Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

PubMed

Wilkinson, J D; Whalley, B J; Baker, D; Pryce, G; Constanti, A; Gibbons, S; Williamson, E M

2003-12-01

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

The psychoactive ingredient of marijuana induces behavioural sensitization.

PubMed

Rubino, T; Viganò, D; Massi, P; Parolaro, D

2001-09-01

Here we describe, for the first time, the occurrence of behavioural sensitization after chronic exposure to Delta9-tetrahydrocannabinol. Rats were treated twice a day, for five days, with increasing doses (5, 10, 20, 40, 40 mg/kg i.p.) of Delta9-tetrahydrocannabinol or its vehicle and after 20 days of withdrawal, animals were challenged with 5 mg/kg (i.p.) of the drug and their behaviour was assessed. Contrary to the motor inhibition induced in control rats, challenge with Delta9-tetrahydrocannabinol in pre-exposed animals elicited a complex behavioural syndrome mainly characterized by oral stereotyped items. Due to the relevance of behavioural sensitization in drug-seeking behaviour that persists long after discontinuation of drug use, our findings suggest that cannabinoids could trigger neurobiological alteration not dissimilar from those observed with more harmful abused drugs.

Effects of acute oral Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers.

PubMed

Roser, Patrik; Juckel, Georg; Rentzsch, Johannes; Nadulski, Thomas; Gallinat, Jürgen; Stadelmann, Andreas M

2008-08-01

Reduced amplitudes of auditory evoked P300 are a robust finding in schizophrenic patients, indicating deficient attentional resource allocation and active working memory. Delta9-Tetrahydrocannabinol (Delta9-THC), the main active constituent of Cannabis sativa, has been known to acutely impair cognitive abilities in several domains, particularly in memory and attention. Given the psychotic-like effects of Delta9-THC, a cannabinoid hypothesis of schizophrenia has been proposed. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on P300 amplitude in 20 healthy volunteers (age 28.2+/-3.1 years, 10 male) by comparing Delta9-THC and standardized cannabis extract containing Delta9-THC and cannabidiol (CBD). P300 waves were recorded during a choice reaction task. As expected, Delta9-THC revealed a significant reduction of P300 amplitude at midline frontal, central, and parietal electrodes. CBD has been known to abolish many of the psychotropic effects of Delta9-THC, but, unexpectedly, failed to demonstrate a reversal of Delta9-THC-induced P300 reduction. Moreover, there were no correlations between cannabinoid plasma concentrations and P300 parameters. These data suggest that Delta(9)-THC may lead to acute impairment of attentional functioning and working memory. It can be speculated whether the lack of effect of CBD may be due to an insufficient dose used or to an involvement of neurotransmitter systems in P300 generation which are not influenced by CBD.

Hair analysis for delta(9)-THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI. Comparison with GC/MS-NCI for delta(9)-THC-COOH.

PubMed

Baptista, Maria João; Monsanto, Paula Verâncio; Pinho Marques, Estela Gouveia; Bermejo, Ana; Avila, Sofia; Castanheira, Alice Martelo; Margalho, Cláudia; Barroso, Mário; Vieira, Duarte Nuno

2002-08-14

A sensitive analytical method was developed for quantitative analysis of delta(9)-tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol-carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in human hair. The identification of delta(9)-THC-COOH in hair would document Cannabis use more effectively than the detection of parent drug (delta(9)-THC) which might have come from environmental exposure. Ketamine was added to hair samples as internal standard for CBN and CBD. Ketoprofen was added to hair samples as internal standard for the other compounds. Samples were hydrolyzed with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling, samples were extracted with a liquid-liquid extraction procedure (with chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate, after acidification), which was developed in our laboratory. The extracts were analysed before and after derivatization with pentafluoropropionic anhydride (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI). Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas chromatographer/mass spectrometer detector, in negative ion chemical ionization mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to 104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was found to be more convenient than GC/MS-EI. The latter may give rise to false negatives due to the detection limit.

Interaction between marihuana and altitude on a complex behavioral task in baboons.

DOT National Transportation Integrated Search

1975-01-01

Marihuana, or its principal active ingredient, delta-9-tetrahydrocannabinol (delta9-THC), impairs performance on complex behavioral tasks in animals and man. Although there exists some evidence that altitude-induced hypoxia potentiates the physiologi...

Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response.

PubMed

McKallip, Robert J; Nagarkatti, Mitzi; Nagarkatti, Prakash S

2005-03-15

In the current study, we tested the central hypothesis that exposure to Delta-9-tetrahydrocannabinol (Delta9-THC), the major psychoactive component in marijuana, can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. We demonstrated that the human breast cancer cell lines MCF-7 and MDA-MB-231 and the mouse mammary carcinoma 4T1 express low to undetectable levels of cannabinoid receptors, CB1 and CB2, and that these cells are resistant to Delta9-THC-induced cytotoxicity. Furthermore, exposure of mice to Delta9-THC led to significantly elevated 4T1 tumor growth and metastasis due to inhibition of the specific antitumor immune response in vivo. The suppression of the antitumor immune response was mediated primarily through CB2 as opposed to CB1. Furthermore, exposure to Delta9-THC led to increased production of IL-4 and IL-10, suggesting that Delta9-THC exposure may specifically suppress the cell-mediated Th1 response by enhancing Th2-associated cytokines. This possibility was further supported by microarray data demonstrating the up-regulation of a number of Th2-related genes and the down-regulation of a number of Th1-related genes following exposure to Delta9-THC. Finally, injection of anti-IL-4 and anti-IL-10 mAbs led to a partial reversal of the Delta9-THC-induced suppression of the immune response to 4T1. Such findings suggest that marijuana exposure either recreationally or medicinally may increase the susceptibility to and/or incidence of breast cancer as well as other cancers that do not express cannabinoid receptors and are resistant to Delta9-THC-induced apoptosis.

Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction.

PubMed

Lamarque, S; Taghzouti, K; Simon, H

2001-07-01

Cannabis sativa preparations are some of the most widely used illicit recreational drugs. In addition to their direct addictive potential, cannabinoids may influence the sensitivity to other drugs. The aim of the present study was to determine if a cross-sensitization between Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and other drugs (amphetamine and heroin) could be demonstrated. We examined the effects of a chronic treatment with Delta(9)-THC (0.6, 3 and 15mg/kg, ip) on the locomotor response to amphetamine (1mg/kg, ip) and heroin (1mg/kg, ip). Chronic treatment with Delta(9)-THC resulted in tolerance to the initial hypothermic and anorexic effects. Pre-treatment with Delta(9)-THC increased the locomotor responses to amphetamine and heroin. This cross-sensitization was time-dependent as it was observed three days after the last injection of Delta(9)-THC for amphetamine, and a relatively long time after the end of chronic treatment (41 days) for heroin. Moreover, the enhanced response to amphetamine or heroin was noted in some individuals only: the high-responder rats (HR). These animals have previously been shown to be vulnerable to drug taking behaviors. It is hypothesised that repeated use of Cannabis derivates may facilitate progression to the consumption of other illicit drugs in vulnerable individuals.

Distribution of Delta 9-Tetrahydrocannabinol and 11-Nor-9-Carboxy-Delta 9-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents

DTIC Science & Technology

2013-12-01

classified as current marijuana ( Cannabis sativa) users in the United States and 5.4 million people aged 12 and older used marijuana on a daily or almost...report from the European Union, cannabis use is common in many parts of the world.3 As a result of such widespread marijuana use and its well...knowledge regarding the postmortem distribution of cannabi - noids in humans primarily because cannabinoid testing is not routine in many postmortem

Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.

PubMed

ElSohly, M A; Stanford, D F; Harland, E C; Hikal, A H; Walker, L A; Little, T L; Rider, J N; Jones, A B

1991-10-01

Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug for delta 9-THC in suppositories using Witepsol H15 base. The bioavailability of delta 9-THC from this formulation was evaluated in monkeys. The plasma levels of delta 9-THC and its metabolite 11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of delta 9-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for delta 9-THC in the body to be 3 h following iv administration of delta 9-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the delta 9-THC hemisuccinate. The observed rectal bioavailability of delta 9-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.

Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to {delta}{sup 9}-tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo

The present study evaluated the consequences of perinatal {delta}{sup 9}-tetrahydrocannabinol ({delta}{sup 9}-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB{sub 1} receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with {delta}{sup 9}-tetrahydrocannabinol, ethanol or their combination causesmore » long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, {delta}{sup 9}-THC, or EtOH + {delta}{sup 9}-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to {delta}{sup 9}-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB{sub 1} receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism.« less

Determination of delta9-tetrahydrocannabinol in indoor air as an indicator of marijuana cigarette smoking using adsorbent sampling and in-injector thermal desorption gas chromatography-mass spectrometry.

PubMed

Chou, Su-Lien; Ling, Yong-Chien; Yang, Mo-Hsiung; Pai, Chung-Yen

2007-08-13

The marijuana leaves are usually mixed with tobaccos and smoked at amusement places in Taiwan. Recently, for investigation-legal purposes, the police asked if we can identify the marijuana smoke in a KTV stateroom (a private room at the entertainment spot for singing, smoking, alcohol drinking, etc.) without marijuana residues. A personal air-sampler pump fitted with the GC liner-tube packed with Tenax-TA adsorbent was used for air sampling. The GC-adsorbent tube was placed in the GC injector port and desorbed directly, followed by GC-MS analysis for the determination of delta9-tetrahydrocannabinol (delta9-THC) in indoor air. The average desorption efficiency and limit of detection for delta9-THC were 89% and 0.1 microg m(-3), respectively, approximately needing 1.09 mg of marijuana leaves smoked in an unventilated closed room (3.0 m x 2.4 m x 2.7 m) to reach this level. The mean delta9-THC contained in the 15 marijuana plants seized from diverse locations was measured to be 0.32%. The delta9-THC in room air can be successfully identified from mock marijuana cigarettes, mixtures of marijuana and tobacco, and an actual case. The characteristic delta9-THC peak in chromatogram can serve as the indicator of marijuana. Positive result suggests marijuana smoking at the specific scene in the recent past, facilitating the formulation of further investigation.

Tetrahydrocannabinol and endocannabinoids in feeding and appetite.

PubMed

Berry, Elliot M; Mechoulam, Raphael

2002-08-01

The physiological control of appetite and satiety, in which numerous neurotransmitters and neuropeptides play a role, is extremely complex. Here we describe the involvement of endocannabinoids in these processes. These endogenous neuromodulators enhance appetite in animals. The same effect is observed in animals and in humans with the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol, which is an approved appetite-enhancing drug. The CB(1) cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced by the endocannabinoids. If administered to mice pups, this antagonist blocks suckling. In obese humans, it causes weight reduction. Very little is known about the physiological and biochemical mechanisms involved in the effects of Delta(9)-tetrahydrocannabinol and the cannabinoids in feeding and appetite.

Effects of perinatal exposure to delta 9-tetrahydrocannabinol on operant morphine-reinforced behavior.

PubMed

González, Begoña; de Miguel, Rosario; Martín, Sonsoles; Pérez-Rosado, Alberto; Romero, Julián; García-Lecumberri, Carmen; Fernández-Ruiz, Javier; Ramos, José Antonio; Ambrosio, Emilio

2003-06-01

The present study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) when administered during the perinatal period on morphine self-administration in adulthood. To this end, pregnant Wistar rats were daily exposed to Delta(9)-THC from the fifth day of gestation up to pup weaning, when they were separated by gender and left to mature to be used for analyses of operant food- and morphine-reinforced behavior in a progressive ratio (PR) schedule. We also analyzed dopaminergic activity (DOPAC/DA) in reward-related structures during specific phases of the behavioral study. In both reinforcement paradigms, food and morphine, females always reached higher patterns of self-administration than males, but this occurred for the two treatment groups, Delta(9)-THC or vehicle. These higher patterns measured in females corresponded with a higher DOPAC/DA in the nucleus accumbens prior to the onset of morphine self-administration in comparison to males. Interestingly, DOPAC/DA was lower in Delta(9)-THC-exposed females compared to oil-exposed females and similar to oil- and Delta(9)-THC-exposed males. In addition, Delta(9)-THC-exposed females also exhibited a reduction in DOPAC/DA in the ventral tegmental area, which did not exist in males. All these changes, however, disappeared after 15 days of morphine self-administration and they did not reappear after 15 additional days of extinction of this response. Our data suggest that females are more vulnerable than males in a PR schedule for operant food and morphine self-administration; perinatal Delta(9)-THC exposure is not a factor influencing this vulnerability. The neurochemical analysis revealed that the activity of limbic dopaminergic neurons prior to morphine self-administration was higher in females than males, as well as that the perinatal Delta(9)-THC treatment reduced the activity of these neurons only in females, although this had no influence on morphine vulnerability in these animals.

Plasma and urine profiles of Delta9-tetrahydrocannabinol and its metabolites 11-hydroxy-Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes.

PubMed

Brenneisen, Rudolf; Meyer, Pascale; Chtioui, Haithem; Saugy, Martial; Kamber, Matthias

2010-04-01

Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes.

An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition.

PubMed

Henquet, Cécile; Rosa, Araceli; Krabbendam, Lydia; Papiol, Sergi; Fananás, Lourdes; Drukker, Marjan; Ramaekers, Johannes G; van Os, Jim

2006-12-01

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

Concentrations of delta9-tetrahydrocannabinol and 11-nor-9-carboxytetrahydrocannabinol in blood and urine after passive exposure to Cannabis smoke in a coffee shop.

PubMed

Röhrich, J; Schimmel, I; Zörntlein, S; Becker, J; Drobnik, S; Kaufmann, T; Kuntz, V; Urban, R

2010-05-01

Cannabinoid concentrations in blood and urine after passive exposure to cannabis smoke under real-life conditions were investigated in this study. Eight healthy volunteers were exposed to cannabis smoke for 3 h in a well-attended coffee shop in Maastricht, Netherlands. An initial blood and urine sample was taken from each volunteer before exposure. Blood samples were taken 1.5, 3.5, 6, and 14 h after start of initial exposure, and urine samples were taken after 3.5, 6, 14, 36, 60, and 84 h. The samples were subjected to immunoassay screening for cannabinoids and analyzed using gas chromatography-mass spectrometry (GC-MS) for Delta(9)-tetrahydrocannabinol (THC), 11-nor-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH). It could be demonstrated that all volunteers absorbed THC. However, the detected concentrations were rather small. None of the urine samples produced immunoassay results above the cutoff concentration of 25 ng/mL. THC-COOH concentrations up to 5.0 and 7.8 ng/mL before and after hydrolysis, respectively, were found in the quantitative GC-MS analysis of urine. THC could be detected in trace amounts close to the detection limit of the used method in the first two blood samples after initial exposure (1.5 and 3.5 h). In the 6 h blood samples, THC was not detectable anymore. THC-COOH could be detected after 1.5 h and was still found in 3 out of 8 blood samples after 14 h in concentrations between 0.5 and 1.0 ng/mL.

A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.

PubMed

Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

2010-08-01

Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.

Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification (Part II): Psychiatric complaints and their relation to delta-9-tetrahydrocannabinol and its metabolites in serum.

PubMed

Bonnet, Udo; Borda, Thorsten; Scherbaum, Norbert; Specka, Michael

2015-10-01

To investigate the impact of inpatient detoxification treatment on psychiatric symptoms of chronic cannabis addicts and to analyze the influence of serum cannabinoid levels on the severity of these symptoms. Thirty five treatment-seeking, not active co-morbid chronic cannabis dependents (ICD-10) were studied on admission and on abstinence days 8 and 16, using several observational and self-report scales, such as Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), and the Symptom Checklist-90-Revised (SCL-90-R). Simultaneously obtained serum was analyzed with regard to levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). At admission, nearly 90% of the patients were not, or only mildly, affected by depression, anxiety or manic symptoms. In contrast, patients' self-description indicated a strong psychiatric burden in approximately 60% of the cases. All patients improved significantly within 16 days of the treatment. Effect sizes ranged from 0.7 to 1.4. (Cohen's d) for the respective scales. Serum THC-levels were positively associated with impairment of cognition in HAMA and motor retardation in BPRS. All other test results were not significantly related to the serum levels of the measured cannabinoids. Effects of the cannabis withdrawal syndrome and executive dysfunctions might explain the discrepancy between the observer ratings and self-reported psychiatric burden. Inpatient cannabis detoxification treatment significantly improved psychiatric symptoms. Serum THC-levels were not associated with affective symptoms and anxiety but predicted cognitive impairment and motor retardation. Copyright © 2015. Published by Elsevier Ireland Ltd.

Automated solid-phase extraction-liquid chromatography-tandem mass spectrometry analysis of 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in human urine specimens: application to a high-throughput urine analysis laboratory.

PubMed

Robandt, P V; Klette, K L; Sibum, M

2009-10-01

An automated solid-phase extraction coupled with liquid chromatography and tandem mass spectrometry (SPE-LC-MS-MS) method for the analysis of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in human urine specimens was developed. The method was linear (R(2) = 0.9986) to 1000 ng/mL with no carryover evidenced at 2000 ng/mL. Limits of quantification and detection were found to be 2 ng/mL. Interrun precision was evaluated at the 15 ng/mL level over nine batches spanning 15 days (n = 45). The coefficient of variation (%CV) was found to be 5.5% over the course of the validation. Intrarun precision of a 15 ng/mL control (n = 5) ranged from 0.58% CV to 7.4% CV for the same set of analytical batches. Interference was tested using (+/-)-11-hydroxy-Delta(9)-tetrahydrocannabinol, cannabidiol, (-)-Delta(8)-tetrahydrocannabinol, and cannabinol. One hundred and nineteen specimens previously found to contain THC-COOH by a previously validated gas chromatographic mass spectrometry (GC-MS) procedure were compared to the SPE-LC-MS-MS method. Excellent agreement was found (R(2) = 0.9925) for the parallel comparison study. The automated SPE procedure eliminates the human factors of specimen handling, extraction, and derivatization, thereby reducing labor costs and rework resulting from human error or technique issues. Additionally, method runtime is greatly reduced (e.g., during parallel studies the SPE-LC-MS-MS instrument was often finished with analysis by the time the technician finished the offline SPE and derivatization procedure prior to the GC-MS analysis).

Simultaneous screening and quantification of 29 drugs of abuse in oral fluid by solid-phase extraction and ultraperformance LC-MS/MS.

PubMed

Badawi, Nora; Simonsen, Kirsten Wiese; Steentoft, Anni; Bernhoft, Inger Marie; Linnet, Kristian

2009-11-01

The European DRUID (Driving under the Influence of Drugs, Alcohol And Medicines) project calls for analysis of oral fluid (OF) samples, collected randomly and anonymously at the roadside from drivers in Denmark throughout 2008-2009. To analyze these samples we developed an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for detection of 29 drugs and illicit compounds in OF. The drugs detected were opioids, amphetamines, cocaine, benzodiazepines, and Delta-9-tetrahydrocannabinol. Solid-phase extraction was performed with a Gilson ASPEC XL4 system equipped with Bond Elut Certify sample cartridges. OF samples (200 mg) diluted with 5 mL of ammonium acetate/methanol (vol/vol 90:10) buffer were applied to the columns and eluted with 3 mL of acetonitrile with aqueous ammonium hydroxide. Target drugs were quantified by use of a Waters ACQUITY UPLC system coupled to a Waters Quattro Premier XE triple quadrupole (positive electrospray ionization mode, multiple reaction monitoring mode). Extraction recoveries were 36%-114% for all analytes, including Delta-9-tetrahydrocannabinol and benzoylecgonine. The lower limit of quantification was 0.5 mug/kg for all analytes. Total imprecision (CV) was 5.9%-19.4%. With the use of deuterated internal standards for most compounds, the performance of the method was not influenced by matrix effects. A preliminary account of OF samples collected at the roadside showed the presence of amphetamine, cocaine, codeine, Delta-9-tetrahydrocannabinol, tramadol, and zopiclone. The UPLC-MS/MS method makes it possible to detect all 29 analytes in 1 chromatographic run (15 min), including Delta-9-tetrahydrocannabinol and benzoylecgonine, which previously have been difficult to incorporate into multicomponent methods.

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings weremore » similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.« less

Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

PubMed

Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

2009-08-01

Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity.

PubMed

Juckel, Georg; Roser, Patrik; Nadulski, Thomas; Stadelmann, Andreas M; Gallinat, Jürgen

2007-12-01

Reduced amplitudes of auditory evoked mismatch negativity (MMN) have often been found in schizophrenic patients, indicating deficient auditory information processing and working memory. Cannabis-induced psychotic states may resemble schizophrenia. Currently, there are discussions focusing on the close relationship between cannabis, the endocannabinoid and dopaminergic system, and the onset of schizophrenic psychosis. This study investigated the effects of cannabis on MMN amplitude in 22 healthy volunteers (age 28+/-6 years, 11 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol (CBD) in a prospective, double-blind, placebo-controlled cross-over design. The MMNs resulting from 1000 auditory stimuli were recorded by 32 channel EEG. The standard stimuli were 1000 Hz, 80 dB SPL, and 100 ms duration. The deviant stimuli differed in frequency (1500 Hz). Significantly greater MMN amplitude values at central electrodes were found under cannabis extract, but not under Delta(9)-THC. There were no significant differences between MMN amplitudes at frontal electrodes. MMN amplitudes at central electrodes were significantly correlated with 11-OH-THC concentration, the most important psychoactive metabolite of Delta(9)-THC. Since the main difference between Delta(9)-THC and standardized cannabis extract is CBD, which seems to have neuroprotective and anti-psychotic properties, it can be speculated whether the greater MMN amplitude that may imply higher cortical activation and cognitive performance is related to the positive effects of CBD. This effect may be relevant for auditory cortex activity in particular because only MMN amplitudes at the central, but not at the frontal electrodes were enhanced under cannabis.

Tetrahydrocannabinols in clinical and forensic toxicology.

PubMed

Kochanowski, Maciej; Kała, Maria

2005-01-01

Cannabinoids are the natural constituents of marihuana (cannabis). The main of them are delta9-tetrahydrocannabinol (9THC)--psychoactive agent, cannabinol (CBN) and cannabidiol (CBD). Cannabis is administered either by smoking or orally. 9THC potency and duration of action as well as its and two of its major metabolites concentrations in organism highly depend on the route of administration. A single active dose of 9THC is estimated on 520 mg. 9THC is rapidly metabolised. It is hydroxylated to an active metabolite, I1 -hydroxy-delta9-tetrahydro-cannabinol (11-OH-THC), then oxidised to an inactive 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), which is conjugated with glucuronic acid and predominantly excreted in the urine. The maximum psychological effect persists for 4-6 h after administration despite of very low 9THC blood concentrations. 9THC plasma concentration declined to values of 2-3 ng/ml during 3-4 h after smoking. Such a low concentration of the active compound in human organism create a demand for use of sensitive analytical methods for detection and determination of 9THC and its metabolites. The most effective techniques for 9THC and related compounds determination in biological material are chromatographic ones (gas and liquid) with mass spectrometric detection and different ionization modes. 9THC and its two metabolites (11-OH-THC and THCCOOH) are present in blood and hair, 9THC in saliva, and THCCOOH in urine. 9THC and related compounds are determined in autopsy material, although deaths by overdose of cannabis are exceptionally rare. Fatalities happen most often after intravenous injection of hashish oil. 9THC and its metabolites determination in different biological materials gives the basis for a wide interpretation of analytical results for clinical and forensic toxicology purposes.

An indoor air quality-pharmacokinetic simulation of passive inhalation of marijuana smoke and the resultant buildup of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in urine.

PubMed

Giardino, N J

1997-03-01

In military courts of law, the good soldier defense is often used by the defendant to explain the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in urine (hereafter referred to as THCA) above the Department of Defense (DOD) established limit of 15 ng/mL. The defense will contend the defendant unwittingly breathed side-stream marijuana smoke, thus resulting in the presence of THCA in the defendant's urine. The purpose of this work was to link an indoor air quality model (IAQ) with a pharmacokinetic (PK) model to predict a passive marijuana smoker's resultant concentration of the major urinary metabolite THCA.

[Simultaneous determination of delta-9-tetrahydrocannabinol cannabidiol and cannabinol in edible oil using ultra performance liquid chromatography-tandem mass spectrometry].

PubMed

Zhang, Aizhi; Wang, Quanlin; Mo, Shijie

2010-11-01

A method for the simultaneous determination of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in edible oil was developed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted with methanol, purified by an LC-Alumina-N solid phase extraction cartridge, separated and detected by the UPLC-MS/MS. Quantitative analysis was corrected by an isotope internal standard method using delta-9-THC-D3 as internal standard. Average recoveries for the target compounds varied from 68.0% to 101.6% with the relative standard deviations ranging from 7.0% to 20.1% at three spiked levels. The limits of detection (LOD) of the method were from 0.06-0.17 microg/kg and the limits of quantification (LOQ) were in the range of 0.20-0.52 microg/kg. The results showed that the method is able to meet the requirements for the simultaneous determination of THC, CBD and CBN in edible oil.

Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats.

PubMed

Parker, Linda A; Burton, Page; Sorge, Robert E; Yakiwchuk, Christine; Mechoulam, Raphael

2004-09-01

Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

Suppression of human macrophage function in vitro by delta 9-tetrahydrocannabinol.

PubMed

Specter, S; Lancz, G; Goodfellow, D

1991-11-01

The ability of macrophages to function in the presence of delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was evaluated. THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. The effects of THC were concentration dependent, with inhibitory effects observed from 10 to 1 micrograms/ml or lower. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function(s) by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.

The tumour suppressor protein, p53, is involved in the activation of the apoptotic cascade by Delta9-tetrahydrocannabinol in cultured cortical neurons.

PubMed

Downer, Eric J; Gowran, Aoife; Murphy, Aine C; Campbell, Veronica A

2007-06-14

Cannabis is the most commonly used illegal drug of abuse in Western society. Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana, regulates a variety of neuronal processes including neurotransmitter release and synaptic transmission. An increasing body of evidence suggests that cannabinoids play a key role in the regulation of neuronal viability. In cortical neurons tetrahydrocannabinol has a neurodegenerative effect, the mechanisms of which are poorly understood, but involve the cannabinoid receptor subtype, CB(1). In this study we report that tetrahydrocannabinol (5 muM) evokes a rapid phosphorylation, and thus activation, of the tumour suppressor protein, p53, in a manner involving the cannabinoid CB(1) receptor, and the stress-activated protein kinase, c-jun N-terminal kinase, in cultured cortical neurons. Tetrahydrocannabinol increased expression of the p53-transcriptional target, Bax and promoted Bcl phosphorylation. These events were abolished by the p53 inhibitor, pifithrin-alpha (100 nM). The tetrahydrocannabinol-induced activation of the pro-apoptotic cysteine protease, caspase-3, and DNA fragmentation was also blocked by pifithrin-alpha. A siRNA knockdown of p53 further verified the role of p53 in tetrahydrocannabinol-induced apoptosis. This study demonstrates a novel cannabinoid signalling pathway involving p53 that culminates in neuronal apoptosis.

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study.

PubMed

van der Pol, Peggy; Liebregts, Nienke; Brunt, Tibor; van Amsterdam, Jan; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

2014-07-01

Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of stronger cannabis use less cannabis per joint or inhale less smoke than those using less potent cannabis and whether these factors predict cannabis dependence severity. Heavy cannabis users (n = 98) brought their own cannabis, rolled a joint and smoked it ad libitum in a naturalistic setting. We analysed the content of the joint, its association with smoking behaviour and the cross-sectional and prospective (1.5-year follow-up) relations between smoking behaviour and cannabis dependence severity (total number of DSM-IV dependence symptoms). THC concentration in cannabis (range 1.10-24.70%) was correlated positively with cannabis dose per joint (b = 0.008, P = 0.01), but the resulting THC concentration per joint (range 0.24-15.72%) was associated negatively with inhalation volume (b = -0.05, P = 0.03). Smoking behaviour measures (number of puffs, inhaled volume, reduction of puff volume and puff duration while smoking) predicted follow-up dependence severity, independently of baseline dependence severity and monthly THC dose (number of joints × cannabis dose × cannabis THC concentration). Monthly THC dose only predicted follow-up dependence severity when unadjusted for baseline severity. Cannabis users titrate their delta-9-tetrahydrocannabinol intake by inhaling lower volumes of smoke when smoking strong joints, but this does not fully compensate for the higher cannabis doses per joint when using strong cannabis. Thus, users of more potent cannabis are generally exposed to more delta-9-tetrahydrocannabinol. Smoking behaviour appears to be a stronger predictor for cannabis dependence severity than monthly delta-9-tetrahydrocannabinol dose. © 2014 Society for the Study of Addiction.

Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt.

PubMed

Souleman, Ahmed M A; Gaafar, Alaa El-Din M; Abdel-Salam, Omar M; ElShebiney, Shaimaa A

2017-03-01

To determine the delta-9-tetrahydrocannabinol (THC) content of cannabis seizures in Egypt. Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves (marijuana) or from the resin (hashish) and subjected to analysis using high performance liquid chromatography (HPLC). The heated resin extract had the peak of THC in a relative ratio of 31.34%, while extracting the resin directly without heating contained only 18.34% of THC. On the other hand, marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating. These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.

PubMed

2017-03-23

On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

Identification of 11-Nor-delta9-tetrahydrocannabinol-9-carboxylic acid in urine by ion trap GC-MS-MS in the context of doping analysis.

PubMed

Caballero, Gerardo M; D'Angelo, Carlos; Fraguío, Mariá Sol; Centurión, Osvaldo Teme

2004-01-01

The purpose of this study is to develop a sensitive and specific alternative to current gas chromatography (GC)-mass spectrometry (MS) selected ion monitoring confirmation methods of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (cTHC) in human urine samples, in the context of doping analysis. An identification procedure based on the comparison, among suspicious and control samples, of the relative abundances of cTHC selected product ions obtained by GC-tandem MS in an ion trap is presented. The method complies with the identification criteria for qualitative assays established by sports authorities; the comparison procedure is precise, reproducible, specific, and sensitive, thus indicating that it is fit for the purpose of identification accordingly to World Antidoping Agency requirements.

