382 antagonizes GHB-induced effect, but a re-evaluation of all data reported in the literature suggests that the antagonistic effect of this compound could be due to an indirect action at GABA(B) receptors. As revealed by several behavioral studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced inhibition of locomotor activity and ataxia or suppression of operant responses. Moreover, it is capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive electrophysiological effects of endogenous and exogenous GHB observed in vivo have not been completely replicated in vitro. The only electrophysiological action of GHB antagonized in vitro by NCS-382 required a previous blockade of GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective antagonist for GHB receptor. PMID:15492774

Castelli, M Paola; Pibiri, Fabio; Carboni, Giovanni; Piras, A Paola

2004-01-01

33

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

34

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

35

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

36

[Gamma-hydroxybutyric acid (GHB): more than a date rape drug, a potentially addictive drug].  

PubMed

According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB. PMID:19762202

Karila, Laurent; Novarin, Johanne; Megarbane, Bruno; Cottencin, Olivier; Dally, Sylvain; Lowenstein, William; Reynaud, Michel

2009-10-01

37

Monitoring of the interconversion of gamma-butyrolactone (GBL) to gamma hydroxybutyric acid (GHB) by Raman spectroscopy.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a drug-of-abuse that has recently become associated with drug-facilitated sexual assault, known as date rape. For this reason the drug is commonly found 'spiked' in alcoholic beverages. When GHB is in solution it may undergo conversion into the corresponding lactone, Gamma-butyrolactone (GBL). Studies have been carried out to determine the detection limits of GHB and GBL in various solutions by Raman spectroscopy and to monitor the interconversion of GHB and GBL in solution with different pH conditions and temperature. In this study, a portable Raman spectrometer was used to study the interconversion of GHB and GBL in water and ethanol solutions as a function of pH, time, and temperature. The aim of this was to determine the optimum pH range for conversion in order to relate this to the pH ranges that the drug is likely to be subjected to, first in spiked beverages and secondly after ingestion in the digestive system. The aim was also to identify a timescale for this conversion in relation to possible scenarios, for example if GHB takes a number of hours to convert to GBL, it is likely for the beverage to be ingested before esterification can take place. GHB and GBL were then spiked into a selection of beverages of known pH in order to study the stability of GHB and GBL in real systems. PMID:23225646

Munshi, Tasnim; Brewster, Victoria L; Edwards, Howell G M; Hargreaves, Michael D; Jilani, Shelina K; Scowen, Ian J

2013-08-01

38

Novel high-affinity and selective biaromatic 4-substituted gamma-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies.  

PubMed

Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands. PMID:19053823

Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte; Frydenvang, Karla; Dahl, Ivar F; Bräuner-Osborne, Hans; Brehm, Lotte; Frølund, Bente; Clausen, Rasmus P

2008-12-25

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

Keywords: 1,4-butanediol, gamma-hydroxybutyrate, poisoning, toy Notes: The information in this study was presented previously in the following venues: Western Regional Society for Academic Emer-  

E-print Network

contained 1,4-butanediol (1,4-BD), a precursor to gamma-hydroxybutyrate (GHB), rather than the intended been completely replaced with a substitute that is metabolized into GHB after inges- tion. Reports in the Australian and American media [2,5­7]. Gamma- hydroxybutyrate (GHB) was detected in biologic samples from

Nizkorodov, Sergey

41

Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.  

PubMed

There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4?g/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study. PMID:22554869

Lott, S; Musshoff, F; Madea, B

2012-09-10

42

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

43

Coma and respiratory depression following the ingestion of GHB and its precursors: three cases.  

PubMed

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 release. We report three cases of ingestion of products containing GHB and chemical precursors of GHB. All three patients had severe presentations followed by full recoveries. Some products containing GBL were withdrawn from the market after the FDA issued a warning regarding these products. Products containing 1,4-butanediol remain on the market today. PMID:10863118

Ingels, M; Rangan, C; Bellezzo, J; Clark, R F

2000-07-01

44

[From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 3: gamma-hydroxybutyric acid ("liquid ecstasy")].  

PubMed

Currently, gamma-hydroxybutyric acid (GHB/"liquid ecstasy") is frequently abused as a knockout substance. Its detection and the interpretation of the results present numerous problems which are illustrated by case reports. In this context, hair analysis and the increasing significance of gamma-butyrolactone (GBL) are also discussed. PMID:22276366

Schütz, Harald; Jansen, Malin; Verhoff, Marcel A

2011-01-01

45

[Current knowledge on gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL) and 1 ,4-butanediol (1,4-BD)].  

PubMed

Gamma-hydroxybutyric acid (GHB) is an old anaesthetic drug which was misused in the 80-90's as an anabolic agent (bodybuilding), recreational drug (drunkenness, euphoric, disinhibiting and aphrodisiac effects) and as a date rape drug (disinhibiting, hypnotic and amnesic effects). Its use in the general population is low, and mainly concerns gay population in nightclubs and young people in parties. The intoxications, above all with alcohol combination, can be severe, with coma and breathing depression, or even fatal. Chronic use leads to psychic and physical dependence; withdrawal syndrome can be severe, with agitation and delirium. In 1999, GHB classification as a narcotic resulted in the increased use of GHB prodrugs gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), which were easily commercially available as solvent and cleaning products. Like GHB, they have a narrow window of use, and share similar toxicity. Their increased cases of recreational use and of severe drug intoxication, abuse and dependence, led the French Ministry of Health in 2011 to prohibit their sale and transfer to the public. PMID:22730800

Dematteis, Maurice; Pennel, Lucie; Mallaret, Michel

2012-05-01

46

Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs.  

PubMed

When interpreting gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens, a possible increase in GHB concentrations because of post-mortem generation must be considered. In this study, endogenous GHB concentrations in post-mortem biological fluids were investigated. Additionally, we review post-mortem GHB concentrations already published in the literature. Heart and peripheral blood samples, cerebrospinal fluid, urine, and vitreous humor were collected from 64 autopsies in subjects where the cause of death excluded GHB exposure. Sample analysis was carried out either on the day of autopsy or later after immediate freezing and storage at -20 °C. GHB concentrations in venous blood samples (n?=?61) were <0.6-28.7 mg/L (mean 11.9 mg/L; median 10.6 mg/L), <0.6-65.3 mg/L (mean 15.2 mg/L; median 12.8 mg/L) in heart blood (n?=?56), <0.6-25.1 mg/L (mean 6.0 mg/L; median 3.8 mg/L) in urine (n?=?50), <0.6-39.0 mg/L (mean 9.6 mg/L; median 7.5 mg/L), in vitreous humor (n?=?54), and <0.6-24.0 mg/L (mean 4.2 mg/L; median 3.2 mg/L) in cerebrospinal fluid (n?=?52). There was no significant difference between GHB concentrations in cases where there were signs of beginning putrefaction at the time of autopsy (n?=?9) and cases without obvious signs of putrefaction. In one case with advanced putrefaction, the GHB concentration in venous blood was 32.7 mg/L. In conclusion, for post-mortem venous blood, urine, and cerebrospinal fluid, an interpretative cut-off of 30 mg/L for GHB concentrations is suggested in cases where GHB analysis is conducted on the day of sample collection at autopsy or if samples have been stored at -20 °C immediately after collection. PMID:25084768

Andresen-Streichert, Hilke; Jensen, P; Kietzerow, J; Schrot, M; Wilke, N; Vettorazzi, E; Mueller, A; Iwersen-Bergmann, S

2015-01-01

47

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

48

A critical evaluation of the gamma-hydroxybutyrate (GHB) model of absence seizures.  

PubMed

Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the ?-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs. PMID:25403866

Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo

2015-02-01

49

A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures  

PubMed Central

Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the ?-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs. PMID:25403866

Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo

2015-01-01

50

Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples.  

PubMed

Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse with numerous names. It has also been involved in various instances of drug-facilitated sexual assault due to its potential incapacitating effects. The first aim of this paper is to measure the post-mortem concentration of endogenous GHB in whole blood and urine samples of 30 GHB free-users, who have been divided according to the post-mortem interval (PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73-192h), trying to evaluate the role of PMI in affecting post mortem levels. Second, the Authors have evaluated the new formation of GHB in vitro in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month. The concentrations were measured by GC-MS after liquid-liquid extraction according to the method validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB concentrations were creatinine-normalized. In the first group the GHB mean concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L (range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g (range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples showed a statistically significant difference among groups (p<0.001) in the first analysis performed immediately after autopsy. Throughout the period of investigation up to 4 weeks, the comparison of storage temperatures within each group showed in blood and urine samples a mean difference at 20°C compared to -20°C not statistically significant at the 10% level. These findings allow us to affirm that the PMI strongly affects the post mortem production of GHB in blood and urine samples. Regarding the new formation of GHB in vitro both in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month, although there was no significant increases of GHB levels throughout the period of investigation, the lowest increases were found both in blood and urine at -20°C, therefore we recommend the latter as optimal storage temperature. PMID:25123534

Busardò, Francesco Paolo; Bertol, Elisabetta; Vaiano, Fabio; Baglio, Giovanni; Montana, Angelo; Barbera, Nunziata; Zaami, Simona; Romano, Guido

2014-10-01

51

Determination of gamma-hydroxybutyric acid (GHB) in plasma and urine by headspace solid-phase microextraction and gas chromatography/positive ion chemical ionization mass spectrometry.  

PubMed

A new method for the qualitative and quantitative analysis of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. It involves the conversion of GHB to gamma-butyrolactone (GBL), its subsequent headspace solid-phase microextraction (SPME), and detection by gas chromatography/positive ion chemical ionization mass spectrometry (GC/PICI-MS), using D(6)-GBL as internal standard. The assay is linear over a plasma GHB range of 1-100 microg/mL (n = 5, r = 0.999) and a urine GHB range of 5-150 microg/mL (n = 5, r = 0. 998). Relative intra- and inter-assay standard deviations, determined for plasma and urine samples at 5 and 50 microg/mL, are all below 5%. The method is simple, specific and reasonably fast. It may be applied for clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring. PMID:11114057

Frison, G; Tedeschi, L; Maietti, S; Ferrara, S D

2000-01-01

52

Gamma-Hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) reduce the volume of cerebral infarction in rodent transient middle cerebral artery occlusion.  

PubMed

gamma-Hydroxybutyric acid (GHB), an endogenous organic acid catabolite of gamma-aminobutyric acid (GABA), has been shown to have tissue-protective effects in various organs, including the brain. We examined the potential neuroprotective effect of GHB and its chemical precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), in the rodent ischemic stroke model by intraluminal filament middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats underwent transient left-sided MCAO and received intraperitoneal treatment with 300 mg/kg of GHB, GBL, 1,4-BD, or control vehicle given at 30 min before, as well as 180 and 360 min after the onset of ischemia. Infarct volumes were determined 24 h after MCAO. In transient MCAO, the mean volume of infarction for control rats was 464.4 +/- 17.9 cu.mm versus 273.6 +/- 53.1, 233.3 +/- 44.7, and 275.4 +/- 39.9 cu.mm for rats treated with 1,4-BD (P < 0.05), GBL (P < 0.05), and GHB (P < 0.05), respectively. We conclude that GHB, GBL, and 1,4-BD protect against rat focal cerebral ischemia from transient MCAO. PMID:17105951

Sadasivan, Shankar; Maher, Timothy J; Quang, Lawrence S

2006-08-01

53

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

54

gamma-Hydroxybutyrate (GHB) induces GABA(B) receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABA(B) receptors of medium spiny neurons in the nucleus accumbens.  

PubMed

We report on cellular actions of the illicit recreational drug gamma-hydroxybutyrate (GHB) in the brain reward area nucleus accumbens. First, we compared the effects of GHB and the GABA(B) receptor agonist baclofen. Neither of them affected the membrane currents of medium spiny neurons in rat nucleus accumbens slices. GABAergic and glutamatergic synaptic potentials of medium spiny neurons, however, were reduced by baclofen but not GHB. These results indicate the lack of GHB as well as postsynaptic GABA(B) receptors, and the presence of GHB insensitive presynaptic GABA(B) receptors in medium spiny neurons. In astrocytes GHB induced intracellular Ca(2+) transients, preserved in slices from GABA(B) receptor type 1 subunit knockout mice. The effects of tetrodotoxin, zero added Ca(2+) with/without intracellular Ca(2+) store depletor cyclopiazonic acid or vacuolar H-ATPase inhibitor bafilomycin A1 indicate that GHB-evoked Ca(2+) transients depend on external Ca(2+) and intracellular Ca(2+) stores, but not on vesicular transmitter release. GHB-induced astrocytic Ca(2+) transients were not affected by the GHB receptor-specific antagonist NCS-382, suggesting the presence of a novel NCS-382-insensitive target for GHB in astrocytes. The activation of astrocytes by GHB implies their involvement in physiological actions of GHB. Our findings disclose a novel profile of GHB action in the nucleus accumbens. Here, unlike in other brain areas, GHB does not act on GABA(B) receptors, but activates an NCS-382 insensitive GHB-specific target in a subpopulation of astrocytes. The lack of either post- or presynaptic effects on medium spiny neurons in the nucleus accumbens distinguishes GHB from many drugs and natural rewards with addictive properties and might explain why GHB has only a weak reinforcing capacity. PMID:19446011

Molnár, T; Antal, K; Nyitrai, G; Emri, Z

2009-08-18

55

Relation of the [3H] gamma-hydroxybutyric acid (GHB) binding site to the gamma-aminobutyric acidB (GABAB) receptor in rat brain.  

PubMed

gamma-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 gamma-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 and a GHB antagonist for the [3H]GABAB binding site, and the effect of guanine nucleotides and pertussis toxin on both, using autoradiographic binding assays. GHB and its antagonist, NCS 382, did not compete for [3H]GABAB binding, nor did (-)-baclofen or the [3H]GABAB antagonists, CGP 35348 or SCH 50911, compete for [3H]GHB binding; however, the GABAB agonist 3-amino-propylphosphinic acid (3-APPA), and the GABAB antagonists phaclofen and 2-hydroxysaclofen (2-OH saclofen) did show a weak affinity for [3H]GHB binding in frontal cortex. GTP and the nonhydrolyzable GTP analogues, GTP gamma S and Gpp(NH)p, depressed [3H]GABAB binding throughout the brain, but increased [3H]GHB binding in frontal cortex and thalamus, those regions involved in GHB-induced absence seizures. Pertussis toxin significantly depressed [3H]GABAB binding throughout the brain, but attenuated [3H]GHB binding only in frontal cortex, and to a lesser degree than [3H]GABAB binding. The guanine nucleotide-induced changes in [3H]GHB and [3H]GABAB binding were due to a change in KD for both. Moreover, GTP gamma S reversed the ability of 3-APPA, phaclofen, and 2-OH saclofen to compete for [3H]GHB binding. These data do not support the hypothesis that GHB acts through the postsynaptic GABAB receptor to produce absence seizures. Rather, they raise the possibility either that the [3H]GHB binding site may be an isoform of the presynaptic GABAB receptor or that an independent GHB site is operative in the GHB model of absence seizures. PMID:8937431

Snead, O C

1996-10-25

56

Report on the analysis of common beverages spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) using NMR and the PURGE solvent-suppression technique.  

PubMed

In forensic evidence, the identification and quantitation of gamma-hydroxybutyric acid (GHB) in "spiked" beverages is challenging. In this report, we present the analysis of common alcoholic beverages found in clubs and bars spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL). Our analysis of the spiked beverages consisted of using (1)H NMR with a water suppression method called Presaturation Utilizing Relaxation Gradients and Echoes (PURGE). The following beverages were analyzed: water, 10% ethanol in water, vodka-cranberry juice, rum and coke, gin and tonic, whisky and diet coke, white wine, red wine, and beer. The PURGE method allowed for the direct identification and quantitation of both compounds in all beverages except red and white wine where small interferences prevented accurate quantitation. The NMR method presented in this paper utilizes PURGE water suppression. Thanks to the use of a capillary internal standard, the method is fast, non-destructive, sensitive and requires no sample preparation which could disrupt the equilibrium between GHB and GBL. PMID:21775083

Lesar, Casey T; Decatur, John; Lukasiewicz, Elaan; Champeil, Elise

2011-10-10

57

Sedative and hypothermic effects of gamma-hydroxybutyrate (GHB) in rats alone and in combination with other drugs: assessment using biotelemetry.  

PubMed

The recreational drug gamma-hydroxybutyrate (GHB) has euphoric effects and can induce sedation and body temperature changes. GHB is frequently combined with other recreational drugs although these interactions are not well characterised. The present study used biotelemetry to provide a fine-grained analysis of the effects of GHB on body temperature and locomotor activity in freely moving rats, and investigated interactions between GHB and 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH) and various antagonist drugs. GHB (1000mg/kg) caused profound sedation for more than 2h and a complex triphasic effect on body temperature: an initial hypothermia (5-40min), followed by hyperthermia (40-140min), followed again by hypothermia (140-360min). A lower GHB dose (500mg/kg) also caused sedation but only a hypothermic effect that lasted up to 6h. The dopamine D(1) receptor antagonist SCH 23390 (1mg/kg), the opioid antagonist naltrexone (1mg/kg), the benzodiazepine antagonist flumazenil (10mg/kg), and the 5-HT(2A/2C) receptor antagonist ritanserin (1mg/kg) did not prevent the overall sedative or body temperature effects of GHB (1000mg/kg). However the GABA(B) antagonist SCH 50911 (50mg/kg) prevented the hyperthermia induced by GHB (1000mg/kg). Repeated daily administration of GHB (1000mg/kg) produced tolerance to the sedative and hyperthermic effects of the drug and cross-tolerance to the sedative effects of the GABA(B) receptor agonist baclofen (10mg/kg). A high ambient temperature of 28 degrees C prevented the hypothermia obtained with GHB (500mg/kg) at 20 degrees C, while GHB (500mg/kg) reduced the hyperthermia and hyperactivity produced by co-administered doses of MDMA (5mg/kg) or METH (1mg/kg) at 28 degrees C. These results further confirm a role for GABA(B) receptors in the hypothermic and sedative effects of GHB and show an interaction between GHB and MDMA, and GHB and METH, that may be relevant to the experience of recreational users who mix these drugs. PMID:19446408

van Nieuwenhuijzen, Petra S; McGregor, Iain S

2009-08-01

58

Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects native and amyloid-precursor-protein-transfected neuroblastoma cells against oxidative stress-induced death.  

PubMed

Clinical observations suggested that gamma-hydroxybutyrate (GHB) protects nerve cells against death but the direct proofs are missing. Here, we combined several approaches to investigate GHB capacity to protect human neuroblastoma SH-SY5Y cells against hydrogen peroxide (H2O2)-induced death. To increase the patho-physiological relevancy of our study, we used native SH-SY5Y cells and SH-SY5Y cells stably transfected with the wild-type amyloid-precursor-protein (APPwt) or control-vector-pCEP4. Trypan Blue exclusion and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium-bromide) assays combined with pharmacological analyses showed that H2O2 reduced native and genetically modified cell viability and APPwt-transfected cells were the most vulnerable. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and activated caspase-3 staining assessed by flow cytometry revealed a basally elevated apoptotic signal in APPwt-transfected cells. Reverse-transcription, real-time quantitative polymerase chain reaction (qPCR) and Western blotting showed that mRNA and protein basal ratios of apoptotic modulators Bax/Bcl-2 were also high in APPwt-transfected cells. GHB efficiently and dose-dependently rescued native and genetically modified cells from H2O2-induced death. Interestingly, GHB, which strongly decreased elevated basal levels of TUNEL-staining, activated caspase 3-labeling and Bax/Bcl-2 in APPwt-transfected cells, also counteracted H2O2-evoked increased apoptotic markers in native and genetically modified SH-SY5Y cells. Since GHB did not promote cell proliferation, anti-apoptotic action through the down-regulation of Bax/Bcl-2 ratios and/or caspase 3 activity appears as a critical mechanism involved in GHB-induced protection of SH-SY5Y cells against APPwt-overexpression- or H2O2-evoked death. Altogether, these results, providing multi-parametric evidence for the existence of neuroprotective action of GHB, also open interesting perspectives for the development of GHB analog-based strategies against neurodegeneration or nerve cell death. PMID:24456637

Wendt, G; Kemmel, V; Patte-Mensah, C; Uring-Lambert, B; Eckert, A; Schmitt, M J; Mensah-Nyagan, A G

2014-03-28

59

Gamma-hydroxybutyrate--a drug of abuse.  

PubMed

Gamma-hydroxybutyrate (GHB) is a drug of abuse that causes euphoria, anxiolysis, and hypnosis. The recent rise in the recreational intake of GHB, as well as its association with 'drug rape', has turned the attention to GHB in acute hospital settings. Acutely admitted GHB intoxicated patients may display various levels of sedation or coma, but may also show paradoxical agitation, combativeness, or self-injurious behaviors. The symptoms can be nonspecific and the definite diagnosis therefore normally relies on the detection of GHB in blood or body fluids, which is an analysis that may not be promptly available. As a basis for understanding the clinical features of GHB intoxication and abuse, we here review the pharmacological and neurophysiological knowledge about GHB, which stems from decades of clinical and basic GHB research. In addition, we discuss the latest discoveries in the quest for distinct GHB receptors in the brain, and their possible implications for future therapies of GHB abuse. PMID:16911342

Drasbek, K R; Christensen, J; Jensen, K

2006-09-01

60

IMPLICATIONS OF RESEARCH FOR TREATMENT: GHB  

Microsoft Academic Search

Gamma hydroxybutyrate (sodium hydroxybutyrate, sodium oxybutyrate, GHB) a naturally occurring fatty acid found in mammals, is a CNS depressant which has intoxicating effects and, at sufficiently high doses, anesthetic properties [1]. One of its precursors, gamma butyrolactone (GBL), is converted to GHB when swallowed. Another precursor is 1,4-butanediol (1,4-BD), which is a Class I health hazard and is an industrial

JANE C. MAXWELL; GULF COAST

61

The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol  

Microsoft Academic Search

INTRODUCTION: Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the

L. J. Schep; K. Knudsen; R. J. Slaughter; J. A. Vale; B. Megarbane

2012-01-01

62

Forensic toxicology findings in deaths involving gamma-hydroxybutyrate  

Microsoft Academic Search

Concentrations of the illicit drug gamma-hydroxybutyrate (GHB) were determined in femoral venous blood and urine obtained\\u000a at autopsy in a series of GHB-related deaths (N?=?49). The analysis of GHB was done by gas chromatography after conversion to gamma-butyrolactone and quantitation of the\\u000a latter with a flame ionization detector. The cutoff concentration of GHB in femoral blood or urine for reporting

Fredrik C. Kugelberg; Anita Holmgren; Arne Eklund; Alan Wayne Jones

2010-01-01

63

Enhancement of microcrystalline identification of gamma-hydroxybutyrate.  

PubMed

An enhancement of the microcrystalline test for the detection of gamma-hydroxybutyrate (GHB) is described. The original test used a silver/copper reagent which consisted of 0.1 g of silver nitrate and 0.1 g of copper nitrate in 10 mL water. The enhanced test utilizes lanthanum nitrate in place of copper nitrate. A detection limit of 0.5 mg/mL was achieved and the visual discrimination was improved because of larger sized crystals. Transient crystals were observed between 0.1 and 0.4 mg/mL. Silver nitrate alone appeared to be suitable for GHB detection but was not specific as other hydroxyl acids, such as glycolic acid, produced a similar crystal pattern. Tests conducted on chemical precursors of GHB and substances with similar biological activity highlight the specificity of the enhanced test. The reagent is therefore selective and sensitive for GHB in aqueous solutions. However, in beverage testing, crystal formation appeared to be inhibited for some drinks. Citric acid was identified as a possible interference depending on its concentration relative to GHB. PMID:18279251

Elie, Mathieu P; Baron, Mark G; Birkett, Jason W

2008-01-01

64

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

65

Sucrose intake: Increase in non-stressed rats and reduction in chronically stressed rats are both prevented by the gamma-hydroxybutyrate (GHB) analogue, GET73  

Microsoft Academic Search

It has been previously shown that the gamma-hydroxybutyrate analogue N-(4-trifluoromethylbenzyl)-4-methoxybutanamide (GET73) inhibits consumption and reinforcing effect of palatable food, in rats, at doses that have no detrimental effect on open-field behaviour. Here we show that GET73 is also able to prevent both the development of preference for a sucrose solution in non-stressed rats, and the reduction of preference for a

Raffaella Tacchi; Anna Ferrari; Antonella Loche; Alfio Bertolini

2008-01-01

66

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

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

Analogues of gamma-hydroxybutyric acid. Synthesis and binding studies.  

PubMed

Substituted 4-hydroxybutyric (GHB) or trans-4-hydroxycrotonic acids (T-HCA) and structurally related compounds were synthesized and submitted to [3H]GHB binding. Structure-activity relationships studies highlighted for [3H]GHB binding (a) the necessity of a nonlactonic, relatively extended conformation of the gamma-hydroxybutyric chain, (b) the existence of some bulk tolerance in the vicinity of the hydroxyl group, and (c) the high sensitivity toward isosteric replacements of the carboxyl or the hydroxyl groups. T-HCA has been recently identified as a naturally occurring substance in the central nervous system (CNS) and shows a better affinity than GHB. Our findings are in favor of the presence in the CNS of specific GHB binding sites, which are different from the GABA and the picrotoxin binding sites, and for which T-HCA may be an endogenous ligand. PMID:3361576

Bourguignon, J J; Schoenfelder, A; Schmitt, M; Wermuth, C G; Hechler, V; Charlier, B; Maitre, M

1988-05-01

70

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

71

A tertiary alcohol analog of gamma-hydroxybutyric acid as a specific gamma-hydroxybutyric acid receptor ligand.  

PubMed

gamma-Hydroxybutyric acid (GHB) shows great promise as a treatment for sleeping disorders but is also increasingly abused. The exact mechanism of action of GHB is yet to be delineated, but it is known to interact with specific GHB binding sites or receptors, to act as a weak agonist at GABA(B) receptors, and that GHB undergoes metabolism to GABA. In drug discrimination studies, GABA(B) agonists, and to a lesser extent GABA(A)-positive modulators, substitute for GHB. To delineate the relative contributions of each receptor system to the profile of GHB, tertiary alcohol analogs of GHB and its homolog, 5-hydroxypentanoic acid (UMB58), were prepared (UMB68 and UMB75, respectively), which cannot be metabolized to GABA-active compounds. Binding studies against [(3)H]NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid] showed that the tertiary alcohol analog of GHB (UMB68) has similar affinity to GHB, with the longer chain analogs possessing lower affinity. Against [(3)H]GABA, UMB68 showed no affinity (IC(50) >100 microM) at GABA(A) or GABA(B) receptors. In vivo studies showed that, at behaviorally active doses, rats trained to discriminate GHB did not recognize the novel ligands as GHB. Thus, UMB68 is a selective GHB receptor ligand in binding assays, will not undergo metabolism to GABA-active compounds, and does not show the same effects as GHB in vivo. These data suggest that, although UMB68 binds to the GHB receptor, it does not have the observed GABA receptor-mediated effects of GHB in vivo and could provide a novel tool for studying the pharmacology of the GHB receptor in the absence of complicating GABAergic effects. PMID:12606613

Wu, Huifang; Zink, Nick; Carter, Lawrence P; Mehta, Ashok K; Hernandez, R Jason; Ticku, Maharaj K; Lamb, Richard; France, Charles P; Coop, Andrew

2003-05-01

72

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

73

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

74

Ethers of 3-hydroxyphenylacetic acid as selective gamma-hydroxybutyric acid receptor ligands.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a drug of abuse, a therapeutic, and purportedly a neurotransmitter with a complex mechanism of action in vivo due to direct actions at GABA(B) as well as GHB receptors and because of its metabolism to GABA. Herein, we describe 3-ethers of 3-hydroxyphenylacetic acid, which have relatively high affinity at GHB sites, no significant affinity at GABA receptors, and would not be expected to be rapidly metabolized to GABAergic ligands. The selectivity of these compounds (UMB108, UMB109, and UMB119) could prove to be useful for studying the biology of GHB receptors, free from GABAergic effects. PMID:15927467

Chen, Weibin; Wu, Huifang; Hernandez, R Jason; Mehta, Ashok K; Ticku, Maharaj K; France, Charles P; Coop, Andrew

2005-07-01

75

Design, synthesis, and in vitro pharmacology of new radiolabeled gamma-hydroxybutyric acid analogues including photolabile analogues with irreversible binding to the high-affinity gamma-hydroxybutyric acid binding sites.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report the design and synthesis of the first (125)I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites. PMID:20715819

Sabbatini, Paola; Wellendorph, Petrine; Høg, Signe; Pedersen, Martin H F; Bräuner-Osborne, Hans; Martiny, Lars; Frølund, Bente; Clausen, Rasmus P

2010-09-01

76

Gamma-hydroxybutyric acid decreases thalamic sensory excitatory postsynaptic potentials by an action on presynaptic GABA B receptors  

Microsoft Academic Search

The effect of gamma-hydroxybutyric acid (GHB) on the excitatory postsynaptic potential (EPSP) evoked in thalamocortical neurones of the rat dorsal lateral geniculate nucleus and ventrobasal thalamus was investigated in vitro. GHB (0.1–5 mM) dose-dependently and reversibly decreased (36–78%) the amplitude of the sensory EPSP. This effect of GHB was blocked by the GABAB receptor antagonist CGP 35348 (1 mM). NCS

Zsuzsa Emri; Kàroly Antal; Vincenzo Crunelli

1996-01-01

77

GHB, GBL and 1,4-BD addiction.  

PubMed

A growing body of evidence shows that gamma-hydroxybutyric acid (GHB) is an addictive substance. Its precursors gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD) show the same properties and may pose even more risks due to different pharmacokinetics. There are indications that problematic GHB use is increasing in the European Union. This review investigates the existing literature on the neurochemistry of GHB and its precursors, their acute toxicity, addiction potential and withdrawal, the proposed molecular mechanism underlying addiction and the treatment of withdrawal and addiction. Current evidence shows that GHB and its precursors are highly addictive, both in humans and animals, probably through a GABAB receptor related mechanism. Severity of withdrawal symptoms can be considered as a medical emergency. Recent studies suggest that benzodiazepines are not very effective, showing a high treatment resistance, whereas detoxification with pharmaceutical GHB proved to be successful. However, relapse in GHB use is frequent and more research is warranted on relapse prevention. This might aid medical practitioners in the field and improve general understanding of the severity of addiction to GHB, GBL and 1,4-BD. PMID:24001290

Brunt, Tibor M; van Amsterdam, Jan G C; van den Brink, Wim

2014-01-01

78

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

79

Validation of high-affinity binding sites for succinic acid through distinguishable binding of gamma-hydroxybutyric acid receptor-specific NCS 382 antipodes.  

PubMed

Gamma-hydroxybutyric acid (GHB) binding to multiple sites for the tricarboxylic acid cycle intermediate succinic acid (SUC) has been disclosed recently. In order to better characterize these targets, distinguishable binding of GHB receptor-specific NCS 382 antipodes to [(3)H]-SUC or [(3)H]-GHB labelled sites in rat brain synaptic membranes was explored. Eutomer binding parameters suggest identity of the high-affinity target for SUC with a synaptic GHB receptor subtype. PMID:18945616

Molnár, Tünde; Visy, Júlia; Simon, Agnes; Moldvai, István; Temesvári-Major, Eszter; Dörnyei, Gábor; Fekete, Erzsébet Kútiné; Kardos, Julianna

2008-12-01

80

[GHB--dangerous, addictive and uncontrollable "party drug"].  

PubMed

This report reviews the pharmacology, toxicity and abuse pattern of gamma-hydroxybutyrate (GHB). The legislative changes pertaining to this substance are also addressed. Examples of abuse, driving under the influence and fatal intoxication are given. It is concluded that GHB is widely abused, particularly among the younger generation, and that further cases of severe intoxication are likely to occur as long as the substance is easily available from countless sources, including via the Internet. Despite the classification of GHB as a narcotic in Sweden and several other countries, continued problems are expected since the precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD) are widely--and legally--available. PMID:11602959

Persson, S A; Eriksson, A; Hallgren, N; Eklund, A; Berkowicz, A; Druid, H

2001-09-19

81

Kinetic characterisation and solubilisation of gamma-hydroxybutyrate receptors from rat brain.  

PubMed

The solubilisation of the gamma-hydroxybutyrate (GHB) receptors from rat brain membranes was undertaken as the first step for their molecular characterisation and purification. Treatment of crude brain membranes with high concentrations of NaCl and Triton X-100 resulted in solubilisation of proteins which retain specific GHB binding activity. Ionic detergents do not solubilise and/or inactivate the receptors. Measurements of kinetic parameters of GHB binding showed that the solubilised receptor, in the presence of detergent, exhibited a reduction of affinity for GHB and its endogenous brain analogue trans-4-hydroxycrotonate (T-HCA). The membrane protein extract, submitted to chromatography by gel filtration, showed a single peak of protein with [3H]GHB binding activity. Association and dissociation constants of GHB for its membrane binding site were in accordance with the Kd determined by the Scatchard method. PMID:8734901

Cash, C D; Hechler, V; Mersel, M; Maitre, M

1996-05-01

82

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

83

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

84

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

85

Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice.  

PubMed

gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high-affinity [3H]GHB-binding sites coupled to G-proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)-/- mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB-binding sites in brains of GABAB(1)-/- and wild-type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene acetic acid (NCS-382) appear unchanged in GABAB(1)-/- compared with wild-type mice, demonstrating that GHB- are distinct from GABAB-binding sites. In the presence of the GABAB receptor positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol GHB induced functional GTPgamma[35S] responses in brain membrane preparations from wild-type but not GABAB(1)-/- mice. The GTPgamma[35S] responses in wild-type mice were blocked by the GABAB antagonist [3-[[1-(S)-(3,4dichlorophenyl)ethyl]amino]-2-(S)-hydroxy-propyl]-cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS-382. Altogether, these findings suggest that the GHB-induced GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta-wave induction seen in wild-type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB-binding sites remain elusive. PMID:14656321

Kaupmann, Klemens; Cryan, John F; Wellendorph, Petrine; Mombereau, Cedric; Sansig, Gilles; Klebs, Klaus; Schmutz, Markus; Froestl, Wolfgang; van der Putten, Herman; Mosbacher, Johannes; Bräuner-Osborne, Hans; Waldmeier, Peter; Bettler, Bernhard

2003-11-01

86

Validation of high-affinity binding sites for succinic acid through distinguishable binding of gamma-hydroxybutyric acid receptor-specific NCS 382 antipodes  

Microsoft Academic Search

Gamma-hydroxybutyric acid (GHB) binding to multiple sites for the tricarboxylic acid cycle intermediate succinic acid (SUC) has been disclosed recently. In order to better characterize these targets, distinguishable binding of GHB receptor-specific NCS 382 antipodes to [3H]-SUC or [3H]-GHB labelled sites in rat brain synaptic membranes was explored. Eutomer binding parameters suggest identity of the high-affinity target for SUC with

Tünde Molnár; Júlia Visy; Ágnes Simon; István Moldvai; Eszter Temesvári-Major; Gábor Dörnyei; Erzsébet Kútiné Fekete; Julianna Kardos

2008-01-01

87

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

88

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

89

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

90

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

91

Effects of Gamma Hydroxybutyric Acid on Inhibition and Excitation in Rat Neocortex  

PubMed Central

The mechanism by which the sedative and amnestic recreational drug gamma hydroxybutyric acid (GHB) acts is controversial. Some studies indicate that it acts at its unique receptor, while others demonstrate effects mediated through the GABAB receptor. We examined the effect of GHB on evoked GABAA receptor mediated mono- and polysynaptic IPSCs as well as on NMDA and AMPA mediated EPSCs in layers II/III pyramidal cells of the frontal cortex of rat brain. One millimolar (mM) GHB suppressed monosynaptic IPSCs by 20%, whereas polysynaptic IPSCs were reduced by 56%. GHB (1mM) also produced a significant suppression of NMDA-mediated EPSCs by 53% compared to 27% suppression of AMPA-mediated EPSCs. All effects of GHB on IPSCs and EPSCs were reversed by the specific GABAB antagonist CGP62349, but not by the GHB receptor antagonist NCS 382. Consistent with a presynaptic site of action, GHB reduced the frequency but not the amplitude of AMPA receptor mediated mEPSCs and had no effect on postsynaptic currents evoked by direct application of NMDA. Finally, even though GHB appeared to be acting at presynaptic GABAB receptors, GHB and the GABAB agonist baclofen appeared to have opposite potencies for depression of NMDA vs AMPA mediated EPSCs. GHB showed a preference for depressing NMDA responses while baclofen more potently suppressed AMPA responses. The suppression of NMDA more than AMPA responses by GHB at intoxicating doses may make it attractive as a recreational drug and may explain why GHB is abused and baclofen is not. PMID:17904295

Li, Qiang; Kuhn, Cynthia M.; Wilson, Wilkie A.; Lewis, Darrell V.

2008-01-01

92

Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate.  

PubMed

The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are chemical substances used recreationally in social settings. Use is increasingly frequent among young people, especially during all-night dance parties. All four agents have been classified as controlled substances. MDMA ("ecstasy") is available as a tablet, a capsule, and a powder; formulations may contain many adulterants. MDMA increases the release of neurotransmitters. The desired effects are euphoria, a feeling of intimacy, altered visual perception, enhanced libido, and increased energy. The most common adverse effects are agitation, anxiety, tachycardia, and hypertension. More serious adverse effects include arrhythmias, hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At higher doses, the drug can cause lack of muscle control and loss of consciousness. Other adverse effects are hypotension, dizziness, confusion, and occasional aggression. Ketamine is a dissociative anesthetic used primarily in veterinary practice. It may be injected, swallowed, snorted, or smoked. Like phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel. Analgesic effects occur at lower doses and amnestic effects at higher doses. Cardiovascular and respiratory toxicity may occur, as well as confusion, hostility, and delirium. GHB, a naturally occurring fatty acid derivative of gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma, and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual assault. Supportive care is indicated for most cases of club drug intoxication. The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB, particularly by young people in social settings such as clubs, should put health care professionals on guard to recognize and manage serious reactions. PMID:12063892

Smith, Kelly M; Larive, Lisa L; Romanelli, Frank

2002-06-01

93

Contribution of GABA(A) and GABA(B) receptors to the discriminative stimulus produced by gamma-hydroxybutyric acid.  

PubMed

The present study examined the involvement of GABA(A) and GABA(B) 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 GABA(B) agonist, baclofen, substituted completely for both training doses of GHB; its potency to substitute for GHB increased moderately as the training dose of GHB was increased. The positive GABA(A) modulator, diazepam, substituted partially for 300 mg/kg GHB, but failed to elicit GHB-appropriate responding in rats trained with the higher GHB dose. Finally, the GABA(B) antagonist, CGP 35348, completely blocked the discriminative stimulus effects of the high training dose of GHB, but only partially antagonized the effects of the low training dose. These results suggest that (a) GHB produces a compound stimulus, and (b) both GABA(B)- and GABA(A)-mediated cues are prominent components of this compound stimulus; the contribution of each component, however, appears to vary as the training dose of GHB is increased. PMID:10515314

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

1999-10-01

94

Gamma-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches.  

PubMed

Previous results have shown that stimulation of the gamma-hydroxybutyrate (GHB) receptor modulates Ca2+ channel permeability in cell cultures. In order to confirm this result, we investigated the consequence of GHB receptor stimulation on nitric oxide synthase (NOS) activity in rat brain cortical punches rich in GHB receptors. The stimulation of these receptors by increasing amounts of GHB induced a progressive decrease in NOS activity. However, for GHB doses above 10 microM, this reduction was progressively lost, either after receptor desensitization or after stimulation of an additional class of GHB receptor having lower affinity. The effect of GHB was reproduced by the GHB receptor agonist NCS-356 and blocked by the GHB receptor antagonist NCS-382. The GHB-induced effect on Ca2+ movement was additive to those produced by veratrine, indicating that GHB modulates a specific Ca2+ conductance, which explains the modification in NOS activity and the increase in cyclic guanosine monophosphate levels previously reported. PMID:10571257

Cash, C D; Gobaille, S; Kemmel, V; Andriamampandry, C; Maitre, M

1999-12-01

95

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. PMID:1389947

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

1992-01-01

96

GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid  

PubMed Central

The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABAB receptors (GABABRs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABAA and GABABRs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABABR agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABABRs and mediated by Ca2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB. PMID:25225100

Gould, Timothy; Chen, Lixin; Emri, Zsuzsa; Pirttimaki, Tiina; Errington, Adam C.; Crunelli, Vincenzo; Parri, H. Rheinallt

2014-01-01

97

GABA(B) receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid.  

PubMed

The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABA(B) receptors (GABA(B)Rs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABA(A) and GABA(B)Rs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABA(B)R agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca(2+) in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABA(B)Rs and mediated by Ca(2+) release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB. PMID:25225100

Gould, Timothy; Chen, Lixin; Emri, Zsuzsa; Pirttimaki, Tiina; Errington, Adam C; Crunelli, Vincenzo; Parri, H Rheinallt

2014-10-19

98

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

99

In vitro production of gamma-hydroxybutyrate in antemortem urine samples.  

PubMed

The in vitro production of gamma-hydroxybutyrate (GHB) in antemortem urine samples was demonstrated over an eight-month period. Positive chemical ionization-gas chromatography-mass spectrometry (PCI-GC-MS) was used to detect trace amounts of GHB produced in vitro under certain storage conditions. Freshly prepared drug-free human urine was stored at 21, 4, and -20 degrees C in the presence of preservative. Although artifactual production of GHB occurred more rapidly at elevated temperatures, the presence of an antimicrobial agent (sodium azide) in the drug-free urine control did not impede GHB production. The preliminary data suggest that although in vitro production was demonstrated, the elevations in concentration were nominal and less than 5 mg/L for all conditions tested over the 244-day period. These preliminary data suggest that urine samples should be preserved and stored at -20 degrees C to minimize artifactual GHB production. Most importantly, conditions of storage and preservative should also be taken into consideration when interpreting GHB results that are close to the administrative cutoff. In order to establish the distribution of GHB concentrations in routine forensic case samples, a series of 100 antemortem urine samples, in which GHB was not suspected, was analyzed. Samples were preserved with sodium fluoride (1%) and had been stored for up to one year at room temperature. Although concentrations as high as 7 mg/L were measured in some samples, the mean and median concentrations were 1.8 mg/L and 1.6 mg/L, respectively. Even following storage at room temperature for an extended period, more than 95% of the urine samples contained less than 5 mg/L GHB and 100% contained less than 10 mg/L. An administrative cutoff of 10 mg/L in antemortem urine was used for routine antemortem casework. PMID:12501915

Kerrigan, Sarah

2002-01-01

100

Development and characterization of an enzymatic method for the rapid determination of gamma hydroxybutyric acid.  

PubMed

Gamma hydroxybutyric acid (GHB) is a regulated therapeutic drug, which naturally occurs in mammalian brain tissues as an intermediate of the GABA (gamma aminobutyric acid) neurotransmitter metabolism. The increasing misuse of GHB as a narcotic or abusing drug in recent years calls for the development of a simple and rapid screening method as an alternative to the currently available, technically demanding diagnostic methods. We have developed a rapid enzymatic assay based on the GHB dehydrogenase of Ralstonia eutropha. The enzyme is expressed as a recombinant protein in Escherichia coli and characterized in terms of reaction mechanism and kinetic parameters for the catalysis of conversion of GHB into succinic semialdehyde (SSA). The concomitant NADH production enables spectrophotometric monitoring of the reaction and the quantification of GHB in physiological fluids depending on initial velocities. We have tested a panel of twelve serum and urine samples containing GHB concentrations from 0.0 to 2.1 mmol/L. GHB dehydrogenase activity obeys a non classical bi bi ping pong mechanism exhibiting substrate inhibition by NAD+. With an optimal NAD+ concentration of 3.7 mmol/L in the reaction, the enzyme yields a K(M) of 1.0 mmol/L for GHB and a Vmax of 3.37 mmol/min/mg. The assay shows a linear standard curve from 0.1 to at least 1 mmol/L of GHB. Spiking experiments result in mean recoveries of 92% for urine and 114% for serum, respectively. The comparison to an ion chromatographic reference method exhibits a mean difference of 10% divergence from the target values in urine and 9% in serum, respectively. PMID:21197843

Sciotti, Michel A; Hasan, Lara; Scholer, Andre; Jermann, Thomas M; Weber, Jakob M; Gygax, Daniel

2010-01-01

101

Multi-faceted aspects of gamma-hydroxybutyric acid: a neurotransmitter, therapeutic agent and drug of abuse.  

PubMed

Gamma hydroxybutyric acid (GHB), an endogenous constituent of the mammalian brain, acts as i) a neurotransmitter or neuromodulator, ii) a medicine used for the treatment of narcolepsy and alcoholism, and iii) a drug illicitly used for its psychotropic effects. GHB is thought to act as a specific GHB receptor agonist as well as a weak gamma-aminobutyric acid type B (GABA(B)) receptor agonist. Here, I review the in vivo and in vitro pharmacological properties of GHB and its interaction with GHB and GABA(B) receptors. When exogenously administered, GHB is rapidly absorbed, crosses the blood-brain barrier, penetrates into the brain and exerts a number of pharmacological effects including anxiolysis, sedation/hypnosis and anesthesia. Due to its effects on the central nervous system, GHB has been used for the treatment of narcolepsy and as an anesthetic adjuvant. More recently, a role for GHB in the pharmacotherapy of alcohol dependence has been described. In this review, I also focus on the abuse liability and reinforcing properties of GHB in humans and laboratory animals. PMID:18855733

Castelli, M Paola

2008-10-01

102

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

103

21 CFR 1304.26 - Additional recordkeeping requirements applicable to drug products containing gamma-hydroxybutyric...  

Code of Federal Regulations, 2010 CFR

...requirements applicable to drug products containing gamma-hydroxybutyric acid. 1304.26 Section...requirements applicable to drug products containing gamma-hydroxybutyric acid. In addition...1304.22, practitioners dispensing gamma-hydroxybutyric acid that is...

2010-04-01

104

3-chloropropanoic acid (UMB66): a ligand for the gamma-hydroxybutyric acid receptor lacking a 4-hydroxyl group.  

PubMed

Gamma-Hydroxybutyric acid (GHB) has gained in notoriety in recent years due to its association with sexual assaults. GHB is an endogenous ligand for GHB receptors, but its complete pharmacological mechanism of action in vivo remains unclear due to apparent GABAergic components. It has been proposed that the hydroxyl group in the 4-position acts as a hydrogen bond donor to the GHB receptor. Herein we show that 3-chloropropanoic acid possesses significant affinity for the GHB receptor, has no affinity for GABA receptors, and cannot undergo metabolism to GABAergic compounds. UMB66 is thus a selective agent for the study of GHB in vivo. These results, in combination with data from quantum mechanical calculations, suggest that the hydroxyl group of GHB actually acts as a hydrogen bond acceptor in contrast to the currently accepted model. This finding is anticipated to facilitate the rational design of novel agents with selectivity for GHB receptors that may be used to elucidate the mechanism of action of this common drug of abuse. PMID:15028257

Macias, Alba T; Hernandez, R Jason; Mehta, Ashok K; MacKerell, Alexander D; Ticku, Maharaj K; Coop, Andrew

2004-04-01

105

gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide.  

PubMed

gamma-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB receptor(s), although with low or very low affinity (IC50 = 150-796 microM). In addition, several reports argue for a role of GHB via GABAB receptors in both in vivo and in vitro electro-physiological experiments. In the present study, we demonstrate that the inhibition of GHB's conversion into GABA by rat brain membranes blocks the ability of GHB to interfere with GABAB binding. In particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding could explain the misinterpretation of in vitro or in vivo experiments where GHB possesses a GABA-like effect. But in addition, it is postulated that the normal metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the administration of valproate or ethosuximide. PMID:9152382

Hechler, V; Ratomponirina, C; Maitre, M

1997-05-01

106

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

107

Determination of gamma-hydroxybutyric acid in dried blood spots using a simple GC-MS method with direct “on spot” derivatization  

Microsoft Academic Search

The objective of this study was the development of an accurate and sensitive method for the determination of gamma-hydroxybutyric\\u000a acid (GHB) in dried whole blood samples using a GC-MS method. The complete procedure was optimized, with special attention\\u000a on the sample pretreatment, and validated. Therefore, dried blood spots of only 50 ?l were prepared and, after the addition\\u000a of internal standard

Ann-Sofie M. E. Ingels; Willy E. Lambert; Christophe P. Stove

2010-01-01

108

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

109

Stability of plasma gamma-hydroxybutyrate determined by gas chromatography-positive ion chemical ionization-mass spectrometry.  

PubMed

An effective method for the determination of gamma-hydroxybutyric acid (GHB) in human plasma is described that utilizes a simple liquid-liquid extraction procedure and gas chromatography-positive ion chemical ionization-mass spectrometry (GC-PCI-MS). The method has been used to study the stability of plasma GHB under several storage conditions. Following the extraction with acetonitrile, GHB and deuterated GHB (GHB-d(6)) were derivatized with N,O-bis[trimethylsilyl] trifluoroacetamide (BSFTA). After the separation on a capillary GC column, the derivatives were ionized with ammonia reagent gas and analyzed by MS. The lower limit of quantitation in 100 microL of plasma was 2.5 microg/mL, over a range from 2.5 to 250 microg/mL. The coefficients of variation did not exceed 3.9% and the mean measured concentrations did not deviate more than 8% from the target for both intra- and interassay precision and accuracy. Plasma GHB was found to be stable at -20 degrees C for up to 9 months, at room temperature for 48 h, and after 3 freeze/thaw cycles. It was also found to be stable in processed samples stored at room temperature for 5 days and for 15 days at -20 degrees C. PMID:14606997

Chen, Meng; Andrenyak, David M; Moody, David E; Foltz, Rodger L

2003-10-01

110

Driving under the influence of GHB?  

PubMed

A driver was found asleep behind the steering wheel of his car, and the vehicle was at rest in a traffic lane with the engine running. His manifestations included horizontal and vertical gaze nystagmus, muscle flaccidity, and severe ataxia. He admitted ingesting a white powder, which he identified as an amino acid, about 1 hour prior to discovery by police. A urine specimen collected approximately 1 hour after the traffic stop contained 1975 mg/L of gamma-hydroxybutyrate (GHB). We tentatively conclude that GHB may cause impairment of the psychomotor skills required for safe operation of a motor vehicle. PMID:7823545

Stephens, B G; Baselt, R C

1994-10-01

111

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

112

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. PMID:20181164

2009-01-01

113

Metabolism of gamma hydroxybutyrate in human hepatoma HepG2 cells by the aldo-keto reductase AKR1A1.  

PubMed

Gamma hydroxybutyrate (GHB) is a recreational and date-rape drug, for which the detection following ingestion is hampered by rapid metabolism and its endogenous presence. GHB catabolism occurs mainly by its oxidation to succinic semialdehyde (SSA), which converts to succinate and enters the tricarboxylic acid cycle. A high Km aldehyde reductase has previously been reported to catalyse the NADP-dependent oxidation of GHB at high concentrations. It is assumed that this enzyme is identical to the aldo-keto reductase AKR1A1, but its role in GHB oxidation has not been fully evaluated. In this study, the extent of AKR1A1 in GHB metabolism has been determined in HepG2 cells using RNA-interference technology. The gene encoding AKR1A1 was targeted by siRNA. Results demonstrate a successful knock-down of the AKR1A1 gene with 92% reduction in total mRNA and 93% reduction in protein expression. Demolishing AKR1A1 expression in HepG2 cells leads to significant 82% decrease in NADP-dependent GHB-dehydrogenase activity at high concentration (10mM) of GHB. Moreover, when exposing the cells to 50 ?M of GHB for 24h, and measuring intracellular and extracellular GHB levels by GC/MS, a significant two-fold increase was observed on GHB intracellular level in silenced cells. In contrast, measuring SSA-reductase activity in silenced cells indicated that AKR1A1 is not involved in endogenous GHB production. These findings describe a pathway for GHB metabolism in the liver which should be useful in GHB exposure cases, and will enable a better understanding of the enzymes participating in its metabolism at natural and overexposed levels. PMID:25256836

Alzeer, Samar; Ellis, Elizabeth M

2014-12-01

114

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. PMID:23742746

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

2013-01-01

115

Do capillary dried blood spot concentrations of gamma-hydroxybutyric acid mirror those in venous blood? A comparative study.  

PubMed

Gamma-hydroxybutyric acid (GHB) is a well-known illicit club and date-rape drug. Dried blood spot (DBS) sampling is a promising alternative for classical venous sampling in cases of (suspected) GHB intoxication since it allows rapid sampling, which is of interest for the extensively metabolized GHB. However, there is limited data if -and how- capillary DBS concentrations correlate with venous concentrations. We conducted a comparative study in 50 patients with suspected GHB intoxication, to determine and to correlate GHB concentrations in venous DBS (vDBS) and capillary DBS (cDBS). This is the first study that evaluates in a large cohort the correlation between capillary and venous concentrations of an illicit drug in real-life samples. Of the 50 paired samples, 7 were excluded: the vDBS concentration was below the LLOQ of 2?µg/mL in 3 cases and 4 samples were excluded after visual inspection of the DBS. Bland-Altman analysis revealed a mean % difference of -2.8% between cDBS and vDBS concentrations, with the zero value included in the 95% confidence interval of the mean difference in GHB concentration. A paired sample t-test confirmed this observation (p?=?0.17). Also the requirement for incurred sample reproducibility was fulfilled: for more than two-thirds of the samples the concentrations obtained in cDBS and those in vDBS were within 20% of their mean. Since equivalent concentrations were observed in cDBS and vDBS, blood obtained by fingerprick can be considered a valid alternative for venous blood for GHB determination. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25565078

Sadones, Nele; Archer, John R H; Ingels, Ann-Sofie M E; Dargan, Paul I; Wood, David M; Wood, Michelle; Neels, Hugo; Lambert, Willy E; Stove, Christophe P

2015-04-01

116

The ontogeny of [3H]gamma-hydroxybutyrate and [3H]GABAB binding sites: relation to the development of experimental absence seizures.  

PubMed

gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound which has the ability to induce generalized absence seizures when given to animals. There is growing evidence that both gamma-aminobutyric acid (GABA)B- and GHB-mediated mechanisms are involved in the pathogenesis of this phenomenon. Because of the fact that absence seizures are a disorder of children the ontogeny of [3H]GHB and [3H]GABAB binding and the developmental appearance of absence seizures in the GHB model of absence was ascertained and compared in developing rats. [3H]GABAB binding was present within the first 3 days of postnatal life and rose to levels which exceeded those found in adults, peaking between the 3rd and 5th postnatal week. [3H]GHB binding on the other hand did not appear until postnatal day 17 when it was detectable in the CA1 region of the hippocampus. There was a steady increase in [3H]GHB binding until adult levels were reached by postnatal day 40. Comparison of [3H]GABAB and [3H]GHB binding revealed that both sites were common to layer I-III of cortex, but otherwise differed in their regional distribution. There was an absolute concordance of the ontogeny of GHB-induced absence seizures with the developmental appearance of [3H]GHB binding in the superficial laminae of cortex; both appeared at postnatal day 18. These data support the hypotheses that the [3H]GHB and [3H]GABAB binding sites are separate from one another and suggest that maturational events in thalamus and cortex in the 3rd postnatal week are involved in the expression of GHB-induced absence seizures. PMID:7820656

Snead, O C

1994-10-01

117

Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens.  

PubMed

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) 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 Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca(2+) transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that Ca(2+) 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 Ca(2+) signal remained in mice lacking GABA(B) 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 GABA(B) 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 Ca(2+) signaling in astrocytic networks. PMID:22180742

Molnár, Tünde; Héja, László; Emri, Zsuzsa; Simon, Agnes; Nyitrai, Gabriella; Pál, Ildikó; Kardos, Julianna

2011-01-01

118

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

119

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

120

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. PMID:25024938

Rousseau, Anne-Françoise; Bargues, Laurent; Bever, Hervé Le; Vest, Philippe; Cavalier, Etienne; Ledoux, Didier; Piérard, Gérald E.; Damas, Pierre

2014-01-01

121

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

122

Endogenous concentrations of GHB in postmortem blood from deaths unrelated to GHB use.  

PubMed

Gamma-hydroxybutyrate (GHB) is an endogenous compound, but its presence in postmortem blood presents a challenge when interpreting elevated levels as GHB is misused as a recreational drug and is also produced postmortem. A total of 387 postmortem cases (273 male and 114 female) submitted to the toxicology laboratory between 2010 and 2012 specifically requested the analysis of the ketoacidosis biomarker, beta-hydroxybutyrate (BHB). No reference to GHB use was identified in any of the case files; however, BHB and GHB are measured simultaneously using deuterated GHB as the internal standard (GHB-d6) within a calibration range of 5-500 mg/L. GHB was not detected or <10 mg/L in 18% of the cases (n = 68), between 10 and 50 mg/L in 73% of the cases (n = 283) and between 51 and 193 mg/L in 9% of the cases (n = 36). The manner of death was classified as accidental (n = 11), alcohol-related (n = 237), drug-related (n = 23), homicide (n = 1), natural (n = 91), suicide (n = 9), medical-related (n = 1) and undetermined (n = 14). Six cases had GHB concentrations in excess of 100 mg/L with advanced decomposition changes noted in five of these cases. Moderate-to-advanced decomposition was also noted in 50% (n = 15) of the cases with GHB concentrations in excess of 50 mg/L but <100 mg/L. Approximately one-third of the blood samples tested contained a preservative and although a higher proportion of these samples had GHB concentrations <10 mg/L or not detected (?30% preserved versus 11% unpreserved), there were still cases with GHB concentrations >51 mg/L (?6% preserved versus 11% unpreserved). This study highlights the danger of only using a cutoff to establish endogenous levels compared with exogenous use of GHB in postmortem blood. PMID:25217550

Korb, Ann-Sophie; Cooper, Gail

2014-10-01

123

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

124

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

125

Comparative profiles of sodium valproate and ethosuximide on electro-behavioural correlates in gamma-hydroxybutyrate and pentylenetetrazol induced absence seizures in rats.  

PubMed

Sodium valproate (VPA) and ethosuximide (ESM) were compared on behavioural and EEG changes in gamma-hydroxybutyrate (GHB) and pentylenetetrazole (PTZ) rat models of Absence Seizures (AS). Both GHB, 100 mg/kg i.p. and PTZ, 20 mg/kg i.p., produced repetitive episodes of staring and immobility with concomitant 6 to 9 Hz spike and wave discharges (SWDs) in the EEG. The parameters used for drug evaluation were the number and duration of SWDs/hour. Though the number of SWDs/hour produced by GHB and PTZ were not significantly different, the duration of SWDs was significantly longer in GHB treated rats (P < 0.001) VPA and ESM, at 200 mg/kg i.p., reduced SWD number and duration in GHB pretreated rats, whereas ESM, 50 mg/kg i.p., was four times more effective than VPA, 200 mg/kg i.p., in the PTZ model. Phenytoin (PHY) 20 and Carbamazepine (CBZ) 10 mg/kg i.p., worsened AS, a feature which has also been reported clinically. Both rat models of experimental AS can be used to defect potential anti-absence activity in new chemical entities. PMID:11214495

Kumaresan, S; David, J; Joseph, T

2000-10-01

126

Gamma-hydroxybutyrate, gamma-butyrolactone, and 1,4-butanediol: a case report and review of the literature.  

PubMed

GHB, GBL, and 1,4-BD are prevalent drugs of abuse in the United States. Unfortunately, attempts to regulate GHB have been circumvented by clandestine trafficking through the Internet and marketing of "natural" chemical precursors . Despite repeated FDA warnings to the public about their dangers as well as recent federal scheduling of GHB and GBL, they remain accessible as "club drugs" on Internet websites, as natural dietary supplements in health food stores, and as illicit products manufactured at home or in clandestine laboratories. EDs and poison control centers nationwide will undoubtedly continue to manage GHB, GBL, and 1,4-BD toxicities. PMID:11138892

Shannon, M; Quang, L S

2000-12-01

127

Design, synthesis and pharmacological evaluation of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid with potential GABA-ergic activity. Part 6. Search for new anticonvulsant compounds.  

PubMed

In the recent study we have extended our investigations to the new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid (GHB). Among the obtained compounds N-benzylamide of alpha-(1,2,3,4-tetrahydroisoquinoline)-GHB (9) has demonstrated activity against maximal electroshock (MES) induced seizures in mice (at 100 mg/kg ip) and in rats (at 30 mg/kg, po dose). Lactone 8 and amide 9 have possessed a weak effect on [3H]-muscimol binding. Molecular modeling studies have revealed that anticonvulsant activity of the alpha-substituted amides of GHB might partially be explained by the orientation of the terminal benzylamide fragment. PMID:17665862

Malawska, Barbara; Kulig, Katarzyna; Gajda, Justyna; Szczeblewski, Dominik; Musia?, Anna; Wieckowski, Krzysztof; Maciag, Dorota; Stables, James P

2007-01-01

128

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. PMID:24350046

Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

2013-01-01

129

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

130

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

131

Use of GHB compounds by HIV-positive individuals.  

PubMed

Gamma hydroxybutyrate (GHB) has been used by body-builders to enhance performance and by young adults in rave parties. Warnings have been posted about its addictive potential. The use of these dietary compounds is currently banned by the Food and Drug Administration, but they are widely available through the Internet and in certain communities. The purpose of the study was to examine the use of these compounds by HIV-positive individuals and to investigate their knowledge of the addictive potential of GHB and its related dietary compounds. One hundred HIV-positive individuals from the UCSD outpatient HIV clinic responded to an anonymous survey that inquired about their knowledge, use, and effects produced by GHB containing dietary compounds. The most common reported dietary compound beside GHB was Growth Hormone Release Extract (GHRE). Fifty-two percent of individuals reported using at least one GHB containing dietary compound. Gay subjects reported the highest use of GHB compounds (76.9%; p < or = 0.001). The most common effect reported by users was increased energy (71%). Only 24% of the total responders knew about GHB's addictive potential. Among reported users of GHB containing compounds, fourteen (27%) knew about its addictive potential and nine (17%) knew that the compound is illegal. This study shows that HIV-positive gay individuals attending our clinic are using GHB compounds. Reported GHB users have limited knowledge about its addictive potential and serious adverse effects. More controlled studies are needed to evaluate long-term effects of dietary compounds containing GHB, especially among HIV-positive individuals who are actively receiving antiretroviral treatment. PMID:15204663

Camacho, Alvaro; Matthews, Scott C; Dimsdale, Joel E

2004-01-01

132

Blood, brain, and hair GHB concentrations following fatal ingestion.  