Therapeutic issues of marijuana and THC (tetrahydrocannabinol).

PubMed

Ungerleider, J T; Andrysiak, T

1985-05-01

This article summarizes current knowledge about the medicinal value of cannabis and its principal psychoactive ingredient, delta 9-tetrahydrocannabinol (THC), particularly in the control of nausea and vomiting, in glaucoma, and in reduction of spasticity in multiple sclerosis. The major issues in the controversy about marijuana and medicine, primarily moral and ethical, are discussed.

Environmental Factors Involved in the Development of Tolerance to Behavioral Effects of Delta-9-Tetrahydrocannabinol

DTIC Science & Technology

1975-08-01

tetrahydrocanrabinol (A -THC), a compound that appears to be the major active constituent of marijuana ( Mechoulam et al.. 1970). The experiments, conducted with...Frankenheim, J. M. and Kennedy, J. S. Z_-4A -trans-tetrahydrocannabinol in pigeons: tolerance to the behavioral effects. Science, 1970, 162, 501-503. Mechoulam

Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats.

PubMed

Fadda, Paola; Robinson, Lianne; Fratta, Walter; Pertwee, Roger G; Riedel, Gernot

2004-12-01

Cannabinoid receptors in the brain (CB(1)) take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place (DMTP) task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial working and short-term memory formation in rats. Delta(9)-THC-rich extracts impaired performance in the memory trial (trial 2) of the DMTP task in a dose-dependent but delay-independent manner. Deficits appeared at doses of 2 or 5 mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as revealed by the bar test. It appears that spatial working/short-term memory is not sensitive to CBD-rich extracts and that potentiation and antagonism of Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between CBD and Delta(9)-THC.

Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis.

PubMed

Morgan, Celia J A; Curran, H Valerie

2008-04-01

Cannabis contains various cannabinoids, two of which have almost opposing actions: Delta9-tetrahydrocannabinol (Delta9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Delta9-THC and CBD in 140 individuals. Three clear groups emerged: ;THC only', ;THC+CBD' and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro.

PubMed

Whalley, Benjamin J; Wilkinson, Jonathan D; Williamson, Elizabeth M; Constanti, Andrew

2004-07-15

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta9-tetrahydrocannabinol (Delta9-THC), and even Delta9-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta9-THC (1 microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta9-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1 microM); interestingly, the potentiation by Delta9-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta9-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1-/-) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1-/- cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta9-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta9-THC (due to attenuation of some of the central Delta9-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally.

Topical delta 9-tetrahydrocannabinol and aqueous dynamics in glaucoma.

PubMed

Merritt, J C; Perry, D D; Russell, D N; Jones, B F

1981-01-01

Systemic delta 9-tetrahydrocannabinol (THC), administered either by smoking marihuana or as synthetic THC in soft gelatin capsules, lowers ocular tension in various glaucomas, but at the expense of significant decreases in systolic blood pressure. Topical THC in light mineral oil vehicles, though effective in laboratory animals, was not shown effective in 0.05 and 0.1% topical solutions when administered to six subjects with primary open-angle glaucoma in a randomized, balanced, double-masked protocol. Light mineral oil, which has an affinity for corneal epithelium, is an optimum vehicle for administering drugs whose mechanisms of action are systemic rather than local within the eye. Further glaucoma research should therefore proceed with marihuanas containing insignificant levels of THC (less than 0.4%) and with various local delivery systems of the ocular-active cannabinoid found in Cannabis sativa.

Marijuana smoking: effects of varying puff volume and breathhold duration.

PubMed

Azorlosa, J L; Greenwald, M K; Stitzer, M L

1995-02-01

Two studies were conducted to quantify biological and behavioral effects resulting from exposure to controlled doses of marijuana smoke. In one study, puff volume (30, 60 and 90 ml) and in a second study, breathhold duration (0, 10 and 20 sec) were systematically varied while holding constant other smoking topography parameters (number of puffs = 10, interpuff interval = 60 sec and inhalation volume = 25% of vital capacity). Each study also varied levels of delta 9-tetrahydro-cannabinol marijuana cigarette content (1.75% and 3.55%). Regular marijuana users served as subjects (n = 7 in each experiment). Subjects smoked 10 puffs in each of six sessions; a seventh, nonsmoking session (all measures recorded at the same times as in active smoking sessions) served as a control. Variations in puff volume produced significant dose-related changes in postsmoking plasma delta 9-tetrahydro-cannabinol levels, carbon monoxide boost and subjective effects (e.g., "high"). In contrast, breathholding for 10 or 20 sec versus 0 sec increased plasma delta 9-tetrahydro-cannabinol levels but not CO boost or subjective effects. Task performance measures were not reliably influenced by marijuana smoke exposure within the dosing ranges examined. These findings confirm the utility of the controlled smoking technology, support the notion that cumulative puff volume systematically influences biological exposure and subjective effects, but cast doubt on the common belief that prolonged breathholding of marijuana smoke enhances classical subjective effects associated with its reinforcing value in humans.

Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure.

PubMed

Gunasekaran, N; Long, L E; Dawson, B L; Hansen, G H; Richardson, D P; Li, K M; Arnold, J C; McGregor, I S

2009-11-01

Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg.kg(-1)) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.

Potency trends of delta9-THC and other cannabinoids in confiscated marijuana from 1980-1997.

PubMed

ElSohly, M A; Ross, S A; Mehmedic, Z; Arafat, R; Yi, B; Banahan, B F

2000-01-01

The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

Marijuana, alcohol and actual driving performance

DOT National Transportation Integrated Search

1999-07-01

The purpose of this study was to empirically determine the separate and combined effects of Delta-9-tetrahydrocannabinol (THC) and alcohol on actual driving performance. This was the first study ever in which the drugs' combined effects were measured...

75 FR 71635 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... have similar properties to delta-9- tetrahydrocannabinol (THC) found in marijuana and have been found... these THC-like synthetic cannabinoids are marketed as ``legal'' alternatives to marijuana and are being...

Suppressive effect of delta 9-tetrahydrocannabinol in vitro on phagocytosis by murine macrophages.

PubMed

Friedman, M; Cepero, M L; Klein, T; Friedman, H

1986-06-01

Incubation of normal mouse peritoneal cells consisting of over 90% phagocytizing macrophages with delta 9-tetrahydrocannabinol (THC) resulted in a inhibition of phagocytic function. The THC in a dose-related manner suppressed the percentage of macrophages per culture which ingested yeast and the average number of yeast particles ingested by the phagocytizing macrophages. The vehicle used to suspend the THC in vitro, i.e., DMSO, had no detectable effect on macrophage function. Suppression of phagocytosis with no effects on viability or cell number occurred with doses of 10 micrograms or less THC per milliliter culture medium. Measurable suppression also occurred after 24- to 48-hr treatment of the macrophages with the THC. This compound had little if any detectable effect on phagocytosis when added directly to the cultures shortly before testing for phagocytosis. Further studies concerning the effects of THC on macrophage function appear warranted.

A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans

PubMed Central

Nahler, Gerhard; Grotenhermen, Franjo; Zuardi, Antonio Waldo; Crippa, José A.S.

2017-01-01

Abstract Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo, even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact. PMID:28861507

A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.

PubMed

Nahler, Gerhard; Grotenhermen, Franjo; Zuardi, Antonio Waldo; Crippa, José A S

2017-01-01

Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. Under acidic conditions, CBD can be transformed to delta9-tetrahydrocannabinol (THC) and other cannabinoids. It has been argued that this may occur also after oral administration in humans. However, the experimental conversion of CBD to THC and delta8-THC in simulated gastric fluid (SGF) is a highly artificial approach that deviates significantly from physiological conditions in the stomach; therefore, SGF does not allow an extrapolation to in vivo conditions. Unsurprisingly, the conversion of oral CBD to THC and its metabolites has not been observed to occur in vivo , even after high doses of oral CBD. In addition, the typical spectrum of side effects of THC, or of the very similar synthetic cannabinoid nabilone, as listed in the official Summary of Product Characteristics (e.g., dizziness, euphoria/high, thinking abnormal/concentration difficulties, nausea, tachycardia) has not been observed after treatment with CBD in double-blind, randomized, controlled clinical trials. In conclusion, the conversion of CBD to THC in SGF seems to be an in vitro artifact.

Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice.

PubMed

Riedel, Gernot; Fadda, Paola; McKillop-Smith, Susan; Pertwee, Roger G; Platt, Bettina; Robinson, Lianne

2009-04-01

Obesity is a severe health problem in the modernized world and understanding the central nervous mechanisms underlying food-seeking behaviour and reward are at the forefront of medical research. Cannabinoid receptors have proven an efficient target to suppress hunger and weight gain by their pharmacological inactivation. A standard fasted protocol and a novel long-term home-cage observation system with free-feeding animals were used to assess the feeding behaviour of mice treated with the CB1 antagonist AM251. Similarly, the effects of the phytocannabinoid Delta9-tetrahydrocannabivarin (Delta9-THCV), which behaves like a CB1 antagonist, were also determined in free-feeding animals. AM251 suppressed food intake and weight gain in fasted and non-fasted animals. The suppression of food intake by AM251 (10 mg.kg-1) endured for a period of 6-8 h when administered acutely, and was continuous when injected for four consecutive days. Pure Delta9-THCV also induced hypophagia and weight reduction at doses as low as 3 mg.kg-1. No rebound was observed on the following day with all drug groups returning to normal activity and feeding regimes. However, a Delta9-THCV-rich cannabis-extract failed to suppress food intake and weight gain, possibly due to residual Delta9-tetrahydrocannabinol (Delta9-THC) in the extract. This Delta9-THC effect was overcome by the co-administration of cannabidiol. The data strongly suggest (i) the long-term home-cage observation system is a sensitive and obesity-relevant tool, and (ii) the phytocannabinoid Delta9-THCV is a novel compound with hypophagic properties and a potential treatment for obesity

A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).

PubMed

Kwiatkowska, Magdalena; Parker, Linda A; Burton, Page; Mechoulam, Raphael

2004-07-01

The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown. To evaluate the potential of: 1) a broad range of doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew. Shrews were injected with various doses of OND (0.02-6.0 mg/kg), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin. OND and delta9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg. A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

Production of Delta(1)-tetrahydrocannabinolic acid by the biosynthetic enzyme secreted from transgenic Pichia pastoris.

PubMed

Taura, Futoshi; Dono, Emi; Sirikantaramas, Supaart; Yoshimura, Kohji; Shoyama, Yukihiro; Morimoto, Satoshi

2007-09-28

Delta(1)-Tetrahydrocannabinolic acid (THCA) synthase is the enzyme that catalyzes the oxidative cyclization of cannabigerolic acid into THCA, the acidic precursor of Delta(1)-tetrahydrocannabinol. We developed a novel expression system for THCA synthase using a methylotrophic yeast Pichia pastoris as a host. Under optimized conditions, the transgenic P. pastoris secreted approximately 1.32nkat/l of THCA synthase activity, and the culture medium, from which the cells were removed, effectively synthesized THCA from cannabigerolic acid with a approximately 98% conversion rate. The secreted THCA synthase was readily purified to homogeneity. Interestingly, endoglycosidase treatment afforded a deglycosylated THCA synthase with more catalytic activity than that of the glycosylated form. The non-glycosylated THCA synthase should be suitable for structure-function studies because it displayed much more activity than the previously reported native enzyme from Cannabis sativa as well as the recombinant enzyme from insect cell cultures.

Adsorption losses from urine-based cannabinoid calibrators during routine use.

PubMed

Blanc, J A; Manneh, V A; Ernst, R; Berger, D E; de Keczer, S A; Chase, C; Centofanti, J M; DeLizza, A J

1993-08-01

The major metabolite of cannabis found in urine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (delta 9-THC), is the compound most often used to calibrate cannabinoid immunoassays. The hydrophobic delta 9-THC molecule is known to adsorb to solid surfaces. This loss of analyte from calibrator solutions can lead to inaccuracy in the analytical system. Because the calibrators remain stable when not used, analyte loss is most probably caused by handling techniques. In an effort to develop an effective means of overcoming adsorption losses, we quantified cannabinoid loss from calibrators during the testing process. In studying handling of these solutions, we found noticeable, significant losses attributable to both the kind of pipette used for transfer and the contact surface-to-volume ratio of calibrator solution in the analyzer cup. Losses were quantified by immunoassay and by radioactive tracer. We suggest handling techniques that can minimize adsorption of delta 9-THC to surfaces. Using the appropriate pipette and maintaining a minimum surface-to-volume ratio in the analyzer cup effectively reduces analyte loss.

Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study.

PubMed

Tomida, Ileana; Azuara-Blanco, Augusto; House, Heather; Flint, Maggie; Pertwee, Roger G; Robson, Philip J

2006-10-01

The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD). A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects. Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after Delta-9-THC administration. A single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.

Enzymatic digestion and selective quantification of underivatised delta-9-tetrahydrocannabinol and cocaine in human hair using gas chromatography-mass spectrometry.

PubMed

Breidi, Salah Eddine; Barker, James; Petróczi, Andrea; Naughton, Declan P

2012-01-01

Gas chromatography-mass spectrometric (GC-MS) methods for drug analysis routinely employ derivatising reagents. The aim of this paper was to develop a method for the analysis of two recreational drugs, delta-9-tetrahydrocannabinol (Δ(9)-THC) and cocaine in hair samples using GC-MS, without prior derivatisation, thus allowing the sample to be reanalysed in its original form. An enzymatic digestion technique was also developed. Ten hair samples, that were known positive for either Δ(9)-THC and/or cocaine, were enzymatically digested, extracted, and then analysed by GC-MS. All samples measured contained Δ(9)-THC and one sample contained cocaine. The limits of detection (LOD) and quantification (LOQ) were 0.02 ng/mg and 0.05 ng/mg, respectively, for cocaine and 0.015 ng/mg and 0.02 ng/mg, respectively, for Δ(9)-THC. The wide detection window, ease of direct analysis by GC-MS, lower detection limits of underivatised samples, and the stability of drugs using this technique may offer an improved method of analysis.

Enzymatic Digestion and Selective Quantification of Underivatised Delta-9-Tetrahydrocannabinol and Cocaine in Human Hair Using Gas Chromatography-Mass Spectrometry

PubMed Central

Breidi, Salah Eddine; Barker, James; Petróczi, Andrea; Naughton, Declan P.

2012-01-01

Gas chromatography-mass spectrometric (GC-MS) methods for drug analysis routinely employ derivatising reagents. The aim of this paper was to develop a method for the analysis of two recreational drugs, delta-9-tetrahydrocannabinol (Δ9-THC) and cocaine in hair samples using GC-MS, without prior derivatisation, thus allowing the sample to be reanalysed in its original form. An enzymatic digestion technique was also developed. Ten hair samples, that were known positive for either Δ9-THC and/or cocaine, were enzymatically digested, extracted, and then analysed by GC-MS. All samples measured contained Δ9-THC and one sample contained cocaine. The limits of detection (LOD) and quantification (LOQ) were 0.02 ng/mg and 0.05 ng/mg, respectively, for cocaine and 0.015 ng/mg and 0.02 ng/mg, respectively, for Δ9-THC. The wide detection window, ease of direct analysis by GC-MS, lower detection limits of underivatised samples, and the stability of drugs using this technique may offer an improved method of analysis. PMID:22567573

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

PubMed Central

Bhattacharyya, Sagnik; Falkenberg, Irina; Martin-Santos, Rocio; Atakan, Zerrin; Crippa, Jose A; Giampietro, Vincent; Brammer, Mick; McGuire, Philip

2015-01-01

There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli. PMID:25249057

Exposure to marijuana smoke impairs memory retrieval in mice.

PubMed

Niyuhire, Floride; Varvel, Stephen A; Martin, Billy R; Lichtman, Aron H

2007-09-01

Marijuana (Cannabis sativa) and its primary psychoactive component, delta-9-tetrahydrocannabinol (Delta(9)-THC), have long been known to disrupt cognition in humans. Although Delta(9)-THC and other cannabinoids disrupt performance in a wide range of animal models of learning and memory, few studies have investigated the effects of smoked marijuana in these paradigms. Moreover, in preclinical studies, cannabinoids are generally administered before acquisition, and because retention is generally evaluated soon afterward, it is difficult to distinguish between processes related to acquisition and retrieval. In the present study, we investigated the specific effects of marijuana smoke and injected Delta(9)-THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered Delta(9)-THC or they were exposed to marijuana smoke either 30 min before acquisition or 30 min before the retention test. Inhalation of marijuana smoke or injected Delta(9)-THC impaired the ability of the mice to learn the location of the hidden platform and to recall the platform location once learning had already taken place. In contrast, neither drug impaired performance in a cued task in which the platform was made visible. Finally, the cannabinoid-1 (CB(1)) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (rimonabant) blocked the memory disruptive effects of both Delta(9)-THC and marijuana. These data represent the first evidence demonstrating that marijuana impairs memory retrieval through a CB(1) receptor mechanism of action and independently of its effects on sensorimotor performance, motivation, and initial acquisition.

Cannabinoid modulation of functional connectivity within regions processing attentional salience.

PubMed

Bhattacharyya, Sagnik; Falkenberg, Irina; Martin-Santos, Rocio; Atakan, Zerrin; Crippa, Jose A; Giampietro, Vincent; Brammer, Mick; McGuire, Philip

2015-05-01

There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.

High-affinity cannabinoid binding site in brain: A possible marijuana receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nye, J.S.

The mechanism by which delta{sup 9} tetrahydrocannabinol (delta{sup 9}THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5{prime}-Trimethylammonium-delta{sup 8}THC (TMA) is a positively charged analog of delta-{sup 8}THC modified on the 5{prime} carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of ({sup 3}H)-5{prime}-trimethylammonium-delta-{sup 8}THC (({sup 3}H)TMA) to rat neuronal membranes. ({sup 3}H)TMA binds saturably and reversibly to brain membranes with high affinity to apparently one classmore » of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of ({sup 3}H)TMA binding activity of approximately 60,000 daltons apparent molecular weight.« less

A qualitative and quantitative HPTLC densitometry method for the analysis of cannabinoids in Cannabis sativa L.

PubMed

Fischedick, Justin T; Glas, Ronald; Hazekamp, Arno; Verpoorte, Rob

2009-01-01

Cannabis and cannabinoid based medicines are currently under serious investigation for legitimate development as medicinal agents, necessitating new low-cost, high-throughput analytical methods for quality control. The goal of this study was to develop and validate, according to ICH guidelines, a simple rapid HPTLC method for the quantification of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and qualitative analysis of other main neutral cannabinoids found in cannabis. The method was developed and validated with the use of pure cannabinoid reference standards and two medicinal cannabis cultivars. Accuracy was determined by comparing results obtained from the HTPLC method with those obtained from a validated HPLC method. Delta(9)-THC gives linear calibration curves in the range of 50-500 ng at 206 nm with a linear regression of y = 11.858x + 125.99 and r(2) = 0.9968. Results have shown that the HPTLC method is reproducible and accurate for the quantification of Delta(9)-THC in cannabis. The method is also useful for the qualitative screening of the main neutral cannabinoids found in cannabis cultivars.

Visual search and urban city driving under the influence of marijuana and alcohol

DOT National Transportation Integrated Search

2000-03-01

The purpose of this study was to empirically determine the separate and combined effects of delta-9-tetrahydrocannabinol (THC) and alcohol on visual search and actual city driving performance. On separate evenings, 16 subjects were given weight-calib...

(+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.

PubMed

Fride, Ester; Feigin, Cfir; Ponde, Datta E; Breuer, Aviva; Hanus, Lumír; Arshavsky, Nina; Mechoulam, Raphael

2004-12-15

Delta9-Tetrahydrocannabinol (Delta9-THC) and (-)-cannabidiol are major constituents of the Cannabis sativa plant with different pharmacological profiles: (-)-Delta9-tetrahydrocannabinol, but not (-)-cannabidiol, activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. We have tested a series of (+)-cannabidiol derivatives, namely, (+)-cannabidiol-DMH (DMH-1,1-dimethylheptyl-), (+)-7-OH-cannabidiol-DMH, (+)-7-OH- cannabidiol, (+)-7-COOH- cannabidiol and (+)-7-COOH-cannabidiol-DMH, for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice. Although all (+)-cannabidiols bind to cannabinoid CB1 and CB2 receptors, only (+)-7-OH-cannabidiol-DMH was centrally active, while all (+)-cannabidiol analogues completely arrested defecation. The effects of (+)-cannabidiol-DMH and (+)-7-OH-cannabidiol-DMH were partially antagonized by the cannabinoid CB1 receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716), but not by the cannabinoid CB2 receptor antagonist N-[-(1S)-endo-1,3,3-trimethil bicyclo [2.2.1] heptan-2-yl-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), and had no effect on CB1(-/-) receptor knockout mice. (+)-Cannabidiol-DMH inhibited the peripheral pain response and arachidonic-acid-induced inflammation of the ear. We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions.

The effects of pH and temperature on the in vitro bindings of delta-9-tetrahydrocannabinol and other cannabinoids to bovine serum albumin.

PubMed

Papa, V M; Shen, M L; Ou, D W

1990-01-01

Albumin is a major carrier of drugs and fatty acids in biological fluids. These protein-drug complexes serve to solubilize, transport these compounds to sites of action, and have been associated with increased half-life for these compounds. The authors are interested in the pH and temperature effects of the binding of delta-9-tetrahydrocannabinol to albumin. Ultrafiltration techniques were used in the separation of free to bound compounds. Cannabinoids bind to bovine serum albumin rapidly. The cannabinoid binding sites are more sensitive to temperature changes (37-47 degrees C) than changes in pH with 37 degrees C and pH 7.4 resulting in optimal binding. These conditions would result in the greatest viability in the cells, while allowing for the use of a variety of compounds in in vitro studies for the administration of compounds to isolated cells and cell lines.

Medicinal applications of delta-9-tetrahydrocannabinol and marijuana.

PubMed

Voth, E A; Schwartz, R H

1997-05-15

The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature. Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite. We evaluated the relevant research published between 1975 and 1996 on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity. Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite. The evidence does not support the reclassification of crude marijuana as a prescribable medicine.

Quantification of 11-Carboxy-Delta-9-Tetrahydrocannabinol (THC-COOH) in Meconium Using Gas Chromatography/Mass Spectrometry (GC/MS).

PubMed

Peat, Judy; Davis, Brehon; Frazee, Clint; Garg, Uttam

2016-01-01

Maternal substance abuse is an ongoing concern and detecting drug use during pregnancy is an important component of neonatal care when drug abuse is suspected. Meconium is the preferred specimen for drug testing because it is easier to collect than neonatal urine and it provides a much broader time frame of drug exposure. We describe a method for quantifying 11-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in meconium. After adding a labeled internal standard (THC-COOH D9) and acetonitrile, samples are sonicated to release both free and conjugated THC-COOH. The acetonitrile/aqueous layer is removed and mixed with a strong base to hydrolyze the conjugated THC-COOH. The samples are then extracted with an organic solvent mixture as part of a sample "cleanup." The organic solvent layer is discarded and the remaining aqueous sample is acidified. Following extraction with a second organic mixture, the organic layer is removed and concentrated to dryness. The resulting residue is converted to a trimethylsilyl (TMS) derivative and analyzed using gas chromatography/mass spectrometry (GC/MS) in selective ion monitoring (SIM) mode.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

PubMed Central

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-01-01

Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349

The effect of conditions influencing endogenous prostaglandins on the activity of delta'-tetrahydrocannabinol in mice.

PubMed

Fairbairn, J W; Pickens, J T

1980-07-01

1 The cataleptic effect of delta'-tetrahydrocannabinol (THC) depends upon the availability of the precursors of prostaglandins and the response is reduced in mice maintained on a diet deficient in arachidonic acid (AA) and restored by exogenous AA given intraperitoneally, or by feeding a normal diet. 2 In yeast-induced fever, which is accompanied by an increase in the synthesis of prostaglandins, THC shows an enhanced cataleptic effect. 3 Exposure to cold which results in depletion of prostaglandins reduces the effect of THC.

Simultaneous determination of amphetamine-type stimulants and cannabinoids in fingernails by gas chromatography-mass spectrometry.

PubMed

Kim, Jin Young; Cheong, Jae Chul; Kim, Min Kyoung; Lee, Jae Il; In, Moon Kyo

2008-06-01

A gas chromatography-mass spectrometric (GC-MS) method was developed and validated for the simultaneous detection and quantification of four amphetamine-type stimulants (amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA)) and two cannabinoids (Delta9-tetrahydrocannabinol (Delta9-THC) and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH)) in fingernails. Fingernail clippings (30 mg) were washed with distilled water and methanol, and then incubated in 1.0 M sodium hydroxide at 95 degrees C for 30 min. The compounds of interest were isolated by liquid-liquid extraction followed by derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) at 70 degrees C for 15 min. The derivatized compounds were analyzed by GC-MS in the selective ion monitoring (SIM) mode. The linear ranges were 0.1-15.0 ng/mg for AP, 0.2-15.0 ng/mg for MDA, Delta9-THC and THCCOOH, and 0.2-30.0 ng/mg for MA and MDMA, with good correlation coefficients (r2 > 0.9991). The intra-day, inter-day, and inter-person precisions were within 10.6%, 6.3%, and 5.3%, respectively. The intra-day, inter-day and inter-person accuracies were between -6.1 and 5.0%, -6.2 and 5.7%, and -6.4 and 5.6%, respectively. The limits of detection (LODs) and quantification (LOQs) for each compound were lower than 0.056 and 0.2 ng/mg, respectively. The recoveries were in the range of 74.0-94.8%. Positive GC-MS results were obtained from specimens of nine suspected MA or cannabis abusers. The concentration ranges of MA, AP, and THCCOOH were 0.10-1.41, 0.12-2.64, and 0.20 ng/mg, respectively. Based on these results, the method proved to be effective for the simultaneous qualification and quantification of amphetamine-type stimulants and cannabinoids in fingernails.

[Analysis of active components of evidence materials secured in the cases of drugs abuse associated with amphetamines and cannabis products].

PubMed

Wachowiak, Roman; Strach, Bogna

2006-01-01

The study takes advantage of the presently available effective physicochemical methods (isolation, crystallization, determination of melting point, TLC, GLC and UV spectrophotometry) for an objective and reliable qualitative and quantitative analysis of frequently abused drugs. The authors determined the conditions for qualitative and quantitative analysis of active components of the secured evidence materials containing amphetamine sulphate, methylamphetamine hydrochloride, 3,4-me-tylenedioxy-methamphetamine hydrochloride (MDMA, Ecstasy), as well as delta(9)-tetrahydrocannabinol (delta(9)-THC) as an active component of cannabis (marihuana, hashish). The usefulness of physicochemical tests of evidence materials for opinionating purposes is subject to a detailed forensic toxicological interpretation.

Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.

PubMed

Takeda, Shuso; Misawa, Koichiro; Yamamoto, Ikuo; Watanabe, Kazuhito

2008-09-01

In the present study it was revealed that cannabidiolic acid (CBDA) selectively inhibited cyclooxygenase (COX)-2 activity with an IC(50) value (50% inhibition concentration) around 2 microM, having 9-fold higher selectivity than COX-1 inhibition. In contrast, Delta(9)-tetrahydrocannabinolic acid (Delta(9)-THCA) was a much less potent inhibitor of COX-2 (IC(50) > 100 microM). Nonsteroidal anti-inflammatory drugs containing a carboxyl group in their chemical structures such as salicylic acid are known to inhibit nonselectively both COX-1 and COX-2. CBDA and Delta(9)-THCA have a salicylic acid moiety in their structures. Thus, the structural requirements for the CBDA-mediated COX-2 inhibition were next studied. There is a structural difference between CBDA and Delta(9)-THCA; phenolic hydroxyl groups of CBDA are freed from the ring formation with the terpene moiety, although Delta(9)-THCA has dibenzopyran ring structure. It was assumed that the whole structure of CBDA is important for COX-2 selective inhibition because beta-resorcylic acid itself did not inhibit COX-2 activity. Methylation of the carboxylic acid moiety of CBDA led to disappearance of COX-2 selectivity. Thus, it was suggested that the carboxylic acid moiety in CBDA is a key determinant for the inhibition. Furthermore, the crude extract of cannabis containing mainly CBDA was shown to have a selective inhibitory effect on COX-2. Taken together, these lines of evidence in this study suggest that naturally occurring CBDA in cannabis is a selective inhibitor for COX-2.

Radioimmunoanalysis of delta-9-THC in blood by means of an /sup 125/I tracer. [Delta-9-Tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owens, S.M.; McBay, A.J.; Reisner, H.M.

A radioimmunoassay for delta-9-THC in plasma, whole blood, or hemolyzed blood specimens has been presented. Samples and standards were diluted with methanol and centrifuged. An aliquot of the supernatant fluid was incubated with RIA buffer, /sup 125/I-labeled delta-8-THC and rabbit anti-THC serum. Solid phase goat anti-rabbit immunoglobulins were added to separate bound from free THC. After centrifugation the supernatant fluid was aspirated and the radioactivity of the precipitate was counted in a gamma counter. The concentration of THC was calculated from a standard curve using the logit-log transformation of the average counts of duplicate tubes. The assay had several advantages.more » Methanol dilution gave better results than direct analysis. The /sup 125/I-labeled THC had high specific activity and could be counted in a gamma counter. The immunological separation of antibody-bound THC from free THC was better than separation techniques using ammonium sulfate and activated charcoal. THC was determined in 0.1 ml of sample with a sensitivity of 1.5 ng/ml in plasma and 3.0 ng/ml in hemolyzed blood.« less

Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats.

PubMed

Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S

2004-06-01

Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.

Frequency and irregularity of heart rate in drivers suspected of driving under the influence of cannabis.

PubMed

Khiabani, Hassan Z; Mørland, Jørg; Bramness, Jørgen G

2008-12-01

Delta 9-tetrahydrocannabinol (THC) is the major active component of cannabis. Cardiovascular effects of THC have previously been reported: tachycardia after intake, but also bradycardia at higher doses. The purpose of this study was, firstly, to investigate the frequency and irregularity of heart rate in a group of cannabis users in their natural surroundings. We also compared THC-positive drivers with a regular pulse with THC-positive drivers with an irregular pulse. The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyzes blood samples from all drivers suspected of driving under the influence of drugs. We studied pulse rate and regularity in 502 THC-positive drivers who tested negative for other substances. As a control group, we randomly selected 125 drug-negative cases from the database of the DFTDA; no alcohol, narcotics, or medicinal drugs of abuse were detected. The Delta9-THC-positive drivers had a higher mean pulse rate than the control group [82.8 beats/min (SD 16.3) versus 75.6 beats/min (SD 9.2)] and more cases with tachycardia were detected in the Delta9-THC-positive group (19.4% versus 1.6%). There was only one driver with an irregular heart beat in the control group, while there were nine among the Delta9-THC-positive drivers. The drivers with an irregular pulse were over-represented amongst those with the lowest blood Delta9-THC concentrations. This report represents a large study of subjects in a real-life situation and includes observations on pulse frequency, regularity, and blood Delta9-THC concentration. A substantial fraction of Delta9-THC-positive drivers had tachycardia, but there was no correlation between blood Delta9-THC concentration and pulse rate in the present study. We had no further diagnostic information on the cause of the pulse irregularities, but our results indicate that occasional users of cannabis tend to have irregular heart rates at low THC concentrations and at low pulse rates.

Contact highs and urinary cannabinoid excretion after passive exposure to marijuana smoke.

PubMed

Cone, E J; Johnson, R E

1986-09-01

Five healthy men were passively exposed under pre- and postplacebo controlled conditions to sidestream smoke from four and 16 standard marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [delta-9-THC]) for 1 hour each day for 6 consecutive days. Subjective effects produced by the 16-cigarette exposure conditions were similar to those observed after active smoking of one 2.8% delta-9-THC marijuana cigarette. Effects after the four-cigarette condition were less pronounced. Concurrent physiologic measurements showed no clear trends or effects of smoke exposure for either condition. Daily mean plasma levels of delta-9-THC ranged from 2.4 to 7.4 ng/ml with an individual high of 18.8 ng/ml for the 16-cigarette condition. With the use of EMIT cannabinoid assays with 20 ng/ml (EMIT 20) and 100 ng/ml (EMIT 100) cutoffs, urines positive per subject under the four- and 16-cigarette passive exposure conditions were 4.6 +/- 2.2 and 35.2 +/- 3.8, respectively, for the EMIT 20 and 0.0 and 1.0 +/- 0.8, respectively, for the EMIT 100 assay. From the results of these studies, caution is clearly indicated for individuals who might be substantially exposed to heavy marijuana cigarette smoke environments and for those interpreting marijuana screening data.

GW-1000. GW Pharmaceuticals.

PubMed

Smith, Paul F

2004-07-01

GW Pharmaceuticals is developing GW-1000 (Sativex), a narrow ratio delta9-tetrahydrocannabinol:cannabidiol product for the potential treatment of multiple sclerosis, spinal cord injury, neurogenic pain and peripheral neuropathy. In March 2003, the company filed for approval for the treatment of MS with the UK Medicines Control Agency, and in May 2004, filed for new drug submission with Health Canada.

Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon?

PubMed

Flom, M C; Adams, A J; Jones, R T

1975-01-01

Normal pressure within the human eye was reduced after smoking a socially relevant dose of marijuana (12 mg. delta9-9-tetrahydrocannabinol), but only for light to moderate users who experienced a substantial "high" and a state of peaceful relaxation from the experimental dose. Analysis suggests an indirect effect of the drug associated with relaxation-a psychophysiologic state that can be produced by drug and nondrug means.

Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability.

PubMed

Jacobsson, S O; Rongård, E; Stridh, M; Tiger, G; Fowler, C J

2000-12-15

In the present study, the effects of the combination of tamoxifen ((Z)-2[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylamine citrate) and three cannabinoids (Delta(9)-tetrahydrocannabinol [Delta(9)-THC], cannabidiol, and anandamide [AEA]) upon the viability of C6 rat glioma cells was assessed at different incubation times and using different culturing concentrations of foetal bovine serum (FBS). Consistent with previous data for human glioblastoma cells, the tamoxifen sensitivity of the cells was increased as the FBS content of the culture medium was reduced from 10 to 0.4 and 0%. The cells expressed protein kinase C alpha and calmodulin (the concentration of which did not change significantly as the FBS concentration was reduced), but did not express estrogen receptors. Delta(9)-THC and cannabidiol, but not AEA, produced a modest reduction in cell viability after 6 days of incubation in serum-free medium, whereas no effects were seen in 10% FBS-containing medium. There was no observed synergy between the effects of tamoxifen and the cannabinoids upon cell viability.

Effect of cannabinoids on estrous cycle, ovulation and reproductive capacity of female A/J mice.

PubMed

Kostellow, A B; Ziegler, D; Kunar, J; Fujimoto, G I; Morrill, G A

1980-01-01

Virgin A/J female mice were intubated daily for 8 days (short term) or 70 days (long term) with 0, 1, 5, or 25 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) or 0, 3, 15, or 75 mg/kg crude marihuana extract (CME) in a sesame oil:polysorbate 80:saline vehicle. These dosages approximate light, moderate, and heavy human usage. Short-term exposure to CME has no significant effect on PMS-HCG-induced ovulation but appears to: (1) delay entry into proestrus at all dose levels; (2) depress serum progesterone during the luteal phase at the highest CME level used (75 mg/kg), and (3) inhibit female receptivity to males at least at the highest dosage. Long-term oral administration of CME or delta 9-thc had no significant effect on length of estrous cycles or mating (plug formation) but term pregnancies were reduced by 32 and 68% for medium and high dosages, respectively. After a 30-day recovery period, 80% of those females that failed to have successful pregnancies now became pregnant.

Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol.

PubMed

Deutsch, Stephen I; Rosse, Richard B; Connor, Julie M; Burket, Jessica A; Murphy, Mary E; Fox, Fiona J

2008-05-01

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

Cannabinoid and Cholinergic Systems Interact during Performance of a Short-Term Memory Task in the Rat

ERIC Educational Resources Information Center

Goonawardena, Anushka V.; Robinson, Lianne; Hampson, Robert E.; Riedel, Gernot

2010-01-01

It is now well established that cannabinoid agonists such as [delta][superscript 9]-tetrahydrocannabinol (THC), anandamide, and WIN 55,212-2 (WIN-2) produce potent and specific deficits in working memory (WM)/short-term memory (STM) tasks in rodents. Although mediated through activation of CB1 receptors located in memory-related brain regions such…

Effect of the psychoactive metabolite of marijuana, delta 9-tetrahydrocannabinol (THC), on the synthesis of tumor necrosis factor by human large granular lymphocytes.

PubMed

Kusher, D I; Dawson, L O; Taylor, A C; Djeu, J Y

1994-03-01

The natural killer cell (NK)/3polymorphonuclear neutrophil axis has recently been identified to be important in early defense against the opportunistic fungi, Candida albicans. Repression of this system is therefore likely to contribute to susceptibility to opportunistic infections. delta 9-Tetrahydrocannabinol (THC), an active constituent of marijuana, has been reported to be immunosuppressive at concentrations that exceed attainable plasma levels. In this report, we examine the possibility that human large granular lymphocytes (LGL) can be immunosuppressed by exposure to THC at physiologically relevant concentrations and probed two functions associated with LGL, i.e., cytokine production and tumoricidal activity. We find that these low levels of THC inhibit tumor necrosis factor-alpha (TNF) induction from LGL by C. albicans and are dependent upon THC dose (0.005-5.0 micrograms/ml) and length of exposure (0.05-3.0 hr). Northern blot analysis indicates that the downregulation of TNF production from LGL by THC resides at the mRNA level. Moreover, exposure of LGL to physiological THC concentrations (0.01-2.0 micrograms/ml) diminishes their cytolytic activity against K562 tumor cells.

On the pharmacological properties of Delta9-tetrahydrocannabinol (THC).

PubMed

Costa, Barbara

2007-08-01

Cannabis is one of the first plants used as medicine, and the notion that it has potentially valuable therapeutic properties is a matter of current debate. The isolation of its main constituent, Delta9-tetrahydrocannabinol (THC), and the discovery of the endocannabinoid system (cannabinoid receptors CB1 and CB2 and their endogenous ligands) made possible studies concerning the pharmacological activity of cannabinoids. This paper reviews some of the most-important findings in the field of THC pharmacology. Clinical trials, anecdotal reports, and experiments employing animal models strongly support the idea that THC and its derivatives exhibit a wide variety of therapeutic applications. However, the psychotropic effects observed in laboratory animals and the adverse reactions reported during human trials, as well as the risk of tolerance development and potential dependence, limit the application of THC in therapy. Nowadays, researchers focus on other therapeutic strategies by which the endocannabinoid system might be modulated to clinical advantage (inhibitor or activator of endocannabinoid biosynthesis, cellular uptake, or metabolism). However, emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis-based medicines as new perspective to revisit the pharmacology of this plant.

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting.

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Mechoulam, Raphael

2006-01-30

Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment. We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity. On the other hand, pretreatment with a dose of ondansetron (a 5-HT(3) antagonist) that interferes with acute vomiting in this species, did not suppress the expression of conditioned retching during re-exposure to the lithium-paired context. These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.

Cannabis and psychosis: an update on course and biological plausible mechanisms.

PubMed

Linszen, Don; van Amelsvoort, Therese

2007-03-01

Cannabis use is the most commonly abused illicit substance. Its relation with psychosis remains a topic of debate. Epidemiological studies suggest that cannabis is a component cause accounting for approximately 10% of cases. An increasing number of studies have been published on neurobiological effects of cannabis and vulnerability of psychosis. Acute cannabis administration can induce memory impairments, sometimes persisting months following abstinence. There is no evidence that residual effects on cognition remain after years of abstinence. The scarce literature on neuro-imaging mainly done in nonpsychotic populations, show little evidence that cannabis has effects on brain anatomy. Acute effects of cannabis include increases of cerebral blood flow, whereas long-term effects of cannabis include attenuation of cerebral blood flow. In animals Delta9-tetrahydrocannabinol enhances dopaminergic neurotransmission in brain regions known to be implicated in psychosis. Studies in humans show that genetic vulnerability may add to increased risk of developing psychosis and cognitive impairments following cannabis consumption. Delta9-tetrahydrocannabinol induces psychotic like states and memory impairments in healthy volunteers. Simultaneously with increasing understanding of neurobiological cannabis effects, there is a lack of studies in people with psychosis. There are plausible mechanisms that might explain the psychotogenic effects of cannabis.

Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, T.; Pross, S.; Newton, C.

Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation wasmore » analyzed by /sup 3/H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects.« less

Toward drugs derived from cannabis.

PubMed

Mechoulam, R; Carlini, E A

1978-04-01

Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.

[Usefulness of the initial medical examination on matters relating to persons suspected of driving under the influence of amphetamine and its analogs or delta9-tetrahydrocannabinol based on the materials the Department of Forensic Medicine, Pomeranian Medical University in Szczecin].

PubMed

Wolski, Stanisław; Lewandowska, Ewa; Kurzejamska-Parafiniuk, Małgorzata

2013-01-01

Polish law forbids persons to drive under the influence of intoxicating substances, and those after the use of substances producing effects similar to alcohol. Therefore, there is a need to give an opinion based on a blood test, to establish whether or not the person from whom the blood was taken was under the influence of an intoxicating substance or after use of the drug while driving. Some authors reported that the final opinion should take into account chemical and toxicology test results identifying the parent compound and/or the metabolite only, but also the sampling time of the material to be analyzed in relation to the driving time, the result of the medical examination conducted prior to the collection of material for analysis, and the results of screening tests executed at the scene. Circumstances relating to the event, the findings and observations of third parties, and the testimony of the suspect are also relevant. The aim of this study was to evaluate the results of the medical examination in the evaluation of cases concerning driving by persons who were potentially under the influence of amphetamine and its analogs, or delta9-tetrahydrocannabinol, (delta9-THC) and conformity assessment of these results with the results of blood tests. An additional aim was to determine the factors considered by doctors when making their evaluation of patient's condition. The study group consisted of 350 persons suspected of driving while under the influence of amphetamine and its analogs, and/or delta9-THC, from whom blood samples were taken to test amphetamine content or its analogues and/or delta9-tetrahydrocannabinol. Blood tests were carried out according to the existing procedure developed by the department. Blood samples were initially analyzed with immunochemical methods. Positive preliminary results were verified by gas chromatography-mass spectrometry. Statistical analysis was conducted with independent tests for multi-way tables, i.e. the Pearson chi2 test and the 2 x 2 tables Yates' correction was used for the low numbers. Comparison of mean concentrations of amphetamine and delta9-THC in the blood was performed using the U Mann-Whitney test. The analysis revealed a significant correlation between the symptoms and the results of the chemical-toxicological blood tests for mood only. There was no significant correlation between the results of toxicological and physical elements contained in the protocol of blood collection as the skin's appearance, speech, heart rate, pupil, pupil reaction to light, walking, lifting objects off the ground, the Romberg test, the finger-to-nose test and orientation in the space time environment. In the analysis of the relationship between the medical assessment and physical elements significant relationships with the assessment of mood, pupils, pupil reaction to light and gait were found. A significant correlation between the prevalence of symptoms in terms of any/none and medical evaluation was found. 1. Preliminary medical examination based on the blood sampling protocol has no practical importance for determining whether a person is tested under the influence of amphetamines or its analogues and/or delta9-THC. 2. The confirmation of the state "under the influence of narcotics or psychotropics" should only be based on blood test results. 3. Doctors, when completing the blood collection report, are often guided by factors other than the test results when making assessment. 4. The low utility of the medical examination is affected by lack of standardization of test items. Doctors often find symptoms in a subjective manner.

Solid-phase extraction and GC-MS analysis of THC-COOH method optimized for a high-throughput forensic drug-testing laboratory.

PubMed

Stout, P R; Horn, C K; Klette, K L

2001-10-01

In order to facilitate the confirmation analysis of large numbers of urine samples previously screened positive for delta9-tetrahydrocannabinol (THC), an extraction, derivitization, and GC-MS analysis method was developed. This method utilized a positive pressure manifold anion-exchange polymer-based solid-phase extraction followed by elution directly into the automated liquid sampling (ALS) vials. Rapid derivitization was accomplished using pentafluoropropionic anhydride/pentafluoropropanol (PFPA/PFPOH). Recoveries averaged 95% with a limit of detection of 0.875 ng/mL with a 3-mL sample volume. Performance of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH)-d3 and THC-COOH-d9 internal standards were evaluated. The method was linear to 900 ng/mL THC-COOH using THC-COOH-d9 with negligible contribution from the internal standard to very weak samples. Excellent agreement was seen with previous quantitations of human urine samples. More than 1000 human urine samples were analyzed using the method with 300 samples analyzed using an alternate qualifier ion (m/z 622) after some interference was observed with a qualifier ion (m/z 489). The 622 ion did not exhibit any interference even in samples with interfering peaks present in the 489 ion. The method resulted in dramatic reductions in processing time, waste production, and exposure hazards to laboratory personnel.

Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: 18F-Fallypride Positron Emission Tomography Study

PubMed Central

Kuepper, Rebecca; Ceccarini, Jenny; Lataster, Johan; van Os, Jim; van Kroonenburgh, Marinus; van Gerven, Joop M. A.; Marcelis, Machteld; Van Laere, Koen; Henquet, Cécile

2013-01-01

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and 18F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ9-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ9-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in 18F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ9-THC administration, reflecting dopamine release. While Δ9-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ9-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ9-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis. PMID:23936196

[What sense in cannabinoid use as regulated by Italian DM 18/04/07? Pharmacological and legal considerations].

PubMed

Molinelli, A; Grossi, S; Bonsignore, A; Martelli, A

2008-06-01

The present article relates to the Italian Ministerial Decree (DM) 18/04/2007 referring to what was established by the Financial Law 2007 on the matter of the use of drugs for the so called ''off-label'' uses. This law introduces three cannabinoid substances, with the common name of Delta 9 and Trans-delta 9 tetrahydrocannabinol and Nabilone, within the possible therapies for the treatment of ''severe pain''. The authors underline the absence of a sufficient pharmacokinetical and pharmacodynamical knowledge supporting the use of cannabinoid substances in the ''severe pain'' therapy. Further more the professional prescriber could go against judicial consequences if the drugs causes as verified the onset of collateral effects even severe that, for the scientific knowledge in possess at the present state, the authors know could take place.

Automated extraction for the analysis of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in urine using a six-head probe Hamilton Microlab 2200 system and gas chromatography-mass spectrometry.

PubMed

Whitter, P D; Cary, P L; Leaton, J I; Johnson, J E

1999-01-01

An automated extraction scheme for the analysis of 11 -nor-delta9-tetrahydrocannabinol-9-carboxylic acid using the Hamilton Microlab 2200, which was modified for gravity-flow solid-phase extraction, has been evaluated. The Hamilton was fitted with a six-head probe, a modular valve positioner, and a peristaltic pump. The automated method significantly increased sample throughput, improved assay consistency, and reduced the time spent performing the extraction. Extraction recovery for the automated method was > 90%. The limit of detection, limit of quantitation, and upper limit of linearity were equivalent to the manual method: 1.5, 3.0, and 300 ng/mL, respectively. Precision at the 15-ng/mL cut-off was as follows: mean = 14.4, standard deviation = 0.5, coefficient of variation = 3.5%. Comparison of 38 patient samples, extracted by the manual and automated extraction methods, demonstrated the following correlation statistics: r = .991, slope 1.029, and y-intercept -2.895. Carryover was < 0.3% at 1000 ng/mL. Aliquoting/extraction time for the automated method (48 urine samples) was 50 min, and the manual procedure required approximately 2.5 h. The automated aliquoting/extraction method on the Hamilton Microlab 2200 and its use in forensic applications are reviewed.

Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

PubMed

Ménétrey, Annick; Augsburger, Marc; Favrat, Bernard; Pin, Marie A; Rothuizen, Laura E; Appenzeller, Monique; Buclin, Thierry; Mangin, Patrice; Giroud, Christian

2005-01-01

Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the molar ratio of main active to inactive cannabinoids, greater than 10 was found to correlate with a strong feeling of intoxication. It also matched with a significant decrease in the willingness to drive, and it matched also with a significant impairment in tracking performances. The mathematic model II proposed by Huestis et al. (1992) provided at best a rough estimate of the time of oral administration with 27% of actual values being out of range of the 95% confidence interval. The sum of THC and 11-OH-THC blood concentrations provided a better estimate of impairment than THC alone. This controlled clinical study points out the negative influence on fitness to drive after medium or high dose oral THC or dronabinol.

Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract.

PubMed

Nadulski, Thomas; Sporkert, Frank; Schnelle, Martin; Stadelmann, Andreas M; Roser, Patrik; Schefter, Tom; Pragst, Fritz

2005-01-01

Besides the psychoactive Delta(9)-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C(18) ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis consumption.

Detection of Delta9-tetrahydrocannabinol and amphetamine-type stimulants in oral fluid using the Rapid Stat point-of-collection drug-testing device.

PubMed

Röhrich, J; Zörntlein, S; Becker, J; Urban, R

2010-04-01

The Rapid Stat assay, a point-of-collection drug-testing device for detection of amphetamines, cannabinoids, cocaine, opiates, methadone, and benzodiazepines in oral fluid, was evaluated for cannabis and amphetamine-type stimulants. The Rapid Stat tests (n = 134) were applied by police officers in routine traffic checks. Oral fluid and blood samples were analyzed using gas chromatography-mass spectrometry (GC-MS) for Delta(9)-tetrahydrocannabinol, amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedioxyethylamphetamine, and methylenedioxyamphetamine. The comparison of GC-MS analysis of oral fluid with the Rapid Stat results for cannabis showed a sensitivity of 85%, a specificity of 87%, and a total confirmation rate of 87%. When compared with serum, the sensitivity of the cannabis assay decreased to 71%, the specificity to 60%, and the total confirmation rate to 66%. These findings were possibly caused by an incorrect reading of the THC test results. Comparison of the Rapid Stat amphetamine assay with GC-MS in oral fluid showed a sensitivity of 94%, a specificity of 97%, and a total confirmation rate of 97%. Compared with serum, a sensitivity of 100%, a specificity of 90%, and a total confirmation rate of 92% was found. The amphetamine assay must, therefore, be regarded as satisfactory.

Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells.

PubMed

Kishimoto, Seishi; Muramatsu, Mayumi; Gokoh, Maiko; Oka, Saori; Waku, Keizo; Sugiura, Takayuki

2005-02-01

2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays important physiological roles in several mammalian tissues and cells, yet the details remain ambiguous. In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells. We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells (a natural killer leukemia cell line) and human peripheral blood natural killer cells. The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, did not induce the migration. Delta9-tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of delta9-tetrahydrocannabinol together with 2-arachidonoylglycerol abolished the migration induced by 2-arachidonoylglycerol. It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells.

Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity.

PubMed

Keating, Gillian M

2017-04-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (THC/CBD, Sativex ® , nabiximols) is available in numerous countries worldwide for the treatment of multiple sclerosis (MS)-related moderate to severe spasticity in patients who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. Twelve weeks' therapy with THC/CBD improved MS-related spasticity in patients with an inadequate response to other anti-spasticity agents who had undergone a successful initial trial of THC/CBD therapy, according to the results of a pivotal phase 3 trial. Improvements in spasticity were maintained in the longer term with THC/CBD with no evidence of dose tolerance, and results of real-world studies confirm the effectiveness of THC/CBD in everyday clinical practice. Improvements in health-related quality of life and activities of daily living were also seen with THC/CBD. THC/CBD is generally well tolerated; adverse effects such as dizziness may occur whilst the THC/CBD dosage is being optimized. THC/CBD has low abuse potential and a low risk of psychoactive effects. In conclusion, THC/CBD oromucosal spray is a useful option for the treatment of MS-related spasticity not completely relieved with current anti-spasticity medication.

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.

PubMed

Zuardi, A W; Crippa, J A S; Hallak, J E C; Moreira, F A; Guimarães, F S

2006-04-01

A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis) component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

Passive inhalation of marijuana smoke: urinalysis and room air levels of delta-9-tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cone, E.J.; Johnson, R.E.; Darwin, W.D.

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol (THC)) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts ofmore » THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.« less

Effects of ultraviolet-B radiation on the growth, physiology and cannabinoid production of Cannabis sativa L

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lydon, J.

The concentration of cannabinoids in Cannabis sativa L. is correlated with high ultraviolet-B (UV-B) radiation environments. ..delta../sup 9/-Tetrahydrocannabinolic acid and cannabidiolic acid, both major secondary products of C. sativa, absorb UV-B radiation and may function as solar screens. The object of this study was to test the effects of UV-B radiation on the physiology and cannabinoid production of C. sativa. Drug and fiber-type C. sativa were irradiated with three levels of UV-B radiation for 40 days in greenhouse experiments. Physiological measurements on leaf tissues were made by infra-red gas analysis. Drug and fiber-type control plants had similar CO/sub 2/ assimilationmore » rates from 26 to 32/sup 0/C. Drug-type control plant had higher dark respiration rates and stomatal conductances than fiber-type control plants. The concentration of ..delta../sup 9/-THC, but not of other cannabinoids) in both vegetative and reproductive tissues increased with UV-B dose in drug-type plants. None of the cannabinoids in fiber-type plants were affected by UV-B radiation. The increased level of ..delta../sup 9/-THC found in leaves after irradiation may account for the physiological and morphological insensitivity to UV-B radiation in the drug-type plants. However, fiber plants showed no comparable change in the level of cannabidoil (CBD). Resin stripped form fresh fiber-type floral tissue by sonication was spotted on filter paper and irradiated continuously for 7 days. Cannabidiol (CBD) gradually decreased when irradiated but ..delta../sup 9/-THC and cannabichromene did not.« less

Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists.

PubMed

Roser, Patrik; Vollenweider, Franz X; Kawohl, Wolfram

2010-03-01

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the principal psychoactive constituent of the Cannabis sativa plant, and other agonists at the central cannabinoid (CB(1)) receptor may induce characteristic psychomotor effects, psychotic reactions and cognitive impairment resembling schizophrenia. These effects of Delta(9)-THC can be reduced in animal and human models of psychopathology by two exogenous cannabinoids, cannabidiol (CBD) and SR141716. CBD is the second most abundant constituent of Cannabis sativa that has weak partial antagonistic properties at the CB(1) receptor. CBD inhibits the reuptake and hydrolysis of anandamide, the most important endogenous CB(1) receptor agonist, and exhibits neuroprotective antioxidant activity. SR141716 is a potent and selective CB(1) receptor antagonist. Since both CBD and SR141716 can reverse many of the biochemical, physiological and behavioural effects of CB(1) receptor agonists, it has been proposed that both CBD and SR141716 have antipsychotic properties. Various experimental studies in animals, healthy human volunteers, and schizophrenic patients support this notion. Moreover, recent studies suggest that cannabinoids such as CBD and SR141716 have a pharmacological profile similar to that of atypical antipsychotic drugs. In this review, both preclinical and clinical studies investigating the potential antipsychotic effects of both CBD and SR141716 are presented together with the possible underlying mechanisms of action.

Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys

PubMed Central

Maguire, David R.; France, Charles P.

2015-01-01

Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756

Amphetamine effects on dopamine levels and behavior following cannabinoid exposure during adolescence.

PubMed

Ellgren, Maria; Hurd, Yasmin L; Franck, Johan

2004-08-23

The cannabis gateway hypothesis purports that early exposure to cannabis is a risk factor for subsequent use of other addictive drugs, e.g., psychostimulants. Neurobiological sensitization, consistent with a gateway hypothesis, was currently studied in regard to amphetamine response. Rats were exposed to the cannabinoid receptor agonist WIN 55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone] 1.25 mg/kg, intraperitoneally; i.p. for 5 days during early adolescence. Amphetamine (0.5 mg/kg, i.p.) or WIN 55,212-2 (1.25 mg/kg, i.p.) was administered in late adolescence and in vivo dopamine levels were simultaneously measured in the nucleus accumbens. Locomotor and stereotyped behaviors were also monitored in rats pretreated with WIN 55,212-2 (0.625, 1.25 or 2.5 mg/kg) or Delta-9-tetrahydrocannabinol (0.75, 1.5 or 3.0 mg/kg, i.p.) for 5 days during early adolescence and challenged with amphetamine (0.5 or 2.0 mg/kg) in late adolescence or as adults. Pretreatment with WIN 55,212-2 or Delta-9-tetrahydrocannabinol during early adolescence did not alter the dopaminergic or behavioral responses to amphetamine in adolescence or adulthood. In conclusion, these findings do not support the cannabis gateway hypothesis in regard to subsequent amphetamine exposure.

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.

PubMed

Busquets-Garcia, Arnau; Gomis-González, Maria; Salgado-Mendialdúa, Victòria; Galera-López, Lorena; Puighermanal, Emma; Martín-García, Elena; Maldonado, Rafael; Ozaita, Andrés

2018-04-01

Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.

Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine.

PubMed

Rodríguez-Gaztelumendi, Antonio; Rojo, M Luisa; Pazos, Angel; Díaz, Alvaro

2009-03-01

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB(1) receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.

Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

PubMed

Malone, Daniel Thomas; Jongejan, Dennis; Taylor, David Alan

2009-08-01

While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

PubMed

Kaufmann, R M; Kraft, B; Frey, R; Winkler, D; Weiszenbichler, S; Bäcker, C; Kasper, S; Kress, H G

2010-01-01

The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary. (c) Georg Thieme Verlag KG Stuttgart . New York.

Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats

PubMed Central

Wakley, Alexa A; Wiley, Jenny L; Craft, Rebecca M

2015-01-01

The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones. Rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX). GDX females received no hormone replacement (GDX+0), estradiol (GDX+E2), progesterone (GDX+P4), or both (GDX+E2/P4). GDX male rats received no hormone (GDX+0) or testosterone (GDX+T). Two weeks later, antinociceptive potency of THC was determined (pre-chronic test) on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex-specific THC dose (females, 5.7 mg/kg, males, 9.9 mg/kg) was administered twice-daily for 9 days, then the THC dose-effect curves were re-determined (post-chronic test). On the pre-chronic test (both assays), THC was more potent in sham-GDX females than males, and gonadectomy did not alter this sex difference. In GDX females, P4 significantly decreased THC’s antinociceptive potency, whereas E2 had no effect. In GDX males, T did not alter THC’s antinociceptive potency. After chronic THC treatment, THC’s antinociceptive potency was decreased more in sham-GDX females than males, on the tail withdrawal test; this sex difference in tolerance was not altered in GDX or hormone-treated groups. These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones. PMID:25863271

Validated method for the simultaneous determination of Delta9-THC and Delta9-THC-COOH in oral fluid, urine and whole blood using solid-phase extraction and liquid chromatography-mass spectrometry with electrospray ionization.