PubMed

Despite the increasing incidence of illicit use of gamma-hydroxybutyrate (GHB), little information is available documenting levels of the drug in GHB fatalities. We measured GHB levels in postmortem blood, brain and hair specimens from a suspected overdose case by gas chromatography/mass spectrometry (GC/MS) following solid phase extraction (SPE) and derivatization with bis(trimethyl-silyl) trifluoroacetamide (BSTFA). Examination found 330 microg/mL GHB in femoral blood and 221 ng/mg GHB in frontal cortex brain tissue, values higher than those typically reported in the literature. The hair shaft was negative for GHB whereas the plucked root bulbs with outer root sheath attached (2,221 ng/mg) and root bulbs after washing and removal of the outer root sheath (47 ng/mg) contained the drug. Our results are consistent with an acute single dose of GHB and, as the toxicology screen was negative for other drugs of abuse, emphasize the significant danger of this drug. PMID:11373018

Kalasinsky, K S; Dixon, M M; Schmunk, G A; Kish, S J

2001-05-01

133

Identification of GHB and morphine in hair in a case of drug-facilitated sexual assault  

Microsoft Academic Search

The authors present the case of a 24-year-old girl who was sexually assaulted after administration of gamma-hydroxybutyrate (GHB) and morphine. She had been living in an international college for foreign students for about 1 year and often complained of a general unhealthy feeling in the morning. At the end of the college period she returned to Italy and received at

Riccardo Rossi; Massimo Lancia; Cristiana Gambelunghe; Antonio Oliva; Nadia Fucci

2009-01-01

134

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

135

Gamma-hydroxybutyrate accumulation in Arabidopsis and tobacco plants is a general response to abiotic stress: putative regulation by redox balance and glyoxylate reductase isoforms.  

PubMed

Enzymes that reduce the aldehyde chemical grouping (i.e. H-C=O) to its corresponding alcohol are probably crucial in maintaining plant health during stress. Succinic semialdehyde (SSA) is a mitochondrially-generated intermediate in the metabolism of gamma-aminobutyrate (GABA), which accumulates in response to a variety of biotic and abiotic stresses. SSA can be reduced to gamma-hydroxybutyrate (GHB) under oxygen deficiency and high light conditions. Recent evidence indicates that distinct cytosolic and plastidial glyoxylate reductase isoforms from Arabidopsis (designated herein after as AtGR1 and AtGR2, respectively) catalyse the in vitro conversion of SSA to GHB, as well as glyoxylate to glycolate, via NADPH-dependent reactions. In the present report, the responses of GHB and related amino acids, as well as NADP(+) and NADPH, were monitored in leaves from Arabidopsis or tobacco plants subjected to various abiotic stresses (i.e. Arabidopsis during exposure to salinity, drought, submergence, cold, or heat; tobacco during exposure to, and recovery from, submergence). Time-course experiments revealed that GHB accumulated in both Arabidopsis and tobacco plants subjected to stress, and that this accumulation was generally accompanied by higher GABA and alanine levels, higher NADPH/NADP(+) ratio, and lower glutamate levels. Furthermore, the analysis of gene expression in Arabidopsis revealed that the relative abundance of GR1 (salinity, drought, submergence, cold, and heat) and GR2 (cold and heat) transcripts was enhanced by the stress tested. Thus, GHB accumulation in plants is a general response to abiotic stress and appears to be regulated by both biochemical and transcriptional processes. PMID:18495640

Allan, Wendy L; Simpson, Jeffrey P; Clark, Shawn M; Shelp, Barry J

2008-01-01

136

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

137

GHB depresses fast excitatory and inhibitory synaptic transmission via GABA(B) receptors in mouse neocortical neurons.  

PubMed

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 is not clear. Using whole-cell patch-clamp recordings, we studied the effects of GHB on neocortical neurons in brain slices from 12- to 33-day-old mice. We found that GHB depressed the frequency and amplitude of GABAergic and glutamatergic spontaneous inhibitory and excitatory post-synaptic currents (IPSCs and EPSCs) driven by presynaptic action potential firing, while the amplitude and frequency of Ca(2+) entry-independent miniature IPSCs were not affected. Using minimal stimulation, GHB reduced the probability of release at inhibitory synapses onto neocortical layer 2/3 pyramidal cells. Also, GHB directly hyperpolarized layer 2/3 non-pyramidal cells by up to 11 mV and inhibited action potential firing. All these effects of GHB were mediated via GABA(B)-receptors. In conclusion, GHB activates both pre- and postsynaptic GABA(B)-receptors in neocortical neurons participating in fast synaptic transmission, leading to a powerful depression of neocortical network activity. We propose that GABA(B)-receptor antagonists may be useful in the treatment of acute GHB intoxication. PMID:11313294

Jensen, K; Mody, I

2001-05-01

138

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

139

Comparative abuse liability of GHB and ethanol in humans  

PubMed Central

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/70kg), ethanol (12, 24, 48, 72, 96, and 120 g/70kg), 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, while 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, post-session measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, due most likely to the delayed aversive ethanol effects (e.g., headache). PMID:23421353

Johnson, Matthew W.; Griffiths, Roland R.

2013-01-01

140

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

141

gamma-Hydroxybutyrate binds to the synaptic site recognizing succinate monocarboxylate: a new hypothesis on astrocyte-neuron interaction via the protonation of succinate.  

PubMed

Succinate (SUC), a citrate (CIT) cycle intermediate, and carbenoxolone (CBX), a gap junction inhibitor, were shown to displace [3H]gamma-hydroxybutyrate ([3H]GHB), which is specifically bound to sites present in synaptic membrane subcellular fractions of the rat forebrain and the human nucleus accumbens. Elaboration on previous work revealed that acidic pH-induced specific binding of [3H]SUC occurs, and it has been shown to have a biphasic displacement profile distinguishing high-affinity (K(i,SUC) = 9.1 +/- 1.7 microM) and low-affinity (K(i,SUC) = 15 +/- 7 mM) binding. Both high- and low- affinity sites were characterized by the binding of GHB (K(i,GHB) = 3.9 +/- 0.5 microM and K(i,GHB) = 5.0 +/- 2.0 mM) and lactate (LAC; K(i,LAC) = 3.9 +/- 0.5 microM and K(i,LAC) = 7.7 +/- 0.9 mM). Ligands, including the hemiester ethyl-hemi-SUC, and the gap junction inhibitors flufenamate, CBX, and the GHB binding site-selective NCS-382 interacted with the high-affinity site (in microM: K(i,EHS) = 17 +/- 5, K(i,FFA) = 24 +/- 13, K(i,CBX) = 28 +/- 9, K(i,NCS-382) = 0.8 +/- 0.1 microM). Binding of the Na+,K+-ATPase inhibitor ouabain, the proton-coupled monocarboxylate transporter (MCT)-specific alpha-cyano-hydroxycinnamic acid (CHC), and CIT characterized the low-affinity SUC binding site (in mM: K(i,ouabain) = 0.13 +/- 0.05, K(i,CHC) = 0.32 +/- 0.07, K(i,CIT) = 0.79 +/- 0.20). All tested compounds inhibited [3H]SUC binding in the human nucleus accumbens and had K(i) values similar to those observed in the rat forebrain. The binding process can clearly be recognized as different from synaptic and mitochondrial uptake or astrocytic release of SUC, GHB, and/or CIT by its unique GHB selectivity. The transient decrease of extracellular SUC observed during epileptiform activity suggested that the function of the synaptic target recognizing protonated succinate monocarboxylate may vary under different (patho)physiological conditions. Furthermore, we put forward a hypothesis on the synaptic activity-regulated signaling between astrocytes and neurons via SUC protonation. PMID:18189322

Molnár, Tünde; Barabás, Péter; Héja, László; Fekete, Erzsébet Kútiné; Lasztóczi, Bálint; Szabó, Pál; Nyitrai, Gabriella; Simon-Trompler, Edit; Hajós, Ferenc; Palkovits, Miklós; Kardos, Julianna

2008-05-15

142

1H NMR analysis of GHB and GBL: further findings on the interconversion and a preliminary report on the analysis of GHB in serum and urine.  

PubMed

A 1H nuclear magnetic resonance (1H NMR) method for the determination of gamma-hydroxybutyric acid (GHB) and gamma-hydroxybutyrolactone (GBL) in human serum and urine using spiked samples has been developed. The method gives linear responses (correlation coefficients of 0.99 or greater) over the concentration range 0.01 mg/mL to 4.0 mg/mL in urine and 0.3 mg/mL to 2.0 mg/mL in serum. No sample pretreatment is required. Studies of the chemical interconversion of GBL and GHB showed hydrolysis of GBL to be rapid at pH 11.54, slower and less complete (30% hydrolysis) at pH 2.54 and slowest at pH 7.0, reaching 30% hydrolysis in about 40 days. No esterification of GHB was observed at any pH. PMID:15831000

Del Signore, Anthony G; McGregor, Michael; Cho, Bongsup P

2005-01-01

143

Gamma-hydroxybutyric acid endogenous production and post-mortem behaviour - the importance of different biological matrices, cut-off reference values, sample collection and storage conditions.  

PubMed

Gamma-Hydroxybutyric Acid (GHB) is an endogenous compound with a story of clinical use, since the 1960's. However, due to its secondary effects, it has become a controlled substance, entering the illicit market for recreational and "dance club scene" use, muscle enhancement purposes and drug-facilitated sexual assaults. Its endogenous context can bring some difficulties when interpreting, in a forensic context, the analytical values achieved in biological samples. This manuscript reviewed several crucial aspects related to GHB forensic toxicology evaluation, such as its post-mortem behaviour in biological samples; endogenous production values, whether in in vivo and in post-mortem samples; sampling and storage conditions (including stability tests); and cut-off reference values evaluation for different biological samples, such as whole blood, plasma, serum, urine, saliva, bile, vitreous humour and hair. This revision highlights the need of specific sampling care, storage conditions, and cut-off reference values interpretation in different biological samples, essential for proper practical application in forensic toxicology. PMID:25287794

Castro, André L; Dias, Mário; Reis, Flávio; Teixeira, Helena M

2014-10-01

144

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

145

Enzymatic assay for GHB determination in forensic matrices.  

PubMed

Current procedures for the determination of gamma-hydroxybutyric acid (GHB) require time-consuming extraction and derivatization steps before chromatographic detection, making a high-throughput alternative desirable. Bühlmann Laboratories offers an enzymatic assay for the quantitative determination of GHB in urine and serum. We report the adaptation of this photometric assay to the Thermo Scientific MGC-240 analyzer and its use in the determination of GHB in forensic matrices including urine, whole blood and vitreous humour. Most matrices require only a brief centrifugation before analysis, while blood requires an additional protein precipitation step. A variety of cases (sexual assaults, impaired drivers and death investigations) have been analyzed alongside the gas chromatography-mass spectrometry (GC-MS) reference method. Correlation with the GC-MS has been found to be acceptable, with no false negatives and few false positives, although postmortem samples appear more prone to testing false positive than do antemortem samples. Simple sample preparation and high throughput allow for a significant reduction in analysis time relative to chromatographic methods. This assay is used as a screening method in our laboratory, with a quantitative GC-MS method serving for the confirmation of positive results. To our knowledge, this represents the first evaluation of an enzymatic assay for GHB in a forensic context. PMID:22722059

Grenier, Vincent; Huppé, Geneviève; Lamarche, Martine; Mireault, Pascal

2012-09-01

146

1 H NMR Analysis of GHB and GBL: Further Findings on the Interconversion and a Preliminary Report on the Analysis of GHB in Serum and Urine  

Microsoft Academic Search

A 1H nuclear magnetic resonance (1H NMR) method for the determination of gamma-hydroxybutyric acid (GHB) and gamma- hydroxybutyrolactone (GBL) in human serum and urine using spiked samples has been developed. The method gives linear responses (correlation coefficients of 0.99 or greater) over the concentration range 0.01mg\\/mL to 4.0mg\\/mL in urine and 0.3mg\\/mL to 2.0mg\\/mL in serum. No sample pretreatment is

Anthony G. Del Signore; Michael McGregor; Bongsup P. Cho

2005-01-01

147

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

148

An Improved Method for the Analysis of GHB in Human Hair by Liquid Chromatography Tandem Mass Spectrometry†.  

PubMed

The abuse of gamma-hydroxybutyric acid (GHB) and its suspicion in cases of suspected drug-facilitated sexual assault is of keen interest to forensic toxicology laboratories. This paper reports an extraction, separation and detection procedure for GHB in hair utilizing a combination of liquid-liquid extraction and solid-phase extraction using ethyl acetate and Oasis Max(®) cartridge, respectively, after the hair sample was digested. Analysis was by LC-MS-MS using a gradient separation on an Acclaim(®) Trinity(TM) P1 column performing three multiple-reaction monitoring (MRM) transitions each for GHB and its internal standard. The procedure was validated over a range from 0.4 to 50 ng/mg with estimated limit of detection (LOD) of 0.33 and an administratively set limit of quantitation (LOQ) of 1.2 ng/mg. Twenty hair specimens collected from individuals with no known exposure to GHB were analyzed for matrix interferences and to establish initial background levels of GHB. A wide range of endogenous GHB levels were observed in these samples (from less than the LOQ to 4.4 ng/mg). The results suggest the need for additional studies to better establish the full range of endogenous GHB levels in hair and that extreme caution is required in interpreting GHB findings in hair samples. PMID:25433016

Jagerdeo, Eshwar; Montgomery, Madeline A; LeBeau, Marc A

2015-03-01

149

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

150

Novel radioiodinated {gamma}-hydroxybutyric acid analogues for radiolabeling and Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites.  

PubMed

?-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analog and characterized its binding in rat brain homogenate and slices. Our data show that [(125)I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([(125)I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d), 7 nM; B(max), 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs, but not by ?-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity derivative of the new GHB ligand, we have performed denaturing protein electrophoresis and detected one major protein band with an apparent mass of 50 kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites. The related photoaffinity linker [(125)I]4-hydroxy-4-[4-(2-azido-5-iodobenzyloxy)phenyl]butanoate can be used as a probe for isolation of the elusive GHB binding protein. PMID:20696866

Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola; Pedersen, Martin H F; Martiny, Lars; Knudsen, Gitte M; Frølund, Bente; Clausen, Rasmus P; Bräuner-Osborne, Hans

2010-11-01

151

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

152

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

153

Distribution of GHB in tissues and fluids following a fatal overdose.  

PubMed

Gamma-hydroxybutyrate (GHB) is encountered in biological specimens as an endogenous neuromodulator, recreational drug, or therapeutic agent. Clinically, the drug is useful for the treatment of cataplexy. Illicit doses are typically 2-4 g, and the onset of action is rapid, occurring 15-30 min following oral ingestion. Dose-dependent effects include drowsiness, euphoria, dizziness, vomiting, respiratory depression, coma, and death. GHB was isolated from biological samples using a simple liquid-liquid extraction. The trimethylsilyl derivative (GHB-di-TMS) was analyzed using gas chromatography-mass spectrometry with positive chemical ionization. Deuterated internal standard and selective ion monitoring were used throughout. We report a GHB fatality involving a 35-year-old male who was partying with friends. Subjects at the party ingested unknown quantities of wine and GHB. A female companion at the party reported seeing the male alive before she herself passed out. She awoke to find the decedent cold and stiff. Postmortem specimens were submitted for comprehensive toxicology testing. No alcohol or common drugs of abuse were detected. A targeted analysis revealed GHB in urine, brain, vitreous fluid, femoral blood, heart blood, and liver at concentrations of 1665 mg/L, 102 mg/kg, 48 mg/L, 461 mg/L, 276 mg/L, and 52 mg/kg, respectively. Concentrations of the drug in urine and vitreous fluid are important in death investigations because of significant postmortem production of GHB in blood specimens. The cause of death was attributed to GHB intoxication, and the manner of death was accidental. PMID:16105269

Mazarr-Proo, Susan; Kerrigan, Sarah

2005-01-01

154

Identification of GHB and morphine in hair in a case of drug-facilitated sexual assault.  

PubMed

The authors present the case of a 24-year-old girl who was sexually assaulted after administration of gamma-hydroxybutyrate (GHB) and morphine. She had been living in an international college for foreign students for about 1 year and often complained of a general unhealthy feeling in the morning. At the end of the college period she returned to Italy and received at home some video clips shot by a mobile phone camera. In these videos she was having sex with a boy she met when she was studying abroad. Toxicological analysis of her hair was done: the hair was 20-cm long. A 2/3-cm segmentation of all the length of the hair was performed. Morphine and GHB were detected in hair segments related to the period of time she was abroad. The analyses of hair segments were performed by gas chromatography/mass spectrometry (GC/MS) and the concentration of morphine and GHB were calculated. A higher value of GHB was found in the period associated with the possible criminal activity and was also associated with the presence of morphine in the same period. PMID:19261401

Rossi, Riccardo; Lancia, Massimo; Gambelunghe, Cristiana; Oliva, Antonio; Fucci, Nadia

2009-04-15

155

Dilated cardiomyopathy and acute liver injury associated with combined use of ephedra, gamma-hydroxybutyrate, and anabolic steroids.  

PubMed

Anabolic-androgenic steroids are synthetic derivatives of testosterone that some athletes have used to enhance muscle mass and improve their athletic performance. Ephedrine is a potent sympathomimetic agent that can lead to cardiomyopathy similar to that seen with catecholamine excess. Adverse cardiovascular events attributed to anabolic steroid and ephedra use, such as arrhythmias, myocardial infarction, cardiomyopathy, and sudden death, are rarely reported. Bodybuilders have used gamma-hydroxybutyrate, a potent secretagogue of growth hormone, to promote muscle development. Although dilated cardiomyopathy is a known complication of excess growth hormone levels, it has not been associated with use of gamma-hydroxybutyrate. A healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury. PMID:15899737

Clark, Brychan M; Schofield, Richard S

2005-05-01

156

Baclofen and ?-Hydroxybutyrate (GHB), a Dangerous Combination.  

PubMed

Baclofen is a ?-aminobutyric acid (GABA)-? receptor agonist with a muscle relaxant effect. It increases GABA activity and reduces the production of glutamate and dopamine. The GABA precursor ?-hydroxybutyrate (GHB) has gained popularity as a drug of abuse. For the first time, we report a case of a GHB-dependent patient, who ingested several days' doses of baclofen (80 mg) simultaneously with 0.3 L (215 g) of illicit GHB. Baclofen (40 mg/d) was prescribed to prevent relapse after a successful detoxification. The patient developed a rapid coma (E2M5V1 with oxygen support), bradypnea, and hypotonia. Physicians should be alert to the danger of this combination because of the hazards of coma and respiratory distress. PMID:25494007

Kamal, Rama M; Qurishi, Rouhollah; De Jong, Cornelis A J

2015-01-01

157

Metabolism of gamma-hydroxybutyrate to d-2-hydroxyglutarate in mammals: further evidence for d-2-hydroxyglutarate transhydrogenase.  

PubMed

gamma-Hydroxybutyratic acid (GHB), and its prodrugs 4-butyrolactone and 1,4-butanediol, represent expanding drugs of abuse, although GHB is also used therapeutically to treat narcolepsy and alcoholism. Thus, the pathway by which GHB is metabolized is of importance. The goal of the current study was to examine GHB metabolism in mice with targeted ablation of the GABA degradative enzyme succinic semialdehyde dehydrogenase (SSADH(-/-) mice), in whom GHB persistently accumulates, and in baboons intragastrically administered with GHB immediately and persistently. Three hypotheses concerning GHB metabolism were tested: (1) degradation via mitochondrial fatty acid beta-oxidation; (2) conversion to 4,5-dihydroxyhexanoic acid (a putative condensation product of the GHB derivative succinic semialdehyde); and (3) conversion to d-2-hydroxyglutaric acid (d-2-HG) catalyzed by d-2-hydroxyglutarate transhydrogenase (a reaction previously documented only in rat). Both d-2-HG and 4,5-dihydroxyhexanoic acid were significantly increased in neural and nonneural tissue extracts derived from SSADH(-/-) mice. In vitro studies demonstrated the ability of 4,5-dihydroxyhexanoic acid to displace the GHB receptor ligand NCS-382 (IC(50) = 38 micromol/L), although not affecting GABA(B) receptor binding. Blood and urine derived from baboons administered with GHB also accumulated d-2-HG, but not 4,5-dihydroxyhexanoic acid. Our results indicate that d-2-HG is a prominent GHB metabolite and provide further evidence for the existence of d-2-hydroxyglutarate transhydrogenase in different mammalian species. PMID:16483879

Struys, Eduard A; Verhoeven, Nanda M; Jansen, Erwin E W; Ten Brink, Herman J; Gupta, Maneesh; Burlingame, Terry G; Quang, Lawrence S; Maher, Timothy; Rinaldo, Piero; Snead, O Carter; Goodwin, Amy K; Weerts, Elise M; Brown, P Rand; Murphy, Tonya C; Picklo, Mathew J; Jakobs, Cornelius; Gibson, K Michael

2006-03-01

158

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

PubMed

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. PMID:25054071

Meyer, Rafael; Jenewein, Josef; Boettger, Soenke

2014-01-01

159

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. PMID:25054071

Meyer, Rafael; Jenewein, Josef

2014-01-01

160

Determination of GHB in human hair by HPLC-MS/MS: Development and validation of a method and application to a study group and three possible single exposure cases.  

PubMed

Gamma-hydroxybutyrate (GHB) over the last two decades has generated increased notoriety as a euphoric and disinhibiting drug of abuse in cases of drug-related sexual assault and for this reason it is considered a 'date rape' drug. The first aim of this paper was to develop and fully validate a method for the detection of GHB in human hair by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) after liquid-liquid extraction (LLE). The second aim was the application of the method to hair samples of 30 GHB-free users in order to determine the basal level. The results obtained showed no significant differences in endogenous concentrations (p?=?0.556) between hair samples of the three groups (black, blonde, and dyed hair) and the age and sex of the subjects did not affect the endogenous levels. Another 12 healthy volunteers, with no previous history of GHB use, were selected and a single dose (25?mg/Kg) was orally administered to all of them and hair samples were collected before the administration of the single dose and other two samples were collected one month and two months later, respectively. The segmental analysis of the latter two samples allowed us to calculate two ratios: 4.45:1 (95% C.I. 3.52-5.63) and 3.35:1 (95% C.I. 2.14-5.18), respectively, which can be recommended as reasonable values for a positive identification of GHB intake. Finally the method was applied to three real cases where a GHB single exposure probably occurred. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24947196

Bertol, Elisabetta; Mari, Francesco; Vaiano, Fabio; Romano, Guido; Zaami, Simona; Baglìo, Giovanni; Busardò, Francesco Paolo

2014-06-19

161

[Effect of gamma-aminobutyric and gamma-hydroxybutyric acids on the arousal of susliks from hibernation].  

PubMed

Experiments on male red-cheeked sousliks were made to examine the effects of substances interfering with different stages of GABA shunt on the animals' awakening assessed from the times of formation of the orthostatic reflex, the time course of rectal temperature, and the moment of the occurrence of active movements. The substances reducing (thiosemicarbazide) GABA content and elevating it (amino-oxyacetic acid) in the cerebral tissue have no effect on the above-indicated parameters of awakening. Meanwhile, p-dipropyl acetate (depakin) provokes a distinct dose-dependent increase in the time required for the recovery of the orthostatic reflex and transition to an active state. Sodium gamma-hydroxybutyric acid (GHBA) produces an analogous but more pronounced action. Both the drugs exhibit this effect when given even in low doses, in which they do not inhibit the thermogenesis. This evidence combined with the reported data on high GHBA concentration in brown fat suggests that GHBA may play a specific role in the mechanisms of hibernation. PMID:6430364

Popova, N K; Ostrovskaia, R U

1984-06-01

162

Regional Fos-expression induced by ?-hydroxybutyrate (GHB): comparison with ?-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.  

PubMed

?-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor ?-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors. PMID:25088910

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

2014-09-26

163

Physical dependence on gamma-hydroxybutrate (GHB) prodrug 1,4-butanediol (1,4-BD): Time course and severity of withdrawal in baboons  

PubMed Central

Background 1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) pro-drug, with multiple commercial uses, and a drug of abuse. Although there are case reports of a withdrawal syndrome following 1,4-BD use, no studies have evaluated the physical dependence potential of 1,4-BD and characterized the time course of withdrawal. Methods Vehicle and then 1,4-BD were administered continuously 24 h/day via intragastric catheters in male baboons (Papio anubis, n=3). Dosing was initiated at 100 mg/kg and increased by 100 mg/kg/day to 400 mg/kg. After a stabilization period, doses of 500 and then 600 mg/kg/day were each maintained for 3-4 weeks. Plasma levels of 1,4-BD and GHB were determined for each dose condition. Physical dependence was assessed via administration of a GABA-B antagonist (precipitated withdrawal test) during administration of the 600 mg/kg dose and via abrupt termination of chronic 1,4-BD administration (spontaneous withdrawal test). Outcome measures included the number of food pellets earned, performance on a fine-motor task, observed behaviors, and plasma levels of GHB and 1,4-BD. Results Following maintenance of 1,4-BD 600 mg/kg for 3 weeks, the number of food pellets earned was significantly decreased. At the end of chronic 1,4-BD dosing, the levels of GHB in plasma ranged from 1290- 2300 ?mol/L and levels of 1,4-BD in plasma ranged from 13.1 -37.9 ?mol/L. Signs of physical dependence were observed following precipitated and spontaneous withdrawal tests. Seizures were not observed. Conclusions These data indicate chronic 1,4-BD produced physical dependence in baboons and the withdrawal syndrome can be characterized as mild to intermediate. PMID:23538206

Goodwin, Amy K.; Gibson, K. Michael; Weerts, Elise M.

2013-01-01

164

Behavioral Analyses of GHB: Receptor Mechanisms  

PubMed Central

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 how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects. PMID:19010351

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

2009-01-01

165

Neuropharmacological profile of tetrahydrofuran in mice  

Microsoft Academic Search

Since the regulation of illicit gamma-hydroxybutyric acid (GHB) as a Federal Schedule I drug, the use of substitute chemical precursors such as gamma-butyrolactone (GBL) and 1,4-butanediol have emerged. Most recently there have been concerns about another potential analog of GHB, namely tetrahydrofuran (THF). While there is some suggestion that THF can be converted to GHB or GBL, little is known

Nuttiya Werawattanachai; Pasarapa Towiwat; Surachai Unchern; Timothy J. Maher

2007-01-01

166

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. PMID:9693100

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

1998-01-01

167

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

Federal Register 2010, 2011, 2012, 2013, 2014

...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

168

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

Federal Register 2010, 2011, 2012, 2013, 2014

...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

169

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

170

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

171

[Glycohemoglobin (GHb): clinical and analytical aspects].  

PubMed

Glycohemoglobin (GHb) has a key role in the assessment of glycemic control in diabetic patients. Several studies have clearly shown that improved glycemic control is strongly associated with decreased development and/or progression of diabetic complications in both type 1 and 2 diabetes mellitus. Therefore, accurate determination of GHb concentration is an important issue for clinical laboratories. Several factors may affect and lead to erroneous results. We discuss the problems of standardization of GHb measurements for monitoring glycemic control and also consider the potential interfering factors on GHb measurements. Moreover, GHb assays may be affected by interference in different ways. The effect of interference may be more clinically relevant with poor metabolic control. Laboratory staff must be aware of all pitfalls to avoid adding more confusion to the clinical interpretation of HbA1c values and physicians should contact laboratories if discrepancies between clinical impressions and laboratory data are observed. PMID:15761508

Camargo, Joíza Lins; Gross, Jorge Luiz

2004-08-01

172

Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric Acid, and Baclofen on EEG activity and sleep regulation.  

PubMed

The role of GABA(B) receptors in sleep is still poorly understood. GHB (?-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA(B) receptors are obligate dimers comprised of the GABA(B2) subunit and either one of the two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b). To better understand the role of GABA(B) receptors in sleep regulation, we performed electroencephalogram (EEG) recordings in mice devoid of functional GABA(B) receptors (1(-/-) and 2(-/-)) or lacking one of the subunit 1 isoforms (1a(-/-) and 1b(-/-)). The distribution of sleep over the day was profoundly altered in 1(-/-) and 2(-/-) mice, suggesting a role for GABA(B) receptors in the circadian organization of sleep. Several other sleep and EEG phenotypes pointed to a more prominent role for GABA(B1a) compared with the GABA(B1b) isoform. Moreover, we found that GABA(B1a) protects against the spontaneous seizure activity observed in 1(-/-) and 2(-/-) mice. We also evaluated the effects of the GHB-prodrug GBL (?-butyrolactone) and of baclofen (BAC), a high-affinity GABA(B) receptor agonist. Both drugs induced a state distinct from physiological sleep that was not observed in 1(-/-) and 2(-/-) mice. Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in 1(-/-) and 2(-/-) mice. The differential effects of GBL and BAC might be attributed to differences in GABA(B)-receptor affinity. These results also indicate that all GBL effects are mediated through GABA(B) receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia. PMID:20962240

Vienne, Julie; Bettler, Bernhard; Franken, Paul; Tafti, Mehdi

2010-10-20

173

Forensic cases involving the use of GHB in The Netherlands.  

PubMed

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 submission, cases of driving under the influence and cases of unknown causes of death.GHB was found in six cases of possible chemical submission. In these cases, relatively low concentrations of GHB were found. The results show that in cases of chemical submission, urine should be analyzed, because GHB is present longer in urine than in blood. The police should collect the samples in containers that do not contain citrate as anticoagulant. Especially at low levels of GHB, the formation of GHB in these tubes hampers an interpretation of the results.GHB was found in 13 cases of driving under the influence. In contrast to the cases of chemical submission, high concentrations of GHB were found, corresponding with observations of extreme sleepiness or temporary loss of consciousness.GHB was found in 16 cases of unexplained death: the measured range of GHB concentrations in blood might correspond to effects such as drowsiness, but not to serious toxicity of GHB. In 4 of these 16 cases, the role of GHB could be excluded. In the remaining cases, the role of GHB remains unclear; more research into "background" concentrations of GHB in post-mortem material is required. The incidence of the use of GHB in The Netherlands cannot be derived from these toxicological data. As GHB is not routinely found during systematical toxicological analyses, these data may seriously underestimate the use of GHB. Therefore, information from the police to the forensic institute is essential. PMID:12742684

Bosman, Ingrid J; Lusthof, Klaas J

2003-04-23

174

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

175

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.

Center for Technology in Teaching and Learning

2011-09-28

176

Crystal and molecular structure analysis of gamma-hydroxybutyrate (GHB) analogs: trans -4-hydroxycrotonic acid (THCA), trans -4-hydroxy-4-0-chlorophenylcrotonic acid (THCCA), and trans -4-hydroxy-4-p-nitrophenylcrotonic acid (THNCA)  

Microsoft Academic Search

The crystal structures oftrans-4-hydroxycrotonic acid (THCA), 4-o-chloro-phenyl-THCA (THCCA), and 4-p-nitrophenyl-THCA (THNCA) have been determined by single-crystal X-ray diffraction techniques, and refined by full-matrix least squares. THCA crystallizes in the monoclinic space groupCc witha=7.847(1),b=8.519(1),c=7.685(4) Å,ß=109.66(2)° andZ=4; THCCA is triclinic, space groupP¯1, witha=7.878(2),b=8.621(1),c=7.653(1) Å,a=92.20(1)°,ß=114.15(2)°, ?=94.40(2)°, andZ=2; THNCA is orthorhombic, space groupPna21, witha=7.488(1),b=19.666(2),c=7.143(3) Å, andZ=4. FinalR-factors are 0.034, 0.045, and 0.031, respectively. The

Thierry Boulanger; Guy Evrard; Daniel P. Vercauteren; Francois Durant

1987-01-01

177

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

178

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

179

Selective breeding of two rat lines differing in sensitivity to GHB and baclofen  

Microsoft Academic Search

Two Wistar-derived rat lines, one sensitive (GHB-S) and the other resistant (GHB-R) to the anesthetic effect of ?-hydroxybutyric acid (GHB), have been selectively bred. GHB-S and GHB-R rats were also sensitive and resistant, respectively, to the anesthetic effect of baclofen, the prototype GABAB receptor agonist, suggesting that they may be useful to elucidate not only the role of endogenous GHB

Giancarlo Colombo; Carla Lobina; Roberta Agabio; Giuliana Brunetti; Giacomo Diaz; Martino Littera; Samuele Melis; Marialaura Pani; Roberta Reali; Salvatore Serra; Giovanni Vacca; Mauro A. M Carai; Gian Luigi Gessa

2001-01-01

180

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

181

?-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. PMID:22561075

Morse, Bridget L.; Vijay, Nisha

2012-01-01

182

An Interactive Lesson in Acid/Base and Pro-Drug Chemistry Using Sodium Gamma-Hydroxybutyrate and Commercial Test Coasters  

PubMed Central

Objective To develop a classroom activity that applied pertinent pharmaceutical concepts to examine the use and limitations of a commercially available test drink coaster in detecting the presence of a date-rape drug, sodium ?-hydroxybutyrate (NaGHB), in beverages. Design An activity exercise involving a combination of self-study, hands on participation, and classroom discussion was developed. Topics incorporated into the activity were drug-assisted rape, the concepts of false positives and negatives, and prodrug and pH chemistry. Assessment Based on questionnaires completed by the students, the intended concepts were reinforced and students demonstrated an increased awareness of the potential shortcomings of the commercial test devices. The activity was well received by the majority of students. Conclusion The developed activity stimulated student awareness and interest in several principles relevant in pharamceutical education, including drug-assisted rape, consumer-based drug testing of NaGHB, and the chemical basis for its limitations. The activity requires no special equipment other than the drink coasters and can be easily completed in one 2-hour classroom session. PMID:17619654

Page, Nathaniel A.; Paganelli, Meaghan; Boje, Kathleen M.K.

2007-01-01

183

Reactivity of lactones and GHB formation.  

PubMed

The behavior of lactones in their hydrolysis reactions is a good indicator of their reactivity as electrophilic molecules. The hydrolysis of four- to six-membered lactones was investigated in neutral (water) and slightly acid media and in water/dioxane media. The following conclusions were drawn: (i) The reactivity of beta-propiolactone in neutral water is more than four times greater than that of beta-butyrolactone, due to the flow of charge caused by the latter's methyl substituent. Reactivity is enthalpy-controlled. (ii) The reactivity of beta-lactones diminishes in water/dioxane media when the percentage of dioxane increases. The increase in the dioxane percentage relaxing the intermolecular hydrogen bonds in the ordered structure of the water reduces DeltaH# and simultaneously increases the -DeltaS# value. (iii) An inverse solvent kinetic isotope effect in the acid-catalyzed hydrolysis of gamma-butyrolactone and delta-valerolactone was observed, this being indicative of acyl cleavage. (iv) The DeltaH# and DeltaS# values permit discrimination between alkyl and acyl cleavage. (v) A correlation was found between the chemical reactivity of lactones and their carcinogenic activity. (vi) The results suggest that orally ingested gamma-butyrolactone remains largely in its nonhydrolyzed form in the stomach before passing into the blood. (vii) The concentration equilibrium constant of GHB formation at human body temperature is Keq (37 degrees C)=0.40. (viii) Study of GHB formation shows that, contrary to earlier results, this is an endothermic process, with DeltarH=3.6 kJ mol(-1). PMID:15651781

Pérez-Prior, M Teresa; Manso, José A; del Pilar García-Santos, M; Calle, Emilio; Casado, Julio

2005-01-21

184

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

185

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

186

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

187

Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB.  

PubMed

In the Netherlands, ?-hydroxybutyric acid (GHB) was recently banned, but ?-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB. Pure GBL is per unit of volume about threefold stronger and therefore threefold more potent than currently used GHB-preparations in the Netherlands. Like GHB, GBL use hardly leads to organ toxicity, although, as with GHB, frequent GBL use may lead to repeated comas that may result in residual impairments in cognitive function and memory. Little is known about the prevalence of GBL use in Europe, but the recent increase in improper trading in GBL confirms that users of GHB gradually switch to the use of GBL. This shift may result in an increase in the number GBL dependent users, because the dependence potential of GBL is as great as that of GHB. Severe withdrawal symptoms and a high relapse rate are seen following cessation of heavy GBL use. GBL-dependent users seem to be severe (dependent, problematic) GHB users who started using GBL, the legal GHB substitute. Subjects who are solely dependent to GBL are rarely reported. About 5-10% of the treatment seeking GHB dependent subjects also use GBL and this subpopulation forms a vulnerable group with multiple problems. Fatal accidents with GBL are rarely reported, but non-fatal GHB (or GBL) overdoses frequently occur for which supportive treatment is needed. It is recommended to monitor the recreational use of GBL, the rate of GBL dependence treatment, and the improper trading of GBL. PMID:25204614

van Amsterdam, Jan; Brunt, Tibor; Pennings, Ed; van den Brink, Wim

2014-11-01

188

GHB receptor targets in the CNS: focus on high-affinity binding sites.  

PubMed

?-Hydroxybutyric acid (GHB) is an endogenous compound in the mammalian brain with both low- and high-affinity receptor targets. GHB is used clinically in the treatment of symptoms of narcolepsy and alcoholism, but also illicitly abused as the recreational drug Fantasy. Major pharmacological effects of exogenous GHB are mediated by GABA subtype B (GABAB) receptors that bind GHB with low affinity. The existence of GHB high-affinity binding sites has been known for more than three decades, but the uncovering of their molecular identity has only recently begun. This has been prompted by the generation of molecular tools to selectively study high-affinity sites. These include both genetically modified GABAB knock-out mice and engineered selective GHB ligands. Recently, certain GABA subtype A (GABAA) receptor subtypes emerged as high-affinity GHB binding sites and potential physiological mediators of GHB effects. In this research update, a description of the various reported receptors for GHB is provided, including GABAB receptors, certain GABAA receptor subtypes and other reported GHB receptors. The main focus will thus be on the high-affinity binding targets for GHB and their potential functional roles in the mammalian brain. PMID:24269284

Bay, Tina; Eghorn, Laura F; Klein, Anders B; Wellendorph, Petrine

2014-01-15

189

The chemical interconversion of GHB and GBL: forensic issues and implications.  

PubMed

In this work, the interconversion of GHB and GBL in a variety of aqueous media was studied. The effects of solution pH and time were determined by spiking GHB or GBL into pure water and buffered aqueous solutions, and determining the GHB and GBL contents at various time intervals. The degree of GBL hydrolysis to GHB was determined for several commercial aqueous-based GBL products, and further studied as a function of time. The effects of temperature and time were also determined for five commercial beverages spiked with GHB or GBL. GHB and GBL contents were determined using high performance liquid chromatography (HPLC). GHB and/or GBL confirmations were made using gas chromatography-mass spectrometry (GC-MS) and/or infrared spectroscopy (IR). Solution pH, time, and storage temperature were determined to be important factors affecting the rate and extent of GBL hydrolysis to GHB. Under strongly alkaline conditions (pH 12.0), GBL was completely converted to GHB within minutes. In pure water, GBL reacted to form an equilibrium mixture comprising ca. 2:1 GBL:GHB over a period of months. This same equilibrium mixture was established from either GHB or GBL in strongly acidic solution (pH 2.0) within days. A substantial portion of GBL (ca. 1/3) was hydrolyzed to GHB in aqueous-based GBL products, and in spiked commercial beverages, after ambient storage for a period ranging from several weeks to several months. Heat increased and refrigeration decreased the rate of GBL hydrolysis relative to ambient conditions. These studies show that hydrolysis of GBL to GHB does occur in aqueous-based solutions, with samples and time frames that are relevant to forensic testing. Implications for forensic testing and recommendations are discussed. PMID:11714141

Ciolino, L A; Mesmer, M Z; Satzger, R D; Machal, A C; McCauley, H A; Mohrhaus, A S

2001-11-01

190

Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB)  

Microsoft Academic Search

Gammahydroxybutyrate (GHB) satisfies many of the criteria for consideration as a neurotransmitter including having specific\\u000a receptor sites, endogenous synthesis, and heterogeneous CNS distribution. GHB has been reported to be illicitly used, to induce\\u000a physical dependence, and to relieve effects from alcohol and heroin withdrawal. GHB has also been shown to have antidopaminergic\\u000a activity to displace 3H[MK-801] binding in brain membranes,

Patrick M. Beardsley; Robert L. Balster; Louis S. Harris

1996-01-01

191

Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB)  

Microsoft Academic Search

Gammahydroxybutyrate (GHB) satisfies many of the criteria for consideration as a neurotransmitter including having specific\\u000a receptor sites, endogenous synthesis, and heterogeneous CNS distribution. GHB has been reported to be illicitly used, to induce\\u000a physical dependence, and to relieve effects from alcohol and heroin withdrawal. GHB has also been shown to have antidopaminergic\\u000a activity to displace3H[MK-801] binding in brain membranes, and

Patrick M. Beardsley; Robert L. Balster; Louis S. Harris

1996-01-01

192

?-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

193

?-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. PMID:24244421

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

2013-01-01

194

A surrogate analyte-based LC-MS/MS method for the determination of ?-hydroxybutyrate (GHB) in human urine and variation of endogenous urinary concentrations of GHB.  

PubMed

?-Hydroxybutyrate (GHB) is a drug of abuse with a strong anesthetic effect; however, proving its ingestion through the quantification of GHB in biological specimens is not straightforward due to the endogenous presence of GHB in human blood, urine, saliva, etc. In the present study, a surrogate analyte approach was applied to accurate quantitative determination of GHB in human urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to overcome this issue. For this, (2)H6-GHB and (13)C2-dl-3-hydroxybutyrate were used as a surrogate standard and as an internal standard, respectively, and parallelism between the surrogate analyte approach and standard addition was investigated at the initial step. The validation results proved the method to be selective, accurate, and precise, with acceptable linearity within calibration ranges (0.1-1?g/ml). The limit of detection and the limit of quantification of (2)H6-GHB were 0.05 and 0.1?g/ml, respectively. No significant variations were observed among urine matrices from different sources. The stability of (2)H6-GHB was satisfactory under sample storage and in-process conditions. However, in vitro production of endogenous GHB was observed when the urine sample was kept under the in-process condition for 4h and under the storage conditions of 4 and -20°C. In order to facilitate the practical interpretation of urinary GHB, endogenous GHB was accurately measured in urine samples from 79 healthy volunteers using the surrogate analyte-based LC-MS/MS method developed in the present study. The unadjusted and creatinine-adjusted GHB concentrations in 74 urine samples with quantitative results ranged from 0.09 to 1.8?g/ml and from 4.5 to 530?g/mmol creatinine, respectively. No significant correlation was observed between the unadjusted and creatinine-adjusted GHB concentrations. The urinary endogenous GHB concentrations were affected by gender and age while they were not significantly influenced by habitual smoking, alcohol drinking, or caffeine-containing beverage drinking. PMID:24929871

Kang, Soyoung; Oh, Seung Min; Chung, Kyu Hyuck; Lee, Sooyeun

2014-09-01

195

GHB and synthetic cathinones: clinical effects and potential consequences.  

PubMed

Designer drugs belong to a group of legally or illegally produced substances that are structurally and pharmacologically very similar to illicit drugs. In the past, designer drugs were often used during all-night dance parties, but they are now consumed in multiple settings from college bars to parks to private house parties. Most of these club drugs can be bought on legal websites and home-delivered for private parties. Recently, legal highs have once again become a burning media issue across the world. Our review will focus on GHB and synthetic cathinones. Literature searches were conducted for the period from 1975 to July 2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental websites using the following keywords alone or in combination: designer drugs, club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone, flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and clinical data for each compound are described. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be careful with GBL or synthetic cathinones, which are being sold and used as substitutes for GHB and MDMA, respectively. Interventions for drug prevention and harm reduction in response to the use of these drugs should be implemented on the Internet and in recreational settings. Prevention, Information, Action, and Treatment are the main goals that must be addressed for this new potentially addictive problem. PMID:21960540

Karila, Laurent; Reynaud, Michel

2011-09-01

196

Three deaths associated with use of Xyrem ®  

Microsoft Academic Search

Fatalities resulting from popular use of gamma hydroxybutyrate (GHB) have previously been reported. We report three deaths associated with use of Xyrem® (sodium oxybate), a pharmaceutical preparation of GHB initially approved for treatment of narcolepsy with cataplexy. One death appears associated with Xyrem® abuse, with extremely high postmortem blood GHB levels documented. Although postmortem blood GHB levels in two other

Deborah L. Zvosec; Stephen W. Smith; Brad J. Hall

2009-01-01

197

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

198

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

199

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

200

1,4-butanediol content of aqua dots children’s craft toy beads  

Microsoft Academic Search

Introduction  The U.S. Consumer Product Safety Commission announced a recall of Aqua Dots (Spin Master Ltd.; Toronto, Canada) on November\\u000a 7, 2007 due to children becoming ill after swallowing beads from these toy craft kits. Reports suggested that the beads contained\\u000a 1,4-butanediol (1,4-BD), a precursor to gamma-hydroxybutyrate (GHB), rather than the intended, but more expensive 1,5-pentanediol\\u000a (1,5-PD). We measured the 1,4-BD

Jeffrey R. Suchard; Sergey A. Nizkorodov; Stacy Wilkinson

2009-01-01

201

Gammahydroxybutyrate: an emerging drug of abuse that causes physical dependence  

Microsoft Academic Search

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects.

GANTT P. GALLOWAY; S. L. FREDERICK; FRANK E. STAGGERS JR; MARCO GONZALES; S. ALEX STALCUP; DAVID E. SMITH

1997-01-01

202

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

203

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

204

Club Drugs  

MedlinePLUS

... of club drugs include Gamma hydroxybutyrate (GHB), Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Ketamine is a dissociative anesthetic, mostly used in veterinary ...

205

Club Drugs  

MedlinePLUS

Club drugs are group of psychoactive drugs. They act on the central nervous system and can cause changes ... Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap ...

206

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

207

?-Hydroxybutyrate (GHB) induces GABA B receptor independent intracellular Ca 2+ transients in astrocytes, but has no effect on GHB or GABA B receptors of medium spiny neurons in the nucleus accumbens  

Microsoft Academic Search

We report on cellular actions of the illicit recreational drug ?-hydroxybutyrate (GHB) in the brain reward area nucleus accumbens. First, we compared the effects of GHB and the GABAB receptor agonist baclofen. Neither of them affected the membrane currents of medium spiny neurons in rat nucleus accumbens slices. GABAergic and glutamatergic synaptic potentials of medium spiny neurons, however, were reduced

T. Molnár; K. Antal; G. Nyitrai; Z. Emri

2009-01-01

208

Near-fatal persistent anion- and osmolal-gap acidosis due to massive gamma-butyrolactone/ethanol intoxication.  

PubMed

We report a case of an ethanol and massive gamma-butyrolactone (GBL) intoxication, the precursor of the recreational drug gamma-hydroxybutyric acid (GHB), resulting in life-threatening metabolic acidosis (pH 6.5) with a highly increased anion- and osmolal gap. Rapid analysis using gas chromatography revealed a GHB plasma concentration of 4400?mg/L, far above the upper limit concentration of 1000?mg/L found in adult fatalities attributed to GBL. Full recovery was established following supportive treatment including haemodialysis. This is the first report of a combined ethanol/GBL intoxication as a cause of high serum anion- and osmolal-gap metabolic acidosis. PMID:25205856

Heytens, Luc; Neels, Hugo; Van Regenmortel, Niels; van den Brink, Wim; Henckes, Manu; Schouwers, Sofie; Dockx, Greet; Crunelle, Cleo L

2015-03-01

209

A colorimetric sensor array for the detection of the date-rape drug ?-hydroxybutyric acid (GHB): a supramolecular approach.  

PubMed

?-Hydroxybutyric acid (GHB), a colourless, odourless and tasteless chemical, has become one of the most dangerous illicit drugs of abuse today. At low doses, this drug is a central nervous system depressant that reduces anxiety and produces euphoria and relaxation, sedating the recipient. There is an urgent need for simple, easy-to-use sensors for GHB in solution. Here, we present a colorimetric sensor array based on supramolecular host-guest complexes of fluorescent dyes with organic capsules (cucurbiturils) for the detection of GHB. PMID:20309968

Baumes, Laurent A; Buaki Sogo, Mireia; Montes-Navajas, Pedro; Corma, Avelino; Garcia, Hermenegildo

2010-04-19

210

Removal of fluoride from aqueous solution using granular acid-treated bentonite (GHB): batch and column studies.  

PubMed

Removal of fluoride from aqueous solution using granular acid-treated bentonite (GHB) was studied by batch and column adsorption experiments. The results of the batch adsorption experiments demonstrated that the maximum fluoride removal was obtained at pH of 4.95 and it took 40 min to attain equilibrium. Kinetics data fitted pseudo-second-order model. Batch adsorption data was better described by Redlich-Peterson and Freundlich isotherm models than Langmuir isotherm model. The adsorption type of GHB was ion exchange. Column experiments were carried out at different influent fluoride concentrations and different flow rates. The capacities of the breakthrough and exhaustion points increased with the decrease of flow rate and the increase of initial fluoride concentration. The experimental results were well fitted with Thomas model. Exhausted GHB was regenerated by alkali/alum treatment. The total sorption capacity of GHB was increased after regeneration and activation. PMID:21044817

Ma, Yuxin; Shi, Fengmei; Zheng, Xilai; Ma, Jun; Gao, Congjie

2011-01-30

211

Efectos de la coadministración de gammahidroxibutirato (GHB) y L-741,741, un antagonista selectivo de los receptores dopaminérgicos D4, sobre la conducta agonística en ratones machos  

Microsoft Academic Search

Effects of coadministration of gammahydroxybutyrate (GHB) and L-741,741, a selective D4 dopami- ne receptor antagonist, on agonistic behaviour in male mice. In previous studies, it has been described a potentiation of the antiaggressive effect after coadministration of gammahydroxybutyrate (GHB) and tiapride, indicating the exisence of an interaction between GHB and D2 dopamine receptors. The aim of this study was to

Gema Luna; Carmen Pedraza; José Francisco Navarro

212

Drug-Facilitated Sexual Assault on Campus: Challenges and Interventions.  

ERIC Educational Resources Information Center

The use of gamma-hydroxybutyric acid (GHB) to facilitate sexual assault is increasing on campuses nationwide. This article provides college counselors with an overview of the use of GHB in campus sexual assault, outlines suggestions for crisis intervention, and discusses the challenges of counseling survivors of drug-facilitated sexual assault.…

Hensley, Laura G.

2002-01-01

213

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

214

Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault?  

PubMed

We have developed a GC-MS-MS assay for GHB in human hair. Five milligrams of washed hair were hydrolyzed by 1M or 0.01M NaOH before a liquid-liquid extraction with ethyl acetate under acidic conditions. GHB-d(6) was used as the internal standard. TMS derivatives were formed before injection. TBDMS derivatives were used in cases of strong chromatographic interferences or in a confirmatory procedure. Analysis of basal levels of GHB in 61 drug-free donors gave the following results: the mean measured concentration for blond hair was 0.60 ng/mg (n = 12), SD = 0.19 ng/mg, and extreme figures were in the range 0.35-0.95 ng/mg. For brown hair, the mean measured concentration was 0.90 ng/mg (n = 30), SD = 0.42 ng/mg, and extreme figures 0.41-1.86 ng/mg. For black hair, the mean measured concentration was 0.90 ng/mg (n = 19), SD = 0.37 ng/mg, and extreme figures 0.32-1.54 ng/mg, showing no significant differences depending on hair color. Analysis of basal levels of GHB of 12 or more specimens in segmented hair showed a mean concentration of 1.22 ng/mg (0.31-8.4 ng/mg) and a relative standard deviation for each individual ranging from 6.75% to 37.98%. GHB was administered to a healthy 53-year-old white male (light brown hair) at oral dosages of 30, 45, and 60 mg/kg. Beard hair was collected just before administration and 24 h after (and each day for one week for the last dose), and a 7.5-cm scalp hair lock was collected 7 days after the last dose. A rise in GHB concentration was observed in beard hair for the 45 and 60 mg/kg dosages with a maximum at 24 h, whereas no change was observed for the 30 mg/kg dosage. Scalp hair was segmented into 3-mm long segments. The three proximal last segments showed significantly (0.0005 < p < 0.005) different concentrations of GHB (1.22, 1.27, and 1.66 ng/mg, respectively) when compared with the basal physiological level of GHB in this same person (mean = 0.62 ng/mg, SD = 0.15 ng/mg). A case of daily GHB abuse during bodybuilding allowed us to determine a concentration of GHB of 14 ng/mg, in a 2-cm long segment (black hair). A case of rape under the influence of GHB was documented through hair analysis (black hair) and positive analysis of the glass she used. Sampled 7 days after the sexual assault, the three last 3-mm long proximal segments tested for GHB exhibited concentrations of 3.1-5.3 and 4.3 ng/mg, respectively, whereas the mean physiological level determined in this woman was 0.71 ng/mg, SD = 0.17 ng/mg. The authors advise a two-step hair sampling as evidence of GHB consumption: the first sample at the time of exposure to show the contamination by sweat of the proximal segment in case of recent administration with a significant rise of hair level at the root, and the second after at least 3 or 4 weeks to avoid this contamination and determine the levels incorporated in the hair matrix before, during, and after the exposure. PMID:14670136

Goullé, Jean Pierre; Chèze, Marjorie; Pépin, Gilbert

2003-01-01

215

Positive allosteric modulation of the GHB high-affinity binding site by the GABAA receptor modulator monastrol and the flavonoid catechin.  

PubMed

?-Hydroxybutyric acid (GHB) is a metabolite of ?-aminobutyric acid (GABA) and a proposed neurotransmitter in the mammalian brain. We recently identified ?4?? GABAA receptors as possible high-affinity GHB targets. GABAA receptors are highly sensitive to allosteric modulation. Thus to investigate whether GHB high-affinity binding sites are also sensitive to allosteric modulation, we screened both known GABAA receptor ligands and a library of natural compounds in the rat cortical membrane GHB specific high-affinity [3H]NCS-382 binding assay. Two hits were identified: Monastrol, a positive allosteric modulator of GABA function at ?-containing GABAA receptors, and the naturally occurring flavonoid catechin. These compounds increased [3H]NCS-382 binding to 185-272% in high micromolar concentrations. Monastrol and (+)-catechin significantly reduced [3H]NCS-382 dissociation rates and induced conformational changes in the binding site, demonstrating a positive allosteric modulation of radioligand binding. Surprisingly, binding of [3H]GHB and the GHB high-affinity site-specific radioligands [125I]BnOPh-GHB and [3H]HOCPCA was either decreased or only weakly increased, indicating that the observed modulation was critically probe-dependent. Both monastrol and (+)-catechin were agonists at recombinant ?4?3? receptors expressed in Xenopus laevis oocytes. When monastrol and GHB were co-applied no changes were seen compared to the individual responses. In summary, we have identified the compounds monastrol and catechin as the first allosteric modulators of GHB high-affinity binding sites. Despite their relatively weak affinity, these compounds may aid in further characterization of the GHB high-affinity sites that are likely to represent certain GABAA receptors. PMID:24973695

Eghorn, Laura F; Hoestgaard-Jensen, Kirsten; Kongstad, Kenneth T; Bay, Tina; Higgins, David; Frølund, Bente; Wellendorph, Petrine

2014-10-01

216

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity ?-Hydroxybutyrate (GHB) Binding Sites  

PubMed Central

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 [3H]-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 [3H]-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.

2013-01-01

217

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

218

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

219

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

220

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

221

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. PMID:24884946

2014-01-01

222

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

223

Ecstasy and Drug Consumption Patterns: A Canadian Rave Population Study  

Microsoft Academic Search

Results: We found a significant rank order for the sequence of first use: 1) alcohol, 2) nicotine, 3) cannabis, 4) LSD, 5) psilocybin, 6) amphetamine, 7) cocaine, 8) MDMA, 9) gamma-hydroxybutyrate (GHB), 10) ephedrine, 11) ketamine. Alcohol and cannabis were the most commonly used substances, both in cumulative number of lifetime uses and in usage in the preceding 30 days.

Samantha R Gross; Sean P Barrett; John S Shestowsky; Robert O Pihl

2002-01-01

224

Genetics Home Reference: Succinic semialdehyde dehydrogenase deficiency  

MedlinePLUS

... the brain (neurotransmitter) called gamma-amino butyric acid (GABA). The primary role of GABA is to prevent the brain from being overloaded ... leads to an increase in the amount of GABA and a related molecule called gamma-hydroxybutyrate (GHB) ...

225

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

226

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

227

A long hangover from party drugs: Residual proteomic changes in the hippocampus of rats 8 weeks after ?-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination  

Microsoft Academic Search

3,4-Methylenedioxymethamphetamine (MDMA) and ?-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in

Petra S. van Nieuwenhuijzen; Mohammed A. Kashem; Izuru Matsumoto; Glenn E. Hunt; Iain S. McGregor

2010-01-01

228

?-Hydroxybutyrate (Xyrem) ameliorates clinical symptoms and neuropathology in a mouse model of Alzheimer's disease.  

PubMed

The chronic decrease of brain amyloid-? (A?) peptides is an emerging therapeutic for Alzheimer's disease, but no such treatment has achieved clinical validation yet. In vivo, some brain proteases, including neprilysin, possess the ability of degrading A? and experimental data suggest their exploitation in strategies to reduce cerebral A? concentration. Previous studies have shown that pharmacologic doses of gamma-hydroxybutyrate (sodium oxybate or Xyrem) induce histone deacetylases (HDACs) inhibition and neprilysin gene expression. Here, we demonstrate that brain neprilysin overexpression induced in vivo by repeated gamma-hydroxybutyrate autoadministration reduces cerebral A? contents and prevents cognitive deficits in APPSWE mice. Oral gamma-hydroxybutyrate also counteracted phosphoramidon-induced brain neprilysin inhibition and A? accumulation. HDACs activities in SH-SY5Y cells were inhibited by gamma-hydroxybutyrate which did not affect amyloid peptide precursor intracellular domain. Together, our results suggest that gamma-hydroxybutyrate, acting via HDAC inhibition, upregulates neprilysin to reduce A? level and related memory deficits. Because gamma-hydroxybutyrate doses used herein are clinically relevant, our data suggest that chronic oral administration of gamma-hydroxybutyrate or its analogs may be considered for strategies against presymptomatic or established Alzheimer's disease. PMID:25457559

Klein, Christian; Mathis, Chantal; Leva, Géraldine; Patte-Mensah, Christine; Cassel, Jean-Christophe; Maitre, Michel; Mensah-Nyagan, Ayikoe G

2015-02-01

229

Isomeric Trisaryloxycyclotriphosphazene Polymer Precursors  

NASA Technical Reports Server (NTRS)

Substances useful for making heat-and fire-resistant polymers. Cyclotriphosphazene-based monomers and polymer precursors led to development of high-temperature materials. Cyclotriphosphazene-derived monomers, polymer precursors, and polymers becoming important from both industrial and scientific points of view. Presence of phosphazene moiety in cyclotriphosphazene-based monomers and polymer precursors expected to impact special properties in desired high-performance materials containing inorganic backbones for aerospace applications. Useful for obtaining heat-and fire-resistant polymers for composites, adhesives, molding powders, and coating laminates. Also used in structures (e.g. secondary structures in aircraft), in construction of spacecraft, and in electronics and computer industries.

St. Clair, Terry L.; Kumar, Devendra

1990-01-01

230

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

231

Earthquakes: Hydrogeochemical precursors  

NASA Astrophysics Data System (ADS)

Earthquake prediction is a long-sought goal. Changes in groundwater chemistry before earthquakes in Iceland highlight a potential hydrogeochemical precursor, but such signals must be evaluated in the context of long-term, multiparametric data sets.

Ingebritsen, S. E.; Manga, M.

2014-10-01

232

A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen.  

PubMed

1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-(14)C-1,4-butanediol to (14)CO2. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. Gamma-butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F1 mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen. PMID:16193534

Irwin, Richard D

2006-01-01

233

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

234

Neuropharmacological profile of tetrahydrofuran in mice.  

PubMed

Since the regulation of illicit gamma-hydroxybutyric acid (GHB) as a Federal Schedule I drug, the use of substitute chemical precursors such as gamma-butyrolactone (GBL) and 1,4-butanediol have emerged. Most recently there have been concerns about another potential analog of GHB, namely tetrahydrofuran (THF). While there is some suggestion that THF can be converted to GHB or GBL, little is known about the pharmacology of THF. Various doses of THF and GBL were studied in neurobehavioral tests to better characterize the pharmacology of THF. The TD(50)'s (with 95% confidence intervals) of THF for loss of the righting reflex and failure of performance on the rotarod test were 15.18 (11.88-19.39) and 7.00 (5.22-9.40) mmol/kg, respectively. These values were significantly greater (p<0.05) than those determined for GBL: 4.60 (3.25-6.51), and 0.85 (0.52-1.38) mmol/kg, respectively. The effects of THF on the impairment of motor function in the rotarod test were antagonized by pretreatment with the GABA(B) receptor antagonist CGP-35348 (200 mg/kg, i.p.). While both THF and GBL had depressant effects on open-field locomotor activity, the pattern of activity at the lower doses of THF and GBL were dissimilar. Chronic treatment with low dose THF (5 or 10 mmol/kg, i.p.) followed by acute challenge with THF (15 mmol/kg, i.p.) demonstrated tolerance to the observed sedative effects. While some of the mechanisms of the THF actions on the central nervous system appear likely to involve direct or indirect interactions with the GABA(B) receptor, some differences in its qualitative and quantitative pharmacology suggests other mechanisms are also likely involved in the observed neurobehavioral effects of these selected doses of THF in mice. PMID:17331547

Werawattanachai, Nuttiya; Towiwat, Pasarapa; Unchern, Surachai; Maher, Timothy J

2007-04-10

235

Avalanche precursors R. Delannay,  

E-print Network

Avalanche precursors R. Delannay, Institut de Physique de Rennes, Université de Rennes 1, CNRS UMR at the top of the tray after some avalanches. · 4 or 5 large avalanches then observed during the slow of small "avalanches" which are recorded by a camera.2mm diameter beads #12;N. Nérone et al. Physica A 283

Gruner, Daniel S.

236

Wilson loops as precursors  

SciTech Connect

There is substantial evidence that string theory on AdS{sub 5}xS{sub 5} 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 (Schroedinger 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. (c) 2000 The American Physical Society.