PubMed

Teixeira, Helena; Verstraete, Alain; Proença, Paula; Corte-Real, Francisco; Monsanto, Paula; Vieira, Duarte Nuno

2007-08-06

A fully validated, sensitive and specific method for the extraction and quantification of Delta(9)-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta(9)-THC (THC-COOH) and for the detection of 11-hydroxy-Delta(9)-THC (11-OH THC) in oral fluid, urine and whole blood is presented. Solid-phase extraction and liquid chromatography-mass spectrometry (LC-MS) technique were used, with electrospray ionization. Three ions were monitored for THC and THC-COOH and two for 11-OH THC. The compounds were quantified by selected ion recording of m/z 315.31, 329.18 and 343.16 for THC, 11-OH THC and THC-COOH, respectively, and m/z 318.27 and 346.26 for the deuterated internal standards, THC-d(3) and THC-COOH-d(3), respectively. The method proved to be precise for THC and THC-COOH both in terms of intra-day and inter-day analysis, with intra-day coefficients of variation (CV) less than 6.3, 6.6 and 6.5% for THC in saliva, urine and blood, respectively, and 6.8 and 7.7% for THC-COOH in urine and blood, respectively. Day-to-day CVs were less than 3.5, 4.9 and 11.3% for THC in saliva, urine and blood, respectively, and 6.2 and 6.4% for THC-COOH in urine and blood, respectively. Limits of detection (LOD) were 2 ng/mL for THC in oral fluid and 0.5 ng/mL for THC and THC-COOH and 20 ng/mL for 11-OH THC, in urine and blood. Calibration curves showed a linear relationship for THC and THC-COOH in all samples (r(2)>0.999) within the range investigated. The procedure presented here has high specificity, selectivity and sensitivity. It can be regarded as an alternative method to GC-MS for the confirmation of positive immunoassay test results, and can be used as a suitable analytical tool for the quantification of THC and THC-COOH in oral fluid, urine and/or blood samples.

Discovery of endocannabinoids and some random thoughts on their possible roles in neuroprotection and aggression.

PubMed

Mechoulam, R

2002-01-01

A short history of the discovery of the main plant cannabinoid, Delta(9)-tetrahydrocannabinol and of the endogenous cannabinoids anandamide, 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether (noladin ether) is presented. The role of the cannabinoids in neuroprotection, with emphasis on the endocannabinoids, is described. The unexpected production of aggression by Cannabis and cannabinoids under stressful conditions, published mainly in the past, is summarized. Copyright 2002 Elsevier Science Ltd. All rights reserved.

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

PubMed

Moldzio, Rudolf; Pacher, Thomas; Krewenka, Christopher; Kranner, Barbara; Novak, Johannes; Duvigneau, Johanna Catharina; Rausch, Wolf-Dieter

2012-06-15

Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP(+) induced cell death. Copyright © 2012 Elsevier GmbH. All rights reserved.

The endocannabinoid system as a target for the treatment of neurodegenerative disease.

PubMed

Scotter, Emma L; Abood, Mary E; Glass, Michelle

2010-06-01

The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years. Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis. Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar. The discovery of the psychoactive component of cannabis resin, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) occurred long before the serendipitous identification of a G-protein coupled receptor at which Delta(9)-THC is active in the brain. The subsequent finding of endogenous cannabinoid compounds, the synthesis of which is directed by neuronal excitability and which in turn served to regulate that excitability, further widened the range of potential drug targets through which the endocannabinoid system can be manipulated. As a result of this, alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders. In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context.

Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

PubMed

Navarro, M; Rubio, P; Rodríguez de Fonseca, F

1994-12-01

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Sullivan, Saoirse E.; Tarling, Elizabeth J.; Bennett, Andrew J.

Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251more » (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.« less

Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

PubMed

Maguire, David R; France, Charles P

2016-04-01

Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

Delta-9-tetrahydrocannabinol + cannabidiol. A reasonable option for some patients with multiple sclerosis.

PubMed

2014-06-01

Conventional drugs have only a limited impact on spasticity associated with multiple sclerosis and are rarely satisfactory. A solution for oral transmucosal delivery (spray) containing a mixture of cannabis extracts (2.7 mg of delta-9-tetrahydrocannabinol + 2.5 mg of cannabidiol per spray) has been granted marketing authorisation in France for patients who are inadequately relieved by standard treatments. Three double-blind, placebo-controlled trials in a total of about 300 patients tested this combination, in addition to ongoing treatment, for periods of 6 to 14 weeks. Individually, none of these trials showed any tangible anti-spastic efficacy, but two combined analyses showed "response rates" of about 35% with the mixture versus about 25% with placebo. In a trial with 572 patients, the 241 patients who "responded" after 4 weeks of treatment were randomised to either continue using the cannabis extract or receive placebo. Twelve weeks later, 75% of patients using the extract were still "responders", versus 51% of patients switched to placebo. The principal adverse effects of the cannabis extracts consist of neuropsychiatric disorders that resolve on treatment withdrawal. The potential for abuse increases with the dose and is tangible from 16 sprays per day. Pharmacokinetic interactions due to P-glycoprotein inhibition are likely. Treatment during pregnancy may lead to neonatal withdrawal symptoms. In practice, about 10% of patients in whom standard anti-spastic medications are unsatisfactory benefit from a specific effect of the cannabis extracts contained in this oral spray.

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages.

PubMed

Moretti, Sarah; Franchi, Silvia; Castelli, Mara; Amodeo, Giada; Somaini, Lorenzo; Panerai, Alberto; Sacerdote, Paola

2015-06-01

Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood.

Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

PubMed Central

Wakley, Alexa A.; Wiley, Jenny L.; Craft, Rebecca M.

2014-01-01

Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. Methods Cumulative dose-effect curves were obtained for THC (1.0–18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. Results On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females, 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. Conclusions These results demonstrate that – even when sex differences in acute THC potency are controlled for – females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. PMID:25131716

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

PubMed

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma.

PubMed

Flach, Allan J

2002-01-01

Evidence exists that the administration of cannabinoid derivatives can lower intraocular pressure. Some patients with glaucoma believe they are being deprived of a potentially beneficial treatment. Therefore, the Research Advisory Panel of California instituted the Cannabis Therapeutic Research Program to permit compassionate access to cannabinoid derivatives. Data about the potential therapeutic usefulness and toxicity of these agents were collected. This study reviews the results of this program with the specific aim of providing further direction for these investigational efforts. A survey of local ophthalmologists indicated an impressive interest in participating in and contributing patients with glaucoma unresponsive to treatment to this study. Appropriate patients were treated with either orally administered delta-9-tetrahydrocannabinol capsules or inhaled marijuana in addition to their existing therapeutic regimen. Although 20 ophthalmologists were approved as investigators, only nine patients were enrolled in the study. An initial decrease in intraocular pressure was observed in all patients, and the investigator's therapeutic goal was met in four of the nine patients. However, the decreases in intraocular pressure were not sustained, and all patients elected to discontinue treatment within 1 to 9 months for various reasons. This uncontrolled, unmasked, nonrandomized study does not permit definitive conclusions about the efficacy or toxicity of cannabinoids in the treatment of glaucoma. There is an impression that this treatment can lower intraocular pressure, but the development of tolerance and significant systemic toxicity appears to limit the usefulness of this potential treatment. Both patients and ophthalmologists greatly appreciated the opportunity to participate in this study.

Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

PubMed Central

Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

2011-01-01

Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC.

PubMed

Hunault, Claudine C; Mensinga, Tjeert T; de Vries, Irma; Kelholt-Dijkman, Hermien H; Hoek, Jani; Kruidenier, Maaike; Leenders, Marianne E C; Meulenbelt, Jan

2008-12-01

Delta9-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). The pharmacokinetics of THC after smoking cannabis cigarettes containing more than approximately 35 mg THC (3.55% THC cigarettes) is unknown. To be able to perform suitable exposure risk analysis, it is important to know if there is a linear relation at higher doses. The present study aimed to characterise the pharmacokinetics of THC, the active metabolite 11-OH-THC and the inactive metabolite THC-COOH after smoking a combination of tobacco and cannabis containing high THC doses. This double-blind, placebo-controlled, four-way, cross-over study included 24 male non-daily cannabis users (two to nine joints per month). Participants were randomly assigned to smoke cannabis cigarettes containing 29.3, 49.1 and 69.4 mg THC and a placebo. Serial serum samples collected over a period of 0-8 h were analysed by liquid chromatography electrospray tandem mass spectrometry. Effects on heart rate, blood pressure and 'high' feeling were also measured. Mean maximal concentrations (Cmax) were 135.1, 202.9 and 231.0 microg/L for THC and 9.2, 16.4 and 15.8 microg/L for 11-OH-THC after smoking a 29.3-, 49.1- and 69.4-mg THC cigarette, respectively. A large inter-individual variability in Cmax was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose. This study demonstrates that the known linear association between THC dose and THC serum concentration also applies for high THC doses.

Integrating environmental and self-report data to refine cannabis prevalence estimates in a major urban area of Switzerland.

PubMed

Been, Frederic; Schneider, Christian; Zobel, Frank; Delémont, Olivier; Esseiva, Pierre

2016-10-01

Cannabis consumption is a topical subject because of discussions about reviewing current regulations. In this context, having a more comprehensive approach to assess and monitor prevalence and consumption is highly relevant. The objective of this work was to refine current estimates about prevalence of cannabis use by combining self-report data and results derived from wastewater analysis. Self-report data was retrieved from surveys conducted in Switzerland and Europe. Wastewater samples were collected at the wastewater treatment plant of Lausanne, western Switzerland, over a 15 months period. The occurrence of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH), a specific metabolite of delta-9-tetrahydrocannabinol (THC), was monitored. Bayesian hierarchical models were used to estimate consumption, prevalence and number of cannabis users in the investigated area. According to survey data, 12-months prevalence in western Switzerland was estimated to 6.2% of the population aged 15 or older, with an estimated daily cannabis consumption of 8.1gday(-1)·1000inhab(-1) (at 11.2% purity). The integrative model comprising self-report and wastewater data substantially reduced the uncertainty in the estimates and suggested a last-year prevalence of 9.4%, with a daily cannabis consumption of 14.0gday(-1)·1000inhab(-1). Although in the same order of magnitude, consumption and prevalence estimates obtained with the integrative model were 78% and 52% higher compared to self-report figures, respectively. Interestingly, these figures are similar to discrepancies observed when comparing self-reported alcohol consumption and sales or tax data. The suggested integrative model allowed to account for known sources of uncertainty and provided refined estimates of cannabis prevalence in a major urban area of Switzerland. Copyright © 2016 Elsevier B.V. All rights reserved.

[Cannabis and cannabinoids. Possibilities of their therapeutic use].

PubMed

Heim, M E

1982-03-04

Newer aspects of therapeutic potentials of cannabis and cannabinoids are reviewed. The major active constituent of cannabis sativa, delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in several clinical trials on their antiemetic efficacy in cancer chemotherapy induced vomiting. 80% of patients refractory to standard antiemetic treatment could be improved with the synthetic cannabinoid levonantradol. Other therapeutic effects, which are presently investigated in clinical trials are analgesia, antispasticity, anticonvulsion and the reduction of intraocular pressure in glaucoma. The future goal of cannabinoid research is the separation between specific pharmacologic activities and undesirable psychotropic effects.

Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

PubMed

Blumstein, Gideon W; Parsa, Arya; Park, Anthony K; McDowell, Beverly L P; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P; Olson, Jon; Buckley, Nancy E

2014-01-01

Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5) C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10(4) C. albicans on day 2, followed by a higher challenge with 5×10(5) C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).

PubMed

Mayer, Tzur Alexander; Matar, Michael Alex; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

2014-07-01

The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

Delta-9-Tetrahydrocannabinol Potentiates Fear Memory Salience Through Functional Modulation of Mesolimbic Dopaminergic Activity States.

PubMed

Fitoussi, Aurelie; Zunder, Jordan; Tan, Huibing; Laviolette, Steven R

2018-05-18

Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NAc (NASh) and examined how THC may modulate the processing of fear-related emotional memory and concomitant activity states of the mesolimbic DA system. We report that intra-NASh THC dose-dependently potentiates the emotional salience of normally sub-threshold fear-conditioning cues. These effects were dependent upon intra-VTA transmission through GABAergic receptor mechanisms and intra-NASh DAergic transmission. Furthermore, doses of intra-NASh THC that potentiated fear memory salience were found to modulate intra-VTA neuronal network activity by increasing the spontaneous firing and bursting frequency of DAergic neurons whilst decreasing the activity levels of a subpopulation of putative GABAergic VTA neurons. These findings demonstrate that THC can act directly in the NASh to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DAergic transmission. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol.

PubMed

Sarafian, Theodore; Habib, Nancy; Mao, Jenny T; Tsu, I-Hsien; Yamamoto, Mitsuko L; Hsu, Erin; Tashkin, Donald P; Roth, Michael D

2005-08-14

Marijuana smoking is associated with inflammation, cellular atypia, and molecular dysregulation of the tracheobronchial epithelium. While marijuana smoke shares many components in common with tobacco, it also contains a high concentration of Delta9-tetrahydrocannabinol (THC). The potential contribution of THC to airway injury was assessed by exposing primary cultures of human small airway epithelial (SAE) cells to THC (0.1-10.0 microg/ml) for either 1 day or 7 days. THC induced a time- and concentration-dependent decrease in cell viability, ATP level, and mitochondrial membrane potential. Using a targeted gene expression array, we observed acute changes (24 h) in the expression of mRNA for caspase-8, catalase, Bax, early growth response-1, cytochrome P4501A1 (CYP1A1), metallothionein 1A, PLAB, and heat shock factor 1 (HSF1). After 7 days of exposure, decrease in expression of mRNA for heat shock proteins (HSPs) and the pro-apoptotic protein Bax was observed, while expression of GADD45A, IL-1A, CYP1A1, and PTGS-2 increased significantly. These findings suggest a contribution of THC to DNA damage, inflammation, and alterations in apoptosis. Treatment with selected prototypical toxicants, 2,3,7,8-tetrachlorodibenznzo-p-dioxin (TCDD) and carbonyl cyanide-p-(trifluoramethoxy)-phenyl hydrazone (FCCP), produced partially overlapping gene expression profiles suggesting some similarity in mechanism of action with THC. THC, delivered as a component of marijuana smoke, may induce a profile of gene expression that contributes to the pulmonary pathology associated with marijuana use.

Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology.

PubMed

Potter, David J; Clark, Peter; Brown, Marc B

2008-01-01

Gas chromatography was used to study the cannabinoid content ("potency") of illicit cannabis seized by police in England in 2004/5. Of the four hundred and fifty two samples, indoor-grown unpollinated female cannabis ("sinsemilla") was the most frequent form, followed by resin (hashish) and imported outdoor-grown herbal cannabis (marijuana). The content of the psychoactive cannabinoid delta 9-tetrahydrocannabinol (THC) varied widely. The median THC content of herbal cannabis and resin was 2.1% and 3.5%, respectively. The median 13.9% THC content of sinsemilla was significantly higher than that recorded in the UK in 1996/8. In sinsemilla and imported herbal cannabis, the content of the antipsychotic cannabinoid cannabidiol (CBD) was extremely low. In resin, however, the average CBD content exceeded that of THC, and the relative proportions of the two cannabinoids varied widely between samples. The increases in average THC content and relative popularity of sinsemilla cannabis, combined with the absence of the anti-psychotic cannabinoid CBD, suggest that the current trends in cannabis use pose an increasing risk to those users susceptible to the harmful psychological effects associated with high doses of THC.

Validation of a two-dimensional gas chromatography mass spectrometry method for the simultaneous quantification of cannabidiol, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC in plasma.

PubMed

Karschner, Erin L; Barnes, Allan J; Lowe, Ross H; Scheidweiler, Karl B; Huestis, Marilyn A

2010-05-01

A sensitive analytical method for simultaneous quantification of sub-nanogram concentrations of cannabidiol (CBD), Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) in plasma is presented for monitoring cannabinoid pharmacotherapy and illicit cannabis use. Analytes were extracted from 1 mL plasma by solid-phase extraction, derivatized with N,O-bis(trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane, and analyzed by two-dimensional gas chromatography mass spectrometry (2D-GCMS) with cryofocusing. The lower calibration curve was linear from 0.25-25 ng/mL for CBD and THC, 0.125-25 ng/mL for 11-OH-THC and 0.25-50 ng/mL for THCCOOH. A second higher linear range from 5-100 ng/mL, achieved through modification of injection parameters, was validated for THC, 11-OH-THC, and THCCOOH and was only implemented if concentrations exceeded the lower curve upper limit of linearity. This procedure prevented laborious re-extraction by allowing the same specimen to be re-injected for quantification on the high calibration curve. Intra- and inter-assay imprecision, determined at four quality control concentrations, were or=72.9% for all analytes. Analytes were stable when stored at 22 degrees C for 16 h, 4 degrees C for 48 h, after three freeze-thaw cycles at -20 degrees C and when stored on the autosampler for 48 h. This sensitive and specific 2D-GCMS assay provides a new means of simultaneously quantifying CBD, THC and metabolite biomarkers in clinical medicine, forensic toxicology, workplace drug testing, and driving under the influence of drugs programs.

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarafian, Theodore; Montes, Cindy; Harui, Airi

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that {delta}{sup 9}-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelialmore » cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p < 0.05) and were 80- to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p < 0.05). THC decreased ATP level and mitochondrial membrane potential ({psi}{sub m}) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher {psi}{sub m} than did control cells. Since both {psi}{sub m} and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of I{kappa}B-{alpha} and JNK was regulated in a CB2R- and THC-dependent manner. We conclude that airway epithelial cells are sensitive to both CB2R-dependent and independent effects mediated by THC.« less

Notes from the Field: Death Following Ingestion of an Edible Marijuana Product--Colorado, March 2014.

PubMed

Hancock-Allen, Jessica B; Barker, Lisa; VanDyke, Michael; Holmes, Dawn B

2015-07-24

In March 2014, the Colorado Department of Public Health and Environment (CDPHE) learned of the death of a man aged 19 years after consuming an edible marijuana product. CDPHE reviewed autopsy and police reports to assess factors associated with his death and to guide prevention efforts. The decedent's friend, aged 23 years, had purchased marijuana cookies and provided one to the decedent. A police report indicated that initially the decedent ate only a single piece of his cookie, as directed by the sales clerk. Approximately 30-60 minutes later, not feeling any effects, he consumed the remainder of the cookie. During the next 2 hours, he reportedly exhibited erratic speech and hostile behaviors. Approximately 3.5 hours after initial ingestion, and 2.5 hours after consuming the remainder of the cookie, he jumped off a fourth floor balcony and died from trauma. The autopsy, performed 29 hours after time of death, found marijuana intoxication as a chief contributing factor. Quantitative toxicologic analyses for drugs of abuse, synthetic cannabinoid, and cathinones ("bath salts") were performed on chest cavity blood by gas chromatography and mass spectrometry. The only confirmed findings were cannabinoids (7.2 ng/mL delta-9 tetrahydrocannabinol [THC] and 49 ng/mL delta-9 carboxy-THC, an inactive marijuana metabolite). The legal whole blood limit of delta-9 THC for driving a vehicle in Colorado is 5.0 ng/mL. This was the first reported death in Colorado linked to marijuana consumption without evidence of polysubstance use since the state approved recreational use of marijuana in 2012.

The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis.

PubMed

Jamontt, J M; Molleman, A; Pertwee, R G; Parsons, M E

2010-06-01

Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief. Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Delta(9)-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders. Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis. The 2,4,6-trinitrobenzene sulphonic acid (TNBS) model of acute colitis in rats was used to assess damage, inflammation (myeloperoxidase activity) and in vitro colonic motility. Sulphasalazine was used as an active control drug. Sulphasalazine, THC and CBD proved beneficial in this model of colitis with the dose-response relationship for the phytocannabinoids showing a bell-shaped pattern on the majority of parameters (optimal THC and CBD dose, 10 mg.kg(-1)). THC was the most effective drug. The effects of these phytocannabinoids were additive, and CBD increased some effects of an ineffective THC dose to the level of an effective one. THC alone and in combination with CBD protected cholinergic nerves whereas sulphasalazine did not. In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis.

PubMed

Nielsen, Suzanne; Sabioni, Pamela; Trigo, Jose M; Ware, Mark A; Betz-Stablein, Brigid D; Murnion, Bridin; Lintzeris, Nicholas; Khor, Kok Eng; Farrell, Michael; Smith, Andrew; Le Foll, Bernard

2017-08-01

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED 50 ) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED 50 of morphine alone. In addition, the ED 50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED 50 of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.

PubMed

Syed, Yahiya Y; McKeage, Kate; Scott, Lesley J

2014-04-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex®] is an oromucosal spray formulation that contains principally THC and CBD at an approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants. The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2), and thus, may modulate the effects of excitatory (glutamate) and inhibitory (gamma-aminobutyric acid) neurotransmitters. THC/CBD is approved in a number of countries, including Germany and the UK, as an add-on treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In the largest multinational clinical trial that evaluated the approved THC/CBD regimen in this population, 12 weeks' double-blind treatment with THC/CBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks' single-blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale. A significantly greater proportion of THC/CBD than placebo recipients achieved a ≥ 30% reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THC/CBD has been also shown in at least one everyday clinical practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials. Dizziness and fatigue were reported most frequently during the first 4 weeks of treatment and resolved within a few days even with continued treatment. Thus, add-on THC/CBD is a useful symptomatic treatment option for its approved indication.

In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rettori, V.; Aguila, M.C.; McCann, S.M.

Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release.more » The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.« less

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury.

PubMed

Hochhauser, Edith; Lahat, Eylon; Sultan, Maya; Pappo, Orit; Waldman, Maayan; Sarne, Yosef; Shainberg, Asher; Gutman, Mordechai; Safran, Michal; Ben Ari, Ziv

2015-01-01

Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours. THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma. © 2015 S. Karger AG, Basel.

Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats.

PubMed

Zamberletti, Erica; Gabaglio, Marina; Prini, Pamela; Rubino, Tiziana; Parolaro, Daniela

2015-12-01

Over 180 million people consume cannabis globally. Cannabis use peaks during adolescence with a trend for continued consumption by adults. Notably, several studies have shown that long-term and heavy cannabis use during adolescence can impair brain maturation and predispose to neurodevelopmental disorders, although the neurobiological mechanisms underlying this association remain largely unknown. In this study, we evaluated whether, in female rats, chronic administration of increasing doses of the psychotropic plant-derived cannabis constituent, delta-9-tetrahydrocannabinol (THC), during adolescence (PND 35-45) could affect microglia function in the long-term. Furthermore, we explored a possible contribution of microglia to the development of THC-induced alterations in mood and cognition in adult female rats. Present data indicate that adolescent THC administration induces a persistent neuroinflammatory state specifically localized within the adult prefrontal cortex (PFC), characterized by increased expression of the pro-inflammatory markers, TNF-α, iNOS and COX-2, and reduction of the anti-inflammatory cytokine, IL-10. This neuroinflammatory phenotype is associated with down-regulation of CB1 receptor on neuronal cells and up-regulation of CB2 on microglia cells, conversely. Interestingly, blocking microglia activation with ibudilast during THC treatment significantly attenuates short-term memory impairments in adulthood, simultaneously preventing the increases in TNF-α, iNOS, COX-2 levels as well as the up-regulation of CB2 receptors on microglia cells. In contrast, THC-induced depressive-like behaviors were unaffected by ibudilast treatment. Our findings demonstrate that adolescent THC administration is associated with persistent neuroinflammation within the PFC and provide evidence for a causal association between microglial activation and the development long-term cognitive deficits induced by adolescent THC treatment. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.

PubMed

Verhoeckx, Kitty C M; Korthout, Henrie A A J; van Meeteren-Kreikamp, A P; Ehlert, Karl A; Wang, Mei; van der Greef, Jan; Rodenburg, Richard J T; Witkamp, Renger F

2006-04-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.

Retention of sequential drug discriminations under fixed-interval schedules for long time periods without training.

PubMed

Li, Mi; McMillan, Donald E

2003-08-22

The experiments showed that sequential drug discriminations can be learned and retained under a fixed-interval (FI) schedule for more than 18 months without additional training under a complex three-choice procedure. Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg D-amphetamine, and saline. After responding stabilized, dose-response curves were determined for other drugs. Subsequently, pentobarbital was replaced with 5 mg/kg morphine as a training drug, and D-amphetamine was replaced with 30 mg/kg caffeine. After the pigeons learned these new discriminations, dose-response curves were redetermined. Initially, chlordiazepoxide substituted for pentobarbital, cocaine substituted for D-amphetamine, and nicotine partially substituted for D-amphetamine. Morphine, Delta9-tetrahydrocannabinol, and caffeine did not substitute for either drug. After retraining with morphine and caffeine, responding occurred on the pentobarbital/morphine key after pentobarbital, chlordiazepoxide and morphine and on the D-amphetamine/caffeine key after D-amphetamine, cocaine and caffeine. After nicotine and Delta9-tetrahyrdocannabinol, responding occurred on the saline key. These data show that drug discriminations learned under fixed-interval schedules are retained for long time periods, even when discrimination training with other drugs occurs during the retention period.

Qualitative and quantitative measurement of cannabinoids in cannabis using modified HPLC/DAD method.

PubMed

Patel, Bhupendra; Wene, Daniel; Fan, Zhihua Tina

2017-11-30

This study presents an accurate and high throughput method for the quantitative determination of various cannabinoids in cannabis plant material using high pressure liquid chromatography (HPLC) with a diode array detector (DAD). Sample extraction and chromatographic analysis conditions for the measurement of cannabinoids in the complex cannabis plant material matrix were optimized. The Agilent Poroshell 120 SB-C18 column provided high resolution for all target analytes with a short run time (10minutes) given the core shell technology. The aqueous buffer mobile phase was optimized with ammonium acetate at pH 4.75. The change in the mobile phase and the new column ensured a separation between cannabidiol (CBD and cannabigerol (CBG) along with cannabigerol and tetrahydrocannabinolic acid (THCA), which were not well separated by previous publications, improved buffering capacity, and provided analytical performance stability. Moreover, baseline drifting was significantly minimized by the use of a low concentration buffer solution (25mM ammonium acetate). In addition, evaporation and reconstitution of the sample residue with a methanol-organic pure (OP) water solution (65:35) significantly reduced the matrix interference. The modified extraction produced good recoveries (>91%) for each of the eight cannabinoids. The optimized method was validated for specificity, linearity, sensitivity, precision, accuracy, and stability. The combined relative standard deviation (%RSD) for intra-day and inter-day precision for all eight analytes varied from 2.5% to 5.2% and 0.28% to 5.5%, respectively. The %RSD for the repeatability study varied from 1.1% to 5.5%. The recoveries from spiked cannabis matrix samples were greater than 90% for all analytes, except delta-8-tetrahydrocannabinol (Δ 8 -THC), which was 80%. The recoveries varied from 81% to 107% with a precision of 0.7-8.1%RSD. Delta-9-tetrahydrocannabinol (Δ 9 -THC) in all of the cannabis samples (n=635) was less than 10%, which is in compliance with the NJ Medicinal Marijuana regulation. Analysis of samples from two cultivars, which included ten individual samples, four composite samples, seven calibration standards, and four quality control standards, can be performed within 24hours by this high throughput method. Published by Elsevier B.V.

Anaerobic biosynthesis of unsaturated fatty acids in the cyanobacterium, Oscillatoria limnetica

NASA Technical Reports Server (NTRS)

Jahnke, L. L.; Lee, B.; Sweeney, M. J.; Klein, H. P.

1989-01-01

The mechanism for synthesis of monounsaturated fatty acids under aerobic and anaerobic conditions was studied in the facultative anaerobic cyanobacterium, Oscillatoria limnetica. The hexadecenoic acid (C16:1) of aerobically grown O. limnetica was shown to contain both the delta 7 (79%) and delta 9 (21%) isomers, while the octadecenoic (C18:1) acid was entirely the delta 9 acid. Incorporation of [2-14C] acetate into the fatty acids under aerobic conditions resulted in synthesis of the delta 7 and delta 9 C16:1 and the delta 9 C18:1. Synthesis of unsaturated fatty acids in the presence of DCMU required sulfide. Anaerobic incubations in the presence of DCMU and sulfide (less than 0.003% atmospheric oxygen) resulted in a two-fold increase in monounsaturated fatty acids of both delta 7 and delta 9 C16:1 and delta 9 and delta 11 C18:1. The synthesis of these is characteristic of a bacterial-type, anaerobic pathway.

What is the mechanism whereby cannabis use increases risk of psychosis?

PubMed

Luzi, Sonija; Morrison, Paul D; Powell, John; di Forti, Marta; Murray, Robin M

2008-10-01

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

Effects of delta-9-tetrahydrocannabinol on evaluation of emotional images

PubMed Central

Ballard, Michael E; Bedi, Gillinder; de Wit, Harriet

2013-01-01

There is growing evidence that drugs of abuse alter processing of emotional information in ways that could be attractive to users. Our recent report that Δ9-tetrahydrocannabinol (THC) diminishes amygdalar activation in response to threat-related faces suggests that THC may modify evaluation of emotionally-salient, particularly negative or threatening, stimuli. In this study, we examined the effects of acute THC on evaluation of emotional images. Healthy volunteers received two doses of THC (7.5 and 15 mg; p.o.) and placebo across separate sessions before performing tasks assessing facial emotion recognition and emotional responses to pictures of emotional scenes. THC significantly impaired recognition of facial fear and anger, but it only marginally impaired recognition of sadness and happiness. The drug did not consistently affect ratings of emotional scenes. THC' effects on emotional evaluation were not clearly related to its mood-altering effects. These results support our previous work, and show that THC reduces perception of facial threat. Nevertheless, THC does not appear to positively bias evaluation of emotional stimuli in general PMID:22585232

Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Burton, Page; Mechoulam, Raphael

2004-01-01

Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

PubMed

Lopez-Cepero, M; Friedman, M; Klein, T; Friedman, H

1986-06-01

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Cannabis, possible cardiac deaths and the coroner in Ireland.