Susskind, Leonard [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States)] [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States); Toumbas, Nicolaos [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States)] [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States)

2000-02-15

237

Wilson Loops as Precursors  

E-print Network

There is substantial evidence that string theory on AdS_5 x S_5 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 (Schroedinger 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.

Leonard Susskind; Nicolaos Toumbas

2000-03-17

238

Typology of club drug use among young adults recruited using time–space sampling  

Microsoft Academic Search

The present study examined patterns of recent club drug use among 400 young adults (18–29) recruited using time–space sampling in NYC. Subjects had used at least one of six club drugs (methylenedioxymethamphetamine (MDMA), ketamine, gamma-hydroxybutyrate (GHB), cocaine, methamphetamine, and d-lysergic acid diethylamide (LSD)) within the prior 3 months. We used latent class analysis (LCA) to estimate latent groups based on

Danielle E. Ramo; Christian Grov; Kevin Delucchi; Brian C. Kelly; Jeffrey T. Parsons

2010-01-01

239

Identifying the Prevalence and Correlates of Ecstasy and Other Club Drug (EOCD) Use Among High School Seniors  

Microsoft Academic Search

A plethora of anecdotal evidence has suggested that the use of “club drugs,” such as lysergic acid diethylamide (LSD), Ketamine, Gamma hydroxybutyrate (GHB), and 3,4-methylenedioxy-methamphe-tamine (MDMA or “ecstasy”), is a serious problem among youth across the United States. Unfortunately, little scientific evidence exists to support this contention. In the current study, we examine the ecstasy and other club drug (EOCD)-using

George S. Yacoubian Jr; Meghan K. Green; Ronald J. Peters

2003-01-01

240

Use of Club Drugs by HIV-Seropositive and HIV-Seronegative Gay and Bisexual Men  

Microsoft Academic Search

Club drugs such as methylenedioxymetham- phetamine (MDMA, ecstasy), gamma hydroxybutyrate (GHB), and ketamine are among the fastest-growing drugs of abuse in the United States. Reports have shown that some gay and bisexual men are likely to engage in club-drug use in a myriad of venues. This is concerning given that the use of club drugs has been linked to high-risk

Frank Romanelli; Kelly M. Smith; Claire Pomeroy

2003-01-01

241

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

242

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

243

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

244

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

245

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

246

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

247

Brillouin precursors in Debye media  

E-print Network

We theoretically study the formation of Brillouin precursors in Debye media. We point out that the precursors are only visible at propagation distances such that the impulse response of the medium is essentially determined by the frequency-dependence of its absorption and is practically Gaussian. By simple convolution, we then obtain explicit analytical expressions of the transmitted waves generated by reference incident waves, distinguishing precursor and main signal by physical arguments. These expressions are in good agreement with the signals obtained in numerical or real experiments performed on water and explain some features of these signals that remained mysterious or unnoticed. In addition, we show quite generally that the shape of the Brillouin precursor appearing alone at large enough propagation distance and the law giving its amplitude as a function of this distance do not depend on the precise form of the incident wave but only on its integral properties. The incidence of a static conductivity o...

Macke, Bruno

2015-01-01

248

REMOVING TRIHALOMETHANE PRECURSORS BY COAGULATION  

EPA Science Inventory

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 polymers, cationic polymers, ...

249

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

250

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

251

Premarital Precursors of Marital Infidelity  

Microsoft Academic Search

Premarital precursors of infidelity were evaluated in a sample of 72 couples (N ¼144) who were taking part in a longitudinal study of marriage. Premarital self-report and observational data were compared for couples who experienced infidelity and those who did not experience infidelity in the first years of marriage. Couples in which the male engaged in marital infidelity were characterized,

ELIZABETH S. ALLEN; GALENA KLINE RHOADES; SCOTT M. STANLEYw; HOWARD J. MARKMANw; TAMARA WILLIAMS; JESSICA MELTON; MARI L. CLEMENTS

2008-01-01

252

Precursor missions to interstellar exploration  

Microsoft Academic Search

This paper summarizes material developed over a three-month period by a JPL team of mission architects\\/analysts and advanced technology developers for presentation to NASA Headquarters in the summer of 1998. A preliminary mission roadmap is suggested that leads to the exploration of star systems within 40 Light years of our Solar System. The precursor missions include technology demonstrations as well

Richard A. Wallace

1999-01-01

253

Precursor missions to interstellar exploration  

Microsoft Academic Search

This paper summarizes material developed over a three-month period by a JPL team of mission architects\\/analysts and advanced technology developers for presentation to NASA Headquarters in the summer of 1998. A preliminary mission roadmap is suggested that leads to the exploration of star systems within 40 light years of our Solar System. The precursor missions include technology demonstrations as well

R. A. Wallace

1999-01-01

254

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers  

Microsoft Academic Search

Rationale  Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there\\u000a is little experimental evidence in support of GHB’s amnestic effects.\\u000a \\u000a \\u000a \\u000a Objectives  This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers.\\u000a \\u000a \\u000a \\u000a Materials and methods  Doses of sodium oxybate (1.125, 2.25, and 4.5 g\\/70 kg), triazolam (0.125, 0.25, and 0.5 mg\\/70 kg), and

Lawrence P. Carter; Roland R. Griffiths; Miriam Z. Mintzer

2009-01-01

255

Radio HF precursors of Earthquakes  

Microsoft Academic Search

The high frequency (HF) earthquake electromagnetic precursors (40-55MHz band) were recorded by the four electromagnetic stations a few days (hours) prior the event associated with earthquakes with magnitude more than 5.0 at Crete Island. These experiments were performed continuously during 1998-2002 and specific peculiarities are found. This is underhorizon epicenter position for main part of events under question. Another unusual

Yu. Ruzhin; C. Nomicos; F. Vallianatos; V. Shpakovsky

2004-01-01

256

Nucleation precursors in protein crystallization.  

PubMed

Protein crystal nucleation is a central problem in biological crystallography and other areas of science, technology and medicine. Recent studies have demonstrated that protein crystal nuclei form within crucial precursors. Here, methods of detection and characterization of the precursors are reviewed: dynamic light scattering, atomic force microscopy and Brownian microscopy. Data for several proteins provided by these methods have demonstrated that the nucleation precursors are clusters consisting of protein-dense liquid, which are metastable with respect to the host protein solution. The clusters are several hundred nanometres in size, the cluster population occupies from 10(-7) to 10(-3) of the solution volume, and their properties in solutions supersaturated with respect to crystals are similar to those in homogeneous, i.e. undersaturated, solutions. The clusters exist owing to the conformation flexibility of the protein molecules, leading to exposure of hydrophobic surfaces and enhanced intermolecular binding. These results indicate that protein conformational flexibility might be the mechanism behind the metastable mesoscopic clusters and crystal nucleation. Investigations of the cluster properties are still in their infancy. Results on direct imaging of cluster behaviors and characterization of cluster mechanisms with a variety of proteins will soon lead to major breakthroughs in protein biophysics. PMID:24598910

Vekilov, Peter G; Vorontsova, Maria A

2014-03-01

257

Precursors of Short Gamma-Ray Bursts  

NASA Technical Reports Server (NTRS)

We carried out a systematic search of precursors on the sample of short GRBs observed by Swift. We found that approx. 8-10% of short GRBs display such early episode 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.; Rosswog, S.; Gehrels, N.

2010-01-01

258

Precursor Lesions of Pancreatic Cancer  

PubMed Central

This review article describes morphological aspects, gene abnormalities, and mucin expression profiles in precursor lesions such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN) of the pancreas, as well as their relation to pancreatic ductal adenocarcinoma (PDAC). The gene abnormalities in precursors of PDAC are summarized as follows: (1) KRAS mutation and p16/CDKN2A inactivation are early events whose frequencies increase with the dysplasia grade in both PanIN and IPMN; (2) TP53 mutation and SMAD4/DPC4 inactivation are late events observed in PanIN3 or carcinomatous change of IPMN in both PanIN and IPMN, although the frequency of the TP53 mutation is lower in IPMN than in PDAC; and (3) also in MCN, KRAS mutation is an early event whose frequency increases with the dysplasia grade, whereas TP53 mutation and SMAD4/DPC4 inactivation are evident only in the carcinoma. The mucin expression profiles in precursors of PDAC are summarized as follows: (1) MUC1 expression increases with the PanIN grade, and is high in PDAC; (2) the expression pattern of MUC2 differs markedly between the major subtypes of IPMN with different malignancy potentials (i.e., IPMN-intestinal type with MUC2+ expression and IPMN-gastric type with MUC2- expression); (3) MUC2 is not expressed in any grade of PanINs, which is useful for differentiating PanIN from intestinal-type IPMN; (4) de novo expression of MUC4, which appears to increase with the dysplasia grade; and (5) high de novo expression of MUC5AC in all grades of PanINs, all types of IPMN, MCN, and PDAC. PMID:20485640

Higashi, Michiyo; Yamada, Norishige; Goto, Masamichi

2008-01-01

259

The synergy of earthquake precursors  

NASA Astrophysics Data System (ADS)

The system of geophysical shells (lithosphere, atmosphere, ionosphere) is considered as an open complex nonlinear system with dissipation where earthquake preparation could be regarded as a self-organizing process leading to the critical state of the system. The processes in atmosphere and ionosphere are considered from the point of view of non-equilibrium thermodynamics. The intensive ionization of boundary layer of atmosphere (probably provided by radon in occasion of earthquake preparation) gives start to the synergetic sequence of coupling processes where the ionosphere and even magnetosphere are the last links in the chain of interactions. Every anomaly observed in different geophysical fields (surface temperature, latent heat flux, electromagnetic emissions, variations in ionosphere, particle precipitation, etc.) is not considered as an individual process but the part of the self-organizing process, the final goal of which is the reaching of the point of the maximum entropy. Radon anomaly before the Kobe earthquake is considered as a perfect example to satisfy the formal seismological determination of the earthquake precursor. What is genetically connected with radon through the ionization process can also be regarded as a precursor. The problem of co-seismic variations of the discussed parameters of atmosphere and ionosphere is considered as well.

Pulinets, Sergey

2011-12-01

260

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

261

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

262

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. PMID:25018772

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

2014-01-01

263

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

PubMed

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 (1)H-NMR, (1)H-COSY, and (1)H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed. PMID:25018772

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

2013-12-31

264

Leading time domain seismic precursors  

NASA Astrophysics Data System (ADS)

The problem of predicting the occurrence of earthquakes is threefold. On one hand it is necessary to predict the date and magnitude of an earthquake, and on the other hand the location of the epicenter. In this work after a brief review of the state of earthquake prediction research, we report on a new leading time precursor for determining time onset of earthquake occurrence. We report the linking between earthquakes of the past with those which happen in the future via Fibonacci, Dual and Lucas numbers (FDL) numbers. We demonstrate it here with two example seed earthquakes at least 100 years old. Using this leading indicator method we can predict significant earthquake events >6.5R, with good accuracy approximately +- 1 day somewhere in the world. From a single seed we produce at least 100 trials simultaneously of which 50% are correct to +- 1day. The indicator is based on Fibonacci, Dual and Lucas numbers (FDL). This result hints that the log periodic FDL numbers are at the root of the understanding of the earthquake mechanism. The theory is based on the assumption that each occurred earthquake discontinuity can be thought of as a generating source of FDL time series. (The mechanism could well be linked to planetary orbits). When future dates are derived from clustering and convergence from previous strong earthquake dates at an FDL time distance, then we have a high probability for an earthquake to occur on that date. We set up a real time system which generates FDL time series from each previous significant earthquake (>7R) and we produce a year to year calendar of high probability earthquake dates. We have tested this over a number of years with considerable success. We have applied this technique for strong (>7R) earthquakes across the globe as well as on a restricted region such as the Greek geographic region where the magnitude is small (>4R-6.5R). In both cases the success of the method is impressive. It is our belief that supplementing this method with other precursors will enhance significantly the prediction of significant earthquakes.

Boucouvalas, A. C.; Gkasios, M.; Keskebes, A.; Tselikas, N. T.

2014-08-01

265

Precursor films in wetting phenomena.  

PubMed

The spontaneous spreading of non-volatile liquid droplets on solid substrates poses a classic problem in the context of wetting phenomena. It is well known that the spreading of a macroscopic droplet is in many cases accompanied by a thin film of macroscopic lateral extent, the so-called precursor film, which emanates from the three-phase contact line region and spreads ahead of the latter with a much higher speed. Such films have been usually associated with liquid-on-solid systems, but in the last decade similar films have been reported to occur in solid-on-solid systems. While the situations in which the thickness of such films is of mesoscopic size are fairly well understood, an intriguing and yet to be fully understood aspect is the spreading of microscopic, i.e. molecularly thin, films. Here we review the available experimental observations of such films in various liquid-on-solid and solid-on-solid systems, as well as the corresponding theoretical models and studies aimed at understanding their formation and spreading dynamics. Recent developments and perspectives for future research are discussed. PMID:22627067

Popescu, M N; Oshanin, G; Dietrich, S; Cazabat, A-M

2012-06-20

266

Precursor films in wetting phenomena  

NASA Astrophysics Data System (ADS)

The spontaneous spreading of non-volatile liquid droplets on solid substrates poses a classic problem in the context of wetting phenomena. It is well known that the spreading of a macroscopic droplet is in many cases accompanied by a thin film of macroscopic lateral extent, the so-called precursor film, which emanates from the three-phase contact line region and spreads ahead of the latter with a much higher speed. Such films have been usually associated with liquid-on-solid systems, but in the last decade similar films have been reported to occur in solid-on-solid systems. While the situations in which the thickness of such films is of mesoscopic size are fairly well understood, an intriguing and yet to be fully understood aspect is the spreading of microscopic, i.e. molecularly thin, films. Here we review the available experimental observations of such films in various liquid-on-solid and solid-on-solid systems, as well as the corresponding theoretical models and studies aimed at understanding their formation and spreading dynamics. Recent developments and perspectives for future research are discussed.

Popescu, M. N.; Oshanin, G.; Dietrich, S.; Cazabat, A.-M.

2012-06-01

267

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

268

A Population of Oligodendrocytes Derived From Multipotent Neural Precursor Cells  

E-print Network

A Population of Oligodendrocytes Derived From Multipotent Neural Precursor Cells Expresses, Georgia Because oligodendrocytes and their precursors possess receptors for classical transmitters in oligodendrocyte function. We used mitogen- proliferated multipotent neuroepithelial precursors (neurospheres

Manitoba, University of

269

Studies of Enzymes in Mitochondrial DNA Precursor Synthesis  

E-print Network

Studies of Enzymes in Mitochondrial DNA Precursor Synthesis Regulatory Mechanisms for Human;Studies of Enzymes in Mitochondrial DNA Precursor Synthesis - Regulatory Mechanisms for Human Thymidine and purine deoxynucleosides, respectively, providing DNA precursors for mitochondrial DNA (mtDNA) replication

270

Joint Robotic Precursor Activity: Providing Strategic Knowledge to  

E-print Network

Joint Robotic Precursor Activity: Providing Strategic Knowledge to Inform Future Exploration Dr. Michael J. Wargo, Chief Exploration Scientist #12;Joint Robotic Precursor Activity (JRPA) Overview · To meet this goal, NASA will jointly fund and conduct Robotic Precursor Activities

Waliser, Duane E.

271

The molecular evolution of the allatostatin precursor in cockroaches  

E-print Network

The molecular evolution of the allatostatin precursor in cockroaches XAVIER BELLE´Sa , LAURIE A that specify the preproallatostatin precursor for the cockroaches, Blatta orientalis, Blattella germanica punctata and Periplaneta americana reported previously. The precursors of all these cockroach species

Belles, Xavier

272

Synthesis and structures of metal chalcogenide precursors  

NASA Technical Reports Server (NTRS)

The reactivity of early transition metal sandwich complexes with sulfur-rich molecules such as dithiocarboxylic acids was studied. Researchers recently initiated work on precursors to CuInSe2 and related chalcopyrite semiconductors. Th every high radiation tolerance and the high absorption coefficient of CuInSe2 makes this material extremely attractive for lightweight space solar cells. Their general approach in early transition metal chemistry, the reaction of low-valent metal complexes or metal powders with sulfur and selenium rich compounds, was extended to the synthesis of chalcopyrite precursors. Here, the researchers describe synthesis, structures, and and routes to single molecule precursors to metal chalcogenides.

Hepp, Aloysius F.; Duraj, Stan A.; Eckles, William E.; Andras, Maria T.

1990-01-01

273

Long range transport of acid rain precursors  

E-print Network

A model of the long range transport of primary and secondary pollutants derived by Fay and Rosenzweig (1) is applied to the problem of the transport of acid rain precursors. The model describes the long term average (annual ...

Fay, James A.

1983-01-01

274

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

275

Optical Precursor of a Single Photon  

NASA Astrophysics Data System (ADS)

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

2011-06-01

276

Precursors and prediction of catastrophic avalanches  

E-print Network

In this work we review the precursors of catastrophic avalanches (global failures) in several failure models, namely (a) Fiber Bundle Model (FBM), (b) Random Fuse Model (RFM), (c) Sandpile Models and (d) Fractal Overlap Model. The precursor parameters identified here essentially reflect the growing correlations within such systems as they approach their respective failure points. As we show, often they help us to predict the global failure points in advance.

Srutarshi Pradhan; Bikas K. Chakrabarti

2006-03-23

277

Acoustic precursor wave propagation in viscoelastic media.  

PubMed

Precursor field theory has been developed to describe the dynamics of electromagnetic field evolution in causally attenuative and dispersive media. In Debye dielectrics, the so-called Brillouin precursor exhibits an algebraic attenuation rate that makes it an ideal pulse waveform for communication, sensing, and imaging applications. Inspired by these studies in the electromagnetic domain, the present paper explores the propagation of acoustic precursors in dispersive media, with emphasis on biological media. To this end, a recently proposed causal dispersive model is employed, based on its interpretation as the acoustic counterpart of the Cole¿Cole model for dielectrics. The model stems from the fractional stress¿strain relation, which is consistent with the empirically known frequency power-law attenuation in viscoelastic media. It is shown that viscoelastic media described by this model, including human blood, support the formation and propagation of Brillouin precursors. The amplitude of these precursors exhibits a sub-exponential attenuation rate as a function of distance, actually being proportional to z(-p), where z is the distance traveled within the medium and 0.5

precursors identified in this work facilitate the design of optimal waveforms for propagation in complex media, creating new possibilities for acoustic-pulse-based communication and imaging systems. PMID:24569254

Zhu, Guangran Kevin; Mojahedi, Mohammad; Sarris, Costas D

2014-03-01

278

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

279

GRB Precursors in the Fallback Collapsar Scenario  

E-print Network

Precursor emission has been observed in a non-negligible fraction of gamma-ray bursts.The time gap between the precursor and the main burst extends in some case up to hundreds of seconds, such as in GRB041219A, GRB050820A and GRB060124. Both the origin of the precursor and the large value of the time gap are controversial. Here we investigate the maximum possible time gaps arising from the jet propagation inside the progenitor star, in models which assume that the precursor is produced by the jet bow shock or the cocoon breaking out of the progenitor. Due to the pressure drop ahead of the jet head after it reaches the stellar surface, a rarefaction wave propagates back into the jet at the sound speed, which re-accelerates the jet to a relativistic velocity and therefore limits the gap period to within about ten seconds. This scenario therefore cannot explain gaps which are hundreds of seconds long. Instead, we ascribe such long time gaps to the behavior of the central engine, and suggest a fallback collapsar scenario for these bursts. In this scenario, the precursor is produced by a weak jet formed during the initial core collapse, possibly related to MHD processes associated with a short-lived proto-neutron star, while the main burst is produced by a stronger jet fed by fallback accretion onto the black hole resulting from the collapse of the neutron star. We have examined the propagation times of the weak precursor jet through the stellar progenitor. We find that the initial weak jet can break out of the progenitor in a time less than ten seconds (a typical precursor duration) provided that it has a moderately high relativistic Lorentz factor \\Gamma>=10 (abridged).

Xiang-Yu Wang; Peter Meszaros

2007-08-27

280

Investigation into new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxy- and gamma-acetoxybutyric acid. Part 5: search for new anticonvulsant compounds.  

PubMed

A series of four N-benzylamides of gamma-hydroxybutyric acid (GHB), that contain N-(4-phenylpiperazine)-, N-(4-benzylpiperazine)rings, N-benzylamino-, or N-(2-phenylethylamine)-groups in the alpha-position of GHB were selected as model compounds, for determining the structural elements responsible for their potential anticonvulsant action. Based on the results of pharmacological, physicochemical, and molecular modelling investigations, the pharmacophore model for anticonvulsant N-substituted amides of GHB was defined. In this model, the presence of the N-benzylamide fragment is essential for activity. In addition, all of the amides contained another hydrophobic unit (aryl ring) as a distal binding site and H-bond donor. In consideration of these model parameters, a number of N-substituted amides of GHB, containing a hydrophobic moiety such as: N-benzylamino or N-(4-chlorobenzylamino) group in the alpha-position of GHB, and a lipophilic substituent in the amide portion, were prepared. It has been shown that the anticonvulsant activities of the newly synthesized compounds might partially be explained on the basis of their lipophilicity (calculated log P values) and the presence of a hydroxyl group in the molecule. PMID:14738973

Malawska, Barbara; Kulig, Katarzyna; Spiewak, Agnieszka; Stables, James P

2004-02-01

281

Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function.  

PubMed

The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-)) represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. In physiological concentrations, GHB acts at the GHB receptor (GHBR), but in high concentrations such as those observed in the brains of children with SSADH deficiency, GHB is thought to be a direct agonist at the GABABR receptor (GABABR). We tested the hypothesis that both GHBR and GABABR-mediated function are perturbed in SSADH deficiency. Therefore, we examined the high affinity binding site for GHB as well as the expression and function of the GABABR in mutant mice made deficient in SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific GABABR antagonist, [3H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-) when compared to wild type control animals (SSADH(+/+)), particularly in hippocampus. GABABR-mediated synaptic potentials were decreased in SSADH(-/-). Immunoblot analysis of GABABR1a, R1b, and R2 in SSADH(-/-) indicated a trend towards a region-specific and time-dependent decrease of GABABR subunit protein expression. There was no difference between SSADH(-/-) and wild type in binding of either [3H]GHB or a specific GHBR antagonist to the GHBR. These data suggest that the elevated levels of GABA and GHB that occur in SSADH(-/-) lead to a use-dependent decrease in GABABR-mediated function and raise the possibility that this GHB- and GABA-induced perturbation of GABABR could play a role in the pathogenesis of the seizures and mental retardation observed in SSADH deficiency. PMID:16647690

Buzzi, Andrea; Wu, Ying; Frantseva, Marina V; Perez Velazquez, Jose L; Cortez, Miguel A; Liu, Chun C; Shen, Li Q; Gibson, K Michael; Snead, O Carter

2006-05-23

282

Error Precursor Analysis Worksheet Page 1 of 6  

E-print Network

Error Precursor Analysis Worksheet Page 1 of 6 Common Error Precursors Error precursors interfere conditions for error, and therefore exist before an error occurs. If discovered and removed, job-site conditions can be changed to minimize the chance for error. #12;Error Precursor Analysis Worksheet Page 2

283

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

284

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

285

Amino acid precursors in lunar samples.  

NASA Technical Reports Server (NTRS)

The use of hot water to extract lunar samples, followed by the hydrolysis of the aqueous extract, appears to be the method of choice for identification and quantitation of amino acid precursors in extraterrestrial sources. The net inferences from the analyses to date are (1) that amino acid precursors are verifiably present in lunar dust, and (2) that they are quite certainly not the consequence of contamination by terrestrial organisms, including man. It is suggested that prebiotic evolutionary pathways such as have been traversed on the earth were terminated on the moon for lack of sufficient water. Although some or all of the amino acid precursors may be indigenous, the low level observed suggests that they may also result from onfall of organic compounds from interstellar matter, comets, tails, solar wind, or meteorites.

Fox, S. W.; Harada, K.; Hare, P. E.

1972-01-01

286

Nozzle designs with pitch precursor ablatives  

NASA Technical Reports Server (NTRS)

Recent developments in carbon phenolic ablatives for solid rocket motor nozzles have yielded a pitch precursor carbon fiber offering significant raw material availability and cost saving advantages as compared to conventional rayon precursor material. This paper discusses the results of an experimental program conducted to assess the thermal performance and characterize the thermal properties of pitch precursor carbon phenolic ablatives. The end result of this program is the complete thermal characterization of pitch fabric, pitch mat, hybrid pitch/rayon fabric and pitch mat molding compound. With these properties determined an analytic capability now exists for predicting the thermal performance of these materials in rocket nozzle liner applications. Further planned efforts to verify material performance and analytical prediction procedures through actual rocket motor firings are also discussed.

Blevins, H. R.; Bedard, R. J.

1976-01-01

287

Sequestration and Transport of Lignin Monomeric Precursors  

SciTech Connect

Lignin is the second most abundant terrestrial biopolymer after cellulose. It is essential for the viability of vascular plants. Lignin precursors, the monolignols, are synthesized within the cytosol of the cell. Thereafter, these monomeric precursors are exported into the cell wall, where they are polymerized and integrated into the wall matrix. Accordingly, transport of monolignols across cell membranes is a critical step affecting deposition of lignin in the secondarily thickened cell wall. While the biosynthesis of monolignols is relatively well understood, our knowledge of sequestration and transport of these monomers is sketchy. In this article, we review different hypotheses on monolignol transport and summarize the recent progresses toward the understanding of the molecular mechanisms underlying monolignol sequestration and transport across membranes. Deciphering molecular mechanisms for lignin precursor transport will support a better biotechnological solution to manipulate plant lignification for more efficient agricultural and industrial applications of cell wall biomass.

Liu, C.J.; Miao, Y.-C.; Zhang, K.-W.

2011-01-18

288

Basics for Testing Large Earthquake Precursors  

NASA Astrophysics Data System (ADS)

Earthquakes, the large or significant ones in particular, are extreme events that, by definition, are the rare ones. Testing candidates to large earthquake precursors implies investigation a small sample of case- histories with the support of specific and sensitive statistical methods and data of different quality, collected in various conditions. Regretfully, in many seismological studies the methods of mathematical statistics are used outside their applicability: earthquakes are evidently not independent events and have heterogeneous, perhaps fractal distribution in space and time. Moreover, the naïve or, conversely, delicately-designed models are considered as a full replacement of seismic phenomena. Although there are many claims of earthquake precursors, most of them should remain in the list of precursor candidates, which have never been tested in any rigorous way, and, in fact, are anecdotal cases of coincidental occurrence. To establish a precursory link between sequences of events of the same or different phenomena, it is necessary to accumulate enough statistics in a rigorous forecast/prediction test, which results, i.e. success-to-failure scores and space-time volume of alarms, must appeal for rejecting hypotheses of random coincidental appearance. We reiterate suggesting to use so-called "Seismic Roulette" null-hypothesis as the most adequate random alternative accounting for the empirical spatial distribution of earthquakes in question and illustrate a few outcomes of Testing Large Earthquake Precursors.

Romashkova, L. L.; Kossobokov, V. G.; Peresan, A.

2008-12-01

289

Peer Review: a Precursor to Peer Assessment  

Microsoft Academic Search

This paper describes a two?year observation of peer review among first year undergraduates at Loughborough University of Technology. Peer review focuses on the learning benefits of small group work and the development of critical skills among students as a precursor to peer assessment of tutorial contributions. The paper outlines the methodology, design and pitfalls of the peer review process and

Keith Pond; Winnie Wade

1995-01-01

290

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

291

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

292

The amyloid precursor protein: beyond amyloid  

Microsoft Academic Search

The amyloid precursor protein (APP) takes a central position in Alzheimer's disease (AD) pathogenesis: APP processing generates the ?-amyloid (A?) peptides, which are deposited as the amyloid plaques in brains of AD individuals; Point mutations and duplications of APP are causal for a subset of early onset of familial Alzheimer's disease (FAD). Not surprisingly, the production and pathogenic effect of

Hui Zheng; Edward H Koo

2006-01-01

293

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

294

ATLANTA OZONE PRECURSOR MONITORING STUDY DATA REPORT  

EPA Science Inventory

Monitoring was conducted during the summer of 1990 to address the measurement of ozone (0a) and ozone precursors in Atlanta, Georgia. ata was collected using automated gas chromatography. esolved individual species were detected via a flame ionization detector (FID) and an electr...

295

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

296

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

297

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2010 CFR

... false Reporting on precursor chemical substances. 766.38 Section...DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a)...

2010-07-01

298

Protein transduction from retroviral Gag precursors.  

PubMed

Retroviral particles assemble a few thousand units of the Gag polyproteins. Proteolytic cleavage mediated by the retroviral protease forms the bioactive retroviral protein subunits before cell entry. We hypothesized that this process could be exploited for targeted, transient, and dose-controlled transduction of nonretroviral proteins into cultured cells. We demonstrate that gammaretroviral particles tolerate the incorporation of foreign protein at several positions of their Gag or Gag-Pol precursors. Receptor-mediated and thus potentially cell-specific uptake of engineered particles occurred within minutes after cell contact. Dose and kinetics of nonretroviral protein delivery were dependent upon the location within the polyprotein precursor. Proteins containing nuclear localization signals were incorporated into retroviral particles, and the proteins of interest were released from the precursor by the retroviral protease, recognizing engineered target sites. In contrast to integration-defective lentiviral vectors, protein transduction by retroviral polyprotein precursors was completely transient, as protein transducing retrovirus-like particles could be produced that did not transduce genes into target cells. Alternatively, bifunctional protein-delivering particle preparations were generated that maintained their ability to serve as vectors for retroviral transgenes. We show the potential of this approach for targeted genome engineering of induced pluripotent stem cells by delivering the site-specific DNA recombinase, Flp. Protein transduction of Flp after proteolytic release from the matrix position of Gag allowed excision of a lentivirally transduced cassette that concomitantly expresses the canonical reprogramming transcription factors (Oct4, Klf4, Sox2, c-Myc) and a fluorescent marker gene, thus generating induced pluripotent stem cells that are free of lentivirally transduced reprogramming genes. PMID:20385817

Voelkel, Christine; Galla, Melanie; Maetzig, Tobias; Warlich, Eva; Kuehle, Johannes; Zychlinski, Daniela; Bode, Juergen; Cantz, Tobias; Schambach, Axel; Baum, Christopher

2010-04-27

299

Pitch Precursor-Origin and Chemical Constitution  

Microsoft Academic Search

\\u000a Pitches are carbonaceous materials derived from organic precursors using variety of processes. These processes may extend\\u000a from solven extraction to a number of low temperature thermal treatments, usually below 700 K. Having a broad range of molecular\\u000a weight constituents, pitches consequently have complex physical and chemical properties. The range of molecular structures\\u000a extends from low molecular weight paraffinic to high

M. F. Yardim; E. Ekinci; K. D. Bartle

300

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

301

?-Amyloid precursor protein in human digital skin  

Microsoft Academic Search

The occurrence and distribution of ?-amyloid precursor protein (?APP) and of ?-amyloid peptide (?\\/A4) was investigated using immunoblotting and immunohistochemical techniques in the digital skin of healthy adult subjects. ?APP-like proteic bands with apparent molecular masses between 55–60 kDa, 100–125 kDa (corresponding to the full-length ?APP isoforms), 145–150 kDa, and 200 kDa were found in pellets and supernatants of whole

J. A. Vega; R. Diaz-Trelles; J. J. Haro; M. E. del Valle; F. J. Naves; M. T. Fernández-Sánchez

1995-01-01

302

Precursors in Swift Gamma Ray Bursts with Redshift  

Microsoft Academic Search

We study a sample of gamma-ray bursts detected by the Swift satellite with known redshift which show a precursor in the Swift BAT light curve. We analyze the spectra of the precursors and compare them with the time-integrated spectra of the prompt emission. We find neither a correlation between the two slopes nor a tendency for the precursors spectra to

D. Burlon; G. Ghirlanda; G. Ghisellini; D. Lazzati; L. Nava; M. Nardini; A. Celotti

2008-01-01

303

Cellular Kinetics of Perivascular MSC Precursors  

PubMed Central

Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration. PMID:24023546

Chen, William C. W.; Murray, Iain R.; Lazzari, Lorenza; Huard, Johnny; Péault, Bruno

2013-01-01

304

Scalar model for frictional precursors dynamics  

PubMed Central

Recent experiments indicate that frictional sliding occurs by nucleation of detachment fronts at the contact interface that may appear well before the onset of global sliding. This intriguing precursory activity is not accounted for by traditional friction theories but is extremely important for friction dominated geophysical phenomena as earthquakes, landslides or avalanches. Here we simulate the onset of slip of a three dimensional elastic body resting on a surface and show that experimentally observed frictional precursors depend in a complex non-universal way on the sample geometry and loading conditions. Our model satisfies Archard's law and Amontons' first and second laws, reproducing with remarkable precision the real contact area dynamics, the precursors' envelope dynamics prior to sliding, and the normal and shear internal stress distributions close to the interfacial surface. Moreover, it allows to assess which features can be attributed to the elastic equilibrium, and which are attributed to the out-of-equilibrium dynamics, suggesting that precursory activity is an intrinsically quasi-static physical process. A direct calculation of the evolution of the Coulomb stress before and during precursors nucleation shows large variations across the sample, explaining why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective. PMID:25640079

Taloni, Alessandro; Benassi, Andrea; Sandfeld, Stefan; Zapperi, Stefano

2015-01-01

305

Scalar model for frictional precursors dynamics.  