PubMed

Tormey, W P

2012-12-01

The elevated risk of triggering a myocardial infarction by smoking cannabis is limited to the first 2 h after smoking. To examine the possible role of cannabis in cardiac deaths. CASES AND RESULTS: From 3,193 coroners' cases over 2 years, there were 13 cases where the clinical information was compatible with a primary cardiac cause of death. An inquest was held in three cases. Myocardial infarction was the primary cause of death in 54%. Other causes were sudden adult death syndrome, sudden death in epilepsy, and poisoning by alcohol and diazepam. Cannabis was mentioned once only on a death certificate, but not as a cause of death. Blood delta9-tetrahydrocannabinol-carboxylic acid was recorded in one case and in no case was plasma tetrahydrocannabinol (THC) measured. To attribute sudden cardiac death to cannabis, plasma THC should be measured in the toxicology screen in coroners' cases where urine cannabinoids are positive. A positive urine cannabinoids immunoassay alone is insufficient evidence in the linkage of acute cardiac death and cannabis.

delta 9-(16 alpha-/sup 125/I)iodo-19-nortestosterone: a gamma-emitting photoaffinity label for the progesterone receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, D.J.; Bullock, D.W.; Hoyte, R.M.

1988-05-01

We have synthesized 16 alpha-iodo-4,9-estradien-17 beta-ol-3-one (delta 9-16 alpha-iodo-19-nortestosterone (delta 9-INT)) labeled with 125I (delta 9-(16 alpha-125I)INT) to provide a new gamma-emitting photoaffinity ligand for the progesterone receptor that has many advantages over the currently available (3H)R5020. We have characterized the interaction of delta 9-(16 alpha-125I)INT with the rabbit uterine progesterone receptor and have demonstrated the usefulness of this compound for studies of receptor structure. The binding of 2 nM (3H)progesterone to receptor in rabbit uterine cytosol was specifically competed for by 19-nortestosterone, 16 alpha-iodo-19-nortestosterone, and delta 9-INT. Scatchard analysis demonstrated that delta 9-(16 alpha-125I)INT and (3H)progesterone estimated the samemore » number of binding sites in rabbit uterine cytosol, with a Kd for delta 9-(16 alpha-125I)INT of about 2.7 nM. The binding of delta 9-(16 alpha-125I)INT was inhibited by both progesterone and R5020, whereas testosterone, estradiol, and 5 alpha-dihydrotestosterone were ineffective. In cytosol, delta 9-(16 alpha-125I)INT covalently labeled the same mol wt receptor forms as (3H)R5020. Although the efficiency of cross-linking was similar for (3H)R5020 (3%) and delta 9-(16 alpha-125I)INT (4%), the radioactivity was 10-fold greater due to the higher specific activity of delta 9-(16 alpha-125I)INT and the lack of sample quench. The use of delta 9-(16 alpha-125I)INT greatly increases the sensitivity and efficiency of the photoaffinity labeling technique; it will provide a valuable tool for further studies of the progesterone receptor, allowing the detection of receptor in dilute cytosol after gel electrophoresis under denaturing conditions.« less

A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-04-01

To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects. Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC). Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported. The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.

Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood

PubMed Central

1989-01-01

We analyzed the V gamma and V delta gene usage in TCR-gamma/delta- bearing T cell clones isolated from human peripheral blood and postnatal thymus using V-specific mAbs and Southern and Northern analyses. In peripheral blood most of the gamma/delta cells express the V gamma 9-JP-C gamma 1 chain paired with a delta chain bearing the V delta 2 gene product. This heterodimer is very rare in the postnatal thymus, where a different and less restricted pairing of V gamma 9 and V delta 2 chains is found. These findings indicate that physical constraints cannot explain the overrepresentation of a particular V gamma 9-JP/V delta 2 heterodimer in the peripheral blood, and we discuss alternative mechanisms that may account for this differential distribution. In addition, this analysis allowed us to map the specificity of the delta TCS1 mAb to V delta 1-J delta 1 and to identify at least five different expressed V delta genes. PMID:2572670

Stability of drugs of abuse in urine samples stored at -20 degrees C.

PubMed

Dugan, S; Bogema, S; Schwartz, R W; Lappas, N T

1994-01-01

Isolated studies of the stability of individual drugs of abuse have been reported. However, few have evaluated stability in frozen urine samples stored for 12 months. We have determined the stability of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (9-COOH-THC), amphetamine, methamphetamine, morphine, codeine, cocaine, benzoylecgonine, and phencyclidine in 236 physiological urine samples. Following the initial quantitative analysis, the samples were stored at -20 degrees C for 12 months and then reanalyzed. All drug concentrations were determined by gas chromatographic-mass spectrometric methods with cutoff concentrations of 5 ng/mL for 9-COOH-THC and phencyclidine and 100 ng/mL for each of the other drugs. The average change in the concentrations of these drugs following this long-term storage was not extensive except for an average change of -37% in cocaine concentrations.

Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit.

PubMed

ElSohly, M A; Harland, E C; Benigni, D A; Waller, C W

1984-06-01

Thirty-two different cannabinoids were tested for their ability to reduce intraocular pressure (IOP) in the rabbit. These included many of delta 9- and delta 8-THC derivatives and metabolites along with other natural and synthetic cannabinoids. In addition, some non-cannabinoid constituents of Cannabis were screened using the same model. All compounds were administered intravenously, while only a few were tested topically in mineral oil. Water soluble derivatives of delta 9- and delta 8-THC were prepared and tested topically in aqueous solution. The data revealed that certain derivatives of delta 9-and delta 8-THC were more active in lowering IOP than the parent cannabinoids. In addition, compounds other than delta 9- and delta 8-THC and their derivatives were shown to have activity.

Thermodynamics of the clusterization process of cis isomers of unsaturated fatty acids at the air/water interface.

PubMed

Vysotsky, Yu B; Belyaeva, E A; Fainerman, V B; Vollhardt, D; Aksenenko, E V; Miller, R

2009-04-02

In the framework of the semiempirical PM3 method, the thermodynamic parameters of cis isomers of unsaturated carboxylic acids at the air/water interface are studied. The model systems used are unsaturated cis fatty acid of the composition Delta = 12-15 and omega = 6-11, where Delta and omega refer to the number of carbon atoms between the functional group and double bond, and that between the double bond and methyl group, respectively. For dimers, trimers, and tetramers of the four acid series, the thermodynamic parameters of clusterization are calculated. It is shown that the position of the double bond does not significantly affect the values of thermodynamic parameters of formation and clusterization of carboxylic acids for equal chain lengths (n = Delta + omega). The calculated results show that for cis unsaturated fatty acid with odd Delta values the spontaneous clusterization threshold corresponds to n = 17-18 carbon atoms in the alkyl chain, while for monounsaturated acids with even Delta values this threshold corresponds to n = 18-19 carbon atoms in the alkyl chain. These differences in the clusterization threshold between the acids with even and odd Delta values are attributed to the formation of additional intermolecular hydrogen bonds between the ketonic oxygen atom of one monomer and the hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with odd Delta values or between the hydroxyl oxygen atom of one monomer and hydrogen atom linked to the alpha-carbon atom of the second monomer for the acids with even Delta values. The results obtained in the study agree satisfactorily with our experimental data for cis unsaturated nervonic (Delta15, omega9) and erucic acids (Delta13, omega9), and published data for some fatty acids, namely cis-16-heptadecenoic (Delta16, omega1), cis-9-hexadecenoic (Delta7, omega9), cis-11-eicosenoic (Delta11, omega9) and cis-9-octadecenoic acid (Delta9, omega9).

Effects of varying marijuana potency on deposition of tar and delta9-THC in the lung during smoking.

PubMed

Matthias, P; Tashkin, D P; Marques-Magallanes, J A; Wilkins, J N; Simmons, M S

1997-12-01

To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired level of intoxication ("high") reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (deltaHR) and "high" during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger MJ preparation.

Assessment of the ion-trap mass spectrometer for routine qualitative and quantitative analysis of drugs of abuse extracted from urine.

PubMed

Vorce, S P; Sklerov, J H; Kalasinsky, K S

2000-10-01

The ion-trap mass spectrometer (MS) has been available as a detector for gas chromatography (GC) for nearly two decades. However, it still occupies a minor role in forensic toxicology drug-testing laboratories. Quadrupole MS instruments make up the majority of GC detectors used in drug confirmation. This work addresses the use of these two MS detectors, comparing the ion ratio precision and quantitative accuracy for the analysis of different classes of abused drugs extracted from urine. Urine specimens were prepared at five concentrations each for amphetamine (AMP), methamphetamine (METH), benzoylecgonine (BZE), delta9-carboxy-tetrahydrocannabinol (delta9-THCCOOH), phencyclidine (PCP), morphine (MOR), codeine (COD), and 6-acetylmorphine (6-AM). Concentration ranges for AMP, METH, BZE, delta9-THCCOOH, PCP, MOR, COD, and 6-AM were 50-2500, 50-5000, 15-800, 1.5-65, 1-250, 500-32000, 250-21000, and 1.5-118 ng/mL, respectively. Sample extracts were injected into a GC-quadrupole MS operating in selected ion monitoring (SIM) mode and a GC-ion-trap MS operating in either selected ion storage (SIS) or full scan (FS) mode. Precision was assessed by the evaluation of five ion ratios for n = 15 injections at each concentration using a single-point calibration. Precision measurements for SIM ion ratios provided coefficients of variation (CV) between 2.6 and 9.8% for all drugs. By comparison, the SIS and FS data yielded CV ranges of 4.0-12.8% and 4.0-11.2%, respectively. The total ion ratio failure rates were 0.2% (SIM), 0.7% (SIS), and 1.2% (FS) for the eight drugs analyzed. Overall, the SIS mode produced stable, comparable mean ratios over the concentration ranges examined, but had greater variance within batch runs. Examination of postmortem and quality-control samples produced forensically accurate quantitation by SIS when compared to SIM. Furthermore, sensitivity of FS was equivalent to SIM for all compounds examined except for 6-AM.

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial

PubMed Central

Wardle, Margaret C.; Marcus, Benjamin A.; de Wit, Harriet

2015-01-01

Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC) in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants’ drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female), aged 21–31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg), alcohol (0.8 g/kg), or THC (7.5 mg), each paired with a placebo session. Participants rated the drugs’ effects on both global measures (e.g. feeling a drug effect at all) and drug-specific measures. In general, participants’ responses to the three drugs were unrelated. Unexpectedly, “wanting more” alcohol was inversely correlated with “wanting more” THC. Additionally, in women, but not in men, “disliking” alcohol was negatively correlated with “disliking” THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity) was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a “drug of choice” model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types of drugs. Trial Registration ClinicalTrials.gov NCT02485158 PMID:26513587

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

PubMed

Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC.

Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine).

PubMed

Erdtmann-Vourliotis, M; Mayer, P; Riechert, U; Höllt, V

1999-08-25

It is regarded as a common pharmacological property responsible for the addictive potential of drugs of abuse that they are able to activate brain areas involved in the sensation of pleasure, especially the nucleus accumbens. To investigate the connection between addictive potential and stimulation of critical brain areas in more detail, we studied c-fos accumulation in response to various addicting drugs in direct comparison. The substances were injected into drug-naive rats, and c-fos mRNA levels were measured throughout the brain by in situ hybridization. Cocaine in a high dose of 50 mg/kg yielded only a discrete c-fos expression in the medial and central striatum. Morphine (50 mg/kg) caused a weak c-fos synthesis in the lateral septum. THC (delta(9)-tetrahydrocannabinol), 25 mg/kg, induced c-fos mRNA again in the lateral septum and furthermore in large parts of the striatum including the nucleus accumbens. LSD (lysergic acid diamide), 1 mg/kg, elicited a similar c-fos expression pattern as THC, but there was additionally a very strong hybridization signal in the cerebral cortex, especially in the upper layers, and in the ventral part of the periaqueductal gray. The widest range of brain areas was activated by MDMA (3, 4-methylenedioxymethamphetamine, 'ecstasy'), 6 mg/kg. In addition to the regions that responded to LSD, there was a very pronounced c-fos signal in the nucleus accumbens core and shell and in the mammillary nuclei. Taken together, our study revealed that the drugs with the highest addictive potential, cocaine and morphine, yielded a very low c-fos synthesis throughout the brain whereas the brain regions closely linked to pleasure (especially the nucleus accumbens) responded strongly to drugs with an apparently lower addictive potential (THC, LSD, MDMA).

Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

PubMed

Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

2016-04-05

It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats.

PubMed

Hempel, Briana J; Wakeford, Alison G P; Clasen, Matthew M; Friar, Mary A; Riley, Anthony L

2016-05-01

In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors

PubMed Central

Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A.; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I.; McCormick, Peter J.; Maldonado, Rafael; Robledo, Patricia

2015-01-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties. PMID:26158621

Just say 'know': how do cannabinoid concentrations influence users' estimates of cannabis potency and the amount they roll in joints?

PubMed

Freeman, Tom P; Morgan, Celia J A; Hindocha, Chandni; Schafer, Gráinne; Das, Ravi K; Curran, H Valerie

2014-10-01

(1) To determine whether measured concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in individuals' own cannabis predict their estimates of drug potency and actual titration; and (2) to ascertain if these effects are influenced by frequency of use and cannabis type. Cross-sectional, naturalistic. Participants' own homes. A total of 247 cannabis users in the United Kingdom: 152 'recreational' (1-24 days/month) and 95 'daily' (≥25 days/month). Participants rated their own cannabis for its potency (1-10) and type ('resin', 'herbal', 'skunk') before smoking it in front of the researcher. The amount of cannabis (g) used in their joints was recorded and an additional sample was analysed for THC and CBD concentrations (%). THC concentrations were related negatively to the amount of cannabis used [unstandardized regression coefficient: b = -0.009, 95% confidence interval (CI) = -0.017, -0.002]. Potency estimates were predicted by increasing THC (b = 0.055, 95% CI = 0.020, 0.090) and decreasing CBD (b = -0.160, 95% CI = -0.284, -0.062), and both of these associations were mediated by cannabis type (THC: b = 0.018, 95% CI = 0.006, 0.037; CBD: b = -0.105, 95% CI = -0.198, -0.028). Potency estimates were more reflective of THC as frequency of use increased (b = 0.004, 95% CI = 0.001, 0.007) and were 7.3 times more so in daily (partial r = 0.381) than recreational users (r = 0.052). When using their own cannabis in a naturalistic setting, people titrate the amount they roll in joints according to concentrations of delta-9-tetrahydrocannabinol (THC) but not cannabidiol (CBD). Recreational users thus show poor understanding of cannabis potency. © 2014 Society for the Study of Addiction.

Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.

PubMed

Strasser, Florian; Luftner, Diana; Possinger, Kurt; Ernst, Gernot; Ruhstaller, Thomas; Meissner, Winfried; Ko, You-Dschun; Schnelle, Martin; Reif, Marcus; Cerny, Thomas

2006-07-20

To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS). Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks. Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms. CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

PubMed

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

PubMed

Cahoon, E B; Ripp, K G; Hall, S E; Kinney, A J

2001-01-26

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Recent Self-Reported Cannabis Use Is Associated With the Biometrics of Delta-9-Tetrahydrocannabinol.

PubMed

Smith, Matthew J; Alden, Eva C; Herrold, Amy A; Roberts, Andrea; Stern, Dan; Jones, Joseph; Barnes, Allan; O'Connor, Kailyn P; Huestis, Marilyn A; Breiter, Hans C

2018-05-01

Research typically characterizes cannabis use by self-report of cannabis intake frequency. In an effort to better understand relationships between measures of cannabis use, we evaluated if Δ-9-tetrahydrocannabinol (THC) and metabolite concentrations (biometrics) were associated with a calibrated timeline followback (TLFB) assessment of cannabis use. Participants were 35 young adult male cannabis users who completed a calibrated TLFB measure of cannabis use over the past 30 days, including time of last use. The calibration required participants handling four plastic bags of a cannabis substitute (0.25, 0.5, 1.0, and 3.5 grams) to quantify cannabis consumed. Participants provided blood and urine samples for analysis of THC and metabolites, at two independent laboratories. Participants abstained from cannabis use on the day of sample collection. We tested Pearson correlations between the calibrated TLFB measures and cannabis biometrics. Strong correlations were seen between urine and blood biometrics (all r > .73, all p < .001). TLFB measures of times of use and grams of cannabis consumed were significantly related to each biometric, including urine 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and blood THC, 11-hydroxy-THC (11-OH-THC), THCCOOH, THCCOOH-glucuronide (times of use: r > .48-.61, all p < .05; grams: r > .40-.49, all p < .05). This study extends prior work to show TLFB methods significantly relate to an extended array of cannabis biometrics. The calibration of cannabis intake in grams was associated with each biometric, although the simple TLFB measure of times of use produced the strongest relationships with all five biometrics. These findings suggest that combined self-report and biometric data together convey the complexity of cannabis use, but allow that either the use of calibrated TLFB measures or biometrics may be sufficient for assessment of cannabis use in research.

Therapeutic potential of cannabis in pain medicine.

PubMed

Hosking, R D; Zajicek, J P

2008-07-01

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Repeated stimulation of D1 dopamine receptors enhances (-)-11-hydroxy-delta 8-tetrahydrocannabinol-dimethyl-heptyl-induced catalepsy in male rats.

PubMed

Rodríguez de Fonseca, F; Martín Calderón, J L; Mechoulam, R; Navarro, M

1994-03-21

Dopaminergic and cannabinoid receptors are localized in the outflow nuclei of the basal ganglia. We have investigated the possible interrelation of these receptors in the regulation of motor activity in male rats. To this end we have first studied the behavioural effects of the highly potent cannabinoid receptor agonist (-)11-hydroxy-delta 8-tetrahydrocannabinol-dimethylheptyl (HU-210, 20 micrograms mg) after chronic stimulation of dopamine D1 and D2 receptors. The catalepsy induced by the synthetic cannabinoid, measured as the descent latency in the bar test, was enhanced in male rats chronically treated with the dopamine D1 receptor agonist SKF38393 (8 mg kg-1, twice a day during 21 days). However, animals exposed to the dopamine D2 agonist quinpirole (1 mg kg-1 daily during 21 days) displayed the same degree of catalepsy as those exposed to HU-210 alone. Although a possible involvement of D2 receptors cannot be excluded, this finding suggests a predominant role for dopamine D1 receptors in the regulation of the cataleptic response to cannabinoids. The possible cross-talk between dopamine D1 and cannabinoid receptors is further supported by the decreased responsiveness to the acute behavioural effects of SKF38393 (8 mg kg-1) observed in animals chronically exposed to HU-210 (20 micrograms kg-1 daily during 14 days).

Delta5-olefinic acids in the seed lipids from four Ephedra species and their distribution between the alpha and beta positions of triacylglycerols. Characteristics common to coniferophytes and cycadophytes.

PubMed

Wolff, R L; Christie, W W; Pédrono, F; Marpeau, A M; Tsevegsüren, N; Aitzetmüller, K; Gunstone, F D

1999-08-01

The fatty acid compositions of the seed lipids from four Ephedra species, E. nevadensis, E. viridis, E. przewalskii, and E. gerardiana (four gymnosperm species belonging to the Cycadophytes), have been established with an emphasis on delta5-unsaturated polymethylene-interrupted fatty acids (delta5-UPIFA). Mass spectrometry of the picolinyl ester derivatives allowed characterization of 5,9- and 5,11-18:2; 5,9,12-18:3; 5,9,12,15-18:4; 5,11-20:2; 5,11,14-20:3; and 5,11,14,17-20:4 acids. Delta5-UPIFA with a delta11-ethylenic bond (mostly C20 acids) were in higher proportions than delta5-UPIFA with a delta9 double bond (exclusively C18 acids) in all species. The total delta5-UPIFA content was 17-31% of the total fatty acids, with 5,11,14-20:3 and 5,11,14,17-20:4 acids being the principal delta5-UPIFA isomers. The relatively high level of cis-vaccenic (11-18:1) acid found in Ephedra spp. seeds, the presence of its delta5-desaturation product, 5,11-18:2 acid (proposed trivial name: ephedrenic acid), and of its elongation product, 13-20:1 acid, were previously shown to occur in a single other species, Ginkgo biloba, among the approximately 170 gymnosperm species analyzed so far. Consequently, Ephedraceae and Coniferophytes (including Ginkgoatae), which have evolved separately since the Devonian period (approximately 300 million yr ago), have kept in common the ability to synthesize C18 and C20 delta5-UPIFA. We postulate the existence of two delta5-desaturases in gymnosperm seeds, one possibly specific for unsaturated acids with a delta9-ethylenic bond, and the other possibly specific for unsaturated acids with a delta11-ethylenic bond. Alternatively, the delta5-desaturases might be specific for the chain length with C18 unsaturated acids on the one hand and C20 unsaturated acids on the other hand. The resulting hypothetical pathways for the biosynthesis of delta5-UPIFA in gymnosperm seeds are only distinguished by the position of 11-18:1 acid. Moreover, 13C nuclear magnetic resonance spectroscopy of the seed oil from two Ephedra species has shown that delta5-UPIFA are essentially excluded from the internal position of triacylglycerols, a characteristic common to all of the Coniferophytes analyzed so far (more than 30 species), with the possibility of an exclusive esterification at the sn-3 position. This structural feature would also date back to the Devonian period, but might have been lost in those rare angiosperm species containing delta5-UPIFA.

delta 6 Hexadecenoic acid is synthesized by the activity of a soluble delta 6 palmitoyl-acyl carrier protein desaturase in Thunbergia alata endosperm.

PubMed

Cahoon, E B; Cranmer, A M; Shanklin, J; Ohlrogge, J B

1994-11-04

delta 6 Hexadecenoic acid (16:1 delta 6) composes more than 80% of the seed oil of Thunbergia alata. Studies were conducted to determine the biosynthetic origin of the double bond of this unusual fatty acid. Assays of fractions of developing T. alata seed endosperm with [1-14C]palmitoyl (16:0)-acyl carrier protein (ACP) revealed the presence of a soluble delta 6 desaturase activity. This activity was greatest when 16:0-ACP was provided as a substrate, whereas no desaturation of the coenzyme A ester of this fatty acid was detected. In addition, delta 6 16:0-ACP desaturase activity in T. alata endosperm extracts was dependent on the presence of ferredoxin and molecular oxygen and was stimulated by catalase. To further characterize this enzyme, a cDNA encoding a diverged acyl-ACP desaturase was isolated from a T. alata endosperm cDNA library using polymerase chain reaction with degenerate oligonucleotides corresponding to conserved amino acid sequences in delta 9 stearoyl (18:0)- and delta 4 16:0-ACP desaturases. The primary structure of the mature peptide encoded by this cDNA shares 66% identity with the mature castor delta 9 18:0-ACP desaturase and 57% identity with the mature coriander delta 4 16:0-ACP desaturase. Extracts of Escherichia coli that express the T. alata cDNA catalyzed the delta 6 desaturation of 16:0-ACP. These results demonstrate that 16:1 delta 6 in T. alata endosperm is formed by the activity of a soluble delta 6 16:0-ACP desaturase that is structurally related to the delta 9 18:0- and delta 4 16:0-ACP desaturases. Implications of this work to an understanding of active site structures of acyl-ACP desaturases are discussed.

Elucidation of the sex-pheromone biosynthesis producing 5,7-dodecadienes in Dendrolimus punctatus (Lepidoptera: Lasiocampidae) reveals Delta 11- and Delta 9-desaturases with unusual catalytic properties.

PubMed

Liénard, Marjorie A; Lassance, Jean-Marc; Wang, Hong-Lei; Zhao, Cheng-Hua; Piskur, Jure; Johansson, Tomas; Löfstedt, Christer

2010-06-01

Sex pheromones produced by female moths of the Lasiocampidae family include conjugated 5,7-dodecadiene components with various oxygenated terminal groups. Here we describe the molecular cloning, heterologous expression and functional characterization of desaturases associated with the biosynthesis of these unusual chemicals. By homology-based PCR screening we characterized five cDNAs from the female moth pheromone gland that were related to other moth desaturases, and investigated their role in the production of the (Z)-5-dodecenol and (Z5,E7)-dodecadienol, major pheromone constituents of the pine caterpillar moth, Dendrolimus punctatus. Functional expression of two desaturase cDNAs belonging to the Delta 11-subfamily, Dpu-Delta 11(1)-APSQ and Dpu-Delta 11(2)-LPAE, showed that they catalysed the formation of unsaturated fatty acyls (UFAs) that can be chain-shortened by beta-oxidation and subsequently reduced to the alcohol components. A first (Z)-11-desaturation step is performed by Dpu-Delta 11(2)-LPAE on stearic acid that leads to (Z)-11-octadecenoic acyl, which is subsequently chain shortened to the (Z)-5-dodecenoic acyl precursor. The Dpu-Delta 11(1)-APSQ desaturase had the unusual property of producing Delta 8 mono-UFA of various chain lengths, but not when transformed yeast were grown in presence of (Z)-9-hexadecenoic acyl, in which case the biosynthetic intermediate (Z9,E11)-hexadecadienoic UFA was produced. In addition to a typical Z9 activity, a third transcript, Dpu-Delta 9-KPSE produced E9 mono-UFAs of various chain lengths. When provided with the (Z)-7-tetradecenoic acyl, it formed the (Z7,E9)-tetradecadienoic UFA, another biosynthetic intermediate that can be chain-shortened to (Z5,E7)-dodecadienoic acyl. Both Dpu-Delta 11(1)-APSQ and Dpu-Delta 9-KPSE thus exhibited desaturase activities consistent with the biosynthesis of the dienoic precursor. The combined action of three desaturases in generating a dienoic sex-pheromone component emphasizes the diversity and complexity of chemical reactions that can be catalysed by pheromone biosynthetic fatty-acyl-CoA desaturases in moths. (c) 2010 Elsevier Ltd. All rights reserved.

Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops.

PubMed

Pijlman, F T A; Rigter, S M; Hoek, J; Goldschmidt, H M J; Niesink, R J M

2005-06-01

The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since 1999. This annual monitoring was issued by the Ministry of Health after reports of increased potency. The level of the main psychoactive compound, Delta9-tetrahydrocannabinol (THC), is measured in marijuana and hashish. A comparison is made between imported and Dutch preparations, and between seasons. Samples of cannabis preparations from randomly selected coffee shops were analyzed using gas chromatography (GC-FID) for THC, CBD and CBN. In 2004, the average THC level of Dutch home-grown marijuana (Nederwiet) (20.4% THC) was significantly higher than that of imported marijuana (7.0% THC). Hashish derived from Dutch marijuana (Nederhasj) contained 39.3% THC in 2004, compared with 18.2% THC in imported hashish. The average THC percentage of Dutch marijuana, Dutch hashish and imported hashish was significantly higher than in previous years. It nearly doubled over 5 years. During this period, the THC percentage in imported marijuana remained unchanged. A higher price had to be paid for cannabis with higher levels of THC. Whether the increase in THC levels causes increased health risks for users can only be concluded when more data are available on adjusted patterns of use, abuse liability, bioavailability and levels of THC in the brain.

Determination of Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) in whole blood and plasma by LC-MS/MS and application in authentic samples from drivers suspected of driving under the influence of cannabis.

PubMed

Raikos, Nikolaos; Schmid, Helene; Nussbaumer, Susanne; Ambach, Lars; Lanz, Stephan; Längin, Andreas; König, Stefan; Roth, Nadine; Auwärter, Volker; Weinmann, Wolfgang

2014-10-01

Delta-9-tetrahydrocannabinolic acid A (THCA-A) is the biosynthetic precursor of delta-9-tetrahydrocannabinol (THC) in cannabis plants, and has no psychotropic effects. THCA-A can be detected in blood and urine, and several metabolites have been identified. THCA-A was also shown to be incorporated in hair by side stream smoke to a minor extent, but incorporation via blood stream or sweat seems unlikely. The detection of THCA-A in biological fluids may serve as a marker for differentiating between the intake of prescribed THC medication - containing only pure THC - and cannabis products containing THC besides THC-acid A and other cannabinoids. However, the knowledge about its usefulness in forensic cases is very limited. The aim of the present work was the development of a reliable method for THCA-A determination in human blood or plasma using LC-MS/MS and application to cases of driving under the influence of drugs. Fifty eight (58) authentic whole blood and the respective plasma samples were collected from drivers suspected of driving under the influence of cannabis from the region of Bern (Switzerland). Samples were first tested for THC, 11-OH-THC and THC-COOH, and then additionally for THCA-A. For this purpose, the existing LC-MS/MS method was modified and validated, and found to be selective and linear over a range of 1.0 to 200ng/mL (the correlation coefficients were above 0.9980 in all validation runs). Limit of detection (LOD) and limit of quantification (LOQ) were 0.3ng/mL and 1.0ng/mL respectively. Intra- and inter-assay accuracy were equal or better than 90% and intra- and inter-assay precision were equal or better than 11.1%. The mean extraction efficiencies were satisfactory being equal or higher than 85.4%. THCA-A was stable in whole blood samples after 3 freeze/thaw cycles and storage at 4°C for 7 days. Re-injection (autosampler) stability was also satisfactory. THC was present in all blood samples with levels ranging from 0.7 to 51ng/mL. THCA-A concentrations ranged from 1.0 to 496ng/mL in blood samples and from 1.4 to 824ng/mL in plasma samples. The plasma:blood partition coefficient had a mean value of 1.7 (±0.21, SD). No correlation was found between the degree of intoxication or impairment stated in the police protocols or reports of medical examinations and the detected THCA-A-concentration in blood. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Expression and evolution of delta9 and delta11 desaturase genes in the moth Spodoptera littoralis.