PubMed

Recent experiments indicate that frictional sliding occurs by nucleation of detachment fronts at the contact interface that may appear well before the onset of global sliding. This intriguing precursory activity is not accounted for by traditional friction theories but is extremely important for friction dominated geophysical phenomena as earthquakes, landslides or avalanches. Here we simulate the onset of slip of a three dimensional elastic body resting on a surface and show that experimentally observed frictional precursors depend in a complex non-universal way on the sample geometry and loading conditions. Our model satisfies Archard's law and Amontons' first and second laws, reproducing with remarkable precision the real contact area dynamics, the precursors' envelope dynamics prior to sliding, and the normal and shear internal stress distributions close to the interfacial surface. Moreover, it allows to assess which features can be attributed to the elastic equilibrium, and which are attributed to the out-of-equilibrium dynamics, suggesting that precursory activity is an intrinsically quasi-static physical process. A direct calculation of the evolution of the Coulomb stress before and during precursors nucleation shows large variations across the sample, explaining why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective. PMID:25640079

Taloni, Alessandro; Benassi, Andrea; Sandfeld, Stefan; Zapperi, Stefano

2015-01-01

306

Scalar model for frictional precursors dynamics  

NASA Astrophysics Data System (ADS)

Recent experiments indicate that frictional sliding occurs by nucleation of detachment fronts at the contact interface that may appear well before the onset of global sliding. This intriguing precursory activity is not accounted for by traditional friction theories but is extremely important for friction dominated geophysical phenomena as earthquakes, landslides or avalanches. Here we simulate the onset of slip of a three dimensional elastic body resting on a surface and show that experimentally observed frictional precursors depend in a complex non-universal way on the sample geometry and loading conditions. Our model satisfies Archard's law and Amontons' first and second laws, reproducing with remarkable precision the real contact area dynamics, the precursors' envelope dynamics prior to sliding, and the normal and shear internal stress distributions close to the interfacial surface. Moreover, it allows to assess which features can be attributed to the elastic equilibrium, and which are attributed to the out-of-equilibrium dynamics, suggesting that precursory activity is an intrinsically quasi-static physical process. A direct calculation of the evolution of the Coulomb stress before and during precursors nucleation shows large variations across the sample, explaining why earthquake forecasting methods based only on accumulated slip and Coulomb stress monitoring are often ineffective.

Taloni, Alessandro; Benassi, Andrea; Sandfeld, Stefan; Zapperi, Stefano

2015-02-01

307

Systems and methods for detection of blowout precursors in combustors  

DOEpatents

The present invention comprises systems and methods for detecting flame blowout precursors in combustors. The blowout precursor detection system comprises a combustor, a pressure measuring device, and blowout precursor detection unit. A combustion controller may also be used to control combustor parameters. The methods of the present invention comprise receiving pressure data measured by an acoustic pressure measuring device, performing one or a combination of spectral analysis, statistical analysis, and wavelet analysis on received pressure data, and determining the existence of a blowout precursor based on such analyses. The spectral analysis, statistical analysis, and wavelet analysis further comprise their respective sub-methods to determine the existence of blowout precursors.

Lieuwen, Tim C.; Nair, Suraj

2006-08-15

308

Neutron-powered precursors of kilonovae  

NASA Astrophysics Data System (ADS)

The merger of binary neutron stars (NSs) ejects a small quantity of neutron-rich matter, the radioactive decay of which powers a day to week long thermal transient known as a kilonova. Most of the ejecta remains sufficiently dense during its expansion that all neutrons are captured into nuclei during the r-process. However, recent general relativistic merger simulations by Bauswein and collaborators show that a small fraction of the ejected mass (a few per cent, or ˜10-4 M?) expands sufficiently rapidly for most neutrons to avoid capture. This matter originates from the shocked-heated interface between the merging NSs. Here, we show that the ?-decay of these free neutrons in the outermost ejecta powers a `precursor' to the main kilonova emission, which peaks on a time-scale of ˜ few hours following merger at U-band magnitude ˜22 (for an assumed distance of 200 Mpc). The high luminosity and blue colours of the neutron precursor render it a potentially important counterpart to the gravitational wave source, that may encode valuable information on the properties of the merging binary (e.g. NS-NS versus NS-black hole) and the NS equation of state. Future work is necessary to assess the robustness of the fast-moving ejecta and the survival of free neutrons in the face of neutrino absorptions, although the precursor properties are robust to a moderate amount of leptonization. Our results provide additional motivation for short latency gravitational wave triggers and rapid follow-up searches with sensitive ground-based telescopes.

Metzger, Brian D.; Bauswein, Andreas; Goriely, Stephane; Kasen, Daniel

2015-01-01

309

On Verification of Earthquake Precursors (Invited)  

NASA Astrophysics Data System (ADS)

Although there are many claims of earthquake precursors, most of them should remain in the list of precursor candidates, which have never been tested in any rigorous way, and, in fact, are anecdotal cases of coincidental occurrence. To establish a precursory link between sequences of events of the same or different phenomena, it is necessary to accumulate enough statistics in a rigorous forecast/prediction test, which results, i.e. success-to-failure scores and space-time volume of alarms, must appeal for rejecting hypotheses of random coincidental appearance. We reiterate suggesting so-called “Seismic Roulette” null-hypothesis as the most adequate random alternative accounting for the empirical spatial distribution of earthquakes in question: (i) Consider a roulette wheel with as many sectors as the number of earthquake locations from a sample catalog, a sector per each location and (ii) make your bet according to prediction (i.e., determine, which locations are inside area of alarm, and put one chip in each of the corresponding sectors); (iii) Nature turns the wheel; (iv) accumulate statistics of wins and losses along with the number of chips spent. If a precursor in charge of prediction exposes an imperfection of Seismic Roulette then, having in mind optional “antipodal strategy”, one can make the predictions efficient, so that the wins will systematically outscore the losses. Sounds easy, we know! Seismology is juvenile and its appropriate statistical tools to-date may have a "medieval flavor" for those who hurry up to apply a fuzzy language of a highly developed probability theory and consider delicately-designed models as a full replacement of seismic phenomena. To become "quantitatively probabilistic" earthquake forecasts/predictions must be defined with a scientific accuracy. Following the most popular objectivists' viewpoint on probability, we cannot claim "probabilities" adequate without a long series of "yes/no" forecast/prediction outcomes. Without "antiquated binary language" of "yes/no" certainty we cannot judge an outcome ("success/failure"), and, therefore, quantify objectively a forecast/prediction method performance. The paper illustrates the complexity of seismic statistics based on a twenty years of experimental earthquake prediction in real time of extreme seismic events on the global and regional scales, along with a few outcomes of independent testing of earthquake precursors.

Kossobokov, V. G.

2009-12-01

310

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

311

Conformal dynamics of precursors to fracture  

NASA Astrophysics Data System (ADS)

An exact integro-differential equation for the conformal map from the unit circle to the boundary of an evolving cavity in a stressed 2-dimensional solid is derived. This equation provides an accurate description of the dynamics of precursors to fracture when surface diffusion is important. The solution predicts the creation of sharp grooves that eventually lead to material failure via rapid fracture. Solutions of the new equation are demonstrated for the dynamics of an elliptical cavity and the stability of a circular cavity under biaxial stress, including the effects of surface stress.

Barra, F.; Herrera, M.; Procaccia, I.

2003-09-01

312

Ascorbate as a Biosynthetic Precursor in Plants  

PubMed Central

Background and Aims l-Ascorbate (vitamin C) has well-documented roles in many aspects of redox control and anti-oxidant activity in plant cells. This Botanical Briefing highlights recent developments in another aspect of l-ascorbate metabolism: its function as a precursor for specific processes in the biosynthesis of organic acids. Scope The Briefing provides a summary of recent advances in our understanding of l-ascorbate metabolism, covering biosynthesis, translocation and functional aspects. The role of l-ascorbate as a biosynthetic precursor in the formation of oxalic acid, l-threonic acid and l-tartaric acid is described, and progress in elaborating the mechanisms of the formation of these acids is reviewed. The potential conflict between the two roles of l-ascorbate in plant cells, functional and biosynthetic, is highlighted. Conclusions Recent advances in the understanding of l-ascorbate catabolism and the formation of oxalic and l-tartaric acids provide compelling evidence for a major role of l-ascorbate in plant metabolism. Combined experimental approaches, using classic biochemical and emerging ‘omics’ technologies, have provided recent insight to previously under-investigated areas. PMID:17098753

Debolt, Seth; Melino, Vanessa; Ford, Christopher M.

2007-01-01

313

Wenchuan Earthquake Ionospheric Precursors: Modeling and Experiment  

NASA Astrophysics Data System (ADS)

Early it was shown, that for strong middle-latitude earthquakes the effects in Total Electron Content (TEC) and in critical frequency of F2-layer (foF2) look like local changes in electron concentration which maxima are located in immediate proximity from epicenter area. Pre-cursory effects of strong near-equatorial earthquakes might be in the form of deepening and widening of electron concentration minimum over the magnetic equator and displacement of equatorial ionization anomaly crests. The problems of physical explanation of possible forma-tion mechanisms of the seismo-ionospheric effects are under discussion now. In Namgaladze et al., 2009 it has been come out with the assumption, that the most probable formation mech-anism of TEC disturbed areas, observable prior strong earthquakes, is the vertical transport of the F2-region ionospheric plasma under the zonal electric field action. The geomagnetic conjugacy of the earthquake ionospheric precursors and effects in equatorial anomaly which development is controlled by zonal electric field are strong arguments in favor of this hypoth-esis. Besides, the analysis of model calculation results with use of the Global Self-consistent Model of the Thermosphere, Ionosphere, Protonosphere (GSM TIP) in Namgaladze et al., 2009 testifies in favor of this hypothesis. There is a question how such electric fields can arise in the ionosphere prior to earthquakes? Now it is not answer to this question. Therefore, for understanding of formation mechanisms of earthquake ionospheric precursors it is necessary to understand the physics of lithosphere-atmosphere-ionosphere coupling prior to earthquake. Many researchers tried to solve this problem. However, until now there is not common opinion concerning to the lithosphere-atmosphere-ionosphere coupling prior to earthquake. Some ba-sic hypotheses for the explanation of this mechanism have been offered: the Internal Gravity Waves (IGWs) of seismogenic origin with the period 1-3 hours, the IGWs with the period from several minutes up to tens minutes, the seismogenic electric field with amplitude from units up to tens mV/m, the abnormal electromagnetic fields and emissions. However, the appearance of local large-scale seismo-ionospheric anomalies in TEC and foF2 it is possible to explain only by two of the mentioned mechanisms: an atmospheric electric field and/or small-scale IGWs. In this study, we present the numerical calculation results for reproduction of observed changes in the ionosphere prior to strong Wenchuan earthquake. This earthquake has been fixed on 12 May 2008. The geomagnetic activity indices for the period on 1-13 May were low. The calcu-lations of Wenchuan earthquake ionospheric precursors were carried out with use of the GSM TIP model. In calculations, the small-scale IGWs and/or the penetration of vertical electric field are considered as the formation mechanisms of earthquake ionospheric precursors. It was carried out the comparison of calculation results with experimental data of TEC and foF2 at various stations, located in China and nearby areas. The obtained results confirm the proposed mechanisms of seismo-ionospheric effect formation by small-scale IGWs and the penetration of the seismogenic vertical electric field from the atmosphere into the ionosphere. References Namgaladze A.A., Klimenko M.V., Klimenko V.V. and Zakharenkova I.E. Physical Mechanism and Mathematical Simulation of Ionosphere Earthquake Precursors Observed in Total Electron Content. Geomagnetism and Aeronomy, 2009, Vol. 49, 252-262.

Klimenko, Maxim; Klimenko, Vladimir; Zhao, Biqiang; Pulinets, Sergej; Zakharenkova, Irina; Bryukhanov, Valerij

314

The precursors of the xylene ring in riboflavine  

PubMed Central

1. The nature of the precursors of the xylene ring in riboflavine was reinvestigated with growing as well as resting cells of Eremothecium ashbyii. 2. The incorporation of acetoin into riboflavine was very low; further, [2-14C]pyruvate and [1-14C]acetate were equally effective as precursors of lumichrome, and pyruvate was much more active as a precursor of acetoin. These results exclude acetoin as a direct precursor of riboflavine. 3. Addition of unlabelled glucose decreased the incorporation of [14C]acetate into riboflavine more than it decreased the conversion of acetate into carbon dioxide, indicating that acetate is not a direct riboflavine precursor. 4. The incorporation of various sugars and dilution experiments suggest that a derivative of the intermediates of the pentose phosphate cycle is the precursor of the xylene ring in riboflavine. PMID:5938640

Ali, S. N.; Al-Khalidi, U. A. S.

1966-01-01

315

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

316

Current Status of Bi-Based Precursors for Integrated Ferroelectrics  

Microsoft Academic Search

Two typical precursors for Bi4Ti3O12 thin films were analyzed spectroscopic methods and the local structure of those were chemically distinguished. Bi?Ti double alkoxide precursor containing Bi?O?Ti bonds promoted the homogeneous crystallization and was applicable to a series of Ca?Bi?Ti layer-structured ferroelectric thin films by addition of Ca ions. A hybrid precursor composed of Bi-triethylhexanoate and Ti-alkoxide needed the additional glass

KAZUMI KATO; KAZUYUKI SUZUKI; KIYOTAKA TANAKA; DESHENG FU; KAORI NISHIZAWA; TAKESHI MIKI

2004-01-01

317

Anomalous radon emission as precursor of earthquake  

NASA Astrophysics Data System (ADS)

Recent years have seen an ever increasing interest in studying the usefulness of radon measurements in earth sciences. Radon emissions that are enhanced by forthcoming geophysical events as earthquakes or volcanic activity have been observed all over the world. The abnormal radon exhalation from the interior of earth, as a precursory phenomenon related to earthquakes and as an indicator of underlying geological faults, is an important field of investigation. For this purpose a number of active and passive methods for getting radon signals have been developed. Several models have been proposed as an explanation of the experimental field data. This paper gives a brief review of the progress made in the field of radon measurements in earth sciences specially in predicting earthquakes. Radon anomalies that have been observed in soil gas as well as groundwater or spring prior to earthquakes have been reviewed in this paper. The models proposed in relating precursor time, epicentral distance, magnitude of earthquake have also been discussed.

Ghosh, Dipak; Deb, Argha; Sengupta, Rosalima

2009-10-01

318

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

319

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). PMID:23658471

Buesser, Beat; Pratsinis, Sotiris E.

2013-01-01

320

Diamond films grown from fullerene precursors  

SciTech Connect

Fullerene precursors have been shown to result in the growth of diamond films from argon microwave plasmas. In contradistinction to most diamond films grown using conventional methane-hydrogen mixtures, the fullerene-generated films are nanocrystalline and smooth on the nanometer scale. They have recently been shown to have friction coefficients approaching the values of natural diamond. It is clearly important to understand the development of surface morphology during film growth from fullerene precursors and to elucidate the factors leading to surface roughness when hydrogen is present in the chemical vapor deposition (CVD) gas mixtures. To achieve these goals, we are measuring surface reflectivity of diamond films growing on silicon substrates over a wide range of plasma processing conditions. A model for the interpretation of the laser interferometric data has been developed, which allows one to determine film growth rate, rms surface roughness, and bulk losses due to scattering and absorption. The rms roughness values determined by reflectivity are in good agreement with atomic force microscope (AFM) measurements. A number of techniques, including high-resolution transmission electron microscopy (HRTEM) and near-edge x-ray absorption find structure (NEXAFS) measurements, have been used to characterize the films. A mechanism for diamond-film growth involving the C{sub 2} molecule as a growth species will be presented. The mechanism is based on (1) the observation that the optical emission spectra of the fullerene- containing plasmas are dominated by the Swan bands of C{sub 2} and (2) the ability of C{sub 2} to insert directly into C-H and C-C bonds with low activation barriers, as shown by recent theoretical calculations of reactions of C{sub 2} with carbon clusters.

Gruen, D.M.; Zuiker, C.D.; Krauss, A.R.

1995-07-01

321

Polymer precursors for ceramic matrix composites  

NASA Technical Reports Server (NTRS)

The synthesis and characterization of a polycyclohexasilane is reported. Because of its cyclic structure, it is anticipated that this polymer might serve as a precursor to SIC having a high char yield with little rearrangement to form small, volatile cyclic silanes, and, as such, would be of interest as a precursor to SiC composite matrices and fibers, or as a binder in ceramic processing. Several approaches to the synthesis of a bifunctional cyclic monomer were attempted; the most successful of these was metal coupling of PhMeSiCl2 and Me2SiCl2. The procedure gives six-membered ring compounds with all degrees of phenyl substitution, from none to hexaphenyl. The compounds with from 0-2 groups were isolated and characterized. The fraction with degree of phenyl substitution equal to 2, a mixture of cis and trans 1,2-; 1,3-; and 1,4 isomers, was isolated in 32 percent yield. Pure 1,4 diphenyldecamethylcyclohexasilane was isolated from the mixed diphenyl compounds and characterized. Diphenyldecamethylcyclohexasilanes were dephenylated to dichlorodecamethylcyclohexasilanes by treating with H2SO4.NH4Cl in benzene. The latter were purified and polymerized by reacting with sodium in toluene. The polymers were characterized by HPGPC, elemental analysis, proton NMR, and IR. Thermogravimetric analyses were carried out on the polymers. As the yield of residual SiC was low, polymers were heat treated to increase the residual char yield. As high as 51.52 percent residual char yield was obtained in one case.

Litt, M. H.; Kumar, K.

1986-01-01

322

DHEA - a precursor of ER? ligands.  

PubMed

What is DHEA and why is there so much public interest in this steroid which has been touted as the fountain of youth and is supposed to have all kinds of health benefits? Endocrinologists have been fascinated with DHEA for a long time because of its high production in the fetal adrenals and its continued high levels until the 7th decade of life. Yet there is still little agreement about its physiological functions. In its simplest terms endocrinology is the communication between at least three organs: one sends a message, one releases a hormone into the blood in response to the message and one responds to the hormone. DHEA is produced by a specific zone of the adrenal cortex, the zona reticularis, whose sole function is to produce this steroid. Glucocorticoids and mineralocorticoids which are C21 steroids are produced in two other zones of the adrenal cortex called the zona fasicularis and the zona glomerulosa, respectively. Being C21 steroids, they cannot be synthesized from DHEA which is a C19 steroid. To date there is no known hormone which specifically stimulates the zona reticularis and there is no known specific receptor for DHEA. Thus DHEA does not qualify as a hormone. DHEA could have autocrine or paracrine effects but, so far, there is no known effect of DHEA on either the cells of the zona glomerulosa or the zona fasicularis. Of course DHEA could have functions as a local precursor of androgens or estrogens and many studies have reported on the beneficial effects of transdermal or transvaginal administration of DHEA in postmenopausal women. This review will consider two of the potential functions of DHEA as a precursor of estrogen receptor beta (ER?) ligands. PMID:25125389

Warner, Margaret; Gustafsson, Jan-Ake

2015-01-01

323

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

324

Human embryonic epidermis contains a diverse Langerhans cell precursor pool.  

PubMed

Despite intense efforts, the exact phenotype of the epidermal Langerhans cell (LC) precursors during human ontogeny has not been determined yet. These elusive precursors are believed to migrate into the embryonic skin and to express primitive surface markers, including CD36, but not typical LC markers such as CD1a, CD1c and CD207. The aim of this study was to further characterize the phenotype of LC precursors in human embryonic epidermis and to compare it with that of LCs in healthy adult skin. We found that epidermal leukocytes in first trimester human skin are negative for CD34 and heterogeneous with regard to the expression of CD1c, CD14 and CD36, thus contrasting the phenotypic uniformity of epidermal LCs in adult skin. These data indicate that LC precursors colonize the developing epidermis in an undifferentiated state, where they acquire the definitive LC marker profile with time. Using a human three-dimensional full-thickness skin model to mimic in vivo LC development, we found that FACS-sorted, CD207(-) cord blood-derived haematopoietic precursor cells resembling foetal LC precursors but not CD14(+)CD16(-) blood monocytes integrate into skin equivalents, and without additional exogenous cytokines give rise to cells that morphologically and phenotypically resemble LCs. Overall, it appears that CD14(-) haematopoietic precursors possess a much higher differentiation potential than CD14(+) precursor cells. PMID:24496618

Schuster, Christopher; Mildner, Michael; Mairhofer, Mario; Bauer, Wolfgang; Fiala, Christian; Prior, Marion; Eppel, Wolfgang; Kolbus, Andrea; Tschachler, Erwin; Stingl, Georg; Elbe-Bürger, Adelheid

2014-02-01

325

Endogenous Nkx2.2+ oligodendrocyte precursor cells fail  

E-print Network

Endogenous Nkx2.2+ /Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination proliferative NG2+ cells within the lesion was observed, none of which expressed the oligodendrocyte lineage

Harkema, Susan

326

Topographical and Functional Properties of Precursors to Severe Problem Behavior  

ERIC Educational Resources Information Center

A literature search identified 17 articles reporting data on 34 subjects who engaged in precursors to severe problem behavior, which we examined to identify topographical and functional characteristics. Unintelligible vocalization was the most common precursor to aggression (27%) and property destruction (29%), whereas self- or nondirected…

Fahmie, Tara A.; Iwata, Brian A.

2011-01-01

327

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

328

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...

329

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

330

INTRODUCTION An organ primordium consists of precursor cells that generate  

E-print Network

). In addition, several transcription factors affect development of the gonadal mesoderm in mice: Wt1, Sf1, Lim1 types of the mature organ. For some organs, `organ selector' genes control all precursor cells within, precursor cells in other organ primordia are specified by the intersection of global patterning genes

Kimble, Judith

331

A fission-powered interstellar precursor mission  

SciTech Connect

An {open_quotes}interstellar precursor mission{close_quotes} lays the groundwork for eventual interstellar exploration by studying the interstellar medium and by stretching technologies that have potential application for eventual interstellar exploration. The numerous scientific goals for such a mission include generating a 3-D stellar map of our galaxy, studying Kuiper-belt and Oort cloud objects, and observing distant objects using the sun{close_quote}s gravitational lens as the primary of an enormous telescope. System equations are developed for a space tug which propels a 2500-kg scientific payload to 550 astronomical units in about 20 years. The tug to transport this payload uses electric propulsion with an lsp of 15,000 seconds and a fission reactor with a closed Brayton cycle to generate the electricity. The optimal configuration may be to thrust for only about 6 years and then coast for the remaining 14 years. This spacecraft does not require any physics breakthroughs or major advances in technology. The fission power system can be engineered and built by drawing upon known technologies developed for related systems over the past 40 years. The tug system would eventually reach 1000 a.u in 33 years, and would have adequate power to relay large amounts of data throughout its journey. {copyright} {ital 1999 American Institute of Physics.}

Lipinski, Ronald J.; Lenard, Roger X.; Wright, Steven A. [Sandia National Laboratories, MS-1146, P.O. Box 5800, Albuquerque, New Mexico 87185 (United States)] West, John L. [Jet Propulsion Laboratory, MS-301-490, Pasadena, California 91109-8099 (United States)

1999-01-01

332

Cystic precursors to invasive pancreatic cancer  

PubMed Central

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

2011-01-01

333

A Fission-Powered Interstellar Precursor Mission  

SciTech Connect

An 'interstellar precursor mission' lays the groundwork for eventual interstellar exploration by studying the interstellar medium and by stretching technologies that have potential application for eventual interstellar exploration. The numerous scientific goals for such a mission include generating a 3-D stellar map of our galaxy, studying Kuiper-belt and Oort cloud objects, and observing distant objects using the sun's gravitational lens as the primary of an enormous telescope. System equations are developed for a space tug which propels a 2500-kg scientific payload to 550 astronomical units in about 20 years. The tug to transport this payload uses electric propulsion with an Isp of 15,000 seconds and a fission reactor with a closed Brayton cycle to genemte the electricity. The optimal configuration may be to thrust for only about 6 years and then coast for the remaining 14 pars. This spacecraft does not require any physics breakthroughs or major advances in technology. The fission power syslem can be engineered and built by drawing upon known technologies developed for relatgd systems over the past 40 years. The tug system would eventually reach 1000 a.u in 33 years, and would have adequate power to relay large amounts of data throughout its journey.

Lenard, R.X.; Lipinski, R.J.; West, J.L.; Wright, S.A.

1998-10-28

334

Identification, selection, and enrichment of cardiomyocyte precursors.  

PubMed

The large-scale production of cardiomyocytes is a key step in the development of cell therapy and tissue engineering to treat cardiovascular diseases, particularly those caused by ischemia. The main objective of this study was to establish a procedure for the efficient production of cardiomyocytes by reprogramming mesenchymal stem cells from adipose tissue. First, lentiviral vectors expressing neoR and GFP under the control of promoters expressed specifically during cardiomyogenesis were constructed to monitor cell reprogramming into precardiomyocytes and to select cells for amplification and characterization. Cellular reprogramming was performed using 5'-azacytidine followed by electroporation with plasmid pOKS2a, which expressed Oct4, Sox2, and Klf4. Under these conditions, GFP expression began only after transfection with pOKS2a, and less than 0.015% of cells were GFP(+). These GFP(+) cells were selected for G418 resistance to find molecular markers of cardiomyocytes by RT-PCR and immunocytochemistry. Both genetic and protein markers of cardiomyocytes were present in the selected cells, with some variations among them. Cell doubling time did not change after selection. Together, these results indicate that enrichment with vectors expressing GFP and neoR under cardiomyocyte-specific promoters can produce large numbers of cardiomyocyte precursors (CMPs), which can then be differentiated terminally for cell therapy and tissue engineering. PMID:23853770

Zanetti, Bianca Ferrarini; Gomes, Walter José; Han, Sang Won

2013-01-01

335

Forecasting a CME by Spectroscopic Precursor?  

NASA Astrophysics Data System (ADS)

Multi-temperature plasma flows resulting from the interaction between a mature active region (AR) inside an equatorial coronal hole (CH) are investigated. Outflow velocities observed by Hinode EIS ranged from a few to 13 km s-1 for three days at the AR’s eastern and western edges. However, on the fourth day, velocities intensified up to 20 km s-1 at the AR’s western footpoint about six hours prior to a CME. 3D MHD numerical simulations of the observed magnetic configuration of the AR-CH complex showed that the expansion of the mature AR’s loops drives persistent outflows along the neighboring CH field (Murray et al. in Solar Phys. 261, 253, 2010). Based on these simulations, intensification of outflows observed pre-eruption on the AR’s western side where same-polarity AR and CH field interface, is interpreted to be the result of the expansion of a sigmoidal AR, in particular, a flux rope containing a filament that provides stronger compression of the neighboring CH field on this side of the AR. Intensification of outflows in the AR is proposed as a new type of CME precursor.

Baker, D.; van Driel-Gesztelyi, L.; Green, L. M.

2012-02-01

336

Precursor and processing conditions to make dense ceramic coatings using the solution precursor plasma spraying process  

NASA Astrophysics Data System (ADS)

The objective of this research is to determine the precursor and processing conditions to produce nanograined ceramic coatings with high density and hardness using the Solution Precursor Plasma Spray (SPPS) process. These dense coatings would find potential applications as optical ceramics, wear resistant coatings and bioactive coatings. Basic operating principles needed to create relatively dense coatings using the SPPS process have been discovered. These principles were then used to produce two new precursors and associated processing methods. It has been shown that dense coatings can be best produced if deposits arriving at the substrate are fully Incited. Multiple factors have been experimentally identified that provide dense coatings, including: (1) high solution concentration: (2) low melting temperature compositions; (3) large diameter gun nozzles: (4) high gun power and low liquid feed rates, (5) better entrainment of the droplets in the hot part of the plasma jet. Based on these principles of dense coating formation, dense eutectic Al2O3-YSZ SPPS coatings were produced. The as-deposited coating has 95.6% density and hardness of 11.8 GPa. The thermal stability of as-sprayed dense eutectic Al2O3-7YSZ coatings was examined. High temperature heat treatments of the coating show that both the phase and nano-grain structure are very stable. The nanocomposite Al 2O3-7YSZ coatings are highly grain growth resistant due to the increased diffusion path of species along interphase boundaries. The reproducibility of the principles to make dense ceramic coatings was successfully demonstrated by deposition of a low melting point TiO 2 coating that has desirable biological properties. A dense TiO 2 coating (96%) with a hardness of 7.6 GPa was achieved. The conditions for making dense coatings have been identified. The discovery and demonstration of basic principles for making dense SPPS coatings is a fundamental advancement of the state of the art for SPPS coating technology.

Chen, Dianying

337

Optical precursors with finite rise and fall time  

NASA Astrophysics Data System (ADS)

We report results of both theoretical and experimental studies of optical precursors generated from a square-modulated probe laser pulse having a finite rise and fall time and propagating through a cold atomic ensemble, under the conditions of either a two-level Lorentz absorber system or a three-level system with electromagnetically induced transparency (EIT). Because of the finiteness of the rise (and fall) time, the precursor signal is observed to decrease with increasing optical depth (?0L). We find that the precursor can experience little absorption even at high optical depth if the rise (and fall) time is sufficiently short. At an optical depth of ?0L = 42, the normalized precursor peak intensity is observed to increase from 9% to 27% when the rise (and fall) time is shortened from 7 to 3 ns. Meanwhile, we reaffirm that there is no violation of Einstein's causality principle in light propagation through both slow and fast light media. In the EIT system with high optical depth, the main field propagates with a subluminal group velocity and it is separated from the precursor. In the two-level system, the effect of negative group velocity in the anomalous dispersion regime is observed, but we detect no advancement in the rising edge of the precursors. In both cases, the leading edges of the precursors show no detectable delay to that through vacuum.

Chen, J. F.; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang

2010-10-01

338

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

339

Amyloid precursor protein modulates ?-catenin degradation  

PubMed Central

Background The amyloid precursor protein (APP) is genetically associated with Alzheimer's disease (AD). Elucidating the function of APP should help understand AD pathogenesis and provide insights into therapeutic designs against this devastating neurodegenerative disease. Results We demonstrate that APP expression in primary neurons induces ?-catenin phosphorylation at Ser33, Ser37, and Thr41 (S33/37/T41) residues, which is a prerequisite for ?-catenin ubiquitinylation and proteasomal degradation. APP-induced phosphorylation of ?-catenin resulted in the reduction of total ?-catenin levels, suggesting that APP expression promotes ?-catenin degradation. In contrast, treatment of neurons with APP siRNAs increased total ?-catenin levels and decreased ?-catenin phosphorylation at residues S33/37/T41. Further, ?-catenin was dramatically increased in hippocampal CA1 pyramidal cells from APP knockout animals. Acute expression of wild type APP or of familial AD APP mutants in primary neurons downregulated ?-catenin in membrane and cytosolic fractions, and did not appear to affect nuclear ?-catenin or ?-catenin-dependent transcription. Conversely, in APP knockout CA1 pyramidal cells, accumulation of ?-catenin was associated with the upregulation of cyclin D1, a downstream target of ?-catenin signaling. Together, these data establish that APP downregulates ?-catenin and suggest a role for APP in sustaining neuronal function by preventing cell cycle reactivation and maintaining synaptic integrity. Conclusion We have provided strong evidence that APP modulates ?-catenin degradation in vitro and in vivo. Future studies may investigate whether APP processing is necessary for ?-catenin downregulation, and determine if excessive APP expression contributes to AD pathogenesis through abnormal ?-catenin downregulation. PMID:18070361

Chen, Yuzhi; Bodles, Angela M

2007-01-01

340

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

341

Schwann Cell-Like Differentiation by Adult Oligodendrocyte Precursor Cells Following Engraftment  

E-print Network

Schwann Cell-Like Differentiation by Adult Oligodendrocyte Precursor Cells Following Engraftment demyelination; remyelination; noggin; adult oligodendrocyte precursor cell; astrocyte; spinal cord ABSTRACT spinal-cord- derived oligodendrocyte precursor cells (adult OPCs). In the present study, we demonstrate

Harkema, Susan

342

A simple way to prepare precursors for zirconium carbide  

Microsoft Academic Search

A precursor for zirconium carbide was obtained by just blending zirconium butoxide Zr(OC4H9)4 (ZTB) and divinylbenzene (DVB). This precursor satisfied the requirements for use in ceramic matrix composites fabrication\\u000a via precursor infiltration and pyrolysis (PIP) process, that is, it was a solution, cross-linked at 150 °C for 2 h, and transformed\\u000a to ZrC matrix upon heat treatment at 1,600 °C with a ceramic

Dan Zhao; Haifeng Hu; Changrui Zhang; Yudi Zhang; Jun Wang

2010-01-01

343

Surface doping of nitrogen atoms on graphene via molecular precursor  

SciTech Connect

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 (F{sub 4}-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 F{sub 4}-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; Ren, Jianguo; Xu, Tingting [Institution of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory of Carbon-based Functional Materials and Devices, Soochow University, Jiangsu (China) [Institution of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory of Carbon-based Functional Materials and Devices, Soochow University, Jiangsu (China); Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, Hong Kong (China); Wang, Chundong; Zhang, Wenjun [Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, Hong Kong (China)] [Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, Hong Kong (China); Lee, Shuit-Tong [Institution of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory of Carbon-based Functional Materials and Devices, Soochow University, Jiangsu (China)] [Institution of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory of Carbon-based Functional Materials and Devices, Soochow University, Jiangsu (China)

2013-02-04

344

Optical Precursors with Electromagnetically Induced Transparency in Cold Atoms  

NASA Astrophysics Data System (ADS)

We report the observation of Sommerfeld-Brillouin optical precursors generated from a long square-modulated laser pulse propagating through a cold atomic ensemble with electromagnetically induced transparency. The optical depth (?0L) of the medium can be varied from 0 up to 50. We demonstrated that the step-on rising and step-off falling edges propagate with the speed of light in vacuum without a slow light effect. At high ?0L, the precursor is separated from the delayed main pulse at the rising edge, while at the falling edge, we observe damped oscillatory structures resulting from the interference between the precursor and main field.

Wei, Dong; Chen, J. F.; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang

2009-08-01

345

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

346

A hydrophilic interaction liquid chromatography electrospray tandem mass spectrometry method for the simultaneous determination of ?-hydroxybutyrate and its precursors in forensic whole blood.  

PubMed

A liquid-chromatography-tandem-mass-spectrometry method using pneumatically assisted electrospray ionisation (LC-ESI-MS/MS) was developed for the simultaneous determination of ?-hydroxybutyric acid (GHB), ?-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in human ante-mortem and post-mortem whole blood. The blood proteins were precipitated using a mixture of methanol and acetonitrile, and the extract was cleaned-up by passage through a polymeric strong cation exchange sorbent. Separation of the analytes and their structural isomers was obtained using a column with a zwitterionic stationary phase. Matrix-matched calibrants, combined with isotope dilution, were used for quantitative analysis. GHB was determined in both positive and negative ion modes. The relative intra-laboratory reproducibility standard deviations were better than 10% and 6% for blood samples at concentrations of 2 mg/L and 20-150 mg/L, respectively. The mean true extraction recoveries were 80% for GHB and greater than 90% for GBL and 1,4-BD at concentration levels of 20-50 mg/L. The limits of detection were approximately 0.5 mg/L for GHB and GBL, and 0.02 mg/L for 1,4-BD in ante-mortem blood. The corresponding lower limits of quantification were less than 1 mg/L for GHB and GBL, and less than 0.1 mg/L for 1,4-BD. GBL was unstable in whole blood freshly preserved with a sodium fluoride oxalate mixture, but the stability could be improved significantly by preservation with a sodium fluoride citrate EDTA mixture. PMID:22917943

Sørensen, Lambert K; Hasselstrøm, Jørgen B

2012-10-10

347

Transportation Center Seminar........ "The Panama Canal as Precursor"  

E-print Network

Transportation Center Seminar........ "The Panama Canal as Precursor" Aaron J. Gellman Professor of Transportation The Transportation Center & Kellogg School of Management Northwestern University; Advisory:30 pm Location: Transportation Center, Chambers Hall Lower Level, 600 Foster St., Evanston Professor

Bustamante, Fabián E.

348

Quarternary Amines as Nitrosamine Precursors: A Role for Consumer Products?  

Technology Transfer Automated Retrieval System (TEKTRAN)

Nitrosamine formation is associated with wastewater-impacted water supplies, but the specific precursors within municipal wastewater effluents have not been identified. Quaternary amines are significant constituents of consumer products, including shampoos, detergents and fabric softeners. Experimen...

349

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

350

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

351

Club Drugs (GHB, Ketamine, and Rohypnol)  

MedlinePLUS

... and respiratory functions. 5 How Widespread Is Club Drug Abuse? Monitoring the Future (MTF) Survey* MTF has reported ... information about club drugs, visit www.drugabuse.gov/drugs-abuse/club-drugs . Data Sources * These data are from ...

352

Modafinil and ?-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep  

PubMed Central

Hypocretin-1 is a hypothalamic neuropeptide that is important in the regulation of wake and the lack of which results in the sleep disorder narcolepsy. Using a monkey that has consolidated wake akin to humans, we examined pharmacological manipulation of sleep and wake and its effects on hypocretin physiology. Monkeys were given the sleep-inducing gamma-hydroxybutyrate (GHB) and the wake-inducing modafinil both in the morning and in the evening. Cerebrospinal fluid (CSF) hypocretin-1 concentrations changed significantly in response to the drugs only when accompanied by a behavioral change (GHB-induced sleep in the morning or modafinil-induced wake in the evening). We also found that there was a large (180-fold) inter-individual variation in GHB pharmacokinetics that explains variability in sleep-induction in response to the drug. Our data indicate that the neurochemical concomitants of sleep and wake are capable of changing the physiological output of hypocretin neurons. Sleep independent of circadian timing is capable of decreasing CSF hypocretin-1 concentrations. Furthermore, hypocretin neurons do not appear to respond to an “effort” to remain awake, but rather keep track of time spent awake as a wake-promoting counterbalance to extended wakefulness. PMID:19752724

Zeitzer, Jamie M.; Buckmaster, Christine L.; Landolt, Hans-Peter; Lyons, David M.; Mignot, Emmanuel

2010-01-01

353

Characterization of specific succinate binding site in brain synaptic membranes.  

PubMed

A synaptic receptor for gamma-hydroxybutyric acid (GHB) --a naturally occurring metabolite of succinic acid--interacting succinate has been disclosed in rat and human nucleus accumbens (NA) subcellular fractions, but the molecular properties of this recognition site were not characterised. To address the presumed recognition site for succinate, the pharmacological profile of [3H]succinate binding to synaptic membranes prepared from rat forebrain and human NA samples has been investigated. Specific [3H]succinate binding sites in the human NA synaptic membrane fraction showed a strong pH-dependence and were characterized by binding of succinate (IC50 succinate=2.9+/-0.6 microM), GHB (IC50 GHB=2.1 +/-1.3 microM) and gap junction blocker carbenoxolone (IC50 = 7.1 +/-5.8 microM). A similar [3H]succinate binding profile was found in rat forebrain synaptic membrane fractions. We conclude the existence of a pHo-dependent synaptic membrane binding site for the intermediary metabolite succinate. The pharmacological properties of this recognition site may possibly suggest the existence of a hemichannel-like target protein for succinate. PMID:17451069

Molnár, Tünde; Fekete, Erzsébet Kutiné; Kardos, Julianna; Palkovits, Miklós

2007-03-30

354

Rapid screening for the detection and differentiation of ?-hydroxybutyrate using ion chromatography.  

PubMed

The analysis of gamma-hydroxybutyric acid (GHB) is problematic because it is hygroscopic, it lacks a good UV chromophore, and it undergoes heat-induced cyclization. This paper presents a new method utilizing ion-exchange chromatography (IC) with conductivity detection. The simple sample preparation, rapid analysis time, and inorganic anion detection capabilities are all advantages over the current methods. The detection of inorganic salts (formed during GHB synthesis) gives insight into the synthetic route utilized and can aid in drug seizure comparison. The developed method has a detection limit for GHB anions of 0.57 mg/L and chloride of 0.22 mg/L. A comparison of this technique with a current gas chromatography-mass spectrometry technique is presented, and a t-test found that the two methods' results are not statistically different at the 99.9% confidence level demonstrating the merits of this fast, simple, and informative IC method as a routine screening tool. PMID:21790598

Hughes, Rachel R; Walker, G Stewart

2011-09-01

355

Precursors for the polymer-assisted deposition of films  

DOEpatents

A polymer assisted deposition process for deposition of metal oxide films is presented. The process includes solutions of one or more metal precursor and soluble polymers having binding properties for the one or more metal precursor. After a coating operation, the resultant coating is heated at high temperatures to yield metal oxide films. Such films can be epitaxial in structure and can be of optical quality. The process can be organic solvent-free.

McCleskey, Thomas M.; Burrell, Anthony K.; Jia, Quanxi; Lin, Yuan

2013-09-10

356

Reverse tracing of short-term earthquake precursors  

NASA Astrophysics Data System (ADS)

We introduce a new approach to short-term earthquake prediction named " Reverse Tracing of Precursors" (RTP), since it considers precursors in reverse order of their appearance. First, we detect the "candidates" for the short-term precursors; in our case, these are newly introduced chains of earthquakes reflecting the rise of an earthquake correlation range. Then we consider each chain, one by one, checking whether it was preceded by an intermediate-term precursor in its vicinity. If yes, we regard this chain as a precursor; in prediction it would start a short-term alarm. The chain indicates the narrow area of possibly complex shape, where an intermediate-term precursor should be looked for. This makes possible to detect precursors undetectable by the direct analysis. RTP can best be described on an example of its application; we describe retrospective prediction of two prominent Californian earthquakes—Landers (1992), M=7.6, and Hector Mine (1999), M=7.3, and suggest a hypothetical prediction algorithm. This paper descripes the RTP methodology, which has potentially important applications to many other data and to prediction of other critical phenomena besides earthquakes. In particular, it might vindicate some short-term precursors, previously rejected as giving too many false alarms. Validation of the algorithm per se requires its application in different regions with a substantial number of strong earthquakes. First (and positive) retrospective results are obtained for 21 more strong earthquakes in California ( M?6.4), Japan ( M?7.0) and the Eastern Mediterranean ( M?6.5); these results are described elsewhere. The final validation requires, as always, prediction in advance for which this study sets up a base. We have the first case of a precursory chain reported in advance of a subsequent strong earthquake (Tokachi-oki, Japan, 25 September 2003, M=8.1). Possible mechanisms underlying RTP are outlined.

Keilis-Borok, V.; Shebalin, P.; Gabrielov, A.; Turcotte, D.

2004-07-01

357

Global Observations of Mantle Discontinuities Using SS and PP Precursors  

Microsoft Academic Search

SS and PP precursors are currently the only body wave data types that have significant coverage in both oceanic and continental\\u000a regions to study the existence and characteristics of mantle discontinuities on a global scale. Here, the techniques used\\u000a by global seismologists to observe SS and PP precursors are reviewed. Seismograms, aligned on SS or PP, are stacked using\\u000a normal

Arwen Deuss

2009-01-01

358

Stacked Optical Precursors from Amplitude and Phase Modulations  

NASA Astrophysics Data System (ADS)

We report the generation of stacked optical precursors from a laser beam whose amplitude or phase is modulated by sequenced on-off step waveforms. Making use of the constructive interference between the precursors produced from different steps, as well as the main field, we generate optical transient pulses having peak powers of eight times the input power with electromagnetically induced transparency in laser-cooled atoms.

Chen, J. F.; Jeong, Heejeong; Feng, L.; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang

2010-06-01

359

Analytical developments in toxicological investigation of drug-facilitated sexual assault.  

PubMed

This paper gives a general overview of the drug-facilitated sexual assault phenomenon. Sexual assault perpetrated on both women and men, while incapacitated by so-called date-rape drugs, recently became the focus of many investigations conducted by law enforcement agencies in the US throughout the 1990s; an alarming increase in reports of this crime as well as in the number of scientific publications on drug-facilitated sexual assault has been observed. The list of drugs reportedly associated with sexual assault is long and among others includes flunitrazepam with other benzodiazepines such as diazepam, temazepam, clonazepam, oxazepam, as well as gamma-hydroxybutyrate (GHB), ketamine, and scopolamine. We discuss the most recent analytical developments in the toxicological investigation of drug-facilitated rape designed to reveal drug presence and that may help successfully prosecute perpetrators. PMID:12682705

Negrusz, Adam; Gaensslen, R E

2003-08-01

360

[Chemical submission: a literature review].  

PubMed

The aim of this review is to describe the present knowledge about chemical submission. The number of scientific publications on this phenomenon has increased over the last 10 years. Perpetrators choose drugs which act rapidly, produce desinhibition, sedation, and anterograde amnesia during the abuse. Ethanol and benzodiazepines are the most frequently used. A few drugs, including flunitrazepam and gamma-hydroxybutyric acid (GHB), have received widespread media coverage. Toxicological investigations on blood, urine or hair samples allow to detect the substance used. Every effort should be made to collect appropriate specimens as quickly as possible. Gas chromatography-mass spectrometry is at present the most appropriate analytical method to detect these drugs in a biological specimen. PMID:16886708

Saint-Martin, Pauline; Furet, Yves; O'Byrne, Patrick; Bouyssy, Marie; Paintaud, Gilles; Autret-Leca, Elisabeth

2006-01-01

361

Active unfolding of precursor proteins during mitochondrial protein import.  

PubMed Central

Precursor proteins made in the cytoplasm must be in an unfolded conformation during import into mitochondria. Some precursor proteins have tightly folded domains but are imported faster than they unfold spontaneously, implying that mitochondria can unfold proteins. We measured the import rates of artificial precursors containing presequences of varying length fused to either mouse dihydrofolate reductase or bacterial barnase, and found that unfolding of a precursor at the mitochondrial surface is dramatically accelerated when its presequence is long enough to span both membranes and to interact with mhsp70 in the mitochondrial matrix. If the presequence is too short, import is slow but can be strongly accelerated by urea-induced unfolding, suggesting that import of these 'short' precursors is limited by spontaneous unfolding at the mitochondrial surface. With precursors that have sufficiently long presequences, unfolding by the inner membrane import machinery can be orders of magnitude faster than spontaneous unfolding, suggesting that mhsp70 can act as an ATP-driven force-generating motor during protein import. PMID:9362487

Matouschek, A; Azem, A; Ratliff, K; Glick, B S; Schmid, K; Schatz, G

1997-01-01

362

Anti-Alcohol and Anxiolytic Properties of a New Chemical Entity, GET73.  

PubMed

N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide (GET73) is a newly synthesized compound structurally related to the clinically used, alcohol-substituting agent, gamma-hydroxybutyric acid (GHB). The present study was designed to assess whether GET73 may share with GHB the capacity to reduce alcohol intake in rats. Additionally, the effect of treatment with GET73 on anxiety-related behaviors and cognitive tasks in rats was investigated. A series of in vitro binding assays investigated the capacity of GET73 to bind to the GHB binding site and multiple other receptors. GET73 (10(-9)-10(-3)?M) failed to inhibit [(3)H]GHB binding at both high- and low-affinity GHB recognition sites in rat cortical membranes. GET73 displayed minimal, if any, binding at dopamine, serotonin, GABA, and glutamate receptors in membranes from different rat brain areas. Acute treatment with low-to-moderate, non-sedative doses of GET73 (5-50?mg/kg, i.g. or i.p.) (a) reduced alcohol intake and suppressed "alcohol deprivation effect" (a model of alcohol relapse) in selectively bred, Sardinian alcohol-preferring (sP) rats, (b) exerted anxiolytic effects in Sprague-Dawley (SD) and sP rats exposed to the Elevated Plus Maze test, and (c) tended to induce promnestic effects in SD rats exposed to a modified water version of the Hebb-Williams maze test. Although the mechanism of GET73 action is currently unknown, the results of the present study suggest that GET73 has a multifaceted pharmacological profile, including the capacity to reduce alcohol drinking and anxiety-related behaviors in rats. PMID:22347868

Loche, Antonella; Simonetti, Francesco; Lobina, Carla; Carai, Mauro A M; Colombo, Giancarlo; Castelli, M Paola; Barone, Domenico; Cacciaglia, Roberto

2012-01-01

363

Gamma-aminobutyric acidB (GABAB)-receptor mediation of different in vivo effects of gamma-butyrolactone.  

PubMed

The endogenous brain constituent, gamma-hydroxybutyric acid (GHB), as well as its prodrug, gamma-butyrolactone (GBL), have recently gained interest in the drug addiction field due to their abuse potential and fatalities caused by overdose. It is known that GHB has two sites of actions: the gamma-aminobutyric acid(B) (GABA(B)) receptor and a specific-GHB binding site. The present study was designed to extend to GBL the investigations on the contribution of the GABA(B) receptor and the specific-GHB binding site to its in vivo effects. To this aim, DBA mice were pretreated either with GABA(B)-receptor antagonists, (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP 35348) and (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), or a putative antagonist of the specific-GHB binding site, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), prior to the administration of doses of GBL that induced hypothermia, motor-incoordination (measured as motor-impairment at the Rota-Rod task), and sedation/hypnosis. The capability of SCH 50911 and NCS-382 to protect against GBL-induced lethality was also investigated. Pretreatment with either GABA(B)-receptor antagonist completely prevented GBL-induced hypothermia, motor-incoordination, and sedation /hypnosis. SCH 50911 also provided complete protection against GBL-associated lethality. Vice versa, NCS-382 failed to exert any antagonistic or protective effect. These results suggest that the in vivo GBL effects tested in the present study are mediated by activation of the GABA(B) receptor. PMID:18270475

Carai, Mauro A M; Lobina, Carla; Maccioni, Paola; Cabras, Claudia; Colombo, Giancarlo; Gessa, Gian Luigi

2008-02-01

364

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

365

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

366

Elements of the tsunami precursors' detection physics  

NASA Astrophysics Data System (ADS)

In accordance with the main physical principles and geophysical data, we formulated a nonlinear mathematical model of seismo-hydro-electromagnetic (EM) geophysical field interaction and calculated generation and propagation of elastic, EM, temperature and hydrodynamic seismically generated disturbances (i.e. signals) in the basin of a marginal sea. We show transferring of seismic and electromagnetic (EM) energy from the upper mantle beneath the sea into its depths and EM emission from the sea surface into the atmosphere. Basing on the calculated characteristics of the signals of different physical nature (computations correspond to measurements of other authors) we develop the project of a Lithosphere-Ocean-Atmosphere Monitoring System (LOAMS) including: a bottom complex, a moored ocean surface buoy complex, an observational balloon complex, and satellite complex. The underwater stations of the bottom complex of the LOAMS will record the earlier signals of seismic activation beneath a seafloor (the ULF EM signals outrun seismic ones, according to the above calculations) and localize the seafloor epicenter of an expected seaquake. These stations will be equipped, in particular, with: magnetometers, the lines for the electric field measurements, and magneto-telluric blocks to discover dynamics of physical parameters beneath a sea floor as signs of a seaquake and/or tsunami preparation process. The buoy and balloon complexes of the LOAMS will record the meteorological and oceanographic parameters' variations including changes of reflection from a sea surface (tsunami ‘shadows’) caused by a tsunami wave propagation. Cables of the balloon and moored buoy will be used as receiving antennas and for multidisciplinary measurements including gradients of the fields (we show the cases are possible when the first seismic EM signal will be registered by an antenna above a sea). Also, the project includes radio-tomography with satellite instrumentation and sounding of the ionosphere from the buoy, balloon and satellite complexes. The balloon and buoy complexes will transmit data to a shore station over satellite link. The frequency ranges and sensitivity thresholds of all of the sensors of the LOAMS will be adapted to the characteristics of expected seismic signals according to the numerical research above. Computational methods and statistical analysis (e.g. seismic changes of coherence of spatially distributed sensors of different nature) of the recorded multidimensional time series will be used for prognostic interpretation. The multilevel recordings will provide a stable noise (e.g. ionosphere Pc pulsations, hard sea, industry) and seismic event detection. An intensive heat flow typical for tectonically active lithosphere zones may be considered as an energy source for advanced modifications of the LOAMS. The latter may be used as a warning system for continental and marine technologies, e.g. a sea bottom geothermal energy production. Indeed, seismic distraction of the nuclear power station Fukushima I demonstrates that similar technology hardly is able to solve the energy problems in seismically active regions. On the other hand, the LOAMS may be considered as a scientific observatory for development of the seaquake/tsunami precursor physics, i.e. seismo-hydro-electromagnetics.

Novik, Oleg; Ruzhin, Yuri; Ershov, Sergey; Volgin, Max; Smirnov, Fedor

367

Chondrules: Precursors and interactions with the nebular gas  

NASA Astrophysics Data System (ADS)

Chondrule compositions suggest either ferroan precursors and evaporation, or magnesian precursors and condensation. Type I chondrule precursors include granoblastic olivine aggregates (planetary or nebular) and fine-grained (dustball) precursors. In carbonaceous chondrites, type I chondrule precursors were S-free, while type II chondrules have higher Fe/Mn than in ordinary chondrites. Many type II chondrules contain diverse forsteritic relicts, consistent with polymict dustball precursors. The relationship between finer and coarser grained type I chondrules in ordinary chondrites suggests more evaporation from more highly melted chondrules. Fe metal in type I, and Na and S in type II chondrules indicate high partial pressures in ambient gas, as they are rapidly evaporated at canonical conditions. The occurrence of metal, sulfide, or low-Ca pyroxene on chondrule rims suggests (re)condensation. In Semarkona type II chondrules, Na-rich olivine cores, Na-poor melt inclusions, and Na-rich mesostases suggest evaporation followed by recondensation. Type II chondrules have correlated FeO and MnO, consistent with condensation onto forsteritic precursors, but with different ratios in carbonaceous chondrites and ordinary chondrites, indicating different redox history. The high partial pressures of lithophile elements require large dense clouds, either clumps in the protoplanetary disk, impact plumes, or bow shocks around protoplanets. In ordinary chondrites, clusters of type I and type II chondrules indicate high number densities and their similar oxygen isotopic compositions suggest recycling together. In carbonaceous chondrites, the much less abundant type II chondrules were probably added late to batches of type I chondrules from different O isotopic reservoirs.

Hewins, Roger H.; Zanda, Brigitte

2012-07-01

368

Thin film solar cells by selenization sulfurization using diethyl selenium as a selenium precursor  

DOEpatents

A method of forming a CIGSS absorber layer includes the steps of providing a metal precursor, and selenizing the metal precursor using diethyl selenium to form a selenized metal precursor layer (CIGSS absorber layer). A high efficiency solar cell includes a CIGSS absorber layer formed by a process including selenizing a metal precursor using diethyl selenium to form the CIGSS absorber layer.

Dhere, Neelkanth G.; Kadam, Ankur A.

2009-12-15

369

Precursor conversion kinetics and the nucleation of cadmium selenide nanocrystals.  

PubMed

The kinetics of cadmium selenide (CdSe) nanocrystal formation was studied using UV-visible absorption spectroscopy integrated with an automated, high-throughput synthesis platform. Reaction of anhydrous cadmium octadecylphosphonate (Cd-ODPA) with alkylphosphine selenides (1, tri-n-octylphosphine selenide; 2, di-n-butylphenylphosphine selenide; 3, n-butyldiphenylphosphine selenide) in recrystallized tri-n-octylphosphine oxide was monitored by following the absorbance of CdSe at ? = 350 nm, where the extinction coefficient is independent of size, and the disappearance of the selenium precursor using {(1)H}(31)P NMR spectroscopy. Our results indicate that precursor conversion limits the rate of nanocrystal nucleation and growth. The initial precursor conversion rate (Q(o)) depends linearly on [1] (Q(o)(1) = 3.0-36 ?M/s) and decreases as the number of aryl groups bound to phosphorus increases (1 > 2 > 3). Changes to Q(o) influence the final number of nanocrystals and thus control particle size. Using similar methods, we show that changing [ODPA] has a negligible influence on precursor reactivity while increasing the growth rate of nuclei, thereby decreasing the final number of nanocrystals. These results are interpreted in light of a mechanism where the precursors react in an irreversible step that supplies the reaction medium with a solute form of the semiconductor. PMID:21128655

Owen, Jonathan S; Chan, Emory M; Liu, Haitao; Alivisatos, A Paul

2010-12-29

370

Gamma-Ray Burst Precursor Activity as Observed with BATSE  

NASA Technical Reports Server (NTRS)

Gamma-ray burst time histories often consist of multiple episodes of emission with the count rate dropping to the background level between adjacent episodes. We define precursor activity as any case in which the first episode (referred to as the precursor episode) has a lower peak intensity than that of the remaining emission (referred to as the main episode) and is separated from the remaining burst emission by a background interval that is at least as long as the remaining emission. We find that approx. 3% of the bursts observed with the Burst and Transient Source Experiment (BATSE) on Compton Gamma Ray Observatory (CGRO) satisfy this definition. We present the results of a study of the properties of these events. The spatial distribution of these sources is consistent with that of the larger set of all BATSE gamma-ray bursts: inhomogeneous and isotropic. A correlation between the duration of the precursor emission and the duration of the main episode emission is observed at about the 3 sigma confidence level. We find no meaningful significant correlations between or among any of the other characteristics of the precursor or main episode emission. It appears that the characteristics of the main episode emission are independent of the existence of the precursor emission.

Koshut, Thomas M.; Kouveliotou, Chryssa; Paciesas, William S.; vanParadijs, Jan; Pendleton, Geoffrey N.; Briggs, Michael S.; Fishman, Gerald J.; Meegan, Charles A.

1995-01-01

371

Fast Light, Slow Light, and Optical Precursors in Cold Atoms  

NASA Astrophysics Data System (ADS)

We report experimental observations of optical precursors generated from a square-modulated probe laser pulse, with finite rise and fall time, propagating through a cold atomic ensemble, in either a two-level Lorentz absorber or a three-level system with electromagnetically induced transparency (EIT). Because of the finite rise (fall) time, the precursor signal decreases as we increase the optical depth (?0 L). We find that the absorption of the precursor peak magnitude can be controlled by varying the rise (fall) time. At ?0 L =42, we increase the precursor peak transmission from 8% to 27% by shortening the rise (fall) time from 7 ns to 3 ns. Meanwhile, we observe no violation to Einstein's causality in both slow and fast light mediums. In the EIT system at a high OD, the main field propagates with a slow group velocity and is separated from the precursor. In the two-level system, we confirm the negative group velocity in the anomalous dispersion regime, but no advancement to the rising edge.

Chen, Jiefei; Loy, Michael M. M. T.; Lun Wong, George Ke; Du, Shengwang

2010-03-01

372

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. PMID:23392755

Morse, Bridget L.

2013-01-01

373

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

374

Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply  

PubMed Central

Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components. PMID:25487822

O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

2014-01-01

375

Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply  

NASA Astrophysics Data System (ADS)

Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components.

O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

2014-12-01

376

Synthetic precursor to vertical TiO2 nanowires  

NASA Astrophysics Data System (ADS)

An easy protocol for improvement in formation of the photoanode in a dye sensitized solar cell is addressed. Specifically, a novel synthesis for the formation of a TiO2 precursor: titanium butanediolate, is detailed. This precursor is found to have higher thermal and temporal stability than commercially available TiO2 precursors and it has successfully been employed in the one-pot synthesis of rutile nanowires grown directly on a conducting substrate: fluorine doped tin oxide (FTO). This synthesis has been further extended to directly form a mixed phase TiO2 film consisting of rutile nanowires along with anatase spherical particles on FTO and this assembly has been used as the photoanode in a dye-sensitized solar cell. The synergistic effect of the two phases has provided a net DSSC efficiency of 4.61% with FF = 61%.

Mishra, B.; Ghildiyal, P.; Agarkar, S.; Khushalani, D.