PubMed

Rodríguez, Sergio; Hao, Guixia; Liu, Weitian; Piña, Benjamín; Rooney, Alejandro P; Camps, Francisco; Roelofs, Wendell L; Fabriàs, Gemma

2004-12-01

Desaturation of fatty acids is a key reaction in the biosynthesis of moth sex pheromones. The main component of Spodoptera littoralis sex pheromone blend is produced by the action of Delta11 and Delta9 desaturases. In this article, we report on the cloning of four desaturase-like genes in this species: one from the fat body (Sls-FL1) and three (Sls-FL2, Sls-FL3 and Sls-FL4) from the pheromone gland. By means of a computational/phylogenetic method, as well as functional assays, the desaturase gene products have been characterized. The fat body gene expressed a Delta9 desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1:4.5) ratio, whereas the pheromone gland Sls-FL2 expressed a Delta9 desaturase that produced (Z)-9-hexadecenoic and (Z)-9-octadecenoic acids in a (1.5:1) ratio. Although both Delta9 desaturases produced (Z)-9-tetradecenoic acid from myristic acid, transformed yeast grown in the presence of a mixture of myristic and (E)-11-tetradecenoic acids produced (Z,E)-9,11-tetradecadienoic acid, but not (Z)-9-tetradecenoic acid. The Sls-FL3 gene expressed a protein that produced a mixture of (E)-11-tetradecenoic, (Z)-11-tetradecenoic, (Z)-11-hexadecenoic and (Z)-11-octadecenoic acids in a 5:4:60:31 ratio. Despite having all the characteristics of a desaturase gene, no function could be found for Sls-FL4.

Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on nausea induced by syrup of ipecac.

PubMed

Söderpalm, A H; Schuster, A; de Wit, H

2001-01-01

Although the public debate about the legalization of marijuana has continued for as long as 25 years, few controlled studies have been conducted to assess its potential medical benefits. The present study examined the antiemetic effect of smoked marijuana cigarettes (8.4 and 16.9 mg Delta(9)-tetrahydrocannabinol [THC]) compared to a highly potent antiemetic drug, ondansetron (8 mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Marijuana significantly reduced ratings of "queasiness" and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked marijuana reduces feelings of nausea and also reduces emesis in this model. However, its effects are very modest relative to ondansetron, and the psychoactive effects of marijuana are likely to limit its clinical usefulness in the general population.

Predominant expansion of V gamma 9/V delta 2 T cells in a tularemia patient.

PubMed Central

Sumida, T; Maeda, T; Takahashi, H; Yoshida, S; Yonaha, F; Sakamoto, A; Tomioka, H; Koike, T; Yoshida, S

1992-01-01

We describe a 58-year-old man with tularemia and expanding gamma delta T cells in his peripheral blood lymphocytes (PBL) (32.7% of total PBL). In the present work, we analyzed the T-cell receptor V gamma/V delta repertoire of these cells by making use of the polymerase chain reaction and flow cytometry and found that they were mostly CD4- CD8- CD3+ V gamma 9/V delta 2+. The sequence analysis of 16 cDNA clones encoding the V gamma 9-J region revealed that the V gamma 9-Jp combination was strikingly overrepresented but that the junctional (N) region was heterogeneous. This suggested that the gamma delta T cells in PBL from a patient with tularemia were polyclonally expanded. Images PMID:1534075

[Neuropsychopharmacology of delta-9-tetrahydrocannabinol].

PubMed

Costentin, J

2008-08-01

Today, the main route of introduction of tetrahydrocannabinol (THC), the main active substance of cannabis, into the human body is via the lungs, from smokes produced by combustion of a haschich-tobacco mixture. The use of a water pipe (nargileh-like) intensifies its fast supply to the body. THC reaches the brain easily where it stimulates CB1 receptors; their ubiquity underlies a wide variety of effects. THC disappears from extracellular spaces by dissolving in lipid rich membranes, and not by excretion from the body. This is followed by a slow release, leading to long lasting effects originating from brain areas containing a large proportion of spare receptors ("reserve receptors"). Far from mimicking the effects of endocannabinoids, THC caricatures and disturbs them. It induces both psychical and physical dependencies, but the perception of withdrawal is weak on account of its very slow elimination. THC disturbs cognition. Acutely, it develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC, thus leading to a tolerance (desensitization of CB1 receptors) making anxiety and depression to reappear more intensely than originally. THC has close relationships with schizophrenia. It incites to tobacco, alcohol and heroine abuses.

In Situ Carbon and Sulfur Isotope Analysis of Archean Organic Matter and Pyrite

NASA Technical Reports Server (NTRS)

Williford, K. H.; Ushikubo, T.; LePot, K.; Kitajima, K.; Spicuzza, M. J.; Valley, J. W.; Hallman, C.; Summons, R.; Eigenbrode, J. L.

2012-01-01

Stable isotopic compositions of biologically important elements (e.g., C and S) in sedimentary rocks are valuable biosignatures to the extent that they indicate the presence and variable expression of microbial metabolisms in space and time. Strong interactions between the carbon and sulfur cycles (e.g., via organic matter remineralization during microbial sulfate reduction) make coordinated, in situ C and S isotope analysis by secondary ion mass spectrometry (SIMS) a particularly powerful tool. In rocks ranging in age from 2.7-2.5 Ga, expansions in the ranges of delta C-13 of organic matter and delta S-34 of pyrite likely reflect the increasing influence of oxygenic photosynthesis in the surface ocean (as well as methane and sulfur metabolisms in deeper waters), whereas the large range of mass independent sulfur isotope fractionation (Delta S-33) suggests that the atmosphere remained anoxic until approx 2.4 Gyr ago. We report in situ delta C-13 measurements of organic matter in the approx 2.7-2.6 Ga Carawine Dolomite, Marra Mamba Iron Formation, and Jeerinah, Wittenoom, and Tumbiana Formations, as well as the approx 2.5 Ga Mount McRae Shale. We also report in situ delta S-24 and Delta S-33 measurements of pyrite associated with organic matter in a subset of these samples. In a single square cm sample of the Tumbiana Formation with bulk delta C-13(sub org) of -49.7% (VPDB), two distinct kerogen types have delta C-13 values, measured in situ, consistent with oxygenic photosynthesis (-33%) and methane metabolism (-52%). In a sample from the ABDP-9 core, radiobitumen associated with a uraniferous mineral grain is C-13-enriched by 8% (-26.8%0) relative to average in situ kerogen (-34.9%0) and similar in delta C-13 to solvent extractable hydrocarbons from the Mount McRae Shale (avg delta C-13 = -27.1 %). Average reproducibility for delta C-13 was 0.4% (2 SD) using a 6 micron spot and 0.8% using a 3 micron spot. In situ sulfur isotope analyses of 33 authigenic pyrite grains in 3 samples of the ABDP-9 core using a 10 micron spot (2 SD reproducibility = 0.4% for delta S-34 and -0.1% for Delta S-33) show a range of 28.1 % in delta S-34 (-10.3 to 17.8%) and 13.3%0 in Delta S-33 (-3.8 to 9.5%), whereas the range from 132 bulk analyses across 84 m of core is 19.4% for delta S-34 and 11.5% for Delta S-33. Coordinated, in situ carbon and sulfur isotope analyses in one ABDP-9 sample are shown. In situ values from this kerogen-pyrite association are within 0.1% of the bulk value in the case of delta C-13 and higher by several permil in the case of delta S-34 and Delta S-33. Coordinated in situ carbon and sulfur isotope analyses in rocks deposited during key intervals of environmental change (e.g., the Great Oxidation Event) can refine our understanding of the mode and tempo of change. In Earth's oldest sedimentary rocks, and in extraterrestrial samples, these coordinated in situ analyses may reveal biosignatures in the form of isotopic correlations at the scale of individual microorganisms and their microhabitats.

Use of synthetic cannabinoids in patients with psychotic disorders: case series.

PubMed

Celofiga, Andreja; Koprivsek, Jure; Klavz, Janez

2014-01-01

An increasing number of synthetic cannabinoids have become available on the black market in recent years, and health professionals have seen a corresponding increase in use of these compounds among patients with psychiatric disorders. Unfortunately, there is almost no research available in the literature on this topic, and what little exists is based on case reports of individuals without psychiatric disorders. Synthetic cannabinoids are functionally similar to, but structurally different from, delta-9-tetrahydrocannabinol, the active principle in cannabis, and are problematic for many reasons. The psychotropic action of synthetic cannabinoids in patients with schizophrenia is unpredictable, with very diverse clinical presentations. These drugs can be much more potent than delta-9-tetrahydrocannabinol, they are readily available and difficult to detect. The gold standard for identification of synthetic cannabinoids is gas chromatography with mass spectrometry, but even this is difficult because new formulations of these designer drugs are constantly emerging. In this manuscript, we provide an overview and discussion of synthetic cannabinoids and present four cases of patients with synthetic cannabinoid intoxication who were hospitalized in our intensive psychiatric unit at the time of intoxication. All patients had a history of schizophrenia and had been hospitalized several times previously. While hospitalized, they smoked an unknown substance brought in by a visitor, which was then confirmed using gas chromatography with mass spectrometry to be the synthetic cannabinoid AM-2201. Our patients experienced predominantly psychiatric adverse clinical effects. We observed the appearance of new psychotic phenomena, without exacerbation of their previously known psychotic symptoms, as well as the occurrence or marked worsening of mood and anxiety symptoms. Despite several similar reactions, and even though they ingested the same exact substance, the clinical picture differed markedly between individual patients. We assume that the acute effects of synthetic cannabinoids in patients with schizophrenia would be different from those in persons without psychotic disorders. The reasons for this difference could be the actual symptomatology of the presenting disorder, the impact of psychopharmacotherapy, individual patient differences and probably many, as yet unknown, factors. The long-term consequences of synthetic cannabinoid use on preexisting psychotic disorders are unclear.

A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana.

PubMed

Weinstein, A; Brickner, O; Lerman, H; Greemland, M; Bloch, M; Lester, H; Chisin, R; Sarne, Y; Mechoulam, R; Bar-Hamburger, R; Freedman, N; Even-Sapir, E

2008-06-01

Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials.

PubMed

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-08-01

To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain

PubMed Central

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-01-01

Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP. PMID:26505059

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

PubMed

Holland, M L; Lau, D T T; Allen, J D; Arnold, J C

2007-11-01

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro. Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2. Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays. The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting. CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line. The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent. The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition. Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression. Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

Stable-isotope ratios of hydrogen and oxygen in precipitation at Norman, Oklahoma, 1996-2008

USGS Publications Warehouse

Jaeschke, Jeanne B.; Scholl, Martha A.; Cozzarelli, Isabelle M.; Masoner, Jason R.; Christenson, Scott; Qi, Haiping

2011-01-01

Precipitation samples for measurement of stable-isotope ratios of hydrogen (delta2H) and oxygen (delta18O) were collected at the Norman Landfill Research Site in Norman, Oklahoma, from May 1996 to October 2008. Rainfall amounts also were measured at the site (U.S. Geological Survey gaging station 07229053) during the collection period. The delta2H of precipitation samples ranged from -121.9 to +8.3 per mil, and the delta18O of precipitation ranged from -16.96 to +0.50 per mil. The volume-weighted average values for delta2H and delta18O of precipitation over the 12-year measurement period were -31.13 per mil for delta2H and -5.57 per mil for delta18O. Average summer-season delta2H and delta18O values of precipitation usually were more positive (enriched in the heavier isotopes) than winter values.

Reaction mechanism of guanidinoacetate methyltransferase, concerted or step-wise.

PubMed

Zhang, Xiaodong; Bruice, Thomas C

2006-10-31

We describe a quantum mechanics/molecular mechanics investigation of the guanidinoacetate methyltransferase catalyzed reaction, which shows that proton transfer from guanidinoacetate (GAA) to Asp-134 and methyl transfer from S-adenosyl-L-methionine (AdoMet) to GAA are concerted. By self-consistent-charge density functional tight binding/molecular mechanics, the bond lengths in the concerted mechanism's transition state are 1.26 A for both the OD1 (Asp-134)-H(E) (GAA) and H(E) (GAA)-N(E) (GAA) bonds, and 2.47 and 2.03 A for the S8 (AdoMet)-C9 (AdoMet) and C9 (AdoMet)-N(E) (GAA) bonds, respectively. The potential-energy barrier (DeltaE++) determined by single-point B3LYP/6-31+G*//MM is 18.9 kcal/mol. The contributions of the entropy (-TDeltaS++) and zero-point energy corrections Delta(ZPE)++ by normal mode analysis are 2.3 kcal/mol and -1.7 kcal/mol, respectively. Thus, the activation enthalpy of this concerted mechanism is predicted to be DeltaH++ = DeltaE++ plus Delta(ZPE)++ = 17.2 kcal/mol. The calculated free-energy barrier for the concerted mechanism is DeltaG++ = 19.5 kcal/mol, which is in excellent agreement with the value of 19.0 kcal/mol calculated from the experimental rate constant (3.8 +/- 0.2.min(-1)).

Homeostasis of the protonmotive force in phosphorylating mitochondria.

PubMed

Duszyński, J; Bogucka, K; Wojtczak, L

1984-12-18

The relationship between the respiration rate and the magnitude of the electrochemical proton potential (delta mu H+) in rat liver mitochondria was investigated. (1) Under the active-state conditions, the action of inhibitors of either phosphorylation (oligomycin) or respiration (rotenone, malonate) on the respiration and delta mu H+ was measured. Both inhibitors diminished the respiration, whereas rotenone resulted in a decrease of delta mu H+, and oligomycin produced an increase of this potential. The effect of the inhibitors was much more pronounced on the respiration rate than on delta mu H+; for example, the excess of oligomycin produced a 90% inhibition of the respiration while delta mu H+ was changed only by 9%. (2) Under the resting-state conditions, small concentrations of the uncoupler stimulated the respiration while changing delta mu H+ to a relatively small extent. The uncoupler concentrations which doubled and tripled the respiration rate produced only 5 and 9% decrease of delta mu H+, respectively. (3) The present results enabled us to propose a model describing the interrelationship between respiration and delta mu H+.

Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort.

PubMed

Yuferov, Vadim; Butelman, Eduardo R; Kreek, Mary Jeanne

2018-01-01

Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp ( PDYN 68 bp) promoter repeats with categorical diagnoses of cannabis dependence ( Diagnostic and Statistical Manual of Mental Disorders-IV criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek-McHugh-Schluger-Kellogg cannabis scale). The PDYN 68 bp genotype (examined as short-short [SS], short-long [SL], or long-long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis ( p <0.05) and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p <0.045). Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group ( p <0.045). Of interest, none of the aforementioned genetic associations were significant in females. This study provides the first data on how the PDYN 68 bp genotype is associated with gender-specific patterns of exposure to cannabis. Overall, this study shows that PDYN 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities.

Gender-specific association of functional prodynorphin 68 bp repeats with cannabis exposure in an African American cohort

PubMed Central

Kreek, Mary Jeanne

2018-01-01

Background Cannabis use disorders (CUDs) cause substantial neuropsychiatric morbidity and comorbidity. There is evidence for gender-based differences in CUDs, for instance, a greater prevalence in males than in females. The main active component of cannabis is delta 9-tetrahydrocannabinol (delta 9-THC), a partial agonist of the cannabinoid type 1 receptor. Preclinical studies show that genetic or pharmacological manipulation of the kappa opioid receptor/dynorphin system modulates the effects of delta 9-THC. Methods In this case-control study of adult African Americans (n=476; 206 females, 270 males), we examined the association of the functional prodynorphin 68 bp (PDYN 68 bp) promoter repeats with categorical diagnoses of cannabis dependence (Diagnostic and Statistical Manual of Mental Disorders-IV criteria), as well as with a rapid dimensional measure of maximum lifetime cannabis exposure (the Kreek–McHugh–Schluger–Kellogg cannabis scale). Results The PDYN 68 bp genotype (examined as short–short [SS], short–long [SL], or long–long [LL], based on the number of repeats) was not significantly associated with categorical cannabis-dependence diagnoses, either in males or in females. However, in males, the PDYN 68 bp SS+SL genotype was associated with both greater odds of any use of cannabis (p<0.05) and earlier age of first cannabis use, compared to the LL genotype (ie, 15 versus 16.5 years of age; p<0.045). Males in the SS+SL group also had greater odds of high lifetime exposure to cannabis, compared to the LL group (p<0.045). Of interest, none of the aforementioned genetic associations were significant in females. Conclusion This study provides the first data on how the PDYN 68 bp genotype is associated with gender-specific patterns of exposure to cannabis. Overall, this study shows that PDYN 68 bp polymorphisms affect behaviors involved in early stages of nonmedical cannabis use and potentially lead to increasing self-exposure. These data may eventually lead to improvements in personalized medicine for the prevention and treatment of highly prevalent CUDs and neuropsychiatric comorbidities. PMID:29713172

Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

PubMed Central

Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

2014-01-01

Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

Effects of recharge and discharge on delta2H and delta18O composition and chloride concentration of high arsenic/fluoride groundwater from the Datong Basin, northern China.

PubMed

Xie, Xianjun; Wang, Yanxin; Su, Chunli; Duan, Mengyu

2013-02-01

To better understand the effects of recharge and discharge on the hydrogeochemistry of high levels of arsenic (As) and fluoride (F) in groundwater, environmental isotopic composition (delta2H and delta18O) and chloride (Cl) concentrations were analyzed in 29 groundwater samples collected from the Datong Basin. High arsenic groundwater samples (As > 50 micog/L) were found to be enriched in lighter isotopic composition that ranged from -92 to -78 per thousand for deuterium (delta2H) and from -12.5 to -9.9 per thousand for oxygen-18 (delta18O). High F-containing groundwater (F > 1 mg/L) was relatively enriched in heavier isotopic composition and varied from -90 to -57 per thousand and from -12.2 to -6.7 per thousand for delta2H and delta18O, respectively. High chloride concentrations and delta18O values were primarily measured in groundwater samples from the northern and southwestern portions of the study area, indicating the effect of evaporation on groundwater. The observation of relatively homogenized and low delta18O values and chloride concentrations in groundwater samples from central part of the Datong Basin might be a result of fast recharge by irrigation returns, which suggests that irrigation using arsenic-contaminated groundwater affected the occurrence of high arsenic-containing groundwater in the basin.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

PubMed

Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

PubMed

Martin-Santos, R; Crippa, J A; Batalla, A; Bhattacharyya, S; Atakan, Z; Borgwardt, S; Allen, P; Seal, M; Langohr, K; Farré, M; Zuardi, A W; McGuire, P K

2012-01-01

Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

Body Temperatures During Exercise in Deconditioned Dogs: Effect of NACL and Glucose Infusion

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Kruk, B.; Nazar, K.; Kaciuba-Usciko, H.

2000-01-01

Infusion of glucose (Glu) into normal exercising dogs attenuates the rise in rectal temperature (Delta-Tre) when compared with delta-Tre during FFA infusion or no infusion. Rates of rise and delta-=Tre levels are higher during exercise after confinement. Therefore, the purpose of this study was to determine if Glu infusion would attenuate the exercise-induced excess hyperthermia after deconditioning. Rectal and quadricep femoris muscle temperatures (Tmu) were measured in 7 male, mongrel dogs dogs (19.6 +/- SD 3.0 kg) during 90 minutes of treadmill exercise (3.1 +/-SD 0.2 W/kg) with infusion (30ml/min/kg) of 40% Glu or 0.9% NaCL before BC) and after confinement (AC) in cages (40 x 110 x 80 cm) for 8 wk. Mean (+/-SE body wt. were 19.6 +/- 1.1 kg BC and 19.5 +/- 1.1kg AC, exercise VO2 were not different (40.0 - 42.0 mi/min/kg-1). With NaCl AC, NaCl BC, GluAC, and GluBC: Delta-Tre were, 1.8, 1.4, 1.3 and 0.9C respectively; and Delta-Tmu were 2.3, 1.9, 1.6, and 1.4C. respectively (P<0.05 from GluBC). Compared with NaCl infusion, attenuated both Delta-Tre and Delta-Tmu BC and AC, respectively. Compared with GluBC, GluAC attenuated Delta-Tmu but not Delta-Tre. Thus. with similar heat production, the mechanism for attenuation at bad body temperature with Glu infusion must affect avenues of heat dissipation.

Control of cell cycle by metabolites of prostaglandin D2 through a non-cAMP mediated mechanism

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.; Fukushima, M.

1993-01-01

The dehydration products of PGD2, 9-deoxy-9 prostaglandin D2(PGJ2), 9-deoxy-delta 9, delta 12, delta 13 dehydroprostaglandin D2 (delta 12 PGJ2), and PGA2 all contain an unsaturated cyclopentenone structure which is characteristic of prostaglandins which effectively inhibit cell growth. It has been suggested that the action of the inhibitory prostaglandins may be through a cAMP mechanism. In this study, we use S49 wild type (WT) and adenylate cyclase variant (cyc-) cells to show that PGD2 and PGJ2 are not acting via a cyclic AMP mechanism. First, the increase in cyclic AMP in wild type S-49 cells is not proportional to its effects on DNA synthesis. More importantly, when S-49 cyc- cells were exposed to PGJ2, the adenylate cyclase (cyc-) mutant had decreased DNA synthesis with no change in its nominal cAMP content. Short-term (2 hours or less) exposure of the cyc- cells to prostaglandin J2 caused an inhibition of DNA synthesis. PGJ2 caused cytolysis at high concentrations. Long-term exposure (>14 hrs) of the cells to PGJ2, delta 12PGJ2 or delta 12, delta 14PGJ2 caused a cell cycle arrest in G1 demonstrating a cell cycle specific mechanism of action for growth inhibition by naturally occurring biological products independent of cAMP.

Event-rate and delta inflation when evaluating mortality as a primary outcome from randomized controlled trials of nutritional interventions during critical illness: a systematic review.

PubMed

Summers, Matthew J; Chapple, Lee-anne S; McClave, Stephen A; Deane, Adam M

2016-04-01

There is a lack of high-quality evidence that proves that nutritional interventions during critical illness reduce mortality. We evaluated whether power calculations for randomized controlled trials (RCTs) of nutritional interventions that used mortality as the primary outcome were realistic, and whether overestimation was systematic in the studies identified to determine whether this was due to overestimates of event rate or delta. A systematic review of the literature between 2005 and 2015 was performed to identify RCTs of nutritional interventions administered to critically ill adults that had mortality as the primary outcome. Predicted event rate (predicted mortality during the control), predicted mortality during intervention, predicted delta (predicted difference between mortality during the control and intervention), actual event rate (observed mortality during control), observed mortality during intervention, and actual delta (difference between observed mortality during the control and intervention) were recorded. The event-rate gap (predicted event rate minus observed event rate), the delta gap (predicted delta minus observed delta), and the predicted number needed to treat were calculated. Data are shown as median (range). Fourteen articles were extracted, with power calculations provided for 10 studies. The predicted event rate was 29.9% (20.0–52.4%), and the predicted delta was 7.9% (3.0–20.0%). If the study hypothesis was proven correct then, on the basis of the power calculations, the number needed to treat would have been 12.7 (5.0–33.3) patients. The actual event rate was 25.3% (6.1–50.0%), the observed mortality during the intervention was 24.4% (6.3–39.7%), and the actual delta was 0.5% (−10.2–10.3%), such that the event-rate gap was 2.6% (−3.9–23.7%) and delta gap was 7.5% (3.2–25.2%). Overestimates of delta occur frequently in RCTs of nutritional interventions in the critically ill that are powered to determine a mortality benefit. Delta inflation may explain the number of "negative" studies in this field of research.

Late quaternary evolution of the Orinoco Delta, Venezuela

USGS Publications Warehouse

Warne, A.G.; Guevara, E.H.; Aslan, A.

2002-01-01

The modern Orinoco Delta is the latest of a series of stacked deltas that have infilled the Eastern Venezuelan Basin (EVB) since the Oligocene. During the late Pleistocene sea-level lowstand (20,000 to 16,000 yrs BP), bedrock control points at the position of the present delta apex prevented the river channel from incising as deeply as many other major river systems. Shallow seismic data indicate that the late Pleistocene Orinoco incised into the present continental shelf, where it formed a braided-river complex that transported sediment to a series of shelf-edge deltas. As sea level rose from 16,000 to 9,500 yrs BP, the Orinoco shoreline shifted rapidly landward, causing shallow-marine waves and currents to form a widespread transgressive sand unit. Decelerating sea-level rise and a warmer, wetter climate during the early Holocene (9,500 to 6,000 yrs BP) induced delta development within the relatively quiet-water environment of the EVB embayment. Sea level approached its present stand in the middle Holocene (6,000 to 3,000 yrs BP), and the Orinoco coast prograded, broadening the delta plain and infilling the EVB embayment. Significant quantities of Amazon sediment began to be transported to the Orinoco coast by littoral currents. Continued progradation in the late Holocene caused the constriction at Boca de Serpientes to alter nearshore and shelf hydrodynamics and subdivide the submarine delta into two distinct areas: the Atlantic shelf and the Gulf of Paria. The increased influence of littoral currents along the coast promoted mudcape development. Because most of the water and sediment were transported across the delta plain through the Rio Grande distributary in the southern delta, much of the central and northwestern delta plain became sediment starved, promoting widespread accumulation of peat deposits. Human impacts on the delta are mostly associated with the Volca??n Dam on Can??o Manamo. However, human activities have had relatively little effect on the delta processes and environments.

Crew Earth Observations (CEO) taken during Expedition 9

NASA Image and Video Library

2004-06-03

ISS009-E-09985 (3 June 2004) --- The Ebro River Delta, located along the eastern coast of Spain, is featured in this image photographed by an Expedition 9 crewmember on the International Space Station (ISS). Taken in partial sun glint, this view defines the Ebro’s fresh water lens— the water density boundary between the upper layer of fresh water issuing from the Ebro River mouth and the saltier, denser Mediterranean Sea water. According to NASA geologists studying the ISS imagery, diversion and impoundment of the Ebro River upstream has led to a decrease in water and sediment delivery to the delta. This decrease has led to increased erosion in some areas to the northeast of El Fangar Bay and along the southwestern shoreline of the delta. The Ebro River Delta is one of the largest wetland areas in the western Mediterranean region. The Ebro delta has grown rapidly—the historical rate of growth of the delta is demonstrated by the city of Amposta. This city was a seaport in the 4th Century, and is now located well inland from the current Ebro river mouth. The rounded form of the delta attests to the balance between sediment deposition by the Ebro River and removal of this material by wave erosion. The modern delta is in intensive agricultural use for rice, fruit, and vegetables. White polygonal areas to the north and south of the Ebro River are paddy fields. The Ebro delta also hosts numerous beaches, marshes, and saltpans that provide habitat for over 300 species of birds. A large part of the delta was designated as Parc Natural del Delta de l'Ebre (Ebre Delta National Park) in 1983. A network of canals and irrigation ditches constructed by both agricultural and conservation groups are helping to maintain the ecologic and economic resources of the Ebro Delta.

Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex.

PubMed

Castaldo, Pasqualina; Magi, Simona; Gaetani, Silvana; Cassano, Tommaso; Ferraro, Luca; Antonelli, Tiziana; Amoroso, Salvatore; Cuomo, Vincenzo

2007-09-01

Prenatal exposure to the CB1 receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta9-tetrahydrocannabinol (Delta9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born from vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of Vmaxl-[3H]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 receptor agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

PubMed

Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

2015-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

PubMed Central

Kollins, Scott H.; Schoenfelder, Erin N.; English, Joseph S.; Holdaway, Alex; Van Voorhees, Elizabeth; O’Brien, Benjamin R.; Dew, Rachel; Chrisman, Allan K.

2014-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. PMID:25175495

Inadvertent ingestion of marijuana - Los Angeles, California, 2009.

PubMed

2009-09-04

On April 8, 2009, the Los Angeles Police Department (LAPD) notified officials from the Los Angeles County Department of Public Health (DPH) in California about a group of preschool teachers with nausea, dizziness, headache, and numbness and tingling of fingertips after consumption of brownies purchased 3 days before from a sidewalk vendor. To characterize the neurologic symptoms and determine whether these symptoms were associated with ingestion of the brownies, the police and health departments launched a collaborative investigation. This report summarizes the results of that investigation, which detected cannabinoids in a recovered sample of the brownies. Two patients sought medical attention, and one patient's urine and serum tested positive for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THC-COOH), a marijuana metabolite. The findings in this report demonstrate the utility of a collaborative investigation by public health and law enforcement.The findings also underscore the need to consider marijuana as a potential contaminant during foodborne illness investigations and the importance of identifying drug metabolites by testing of clinical specimens soon after symptom onset.

Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers.

PubMed

Kraft, Birgit; Frickey, Nathalie A; Kaufmann, Rainer M; Reif, Marcus; Frey, Richard; Gustorff, Burkhard; Kress, Hans G

2008-07-01

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

Properties of colour reference solutions of the European Pharmacopoea in CIE L*a*b* colour space.

PubMed

Subert, J; Farsa, O; Gajdosová, Z

2006-12-01

The coordinates of CIE L*a*b* uniform colour space have been acquired from the transmitance spectra of colour reference solutions of European Pharmacopoeia (Ph.Eur.). Calculation of colour differences of these solutions from purified water deltaE* gave their values in the range between 0.7 (B9 solution) to 36 (Y1 solution) CIE units. Excluding red colour reference soulutions, deltaE* values did not depend on concentrations of colour compounds linearly. Small deltaE* values founded by the brown and brownish-yellow colour reference solutions of the lowest concentrations can possibly cause some problems of visual examination of the degree of coloration of liquids according to Ph.Eur.

Measuring delta volumetric change and composition using a streakline-based method on the Wax Lake Delta

NASA Astrophysics Data System (ADS)

Hurlbut, K.; Estep, J. D.; Shaw, J.; Edmonds, D. A.

2016-12-01

Estimating river delta growth is essential for determining coastal sustainability. We use a new method to quantify the recent accretion and composition of the Wax Lake Delta, a rapidly prograding delta in Louisiana. The method identifies the area of significant (subaqueous) delta aggradation from delta flow patterns, which are visible in aerial imagery through biogenic streaklines that naturally occur on the water surface. Comparison of bathymetric maps and streaklines shows that channel tips and the associated seaward extent of significant delta deposition occur where the divergence of flow direction equals 0 (+/- 400 m). Delta volumes calculated using this method, the 1974 pre-delta shoreline, and a measured average delta thickness of 1.6 m provide an estimate of the delta volume which we found to increase by 2.0*106 m3/yr between 1992 and 2014. We then compared this rate to the total volume of silt and sand discharged to the WLD using USGS measurements. Over the same period, the WLD received 1.4*106 m3/yr of sand and 9.0*106 m3/yr of silt and clay. Assuming all sand supplied to the delta is sequestered, volume comparisons show that the sand fraction of the WLD is between 18-38%, lower than previous estimates. Further, between 44-69% of the total suspended silt and clay bypasses the delta. These composition estimates can be used to predict land growth from engineered diversions, and the method can be used to monitor the resulting delta growth.

78 FR 24785 - Public Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... hearing will be conducted at the Pennsylvania State Capitol, Room 8E-B, East Wing, Commonwealth Avenue....283 mgd (peak day). 9. Project Sponsor: Delta Borough Municipal Authority. Project Facility: Delta... to 0.073 mgd (30-day average) from Well 5. 10. Project Sponsor: Delta Borough Municipal Authority...

[Distribution characteristics of soil humus fractions stable carbon isotope natural abundance (delta 13C) in paddy field under long-term ridge culture].

PubMed

Tang, Xiao-hong; Luo, You-jin; Ren, Zhen-jiang; Lü, Jia-ke; Wei, Chao-fu

2011-04-01

A 16-year field experiment was conducted in a ridge culture paddy field in the hilly region of Sichuan Basin, aimed to investigate the distribution characteristics of stable carbon isotope natural abundance (delta 13C) in soil humus fractions. The soil organic carbon (SOC) content in the paddy field under different cultivation modes ranked in the order of wide ridge culture > ridge culture > paddy and upland rotation. In soil humus substances (HS), humin (HU) was the main composition, occupying 21% - 30% of the total SOC. In the extracted soil carbon, humic acid (HA) dominated, occupying 17% - 21% of SOC and 38% - 65% of HS. The delta 13C value of SOC ranged from -27.9 per thousand to -25.6 per thousand, and the difference of the delta 13C value between 0-5 cm and 20-40 cm soil layers was about 1.9 per thousand. The delta 13C value of HA under different cultivation modes was 1 per thousand - 2 per thousand lower than that of SOC, and more approached to the delta 13C value of rapeseed and rice residues. As for fulvic acid (FA), its delta 13C value was about 2 per thousand and 4 per thousand higher than that of SOC and HA, respectively. The delta 13C value of HU in plough layer (0-20 cm) and plow layer (20-40 cm) ranged from -23.7 per thousand - -24.9 per thousand and -22.6 per thousand - -24.2 per thousand, respectively, reflecting the admixture of young and old HS. The delta 13C value in various organic carbon fractions was HU>FA>SOC>rapeseed and rice residues>HA. Long-term rice planting benefited the increase of SOC content, and cultivation mode played an important role in affecting the distribution patterns of soil humus delta 13C in plough layer and plow layer.

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

PubMed

Volkow, N D; Gillespie, H; Mullani, N; Tancredi, L; Grant, C; Valentine, A; Hollister, L

1996-05-31

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

Cannabinoids: between neuroprotection and neurotoxicity.

PubMed

Sarne, Yosef; Mechoulam, Raphael

2005-12-01

Cannabinoids, such as the delta9-tetrahydrocannabinol (THC), present in the cannabis plant, as well as anandamide and 2-arachidonoyl glycerol, produced by the mammalian body, have been shown to protect the brain from various insults and to improve several neurodegenerative diseases. The current review summarizes the evidence for cannabinoid neuroprotection in vivo, and refers to recent in vitro studies, which help elucidate possible molecular mechanisms underlying this protective effect. Some of these mechanisms involve the activation of CB1 and CB2 cannabinoid receptors, while others are not dependent on them. In some cases, protection is due to a direct effect of the cannabinoids on neuronal cells, while in others, it results from their effects on non-neuronal elements within the brain. In many experimental set-ups, cannabinoid neurotoxicity, particularly by THC, resides side by side with neuroprotection. The current review attempts to shed light on this dual activity, and to dissociate between the two contradictory effects.

Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

PubMed

Koek, Wouter; Gerak, Lisa R; France, Charles P

2015-08-01

In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks.

Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.

PubMed

Puighermanal, Emma; Marsicano, Giovanni; Busquets-Garcia, Arnau; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

2009-09-01

Cognitive impairment is one of the most important negative consequences associated with cannabis consumption. We found that CB1 cannabinoid receptor (CB1R) activation transiently modulated the mammalian target of rapamycin (mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse hippocampus, which correlated with the amnesic properties of delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated the amnesic-like effects of THC, pointing to a mechanism involving new protein synthesis. Moreover, using pharmacological and genetic tools, we found that THC long-term memory deficits were mediated by CB1Rs expressed on GABAergic interneurons through a glutamatergic mechanism, as both the amnesic-like effects and p70S6K phosphorylation were reduced in GABA-CB1R knockout mice and by NMDA blockade.

Marijuana effects on long-term memory assessment and retrieval.

PubMed

Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

1977-05-09

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

An investigation of the stability of free and glucuronidated 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in authentic urine samples.

PubMed

Skopp, Gisela; Pötsch, Lucia

2004-01-01

Preanalytical stability of a drug and its major metabolites is an important consideration in pharmacokinetic studies or whenever the analyte pattern is used to estimate drug habits. Firstly, the stability of free and glucuronidated 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH, THCCOOglu) in authentic urine samples was investigated. Random urine samples of cannabis users (n = 38) were stored at -20, 4, and 20 degrees C up to 15 days and up to 5 days at 40 degrees C, and alterations of the analyte pattern during storage were followed by liquid chromatography-tandem mass spectrometry. Secondly, the influence of pH (range 5.0-8.0) on the stability of the analytes was studied using spiked urine to elucidate the results obtained from authentic samples. In authentic urine samples, the initial pH ranged from 5.1 to 8.8. The glucuronide was found to be highly labile at a storage temperature of 4 degrees C and above. Initially, 18 urine samples tested positive for THCCOOH. After 2 days storage at 20 degrees C, THCCOOH was detectable in a further 4 samples, and 7 more samples tested positive for THCCOOH (5-81 ng/mL) after 15 days. Depending on time and temperature, the glucuronide concentration decreased, resulting in an increase of THCCOOH concentration. However, a loss in mean total THCCOOH concentration was found, which was significantly higher in deteriorated samples than in samples without signs of deterioration after 15 days of storage at 20 degrees C. In the drug-free urine sample separately spiked with THCCOOglu or THCCOOH, the investigations on the stability of the target analytes at various pH values revealed that THCCOOH was stable at pH 5.0. At higher pH values, its concentration slightly decreased with time, and about 69% of the initial THCCOOH concentration was still present at pH 8.0 on day 5. THCCOOglu concentrations rapidly decreased with increasing pH value. For example, only 72% of the initial THCCOOglu concentration could be detected at pH 5.0 on day 1. Degradation of the glucuronide resulted in formation of THCCOOH, which was observed even at pH 5.0. In light of the present findings, advanced forensic interpretations based on the presence of THCCOOH or the pattern of THCCOOH and THCCOOglu in stored urine samples seems questionable.

Prevalence and Correlates of Alpha-Delta Sleep in Major Depressive Disorders

PubMed Central

Jaimchariyatam, Nattapong; Rodriguez, Carlos L.

2011-01-01

Objective. Major depressive disorder is associated with sleep disturbances. An electroencephalographic pattern of alpha wave intrusion in delta wave sleep (alpha-delta sleep) is observed in some subjects with major depressive disorder. The treatment-resistant symptoms in major depressive disorder, nonrestorative sleep and fatigue, are associated with alpha-delta sleep. The objective of this study is to identify the prevalence and clinical correlates of alpha-delta sleep in major depressive disorder. Design. Retrospective study Setting. Sleep Disorders Center, Cleveland Clinic, Cleveland, Ohio Participants. Polysomnograms were conducted on 150 subjects 18 years of age or older (75 with and 75 without major depressive disorder) were reviewed. Measurements. The percent of delta waves with alpha intrusion was collected and analyzed. Results. Subjects with major depressive disorder compared to nondepressed subjects had a higher sleep efficiency (83.0±9.6; 78.1±8.2%), shorter rapid eye movement latency (85.0±44.5; 189.9±25.6 min), less slow wave sleep (8.3±3.0; 13.5±6.2%), and greater rapid eye movement (24.7±7.0; 19.2±8.2%), and all of these findings were statistically significant. Patients with major depressive disorder had higher alpha-delta sleep (23.4±14.2%; 2.3±6.7%, p<0.01). Patients with major depressive disorder were categorized into high and low alpha-delta sleep based on percentage of alpha-delta sleep present in slow wave sleep (alpha-delta sleep was present ≥15% or ≤15% of slow wave sleep, respectively). Patients with major depressive disorder with high alpha-delta sleep were at 3.15 greater odds (1.22–8.14; p=0.018) to have excessive daytime sleepiness. Conclusion. Patients with major depressive disorder have a higher prevalence of alpha-delta sleep. Alpha-delta sleep is associated with daytime sleepiness in patients with major depressive disorder. Study limitations include the retrospective nature of the project and the fact that the principle investigator, who scored and interpreted alpha intrusion, was not blind to group membership. PMID:21860844

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, R.P.; Ritter, L.

1989-01-01

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of themore » forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.« less

Dronabinol and chronic pain: importance of mechanistic considerations.

PubMed

de Vries, Marjan; van Rijckevorsel, Dagmar C M; Wilder-Smith, Oliver H G; van Goor, Harry

2014-08-01

Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. The pharmacokinetics, pharmacodynamics and mechanisms of action of products with a defined dronabinol content are summarized. Additionally, randomized clinical trials investigating the analgesic efficacy of pharmaceutical cannabis based products are reviewed for the treatment of chronic nonmalignant pain. We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.

Some Phytomonas and Herpetomonas species form unique iso-branched polyunsaturated fatty acids.

PubMed

Fish, W R; Holz, G G; Beach, D H

1982-01-01

Four trypanosomatid flagellates of the genera Phytomonas and Herpetomonas have been found to carry out the de novo biosynthesis of a variety of iso-branched, C18, C20 and C22, polyunsaturated fatty acids, with 2-5 methylene-interrupted double bonds, which have not been described heretofore from natural materials; iso-C18 delta 6,9, iso-C18 delta 9,12, iso-C20 delta 8,11,14, iso-C 20 delta 5,8,11,14, iso-C22 delta 4,7,10,13,16. Identifications were based upon combinations of chromatographic, chemical degradative, mass spectrometric and proton nuclear magnetic resonance spectrometric techniques. Under appropriate culture conditions, 85% of the total fatty acids of the organisms were branched. The subject trypanosomatids are recommended as model organisms with which to investigate influences of the physical properties of phospholipid fatty acyl groups on eukaryotic cell membrane functions.

Psychoactive drugs and false memory: comparison of dextroamphetamine and delta-9-tetrahydrocannabinol on false recognition

PubMed Central

Ballard, Michael E.; Gallo, David A.; de Wit, Harriet

2014-01-01

Rationale Several psychoactive drugs are known to influence episodic memory. However, these drugs’ effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Objectives Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ9-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger–McDermott (DRM) illusion. Methods Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. Results As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs’ effects on true memory were positively correlated with their effects on false memory. Conclusions Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories. PMID:21647577

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users.

PubMed

Keles, Hasan O; Radoman, Milena; Pachas, Gladys N; Evins, A Eden; Gilman, Jodi M

2017-01-01

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task ( n -back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20-50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.

Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract.

PubMed

Nadulski, Thomas; Pragst, Fritz; Weinberg, Gordon; Roser, Patrik; Schnelle, Martin; Fronk, Eva-Maria; Stadelmann, Andreas Michael

2005-12-01

Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentrations of THC, of its metabolites 11-OH-THC, THC-COOH and of CBD in the plasma samples were determined by automatic solid phase extraction, derivatization with N,O-bis(trimethylsilyl)triflouroacetamide and gas chromatography-mass spectrometry. The concentration versus time curves (maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC) were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC-set. Furthermore, the intra-individual ratios of Cmax and AUC for 11-OH-THC/THC, THC-COOH/THC and THC-COOH/11-OH-THC were compared between the THC-set and the CAN-set. Despite the large variation of the data, evidence emerged from the total of the results that CBD partially inhibits the CYP 2C catalyzed hydroxylation of THC to 11-OH-THC. The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at the doses chosen in this study. Significantly higher AUC and Cmax and shorter tmax were found for females as compared with males.

Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence.

PubMed

Colizzi, Marco; McGuire, Philip; Pertwee, Roger G; Bhattacharyya, Sagnik

2016-05-01

Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated with psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission. Here we systematically review all studies examining acute and chronic effects of cannabis or Δ9-THC on glutamate signalling in both animals and man. Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Relation of variant rs180077 of gen cholesterol ester transfer protein variant, with fat mass, HDL-cholesterol in obese subjects with diabetes mellitus type 2].

PubMed

De Luis, Daniel Antonio; Izaola, Olatz; Primo, David; García Calvo, Susana; Gómez Hoyos, Emilia; López Gómez, Juan José; Ortola, Ana; Serrano, Cristina; Delgado, Esther; Torres Torres, Beatriz

2017-11-14

There is few evidence of cholesterol ester transfer protein (CETP) in subjects with obesity and diabetes mellitus. We examined the association of the polymorphism (rs1800777) of CETP gene on anthropometric parameters, lipid profile and adipokines in subjects with obesity and diabetes mellitus type 2. A population of 229 obese subjects with diabetes mellitus type 2 was enrolled. An electrical bioimpedance, blood pressure, dietary intake, exercise and biochemical analyses were recorded. Two hundred and seventeen subjects (94.8%) had genotype GG and 12 GA (5.2%) (genotype AA was not detected). Weight (delta: 14.4 ± 2.1 kg, p = 0.01), body mass index (delta: 2.2 ± 1.1 kg/m2, p = 0.01), fat mass (delta: 11.2 ± 3.1 kg, p = 0.02), waist circumference (delta: 3.9 ± 2.0 cm, p = 0.02), waist to hip ratio (delta: 0.04 ± 0.02 cm; p = 0.01), tryglicerides (delta: 48.6 ± 9.1 mg / dl, p = 0.03) and leptin levels (delta: 58.6 ± 15.9 mg/dl, p = 0.02) were higher in A allele carriers than non A allele carriers. Levels of HDL-cholesterol were lower in A allele carriers than non-carriers (delta: 5.6 ± 1.1 mg/dl, p = 0.03). In regression analysis, HDl cholesterol, weight and fat mass remained in the model with the SNP. Our results show an association of this CETP variant at position +82 on HDL cholesterol, levels and adiposity parameters in obese subjects with diabetes mellitus type 2.

Coal-type gas provinces in China and their geochemical characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Xiaobao; Xu Yonghang; Shen Ping

1996-12-31

The distribution of coal - type gases in China can be divided into the east gas province, the central gas province and the west gas province the east gas province lies in the East China Meso - Cenozoic Rift Belt, including Donghai Basin and Bohaiwan Basin. The ages of gas source rocks are Carbo - Permian and Tertiary. The types of gas reservoirs are a anticline or a hidden mountain - fault block combination reservoir. The CH{sub 4} content ofthe gases there is 83 -90%, with {delta}{sup 13}C{sub 1} -35.5 {approximately} -39.9{per_thousand}, and {delta}{sup 13}C{sub 2} -24.0 {approximately} -26.8{per_thousand}. Themore » {delta}{sup 13}C of condensate oils associated with the gases ranges from -25.4{per_thousand} to -26.8{per_thousand}. The central gas province is inside the Central China Paleozoic Plates, including Orclos Basin and Sichuan Basin. The gas source rocks are Carbo - Permian and Triassic. The types of gas reservoirs are an anticline-fault combination or a lithological-tectonic combination reservoir. The {delta}{sup 13}C{sub 1} of the gases there is -37.9 {approximately} -37. l{per_thousand}, with the {delta}{sup 13}C of condensate oil accompanying them - 25.1 {approximately} -26.6{per_thousand}. The west gas province is within the West China Late Paleozoic Intracontinental Compressive Belt, including Tarim Basin, Jungar Basin and Tuna Basin. The age of gas source rocks is Jurassic. The types of gas reservoirs are an anticline or an anticline-fault reservoir. The CH{sub 4} content of the gases there varies from 60 to 90%, with {delta}{sup 13}C{sub 1} from - 38.7 to -43.7{per_thousand} and {delta} {sup 13}C{sub 2} from -25.9{per_thousand} to -29.9{per_thousand}. The {delta} {sup 13}C of light oils and condensate oils accompanying the gases changes from 24.3{per_thousand} to 27.8{per_thousand}.« less

Coal-type gas provinces in China and their geochemical characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Xiaobao; Xu Yonghang; Shen Ping

1996-01-01

The distribution of coal - type gases in China can be divided into the east gas province, the central gas province and the west gas province the east gas province lies in the East China Meso - Cenozoic Rift Belt, including Donghai Basin and Bohaiwan Basin. The ages of gas source rocks are Carbo - Permian and Tertiary. The types of gas reservoirs are a anticline or a hidden mountain - fault block combination reservoir. The CH[sub 4] content ofthe gases there is 83 -90%, with [delta][sup 13]C[sub 1] -35.5 [approximately] -39.9[per thousand], and [delta][sup 13]C[sub 2] -24.0 [approximately] -26.8[permore » thousand]. The [delta][sup 13]C of condensate oils associated with the gases ranges from -25.4[per thousand] to -26.8[per thousand]. The central gas province is inside the Central China Paleozoic Plates, including Orclos Basin and Sichuan Basin. The gas source rocks are Carbo - Permian and Triassic. The types of gas reservoirs are an anticline-fault combination or a lithological-tectonic combination reservoir. The [delta][sup 13]C[sub 1] of the gases there is -37.9 [approximately] -37. l[per thousand], with the [delta][sup 13]C of condensate oil accompanying them - 25.1 [approximately] -26.6[per thousand]. The west gas province is within the West China Late Paleozoic Intracontinental Compressive Belt, including Tarim Basin, Jungar Basin and Tuna Basin. The age of gas source rocks is Jurassic. The types of gas reservoirs are an anticline or an anticline-fault reservoir. The CH[sub 4] content of the gases there varies from 60 to 90%, with [delta][sup 13]C[sub 1] from - 38.7 to -43.7[per thousand] and [delta] [sup 13]C[sub 2] from -25.9[per thousand] to -29.9[per thousand]. The [delta] [sup 13]C of light oils and condensate oils accompanying the gases changes from 24.3[per thousand] to 27.8[per thousand].« less

St8sia2 deficiency plus juvenile cannabis exposure in mice synergistically affect higher cognition in adulthood.

PubMed

Tantra, Martesa; Kröcher, Tim; Papiol, Sergi; Winkler, Daniela; Röckle, Iris; Jatho, Jasmin; Burkhardt, Hannelore; Ronnenberg, Anja; Gerardy-Schahn, Rita; Ehrenreich, Hannelore; Hildebrandt, Herbert

2014-12-15

The neural cell adhesion molecule (NCAM) and its functionally linked polysialyltransferases, ST8SIA2 and ST8SIA4, are crucial for synaptic plasticity. Variations in encoding genes have been associated with mental illness. Since cannabinoids can alter NCAM polysialylation, we hypothesized that delta-9-tetrahydrocannabinol (Δ9-THC) might act as environmental 'second hit' regarding cognition of St8sia2(-/-) mice. These mice show per se minor behavioral abnormalities, consisting of reduced anxiety and mild cognitive deficits. Chronic Δ9-THC treatment of juvenile male wildtype mice (St8sia2(+/+)) (7mg/kg every other day over 3 weeks) did not appreciably affect cognition. St8sia2(-/-) mice, however, displayed a synergistic negative consequence of Δ9-THC on learning/memory, accompanied by polysialic acid-free NCAM-180 reduction in hippocampus and polysialic acid increase in dentate outer molecular layer. These synergistic effects became obvious only months after the last Δ9-THC. We conclude that juvenile cannabis exposure may cause delayed but lasting damage on cognition in subjects genetically predisposed to altered NCAM polysialylation. Copyright © 2014 Elsevier B.V. All rights reserved.

Dose-related effects of delta-9-THC on emotional responses to acute psychosocial stress.

PubMed

Childs, Emma; Lutz, Joseph A; de Wit, Harriet

2017-08-01

Cannabis smokers often report that they use the drug to relax or to relieve emotional stress. However, few clinical studies have shown evidence of the stress-relieving effects of cannabis or cannabinoid agonists. In this study, we sought to assess the influence of delta-9-tetrahydrocannabinol (THC), a main active ingredient of cannabis, upon emotional responses to an acute psychosocial stressor among healthy young adults. Healthy volunteers (N=42) participated in two experimental sessions, one with psychosocial stress (Trier Social Stress Test, TSST) and another with a non-stressful task, after receiving 0 (N=13), 7.5mg (N=14) or 12.5mg (N=15) oral THC. Capsules were administered under randomized, double blind conditions, 2.5h before the tasks began. We measured subjective mood and drug effects, vital signs and salivary cortisol before and at repeated times after the capsule and tasks. Subjects also appraised the tasks, before and after completion. In comparison to placebo, 7.5mg THC significantly reduced self-reported subjective distress after the TSST and attenuated post-task appraisals of the TSST as threatening and challenging. By contrast, 12.5mg THC increased negative mood overall i.e., both before and throughout the tasks, and pre-task ratings of the TSST as threatening and challenging. It also impaired TSST performance and attenuated blood pressure reactivity to the stressor. Our findings suggest that a low dose of THC produces subjective stress-relieving effects in line with those commonly reported among cannabis users, but that higher doses may non-specifically increase negative mood. Copyright © 2017. Published by Elsevier B.V.

The endocannabinoid system as a target for the treatment of cannabis dependence.

PubMed

Clapper, Jason R; Mangieri, Regina A; Piomelli, Daniele

2009-01-01

The endocannabinoid system modulates neurotransmission at inhibitory and excitatory synapses in brain regions relevant to the regulation of pain, emotion, motivation, and cognition. This signaling system is engaged by the active component of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), which exerts its pharmacological effects by activation of G protein-coupled type-1 (CB1) and type-2 (CB2) cannabinoid receptors. During frequent cannabis use a series of poorly understood neuroplastic changes occur, which lead to the development of dependence. Abstinence in cannabinoid-dependent individuals elicits withdrawal symptoms that promote relapse into drug use, suggesting that pharmacological strategies aimed at alleviating cannabis withdrawal might prevent relapse and reduce dependence. Cannabinoid replacement therapy and CB1 receptor antagonism are two potential treatments for cannabis dependence that are currently under investigation. However, abuse liability and adverse side-effects may limit the scope of each of these approaches. A potential alternative stems from the recognition that (i) frequent cannabis use may cause an adaptive down-regulation of brain endocannabinoid signaling, and (ii) that genetic traits that favor hyperactivity of the endocannabinoid system in humans may decrease susceptibility to cannabis dependence. These findings suggest in turn that pharmacological agents that elevate brain levels of the endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol (2-AG), might alleviate cannabis withdrawal and dependence. One such agent, the fatty-acid amide hydrolase (FAAH) inhibitor URB597, selectively increases anandamide levels in the brain of rodents and primates. Preclinical studies show that URB597 produces analgesic, anxiolytic-like and antidepressant-like effects in rodents, which are not accompanied by overt signs of abuse liability. In this article, we review evidence suggesting that (i) cannabis influences brain endocannabinoid signaling and (ii) FAAH inhibitors such as URB597 might offer a possible therapeutic avenue for the treatment of cannabis withdrawal.

Enhancing the understanding of earthworm feeding behaviour via the use of fatty acid delta13C values determined by gas chromatography-combustion-isotope ratio mass spectrometry.

PubMed

Dungait, Jennifer A J; Briones, Maria J I; Bol, Roland; Evershed, Richard P

2008-06-01

Litter-dwelling (epigeic) Lumbricus rubellus and soil-dwelling (endogeic) Allolobophora chlorotica earthworms were observed aggregating under C(3) (delta(13)C = -31.3 per thousand; delta(15)N = 10.7 per thousand) and C(4) (delta(13)C = -12.6 per thousand; delta(15)N = 7.5 per thousand) synthetic dung pats applied to a temperate grassland (delta(13)C = -30.3 per thousand; delta(15)N = 5.7 per thousand) in an experiment carried out for 372 days. Bulk delta(13)C values of earthworms collected from beneath either C(3) or C(4) dung after 28, 56, 112 and 372 days demonstrated that (i) L. rubellus beneath C(4) dung were significantly (13)C-enriched after 56 days (delta(13)C = -23.8 per thousand) and 112 days (delta(13)C = -22.4 per thousand) compared with those from C(3) dung treatments (56 days, delta(13)C = -26.5 per thousand; 112 days, delta(13)C = -27.0 per thousand), and (ii) A. chlorotica were 2.1 per thousand (13)C-enriched (delta(13)C = -24.2 per thousand) relative to those from C(3) dung (delta(13)C = -26.3 per thousand) treatments after 372 days. Bulk delta(15)N values did not suggest significant uptake of dung N by either species beneath C(3) or C(4) dung, but showed that the endogeic species (total mean delta(15)N = 3.3 per thousand) had higher delta(15)N values than the epigeic species (total mean delta(15)N = 5.4 per thousand). Although the two species exhibited similar fatty acid profiles, individual fatty acid delta(13)C values revealed extensive routing of dietary C into body tissue of L. rubellus, but minor incorporation into A. chlorotica. In particular, the direct incorporation of microbial biomarker fatty acids (iC(17:0), aC(17:0)) from (13)C-labelled dung in situ, the routing of dung C into de novo synthesised compounds (iC(20:4)(omega)(6),C(20:5)(omega)(3), and the assimilation of essential fatty acids ((C(18:1)(omega)(9), C(18:1)(omega(7), C(18:2)(omega(6), C(18:3)(omega)(3)) derived from dung, were determined. John Wiley & Sons, Ltd

Comparative study of sex pheromone composition and biosynthesis in Helicoverpa armigera, H. assulta and their hybrid.

PubMed

Wang, Hong-Lei; Zhao, Cheng-Hua; Wang, Chen-Zhu

2005-06-01

Two Helicoverpa species, H. armigera and H. assulta use (Z)-11-hexadecenal and (Z)-9-hexadecenal as their sex attractant pheromone components but in opposite ratios. Since both female and male interspecific hybrids produced by female H. assulta and male H. armigera have been obtained in our laboratory, we can make a comparative study of sex pheromone composition and biosynthesis in the two species and their hybrid. With GC and GC-MS analyses using single gland extracts, the ratio of (Z)-9-hexadecenal to (Z)-11-hexadecenal was determined as 2.1:100 in H. armigera, and 1739:100 in H. assulta. The hybrid has a ratio of 4.0: 100, which is closer to that of H. armigera, but significantly different from H. armigera. We investigated pheromone biosynthesis with labeling experiments, using various fatty acid precursors in H. armigera, H. assulta and the hybrid. In H. armigera, (Z)-11-hexadecenal is produced by delta11 desaturation of palmitic acid, followed by reduction and terminal oxidation; (Z)-9-hexadecenal results from delta11 desaturation of stearic acid, followed by one cycle of chain shortening, reduction and terminal oxidation. delta11 desaturase is the unique desaturase for the production of the two pheromone components. In our Chinese strain of H. assulta, palmitic acid is used as the substrate to form both the major pheromone component, (Z)-9-hexadecenal and the minor one, (Z)-11-hexadecenal. Our data suggest that delta9 desaturase is the major desaturase, and delta11 desaturase is responsible for the minor component in H. assulta, which is consistent with previous work. However, the weak chain shortening acting on (Z)-9 and (Z)-11-octadecenoic acid, which is present in the pheromone glands, does occur in this species to produce (Z)-7 and (Z)-9-hexadecenoic acid. In the hybrid, the major pheromone component, (Z)-11-hexadecenal is produced by delta11 desaturation of palmitic acid, followed by reduction and terminal oxidation. The direct fatty acid precursor of the minor component, (Z)-9-hexadecenoic acid is mainly produced by delta9 desaturation of palmitic acid, but also by delta11 desaturation of stearic acid and one cycle of chain shortening. The greater relative amounts of (Z)-9-hexadecenal in the hybrid are due to the fact that both palmitic and stearic acids are used as substrates, whereas only stearic acid is used as substrate in H. armigera. The evolutionary relationships between the desaturases in several Helicoverpa species are also discussed in this paper.

EMG and oxygen uptake responses during slow and fast ramp exercise in humans.