2014-04-01

377

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

378

The behaviors of optimal precursors during wintertime Eurasian blocking onset  

NASA Astrophysics Data System (ADS)

In this paper the optimal precursors for wintertime Eurasian blocking onset are acquired by solving a nonlinear optimization problem whose objective function is constructed based on a blocking index with a triangular T21, three-level, quasi-geostrophic global spectral model. The winter climatological state is chosen as the reference basic state. Numerical results show that the optimal precursors are characterized by a baroclinic pattern with a westward tilt with height, which are mainly located upstream of the blocking region. For an optimization time of 5 days, these perturbations are mainly localized over the Northeast Atlantic Ocean and continental Europe. With the extension of the optimization time to 8 days, these perturbations are distributed more upstream and extensively in the zonal direction. Wave spectrum analysis reveals that the optimal precursors are composed of not only synoptic-scale (wave numbers 5-18) waves, but planetary-scale (wave numbers 0-4) waves as well. The synoptic-scale optimal precursors are mainly located in the mid-latitude area, while the planetary-scale optimal precursors focus primarily on the high-latitude region. The formation of a strong planetary-scale positive blocking anomaly is accompanied by the reinforcement of synoptic-scale perturbations and further fragmentation into two branches, in which the northern branch is generally stronger than the southern one. The eddy forcing arising from the self-interaction of synoptic-scale disturbances is shown to be crucial in triggering the dipole blocking anomaly, and the planetary-scale optimal precursor provides the initial favorable background conditions for blocking onset.

Jiang, Zhina; Wang, Donghai

2012-11-01

379

Galiellalactone analogs and their possible precursors from Sarcosomataceae.  

PubMed

Galiellalactone analogs (1-4) (including two new compounds), together with their possible precursors (5-9, named pregaliellalactone B-F), were obtained from the solid cultures of an endophytic fungus Sarcosomataceae NO.45-1-8-1. Their chemical structures were elucidated by analyses of HR ESI-TOF MS, 1D-, 2D-NMR, CD spectra and single crystal X-ray diffraction methods. Compounds 5-9, the possible precursors of galiellalactone analogs, were found to exist as enantiomers for the first time. The cytotoxicity of these compounds against six tumor cell lines was examined and preliminary structure-activity relationship (SAR) was also discussed. PMID:25592721

Tian, Jie-Feng; Yu, Ru-Jian; Li, Xiao-Xia; Gao, Hao; Guo, Liang-Dong; Li, Yan; Li, Jia; Tang, Jin-Shan; Yao, Xin-Sheng

2015-03-01

380

Impact of delayed neutron precursor mobility in fissile solution systems  

SciTech Connect

A research version of the Monte Carlo software package MCNP6 is modified to incorporate advection and diffusion of delayed neutron precursors, resulting in the emission of delayed neutrons at locations different from the original fission sites. Results of two test problems, a pipe carrying flowing fissile solution and a sphere of fissile solution with precursor diffusion, show that the fission product mobility tends to perturb the fundamental mode, has a negative reactivity effect, and, perhaps most importantly, causes a decrease in the effective delayed neutron fraction. (authors)

Kiedrowski, B. C. [X-Computational Physics Div., Los Alamos National Laboratory, MS A143, P.O. Box 1663, Los Alamos, NM 87545 (United States)

2012-07-01

381

Precursor mass dependent filtering of mass spectra for proteomics analysis.  

PubMed

Identification and elimination of noise peaks in mass spectra from large proteomics data streams simultaneously improves the accuracy of peptide identification and significantly decreases the size of the data. There are a number of peak filtering strategies that can achieve this goal. Here we present a simple algorithm wherein the number of highest intensity peaks retained for further analysis is proportional to the mass of the precursor ion. We show that this technique provides an improvement over other intensity based strategies, especially for low mass precursors. PMID:23855660

Reiz, Beata; Myers, Michael P; Pongor, Sandor; Kertesz-Farkas, Attila

2014-01-01

382

Neuronal Differentiation from Postmitotic Precursors in the Ciliary Ganglion  

E-print Network

placed in culture, nonneuronal cells acquired immunoreactivity for HuD, suggesting that they had of this precursor pool was transient because nonneuronal cells isolated from St. 38 ganglia failed to form neurons migration and/or after reaching their destina- tions, with the exception of neural crest-derived stem cells

Nishi, Rae

383

Precursors and Consequences of Membership in Youth Gangs.  

ERIC Educational Resources Information Center

Studied explanations for gang membership in a population of 11,000 secondary school students. Lower self-esteem, perceived academic ability, psychosocial health, and bonds with institutions appeared to precede gang membership. Other precursors and consequences identified were also consistent with a lack of social integration. (SLD)

Dukes, Richard L.; Martinez, Ruben O.; Stein, Judith A.

1997-01-01

384

Fullerenes from aromatic precursors by surface-catalysed cyclodehydrogenation.  

PubMed

Graphite vaporization provides an uncontrolled yet efficient means of producing fullerene molecules. However, some fullerene derivatives or unusual fullerene species might only be accessible through rational and controlled synthesis methods. Recently, such an approach has been used to produce isolable amounts of the fullerene C(60) from commercially available starting materials. But the overall process required 11 steps to generate a suitable polycyclic aromatic precursor molecule, which was then dehydrogenated in the gas phase with a yield of only about one per cent. Here we report the formation of C(60) and the triazafullerene C(57)N(3) from aromatic precursors using a highly efficient surface-catalysed cyclodehydrogenation process. We find that after deposition onto a platinum (111) surface and heating to 750 K, the precursors are transformed into the corresponding fullerene and triazafullerene molecules with about 100 per cent yield. We expect that this approach will allow the production of a range of other fullerenes and heterofullerenes, once suitable precursors are available. Also, if the process is carried out in an atmosphere containing guest species, it might even allow the encapsulation of atoms or small molecules to form endohedral fullerenes. PMID:18704082

Otero, Gonzalo; Biddau, Giulio; Sánchez-Sánchez, Carlos; Caillard, Renaud; López, María F; Rogero, Celia; Palomares, F Javier; Cabello, Noemí; Basanta, Miguel A; Ortega, José; Méndez, Javier; Echavarren, Antonio M; Pérez, Rubén; Gómez-Lor, Berta; Martín-Gago, José A

2008-08-14

385

Ultrasonic Thickness Measurement of Multilayered Aluminum Foam Precursor Material  

Microsoft Academic Search

Metallic foams are prospective materials for use in the aerospace and automotive industry for crash energy absorption safety parts or lightweight constructions. During manufacturing, artifacts in the foamable precursor material or material quality variations can influence the foam structure after the foaming process; thus, such a process requires quality control. The advantage of ultrasonic techniques is the possibility to perform

Renaldas Raisutis; Rymantas Kazys; Liudas Mazeika

2008-01-01

386

Deoxythymidine sugars are not direct precursors of DNA-thymine.  

PubMed Central

A theoretical model for the kinetics of uptake of a putative precursor molecule into nucleotide pools and into replicating DNA has been developed. The relationship between the accumulation of radioactively labeled precursors in the pool and the appearance of radioactivity in DNA is then derived. Experiments have been carried out in bacteria to compare the uptake of radioactive thymine into deoxythymidine triphosphate, deoxythymidine diphosphate sugars, and DNA to test the suitability of either compound as the direct precursor of thymine in DNA. New one-dimensional, thin-layer chromatographic procedures were used to determine the specific activity of deoxythymidine triphosphate and deoxythymidine triphosphate and deoxythymidine diphosphate sugars in growing cultures of 32PO4-labeled Escherichia coli during pulse labeling with [3H]-thymine. A comparison of the experimental data with our theoretical model supports the hypothesis that deoxythymidine triphosphate, but not deoxythymidine sugar, is the direct precursor of thymine in normally replicating DNA in vivo. Images FIGURE 4 FIGURE 5 PMID:400471

Loehr, J; Hanawalt, P

1979-01-01

387

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

388

Synthesis and Characterization of Nanocrystalline Magnetic Pigment via Coordinated Precursors  

Microsoft Academic Search

anocrystalline cobalt ferrite as a magnetic black pigment was synthesized via coordinated precursors with a significant decrease of the synthesis temperature using citric acid as a coordinating agent. The structure and properties of the cobalt ferrite powder were characterized by X-ray diffraction (XRD), colorimetric analysis (L * a * b * color parameters), diffuse reflectance spectroscopy and vibrating sample magnetometer

M. Gharagozlou

389

EMPIRICAL RELATIONSHIPS BETWEEN ATMOSPHERIC NITROGEN DIOXIDE AND ITS PRECURSORS  

EPA Science Inventory

Aerometric data were examined to define relationships between atmospheric NO2 and its precursors. A descriptive and critical analysis of the nationwide data base of NO2 was carried out, followed by the formulation application and testing of empirical models relating ambient NO2 c...

390

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

391

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...

392

Introduction In many vertebrate cell lineages, precursor cells divide a  

E-print Network

been studying the stopping mechanisms in the oligodendrocyte cell lineage in the rodent optic nerve. Oligodendrocyte precursor cells (OPCs) migrate from the brain into the developing rat optic nerve before birth differentiate into oligodendrocytes (Temple and Raff, 1986), which then myelinate the axons in the nerve

Richardson, William D.

393

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

394

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. PMID:18258847

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

395

RIVERBANK FILTRATION: FATE OF DBP PRECURSORS AND SELECTED MICROORGANISMS  

EPA Science Inventory

The fate of disinfection by-product (DBP) precursors and selected microorganisms during riverbank filtration (RBF) was monitored at three different mid-Western drinking water utilities. At all three sites, filtration (RBF) was monitored at three different mid-Western drinking wa...

396

A systematic search for mantle discontinuities using SS-precursors  

Microsoft Academic Search

We perform a systematic search for reflectors in the upper and lower mantle using SS-precursors. The largest number of robust reflections comes from a depth of 220 km, which we associate with the Lehmann discontinuity. This discontinuity is observed below both continental and oceanic areas, though the largest amplitudes appear beneath the continents. There is also evidence for weak discontinuities

Arwen Deuss; John H. Woodhouse

2002-01-01

397

Technical Note: Methionine, a precursor of methane in living plants  

NASA Astrophysics Data System (ADS)

When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued not only about their contribution to the global methane budget but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds to be identified. We made use of stable isotope techniques to verify the in vivo formation of methane, and, in order to identify the carbon precursor, 13C positionally labeled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labeled methionine clearly identified the sulfur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

2015-03-01

398

Comparative Proteomics Indicates That Biosynthesis of Pectic Precursors Is Important  

E-print Network

-1 mutants were complemented either by genetic transformation of the respective cotton cDNA or by add- ingComparative Proteomics Indicates That Biosynthesis of Pectic Precursors Is Important for Cotton, Yong-Mei Qin, Tamara L. Western , Shu-Xun Yu¶§**, and Yu-Xian Zhu §§¶¶ The quality of cotton fiber

Western, Tamara L.

399

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...

400

How Amyloid Precursor Protein Protects itself from Cleavage  

PubMed Central

SUMMARY Steven Smith and co-workers probe how the Flemish mutation in amyloid precursor protein (APP) affects its conformation and cleavage by ?-secretase (Tang et al., 2014). They provide molecular insight into how an extracellular inhibitory element and cholesterol interactions affect the generation of A? peptides. PMID:24607141

Lin, Hsiang-Kai; van der Wel, Patrick C A

2014-01-01

401

Sphingolipids and their precursors in human brain (Normal and MS)  

Microsoft Academic Search

In view of the deficits of sphingolipids and of nervonic acid in presence of normal quantities of cholesterol and total proteins in MS white matter reported earlier, the fatty acids of these lipids and of their possible precursors were analyzed. Small quantities of ceramides were present in all specimens. These, as well as the cerebrosides of 2 MS gray matters

B. Gerstl; M. G. Tavaststjerna; L. F. Eng; J. K. Smith

1972-01-01

402

Precursors of Insight in Event-related Brain Potentials  

Microsoft Academic Search

Event-related potentials (ERPs) were investigated to find precursors of insightful behavior. Participants had to process successive pairs in strings of digits to obtain a final response in each trial. Within the sequence of five responses required in each trial, the last two responses mirrored the two preceding ones. This hidden regularity, allowing for shortcutting each trial from five to two

Simone Lang; Nadine Kanngieser; Piotr Ja??kowski; Hilde Haider; Michael Rose; Rolf Verleger

2006-01-01

403

Technical note: Methionine, a precursor of methane in living plants  

NASA Astrophysics Data System (ADS)

When terrestrial plants were identified as producers of the greenhouse gas methane, much discussion and debate ensued, not only about their contribution to the global methane budget, but also with regard to the validity of the observation itself. Although the phenomenon has now become more accepted for both living and dead plants, the mechanism of methane formation in living plants remains to be elucidated and its precursor compounds identified. We made use of stable isotope techniques to verify in vivo formation of methane and, in order to identify the carbon precursor, 13C-positionally labelled organic compounds were employed. Here we show that the amino acid L-methionine acts as a methane precursor in living plants. Employing 13C-labelled methionine clearly identified the sulphur-bound methyl group of methionine as a carbon precursor of methane released from lavender (Lavandula angustifolia). Furthermore, when lavender plants were stressed physically, methane release rates and the stable carbon isotope values of the emitted methane greatly increased. Our results provide additional support that plants possess a mechanism for methane production and suggest that methionine might play an important role in the formation of methane in living plants, particularly under stress conditions.

Lenhart, K.; Althoff, F.; Greule, M.; Keppler, F.

2014-11-01

404

Glutamine: Precursor or nitrogen donor for citrulline synthesis?  

Technology Transfer Automated Retrieval System (TEKTRAN)

Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton, versus nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutami...

405

Manufacture of monolithic ceramic bodies from polysilazane precursor  

Microsoft Academic Search

A low temperature process for the manufacture of non-oxide monolithic ceramic bodies is presented. This process is based on the pyrolysis at temperatures between 1000 and 1400 °C of the polysilazane precursor.The different steps of the process are precisely described. The physical (porosity, density, crystalline phases) and mechanical properties (flexural strength, Young's modulus, toughness and hardness) of the bodies obtained

M. F. Gonon; G. Fantozzi; M. Murat; J. P. Disson

1995-01-01

406

Amyloid Precursor Protein and Presenilin Involvement in Cell Signaling  

Microsoft Academic Search

To date the most relevant role for the amyloid precursor protein (APP) and for the presenilins (PSs) on Alzheimer’s disease (AD) genesis is linked to the ‘amyloid hypothesis’, which considers an aberrant formation of amyloid-? peptides the cause of neurodegeneration. In this view, APP is merely a substrate, cleaved by the ?-secretase complex to form toxic amyloid peptides, PSs are

Valentina Venezia; Mario Nizzari; Pia Carlo; Alessandro Corsaro; Tullio Florio; Claudio Russo

2007-01-01

407

Particulate and THM precursor removal with ferric chloride  

SciTech Connect

Pilot-scale experiments were performed to investigate the effectiveness of enhanced coagulation in removing particles and trihalomethane (THM) precursors from two surface source waters: California State Project water and Colorado River water. The removal of suspended particles and natural organic matter at various ferric chloride doses and coagulation pHs was assessed through source water and filter effluent measurements of turbidity, particle count. UV{sub 254}, TOC, and THM formation potential. Overall, it was found that optimal removal of particles and THM precursors by enhanced coagulation with ferric chloride is obtained at high coagulant doses and low pH conditions. Generally, turbidity removal is more efficient and head loss is more moderate at ambient pH compared with pH 5.5. Additionally, filter effluent particle counts were found to be consistent with residual turbidity data. The removal of THM precursors by enhanced coagulation is significantly enhanced at pH 5.5 compared with ambient pH. The reduction in THM formation potential is consistent with the trends observed for the THM precursor removal data. Furthermore, specific UV absorbance was used to estimate the proportion of humic substances in the raw waters. Enhanced coagulation was found to be less effective for the source water with the lower specific UV absorbance.

Childress, A.E.; Vrijenhoek, E.M.; Elimelech, M.; Tanaka, T.S.; Beuhler, M.D.

1999-11-01

408

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

409

Anise oil as para-methoxyamphetamine (PMA) precursor  

Microsoft Academic Search

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

Dieter Waumans; Noël Bruneel; Jan Tytgat

2003-01-01

410

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

411

Apoptotic Osteocytes Regulate Osteoclast Precursor Recruitment and Differentiation In Vitro  

E-print Network

Apoptotic Osteocytes Regulate Osteoclast Precursor Recruitment and Differentiation In Vitro Saja A, Toronto, ON, Canada ABSTRACT Fatigue loading causes a spatial distribution of osteocyte apoptosis co-localized with bone resorption spaces peaking around microdamage sites. Since osteocytes have been shown to regulate

You, Lidan

412

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

413

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2011 CFR

...formation under favorable reaction conditions when they are used to produce other chemicals or products. The following...made from precursor chemical substances identified...must report process and reaction condition data on Part...Form 7710-51 for each chemical product. A...

2011-07-01

414

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2013 CFR

...formation under favorable reaction conditions when they are used to produce other chemicals or products. The following...made from precursor chemical substances identified...must report process and reaction condition data on Part...Form 7710-51 for each chemical product. A...

2013-07-01

415

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2012 CFR

...formation under favorable reaction conditions when they are used to produce other chemicals or products. The following...made from precursor chemical substances identified...must report process and reaction condition data on Part...Form 7710-51 for each chemical product. A...

2012-07-01

416

40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2014 CFR

...formation under favorable reaction conditions when they are used to produce other chemicals or products. The following...made from precursor chemical substances identified...must report process and reaction condition data on Part...Form 7710-51 for each chemical product. A...

2014-07-01

417

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

418

Making Single-Source Precursors of Ternary Semiconductors  

NASA Technical Reports Server (NTRS)

A synthesis route has been developed for the commercial manufacture of single- source precursors of chalcopyrite semiconductor absorber layers of thin-film solar photovoltaic cells. A closely related class of single-source precursors of these semiconductors, and their synthesis routes, were reported in "Improved Single-Source Precursors for Solar-Cell Absorbers" (LEW-17445-1), NASA Tech Briefs, Vol. 31, No. 6 (June 2007), page 56. The present synthesis route is better suited to commercialization because it is simpler and involves the use of commercially available agents, yet offers the flexibility needed for synthesis of a variety of precursors. A single-source precursor of the type of interest here is denoted by the general formula L2M'(mu-ER)2M(ER)2, where L signifies a Lewis base; M signifies Al, In, or Ga; M' signifies Ag or Cu; R signifies an alkyl, aryl, silyl, or perfluorocarbon group; E signifies O, S, Se, or Te; and mu signifies a bridging ligand. This compound can be synthesized in a "one-pot" procedure from ingredients that are readily available from almost any chemical supplier. In a demonstration, the following synthesis was performed: Under anaerobic conditions, InCl3 was reacted with sodium ethanethiolate in methanol in a 1:4 molar ratio to afford the ionic stable intermediate compound Na+[In(SEt)4]- (where Et signifies ethyl group). After approximately 15 minutes, a heterogeneous solution of CuCl and the Lewis base PPh3 (where Ph signifies phenyl) in a 1:2 ratio in a mixture of CH3CN and CH2Cl2 was added directly to the freshly prepared Na+[In(SEt)4]-. After 24 hours, the reaction was essentially complete. The methanolic solution was concentrated, then the product was extracted with CH2Cl2, then the product was washed with dry ether and pentane. The product in its final form was a creamy white solid. Spectroscopic and elemental analysis confirmed that the product was (PPh3)2Cu(mu-SEt)2In(mu-SEt)2, which is known to be a precursor of the ternary semiconductor CuInS2.

Hepp, Aloysius; Banger, Kulbindre K.

2007-01-01

419

Precursor Analysis for Flight- and Ground-Based Anomaly Risk Significance Determination  

NASA Technical Reports Server (NTRS)

This slide presentation reviews the precursor analysis for flight and ground based anomaly risk significance. It includes information on accident precursor analysis, real models vs. models, and probabilistic analysis.

Groen, Frank

2010-01-01

420

Putative Disulfide-Forming Pathway of Porcine Insulin Precursor during Its Refolding in Vitro  

E-print Network

Putative Disulfide-Forming Pathway of Porcine Insulin Precursor during Its Refolding in Vitro Zhi the in vitro disulfide-forming pathway of a recombinant porcine insulin precursor (PIP). In redox buffer

Tian, Weidong

421

Precursors in the preparation of transition metal nitrides and transition metal carbonitrides and their reaction intermediates  

DOEpatents

A process for making ammonolytic precursors to nitride and carbonitride ceramics. Extreme reaction conditions are not required and the precursor is a powder-like substance that produces ceramics of improved purity and morphology upon pyrolysis.

Maya, Leon (Oak Ridge, TN)

1991-01-01

422

Novel valuable fluorine free copper(I) precursors for copper chemical vapor deposition  

Microsoft Academic Search

Novel fluorine free (?-diketonate)Cu(I)BTMSA precursors (where BTMSA is bis(trimethylsilyl) acetylene) were prepared in good yield (63–80%) by a simple acid–base reaction. The starting ?-diketone structure was modified for tailoring physico-chemical properties of synthesized precursors. High volatile, relative thermally stable and low-melting precursors were prepared when asymmetric ?-diketones were used. By using the (1-(cyclobutyl)-1,3-butandionate)Cu(I)BTMSA precursor, highly pure, compact and smooth copper

Phong Dinh Tran; Audrey Allavena-Valette; Farah Kamous; Pascal Doppelt

2009-01-01

423

Precursors to the shear failure of rock discontinuities  

NASA Astrophysics Data System (ADS)

Active geophysical monitoring of potential failure along mechanical discontinuities in rock requires identification of precursory signatures to failure in geophysical signals. Active ultrasonic monitoring of shear failure along frictional discontinuities was performed to determine the signatures of potential failure. An instrumented direct shear apparatus was used to apply a constant shearing rate to a discontinuity that was held under a constant normal stress. Transmitted and reflected compressional and shear waves were recorded during the shearing process. Ultrasonic precursors were identified as distinct maxima in the amplitude of transmitted shear waves as well as minima in the amplitude of reflected shear waves that occurred well before the peak shear strength of a frictional discontinuity. The precursors are linked to changes in the local shear specific stiffness along the discontinuity, while the discontinuity's macroscopic shear strength continues to increase prior to failure.

Hedayat, Ahmadreza; Pyrak-Nolte, Laura J.; Bobet, Antonio

2014-08-01

424

Crack roughness and avalanche precursors in the random fuse model.  

PubMed

We analyze the scaling of the crack roughness and of avalanche precursors in the two-dimensional random fuse model by numerical simulations, employing large system sizes and extensive sample averaging. We find that the crack roughness exhibits anomalous scaling, as recently observed in experiments. The roughness exponents (zeta, zeta(loc) ) and the global width distributions are found to be universal with respect to the lattice geometry. Failure is preceded by avalanche precursors whose distribution follows a power law up to a cutoff size. While the characteristic avalanche size scales as s(0) approximately L(D) , with a universal fractal dimension D , the distribution exponent tau differs slightly for triangular and diamond lattices and, in both cases, it is larger than the mean-field (fiber bundle) value tau=5/2 . PMID:15783377

Zapperi, Stefano; Nukala, Phani Kumar V V; Simunovi?, Srdan

2005-02-01

425

Detection of hydrothermal precursors to large northern california earthquakes.  

PubMed

During the period 1973 to 1991 the interval between eruptions from a periodic geyser in Northern California exhibited precursory variations 1 to 3 days before the three largest earthquakes within a 250-kilometer radius of the geyser. These include the magnitude 7.1 Loma Prieta earthquake of 18 October 1989 for which a similar preseismic signal was recorded by a strainmeter located halfway between the geyser and the earthquake. These data show that at least some earthquakes possess observable precursors, one of the prerequisites for successful earthquake prediction. All three earthquakes were further than 130 kilometers from the geyser, suggesting that precursors might be more easily found around rather than within the ultimate rupture zone of large California earthquakes. PMID:17738277

Silver, P G; Valette-Silver, N J

1992-09-01

426

Antarctic new particle formation from continental biogenic precursors  

NASA Astrophysics Data System (ADS)

Over Antarctica, aerosol particles originate almost entirely from marine areas, with minor contribution from long-range transported dust or anthropogenic material. The Antarctic continent itself, unlike all other continental areas, has been thought to be practically free of aerosol sources. Here we present evidence of local aerosol production associated with melt-water ponds in continental Antarctica. We show that in air masses passing such ponds, new aerosol particles are efficiently formed and these particles grow up to sizes where they may act as cloud condensation nuclei (CCN). The precursor vapours responsible for aerosol formation and growth originate very likely from highly abundant cyanobacteria Nostoc commune (Vaucher) communities of local ponds. This is the first time freshwater vegetation has been identified as an aerosol precursor source. The influence of the new source on clouds and climate may increase in future Antarctica, and possibly elsewhere undergoing accelerating summer melting of semi-permanent snow cover.

Kyrö, E.-M.; Kerminen, V.-M.; Virkkula, A.; Dal Maso, M.; Parshintsev, J.; Ruíz-Jimenez, J.; Forsström, L.; Manninen, H. E.; Riekkola, M.-L.; Heinonen, P.; Kulmala, M.

2013-04-01

427

Antarctic new particle formation from continental biogenic precursors  

NASA Astrophysics Data System (ADS)

Over Antarctica, aerosol particles originate almost entirely from marine areas, with minor contribution from long-range transported dust or anthropogenic material. The Antarctic continent itself, unlike all other continental areas, has been thought to be practically free of aerosol sources. Here we present evidence of local aerosol production associated with melt-water ponds in the continental Antarctica. We show that in air masses passing such ponds, new aerosol particles are efficiently formed and these particles grow up to sizes where they may act as cloud condensation nuclei (CCN). The precursor vapours responsible for aerosol formation and growth originate very likely from highly abundant cyanobacteria Nostoc commune (Vaucher) communities of local ponds. This is the first time when freshwater vegetation has been identified as an aerosol precursor source. The influence of the new source on clouds and climate may increase in future Antarctica, and possibly elsewhere undergoing accelerating summer melting of semi-permanent snow cover.

Kyrö, E.-M.; Kerminen, V.-M.; Virkkula, A.; Dal Maso, M.; Parshintsev, J.; Ruíz-Jimenez, J.; Forsström, L.; Manninen, H. E.; Riekkola, M.-L.; Heinonen, P.; Kulmala, M.

2012-12-01

428

Cloning and characterization of the pseudonajatoxin b precursor.  

PubMed

An Australian common brown snake, Pseudonaja textilis, is known to contain highly lethal neurotoxins. Among them, a long-chain alpha-neurotoxin, pseudonajatoxin b, has been identified. In this report, while presenting evidence for the presence of at least four such long-chain alpha-neurotoxins in the venom of P. textilis, we describe the characteristics of both the mRNA and the gene responsible for the synthesis of these neurotoxins. A precursor toxin synthesized from the gene has been identified as being capable of producing the isoforms possibly by post-translational modifications at its C-terminal end. Recombinant toxins corresponding to the precursor and its product have been found to possess similar binding affinities for muscular acetylcholine receptors (IC(50)=3x10(-8) M) and a lethality, LD(50), of 0.15 microg/g in mice. PMID:11535126

Gong, N; Armugam, A; Mirtschin, P; Jeyaseelan, K

2001-09-15

429

Cloning and characterization of the pseudonajatoxin b precursor.  

PubMed Central

An Australian common brown snake, Pseudonaja textilis, is known to contain highly lethal neurotoxins. Among them, a long-chain alpha-neurotoxin, pseudonajatoxin b, has been identified. In this report, while presenting evidence for the presence of at least four such long-chain alpha-neurotoxins in the venom of P. textilis, we describe the characteristics of both the mRNA and the gene responsible for the synthesis of these neurotoxins. A precursor toxin synthesized from the gene has been identified as being capable of producing the isoforms possibly by post-translational modifications at its C-terminal end. Recombinant toxins corresponding to the precursor and its product have been found to possess similar binding affinities for muscular acetylcholine receptors (IC(50)=3x10(-8) M) and a lethality, LD(50), of 0.15 microg/g in mice. PMID:11535126

Gong, N; Armugam, A; Mirtschin, P; Jeyaseelan, K

2001-01-01

430

Can precursors improve the transmission of energy at optical frequencies?  

PubMed

The recent interest in precursors has been fuelled by the possibility of using them for the efficient transmission of information through absorbing media at radio or optical frequencies. Here we demonstrate that the low attenuation experienced by the Brillouin precursor is attributed to the inherently low absorption of dispersive media near DC, a characteristic already exploited with communications systems using the extremely low frequency (ELF) band. Pulses, regardless of their temporal width and carrier frequency, always obey Beer's law as long as they propagate in the linear time invariant regime. We conclude with an FDTD simulation of the Maxwell-Bloch equations that shows how optical coherent bleaching effects, which take place in the linear time variant regime of the Lorentz oscillator model, can cause sustained deviations from Beer's law over relatively long distances of water. PMID:19639054

Lukofsky, David; Bessette, Jonathan; Jeong, Heejeong; Garmire, Elsa; Osterberg, Ulf

2009-05-01

431

Directed differentiation of telencephalic precursors from embryonic stem cells.  

PubMed

We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells ( approximately 90%). In the presence of Dkk1, with or without LeftyA, SFEB induces efficient generation ( approximately 35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or Islet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals. PMID:15696161

Watanabe, Kiichi; Kamiya, Daisuke; Nishiyama, Ayaka; Katayama, Tomoko; Nozaki, Satoshi; Kawasaki, Hiroshi; Watanabe, Yasuyoshi; Mizuseki, Kenji; Sasai, Yoshiki

2005-03-01

432

Fission-Based Electric Propulsion for Interstellar Precursor Missions  

SciTech Connect

This paper reviews the technology options for a fission-based electric propulsion system for interstellar precursor missions. To achieve a total {Delta}V of more than 100 km/s in less than a decade of thrusting with an electric propulsion system of 10,000s Isp requires a specific mass for the power system of less than 35 kg/kWe. Three possible configurations are described: (1) a UZrH-fueled,NaK-cooled reactor with a steam Rankine conversion system,(2) a UN-fueled gas-cooled reactor with a recuperated Brayton conversion system, and (3) a UN-fueled heat pipe-cooled reactor with a recuperated Brayton conversion system. All three of these systems have the potential to meet the specific mass requirements for interstellar precursor missions in the near term. Advanced versions of a fission-based electric propulsion system might travel as much as several light years in 200 years.

HOUTS,MICHAEL G.; LENARD,ROGER X.; LIPINSKI,RONALD J.; PATTON,BRUCE; POSTON,DAVID; WRIGHT,STEVEN A.

1999-11-03

433

Intraspinal transplantation of mouse and human neural precursor cells  

PubMed Central

This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. Here we show NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viralmediated demyelination can efficiently be detected via eGFP expression. Transplantation of these cells into the spinal cord is an efficacious way to determine their effects in neurological disorders such as multiple sclerosis, Alzheimer's disease, and spinal cord injury. PMID:24510791

Weinger, Jason G.; Chen, Lu; Coleman, Ronald; Leang, Ronika; Plaisted, Warren C.; Loring, Jeanne F.; Lane, Thomas E.

2013-01-01

434

Neural precursor cells possess multiple p53-dependent apoptotic pathways  

Microsoft Academic Search

Neural precursor cells (NPCs) are markedly sensitive to apoptotic insults. p53-dependent transcriptional activation of proapoptotic genes has been hypothesized to regulate NPC death in response to DNA damage. Recent studies of non-NPCs have also indicated that p53 may directly interact with Bcl-2 molecules and thereby regulate death independently of transcription. The contribution of transcription-independent p53 activation in NPC death has

R S Akhtar; Y Geng; B J Klocke; K A Roth; KA Roth

2006-01-01

435

Single-walled hollow nanospheres assembled from the aluminogermanate precursors.  

PubMed

Ordered single-walled hollow aluminogermanate (ALGE) nanospheres (NSs) with average monodisperse diameters of 5 nm have been synthesized for the first time using simple pH control. This involved basification of the ALGE precursors (having