PubMed

Scheuermann, Barry W; Tripse McConnell, Joyce H; Barstow, Thomas J

2002-01-01

This study examined the relationship between muscle recruitment patterns using surface electromyography (EMG) and the excess O(2) uptake (Ex.V(O(2))) that accompanies slow (SR, 8 W min(-1)) but not fast (FR, 64 W min(-1)) ramp increases in work rate (WR) during exercise on a cycle ergometer. Nine subjects (2 females) participated in this study (25 +/- 2 years, +/- S.E.M.). EMG was obtained from the vastus lateralis and medialis and analysed in the time (root mean square, RMS) and frequency (median power frequency, MDPF) domain. Results for each muscle were averaged to provide an overall response and expressed relative to a maximal voluntary contraction (%MVC). Delta.V(O(2))/DeltaWR was calculated for exercise below (S(1)) and above (S(2)) the lactate threshold (LT) using linear regression. The increase in RMS relative to the increase in WR for exercise below the LT (DeltaRMS/DeltaWR-S(1)) was determined using linear regression. Due to non-linearities in RMS above the LT, DeltaRMS/DeltaWR-S(2) is reported as the difference in RMS (DeltaRMS) and the difference in WR (DeltaWR) at end-exercise and the LT. SR was associated with a higher (P < 0.05) Delta.V(O(2))/DeltaWR (S(1), 9.3 +/- 0.3 ml min(-1) W(-1); S(2), 12.5 +/- 0.6 ml min(-1) W(-1)) than FR (S(1), 8.5 +/- 0.4 ml min(-1) W(-1); S(2), 7.9 +/- 0.4 ml min(-1) W(-1)) but a similar DeltaRMS/DeltaWR-S(1) (SR, 0.11 +/- 0.01% W(-1); FR, 0.10 +/- 0.01 % W(-1)). Ex.V(O(2)) was greater (P < 0.05) in SR (3.6 +/- 0.7 l) than FR (-0.7 +/- 0.4 l) but was not associated with a difference in either DeltaRMS/DeltaWR-S(2) (SR, 0.14 +/- 0.01% W(-1); FR, 15 +/- 0.02 % W(-1)) or MDPF (SR, 2.6 +/- 5.9 %; FR, -15.4 +/- 4.5 %). The close matching between power output and RMS during SR and FR suggests that the Ex.V(O(2)) of heavy exercise is not associated with the recruitment of additional motor units since Ex.V(O(2)) was observed during SR only. Compared to the progressive decrease in MDPF observed during FR, the MDPF remained relatively constant during SR suggesting that either (i) there was no appreciable recruitment of the less efficient type II muscle fibres, at least in addition to those recruited initially at the onset of exercise, or (ii) the decrease in MDPF associated with fatigue was offset by the addition of a higher frequency of type II fibres recruited to replace the fatigued motor units.

Bimetallo-radical carbon-hydrogen bond activation of methanol and methane.

PubMed

Cui, Weihong; Zhang, X Peter; Wayland, Bradford B

2003-04-30

Carbon-hydrogen bond cleavage reactions of CH3OH and CH4 by a dirhodium(II) diporphyrin complex with a m-xylyl tether (.Rh(m-xylyl)Rh.(1)) are reported. Kinetic-mechanistic studies show that the substrate reactions are bimolecular and occur through the use of two Rh(II) centers in the molecular unit of 1. Second-order rate constants (T = 296 K) for the reactions of 1 with methanol (k(CH3OH) = 1.45 x 10-2 M-1 s-1) and methane (k(CH4) = 0.105 M-1 s-1) show a clear kinetic preference for the methane activation process. The methanol and methane reactions with 1 have large kinetic isotope effects (k(CH3OH)/k(CD3OD) = 9.7 +/- 0.8, k(CH4)/k(CD4) = 10.8 +/- 1.0, T = 296 K), consistent with a rate-limiting step of C-H bond homolysis through a linear transition state. Activation parameters for reaction of 1 with methanol (DeltaH = 15.6 +/- 1.0 kcal mol-1; DeltaS = -14 +/- 5 cal K-1 mol-1) and methane (DeltaH = 9.8 +/- 0.5 kcal mol-1; DeltaS = -30 +/- 3 cal K-1 mol-1) are reported.

The Natural Diyne-Furan Fatty Acid EV-086 Is an Inhibitor of Fungal Delta-9 Fatty Acid Desaturation with Efficacy in a Model of Skin Dermatophytosis

PubMed Central

Diefenbacher, Melanie; Greve, Katrine B. V.; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A.; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A.; Schneiter, Roger; Sorensen, Alexandra S.

2014-01-01

Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids—but not saturated fatty acids—antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086–phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses. PMID:24189258

The natural diyne-furan fatty acid EV-086 is an inhibitor of fungal delta-9 fatty acid desaturation with efficacy in a model of skin dermatophytosis.

PubMed

Knechtle, Philipp; Diefenbacher, Melanie; Greve, Katrine B V; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A; Schneiter, Roger; Sorensen, Alexandra S

2014-01-01

Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids-but not saturated fatty acids-antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086-phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

The formation of weathering products on the LEW 85320 ordinary chondrite - Evidence from carbon and oxygen stable isotope compositions and implications for carbonates in SNC meteorites

NASA Technical Reports Server (NTRS)

Grady, Monica M.; Wright, I. P.; Pillinger, C. T.; Gibson, E. K., Jr.

1989-01-01

Isotopic analysis of nesquehonite recovered from the surface of the LEW 85320 H5 ordinary chondrite shows that the delta C-13 and delta O-18 values of the two generations of bicarbonate (Antarctic and Texas) are different: delta C-13 = + 7.9 per mil and + 4.2 per mil; delta O-18 = + 17.9 per mil and + 12.1 per mil, respectively. Carbon isotopic compositions are consistent with equilibrium formation from atmospheric carbon dioxide at - 2 + or - 4 C (Antarctic) and + 16 + or - 4 C (Texas). Oxygen isotopic data imply that the water required for nesquehonite precipitation was derived from atmospheric water vapor or glacial meltwater which had locally exchanged with silicates, either in the meteorite or in underlying bedrock. Although carbonates with similar delta C-13 values have been identified in the SNC meteorites EETA 79001 and Nakhla, petrographic and temperature constraints argue against their simply being terrestrial weathering products.

Authenticity assessment of gamma- and delta-decalactone from prunus fruits by gas chromatography combustion/pyrolysis isotope ratio mass spectrometry (GC-C/P-IRMS).

PubMed

Tamura, Hirotoshi; Appel, Markus; Richling, Elke; Schreier, Peter

2005-06-29

Authenticity assessment of gamma-decalactone (1) and delta-decalactone (2) from peach (Prunus persica var. persica), apricot (Prunus armeniaca), and nectarine (Prunus persica var. nectarina) was performed using gas chromatography-isotope ratio mass spectrometry (GC-IRMS) in the combustion (C) and pyrolysis (P) mode. In addition, commercially available synthetic (nature-identical) 1 and 2 as well as biotechnologically produced samples (declared to be "natural") were characterized by their delta(2)H(V)(-)(SMOW) and delta(13)C(V)(-)(PDB) values. For the Prunus fruits under study, rather narrow ranges of delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data of 1, varying from - 34.6 per thousand to - 38.4 per thousand and -160 per thousand to -206 per thousand, respectively, were obtained. Synthetic references of 1 showed delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data ranging from -27.4 per thousand to -28.3 per thousand and -151 per thousand to -184 per thousand, respectively. Samples of 1 declared to be "natural" exhibited ranges from -28.1 per thousand to -29.2 per thousand and -192 per thousand to -286 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. For 2 from peach, apricot, and nectarine, delta(13)C(V)(-)(PDB) values ranging from -34.0 per thousand to -37.9 per thousand were determined; the delta(2)H(V)(-)(SMOW) values ranged from -171 per thousand to -228 per thousand. The delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data for synthetic 2 were -28.2 per thousand and -171 per thousand, respectively, that is, similar to those of 2 from "natural" origin, ranging from -27.7 per thousand to -30.1 per thousand and -185 per thousand to -230 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. GC-C/P-IRMS allowed clear-cut analytical differentiation of the synthetic and "ex-plant" origin of 1 and 2, whereas narrow ranges of delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data were found for samples of synthetic and "natural" origin.

Memory impairment in transgenic Alzheimer mice requires cellular prion protein.

PubMed

Gimbel, David A; Nygaard, Haakon B; Coffey, Erin E; Gunther, Erik C; Laurén, Juha; Gimbel, Zachary A; Strittmatter, Stephen M

2010-05-05

Soluble oligomers of the amyloid-beta (Abeta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). Recently, we reported that synthetic Abeta oligomers bind to cellular prion protein (PrP(C)) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric Abeta peptide. We hypothesized that PrP(C) is essential for the ability of brain-derived Abeta to suppress cognitive function. Here, we crossed familial AD transgenes encoding APPswe and PSen1DeltaE9 into Prnp-/- mice to examine the necessity of PrP(C) for AD-related phenotypes. Neither APP expression nor Abeta level is altered by PrP(C) absence in this transgenic AD model, and astrogliosis is unchanged. However, deletion of PrP(C) expression rescues 5-HT axonal degeneration, loss of synaptic markers, and early death in APPswe/PSen1DeltaE9 transgenic mice. The AD transgenic mice with intact PrP(C) expression exhibit deficits in spatial learning and memory. Mice lacking PrP(C), but containing Abeta plaque derived from APPswe/PSen1DeltaE9 transgenes, show no detectable impairment of spatial learning and memory. Thus, deletion of PrP(C) expression dissociates Abeta accumulation from behavioral impairment in these AD mice, with the cognitive deficits selectively requiring PrP(C).

Comparison between self-report of cannabis use and toxicological detection of THC/THCCOOH in blood and THC in oral fluid in drivers in a roadside survey.

PubMed

Van der Linden, Trudy; Silverans, Peter; Verstraete, Alain G

2014-01-01

The objective of this study was to compare the number of drivers who self-reported cannabis use by questionnaires to the results of toxicological analysis. During roadside surveys, 2957 respondents driving a personal car or van completed a questionnaire to report their use of drugs and medicines during the previous two weeks and to indicate the time of their last intake. Cannabis was analyzed in oral fluid by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), in blood by gas chromatography-mass spectrometry (GC-MS). Frequencies in the time categories were calculated and compared with toxicological results. Diagnostic values were calculated for the time categories in which positive findings were to be expected (<4 h and <2 4h, respectively for tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinol (THCCOOH) in blood, <12 h for THC in oral fluid). Most self-reported cannabis use was more than 12 h before driving. The sensitivity of the questionnaire was low, while the specificity and accuracy were high. Kappa statistics revealed a fair agreement between self-report and positive findings for THC in oral fluid and blood and moderate agreement with THCCOOH in blood. Self-report largely underestimates driving under the influence of cannabis, particularly recent cannabis use; therefore analysis of biological samples is necessary. Copyright © 2013 John Wiley & Sons, Ltd.

Holocene Flexural Deformation over the Nile Delta: Evidence from Radar Interferometry

NASA Astrophysics Data System (ADS)

Gebremichael, E.; Sultan, M.; Becker, R.

2017-12-01

Isostatic adjustment and subsequent subsidence and uplift due to sediment and water loading and unloading mechanisms is one of the major factors that produce regional deformational patterns across river deltas. Using 84 Envisat ASAR scenes that were acquired (2004 - 2010) along three tracks and applying Persistent scatterer (PS) radar interferometric techniques, we documented flexural deformational patterns over the entire Nile Delta (length: 186 km; width: 240 km) of Egypt. The passive continental margin of Africa subsided from Jurassic time onwards due to isostatic loading creating an accommodation space and consequently, the deposition of relatively younger sediments on the oceanic crust. In river deltas, the flexural isostasy model dictates that a subsidence in the oceanic crust side should be balanced by a bulge (uplift) in the flanking regions. Using radar interferometry, we were able to identify the flexural deformation pattern and map its spatial extent over the northern and central Nile Delta region. Findings include: (1) the northern Nile Delta region (block) is separated from the southern delta region by an east-west trending, extensively faulted, hinge line that signifies the boundary between two deformational patterns (subsidence and uplift). It separates the highly subsiding (up to 9.8 mm/yr) northern delta block (up to 85 km long) from the nearly stable (0.4 mm/yr; averaged) southern delta block (up to 91 km long). The hinge line marks the end of the passive continental margin of Africa and the beginning of the oceanic crust of the Mediterranean. (2) We mapped the extent of a 20-40 km wide flexural uplift zone to the south of the hinge line. Within the flexural uplift zone (2.5 mm/yr; averaged), there is a gradual increase in uplift rate reaching peak value (up to 7 mm/yr) near the midpoint of the zone. (3) The uplift rate gradually decreases south of the flexure boundary reaching 0.3 mm/yr at the southern periphery of the delta. (4) The flexural deformation pattern is interrupted (replaced by subsidence) in some areas due to local deformation caused by high groundwater extraction rates in western (6 mm/yr) and gas extraction in north central delta (9 mm/yr).

Trophodynamic linkage between river runoff and coastal fishery yield elucidated by stable isotope data in the Gulf of Lions (NW Mediterranean).

PubMed

Darnaude, Audrey M; Salen-Picard, Chantal; Polunin, Nicholas V C; Harmelin-Vivien, Mireille L

2004-02-01

The link between climate-driven river runoff and sole fishery yields observed in the Gulf of Lions (NW Mediterranean) was analysed using carbon- and nitrogen stable isotopes along the flatfish food webs. Off the Rhone River, the main terrestrial (river POM) and marine (seawater POM) sources of carbon differed in delta(13)C (-26.11 per thousand and -22.36 per thousand, respectively). Surface sediment and suspended POM in plume water exhibited low delta(13)C (-24.38 per thousand and -24.70 per thousand, respectively) that differed more from the seawater POM than from river POM, demonstrating the dominance of terrestrial material in those carbon pools. Benthic invertebrates showed a wide range in delta(15)N (mean 4.30 per thousand to 9.77 per thousand ) and delta(13)C (mean -23.81 per thousand to -18.47 per thousand ), suggesting different trophic levels, diets and organic sources. Among the macroinvertebrates, the surface (mean delta(13)C -23.71 per thousand ) and subsurface (mean delta(13)C -23.81 per thousand ) deposit-feeding polychaetes were particularly (13)C depleted, indicating that their carbon was mainly derived from terrestrial material. In flatfish, delta(15)N (mean 9.42 to 10.93 per thousand ) and delta(13)C (mean -19.95 per thousand to -17.69 per thousand ) varied among species, indicating differences in food source and terrestrial POM use. A significant negative correlation was observed between the percentage by weight of polychaetes in the diet and the delta(13)C of flatfish white muscle. Solea solea (the main polychaete feeder) had the lowest mean delta(13)C, Arnoglossus laterna and Buglossidium luteum (crustacean, mollusc and polychaete feeders) had intermediate values, and Solea impar (mollusc feeder) and Citharus linguatula (crustacean and fish feeder) exhibited the highest delta(13)C. Two different benthic food webs were thus identified off the Rhone River, one based on marine planktonic carbon and the other on the terrestrial POM carried by the river. Deposit-feeding polychaetes were responsible for the main transfer of terrestrial POM to upper trophic levels, linking sole population dynamics to river runoff fluctuations.

Acute systemic and renal hemodynamic effects of meglumine/sodium diatrizoate 76% and iopamidol in euvolemic and dehydrated dogs.

PubMed

Katzberg, R W; Morris, T W; Lasser, E C; DiMarco, P L; Merguerian, P A; Ventura, J A; Pabico, R C; McKenna, B A

1986-10-01

We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.

The Undiscovered Country: How Many Low-Delta-V Near-Earth Objects Remain to be Found?

NASA Astrophysics Data System (ADS)

Elvis, Martin; Ranjan, Sukrit; Galache, Jose Luis

2014-11-01

Low delta-v near-Earth objects (NEOs) are of great interest as targets for science and human missions, for possible retrieval to cis-lunar space and as potential resource targets for both exploration and commercial uses. This interest stems from the exponential nature of the rocket equation that imposes a harsh mass penalty on any mission to a higher delta-v. We have compared the known NEO population from the IAU Minor Planet Center (MPC) with the NEOSSat-1 model residence times for the NEO population (Greenstreet & Gladman, 2012) to assess how many undiscovered NEOs there are as a function of H magnitude and delta-v. We find that the median of known NEOs is at lower delta-v (7.3 km/s) than the model population (9.8 km/s), suggesting a bias toward detecting lower delta-v NEOs. To the precision of our data, which is as low as 40% for the 300-500 m diameter (D) objects, the bulk of the larger D>300 m NEOs have been found from delta-v<10.3 km/s. However in the 50 < D < 300 m range there are tens of thousands of delta-v < 10.3 km/s to be found. We examine the total number of undiscovered NEOs as a function of delta-v and find that to find at least 100 now unknown NEOs requires a threshold delta-v of 5.7 km/s, while to find at least 1000 of them requires a threshold delta-v of 6.2 km/s. These numbers can be used to determine mission delta-v requirements for a given number of suitable targets, that will likely be restricted by other criteria (size, composition, spin state) to a few percent of the total population.

Temperature and vital effect controls on Bamboo coral (Isididae) isotopegeochemistry: A test of the "lines method"

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, T M; Spero, H J; Guilderson, T P

Deep-sea bamboo corals hold promise as long-term climatic archives, yet little information exists linking bamboo coral geochemistry to measured environmental parameters. This study focuses on a suite of 10 bamboo corals collected from the Pacific and Atlantic basins (250-2136 m water depth) to investigate coral longevity, growth rates, and isotopic signatures. Calcite samples for stable isotopes and radiocarbon were collected from the base the corals, where the entire history of growth is recorded. In three of the coral specimens, samples were also taken from an upper branch for comparison. Radiocarbon and growth band width analyses indicate that the skeletal calcitemore » precipitates from ambient dissolved inorganic carbon and that the corals live for 150-300 years, with extension rates of 9-128 {micro}m/yr. A linear relationship between coral calcite {delta}{sup 18}O and {delta}{sup 13}C indicates that the isotopic composition is influenced by vital effects ({delta}{sup 18}O:{delta}{sup 13}C slope of 0.17-0.47). As with scleractinian deep-sea corals, the intercept from a linear regression of {delta}{sup 18}O versus {delta}{sup 13}C is a function of temperature, such that a reliable paleotemperature proxy can be obtained, using the 'lines method.' Although the coral calcite {delta}{sup 18}O:{delta}{sup 13}C slope is maintained throughout the coral base ontogeny, the branches and central cores of the bases exhibit {delta}{sup 18}O:{delta}{sup 13}C values that are shifted far from equilibrium. We find that a reliable intercept value can be derived from the {delta}{sup 18}O:{delta}{sup 13}C regression of multiple samples distributed throughout one specimen or from multiple samples within individual growth bands.« less

Isotopic compositions and sources of nitrate in ground water from western Salt River Valley, Arizona

USGS Publications Warehouse

Gellenbeck, D.J.

1994-01-01

Isotopic and chemical compositions of ground water from western Salt River Valley near Phoenix, Arizona, were used to develop identification tech- niques for sources of nitrate in ground water. Four possible sources of nitrate were studied: dairies and feedlots, sewage-treatment plants, agricultural activities, and natural source. End members that represent these sources were analyzed for a variety of chemical and isotopic constituents; contents of the end-member and the ground water were compared to identify nitrate from these sources. Nitrate from dairies and feedlots was identified by delta 15N values higher than +9.0 per mil. Nitrate from sewage treatment plants was identified by some chemical constituents and values of delta 15N, delta 34S, delta 7Li, and delta 11B that were lighter than the values determined for ground water not affected by sewage-treatment plants. Nitrate from agricultural activities was identified by delta 15N, 3H, and delta 34S compositions. Natural nitrate derived from decomposing plants and accumulated by biological fixation was identified by delta 15N values that range between +2 and +8 per mil. In addition to identifying nitrate sources, some chemical and isotopic charabteristics of ground water were determined on the basis of data collected during this study. Concentrations of major ions, lithium, and boron and delta 7Li, delta 11B, 3H, delta D, and delta 18O data identify ground water in different geographic regions in the study area. These differences probably are related to different sources of ground water, geochemical processes, or geologic deposits. The Luke salt body and a geothermal anomaly alter the chemical and isotopic content of some ground water.

Studies on long chain cis- and trans-acyl-CoA esters and Acyl-CoA dehydrogenase from rat heart mitochondria.

PubMed

Korsrud, G O; Conacher, H B; Jarvis, G A; Beare-Rogers, J L

1977-02-01

The beta-oxidation of long chain fatty acids was investigated in a preparation of rat heart mitochondria. The acyl-CoA esters of the cis and trans isomers of delta9-hexadecenoic, delta9-octadecenoic, delta11-eicosenoic, and delta13-docosenoic acids were prepared. Rates of the acyl-CoA reaction were determined with an extract from rat heart mitochondria. The apparent Michaelis constant (Km) and maximum velocity (Vmax) were calculated for each substrate. In general, apparent Vmax values decreased with increasing chain length of the monoenoic substrates. Reduced activity of acyl-CoA dehydrogenase with long chain acyl-CoA esters could have contributed to accumulation of lipids in hearts of rats fed diets containing long chain fatty acids.

Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.

PubMed

Kogan, Natalya M; Rabinowitz, Ruth; Levi, Paloma; Gibson, Dan; Sandor, Peter; Schlesinger, Michael; Mechoulam, Raphael

2004-07-15

Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.

Chemistry, metabolism, and toxicology of cannabis: clinical implications.

PubMed

Sharma, Priyamvada; Murthy, Pratima; Bharath, M M Srinivas

2012-01-01

Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵(9_)THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.

Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications

PubMed Central

Murthy, Pratima; Bharath, M.M. Srinivas

2012-01-01

Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵9_THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders. Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects. Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use. In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis. PMID:23408483

Geomorphology of the Chippewa River delta of Glacial Lake Saginaw, central Lower Michigan, USA

NASA Astrophysics Data System (ADS)

Connallon, Christopher B.; Schaetzl, Randall J.

2017-08-01

We introduce, characterize, and interpret the geomorphic history of a relict, Pleistocene-aged delta of the Chippewa River in central Lower Michigan. The broad, sandy Chippewa delta developed into various stages of Glacial Lake Saginaw, between ca. ≈ 17 and 15 ka·BP (calibrated ages). Although the delta was first identified in 1955 on a statewide glacial geology map, neither its extent nor its Pleistocene history had been previously determined. The delta is typically forested, owing to its wet, sandy soils, which stand out against the agricultural fields of the surrounding, loamy lake plain sediments. The delta heads near the city of Mt Pleasant and extends eastward onto the Saginaw Lowlands, i.e., the plain of Glacial Lake Saginaw. Data from 3285 water well logs, 180 hand augered sites, and 185 points randomly located in a GIS on two-storied (sand over loam) soils were used to determine the extent, textural properties, and thickness of the delta. The delta is ≈ 18 km wide and ≈ 38 km long and is sandy throughout. Deltaic sediments from neighboring rivers that also drained into Glacial Lake Saginaw merge with the lower Chippewa delta, obscuring its boundary there. The delta is thickest near the delta's head and in the center, but thins to 1-2 m or less on its eastern margins. Mean thicknesses are 2.3-2.9 m, suggestive of a thin sediment body, frequently impacted by the waves and fluctuating waters of the lakes. Although beach ridges are only weakly expressed across the delta because of the sandy sediment, the coarsest parts of the delta are generally coincident with some of these inferred former shorezones and have a broad, incised channel that formed while lake levels were low. The thick upper delta generally lies above the relict shorelines of Glacial Lakes Saginaw and Arkona (≈ 17.1 to ≈ 16 ka·BP), whereas most of the thin, distal delta is associated with Glacial Lake Warren (≈ 15 ka·BP). Together, these data suggest that the Chippewa delta formed and prograded as lake levels in the Saginaw Lowlands alternated and episodically fell. The result is a delta that is comparatively thin, expansive, and sandy. In some places, these sands have subsequently been reworked into fields of small parabolic dunes.

Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.

PubMed

Römer, W; Oettel, M; Menzenbach, B; Droescher, P; Schwarz, S

1997-11-01

Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.

Pheromone biosynthetic pathways in the moths Heliothis subflexa and Heliothis virescens.

PubMed

Choi, Man-Yeon; Groot, Astrid; Jurenka, Russell A

2005-06-01

Sex pheromones of many moth species have relatively simple structures consisting of a hydrocarbon chain with a functional group and one to several double bonds. These sex pheromones are derived from fatty acids through specific biosynthetic pathways. We investigated the incorporation of deuterium-labeled tetradecanoic, hexadecanoic, and octadecanoic acid precursors into pheromone components of Heliothis subflexa and Heliothis virescens. The two species utilize (Z)11-hexadecenal as the major pheromone component, which is produced by Delta11 desaturation of hexadecanoic acid. H. subflexa also produced (Z)11-hexadecanol and (Z)-11-hexadecenyl acetate via Delta11 desaturation. In H. subflexa, octadecanoic acid was used to biosynthesize the minor pheromone components (Z)9-hexadecenal, (Z)9-hexadecenol, and (Z)9-hexadecenyl acetate. These minor components are produced by Delta11 desaturation of octadecanoic acid followed by one round of chain-shortening. In contrast, H. virescens used hexadecanoic acid as a substrate to form (Z)11-hexadecenal and (Z)11-hexadecenol and hexadecenal. H. virescens also produced (Z)9-tetradecenal by Delta11 desaturation of the hexadecanoic acid followed by one round of chain-shortening and reduction. Tetradecanoic acid was not utilized as a precursor to form Z9-14:Ald in H. virescens. This labeling pattern indicates that the Delta11 desaturase is the only active desaturase present in the pheromone gland cells of both species.

Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.

PubMed

Whitescarver, S A; Roberts, A M; Stremel, R W; Jimenez, A E; Passmore, J C

1991-02-01

Smoking exacerbates the increase in arterial pressure in hypertension. The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid infiltration of the Tudor Gabbro during regional metamorphism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunn, S.R.; Valley, J.W.

1985-01-01

The Tudor Gabbro (TG), an ovate body (4 x 9 km) 40 km SE of Bancroft. Ontario, was metamorphosed to upper greenschist facies along with surrounding sediments and volcanics. Allen (1976) delineated concentric isograds around the gabbro, including +sphene, +tremolite (to 1.5 km), +tremolite + clinozoisite, +diopside (approx. 120 m), and +garnet (approx. 80 m). Metamorphic conditions are inferred to be 490+/-50/sup 0/C, 5 kb with no thermal gradient. Allen suggested that H/sub 2/O infiltration of the marble and calc-schist accounts for the isograds. The gabbro mineralogy of titanaugite, andesine to labradorite, and minor hornblende is extensively recrystallized to albitemore » and/or oligoclase + actinolite + epidote + ilmenite + calcite (up to 4 wt%) +/- biotite +/- chlorite +/- sphene +/- scapolite. Isotopic analyses of calcite from 39 TG samples show delta/sup 18/O = 9.4 to 16.6 and delta/sup 13/C = -1.9 to 3.4. Bulk silicate delta/sup 18/O of TG range from 7.1 to 10.2. Calcites in metasediment have delta/sup 18/O = 18.1 to 25.3 and delta/sup 13/C = 1.3 to 5.6. Two whole rock silicate analyses of a skarn developed locally at the contact show intermediate delta/sup 18/O of 16.2 and 17.3. The stability of Czo component in epidote requires H/sub 2/O-rich fluids. The delta/sup 13/C of TG calcites average +0.7 nearly identical to the average of 178 carbonates from Grenville marbles (+1.0), showing that metasediment-derived CO/sub 2/ pervasively infiltrated the TG. The infiltration of H/sub 2/O into both the TG and the metasediment suggests that H/sub 2/O-rich fluids migrated upward along the contact.« less

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD.

PubMed

Ambach, Lars; Penitschka, Franziska; Broillet, Alain; König, Stefan; Weinmann, Wolfgang; Bernhard, Werner

2014-10-01

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN). Copyright © 2014. Published by Elsevier Ireland Ltd.

On-line gas chromatography combustion/pyrolysis isotope ratio mass spectrometry (HRGC-C/P-IRMS) of pineapple (Ananas comosus L. Merr.) volatiles.

PubMed

Preston, Christina; Richling, Elke; Elss, Sandra; Appel, Markus; Heckel, Frank; Hartlieb, Ariane; Schreier, Peter

2003-12-31

By use of extracts prepared by liquid-liquid separation of the volatiles from self-prepared juices of pineapple fruits (Ananas comosus) (n = 14) as well as commercial pineapple recovery aromas/water phases (n = 3), on-line capillary gas chromatography-isotope ratio mass spectrometry was employed in the combustion (C) and the pyrolysis (P) modes (HRGC-C/P-IRMS) to determine the delta(13)C(VPDB) and delta(2)H(VSMOW) values of selected pineapple flavor constituents. In addition to methyl 2-methylbutanoate 1, ethyl 2-methylbutanoate 2, methyl hexanoate 3, ethyl hexanoate 4, and 2,5-dimethyl-4-methoxy-3[2H]-furanone 5, each originating from the fruit, the delta(13)C(VPDB) and delta(2)H(VSMOW) data of commercial synthetic 1-5 and "natural" (biotechnologically derived) 1-4 were determined. With delta(13)C(VPDB) data of pineapple volatiles 1-4 varying from -12.8 to -24.4 per thousand, the range expected for CAM metabolism was observed. Compound 5 showed higher depletion from -20.9 to -28.6 per thousand. A similar situation was given for the delta(2)H(VSMOW) values of 3-5 from pineapple ranging from -118 to -191 per thousand, whereas 1 and 2 showed higher depleted values from -184 to -263 per thousand. In nearly all cases, analytical differentiation of 1-5 from pineapple and natural as well as synthetic origin was possible. In general, natural and synthetic 1-5 exhibited delta(13)C(VPDB) data ranging from -11.8 to -32.2 per thousand and -22.7 to -35.9 per thousand, respectively. Their delta(2)H(VSMOW) data were in the range from -242 to -323 per thousand and -49 to -163 per thousand, respectively.

Cannabis, Cannabinoids, and Sleep: a Review of the Literature.

PubMed

Babson, Kimberly A; Sottile, James; Morabito, Danielle

2017-04-01

The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication. Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.

Neuroprotective antioxidants from marijuana.

PubMed

Hampson, A J; Grimaldi, M; Lolic, M; Wink, D; Rosenthal, R; Axelrod, J

2000-01-01

Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.

Collaborating with Alexander Scriabine and the Miles Institute for Preclinical Pharmacology.

PubMed

Janis, Ronald A

2015-11-15

This article represents a timely opportunity to express my affection, admiration and gratitude to Professor David Triggle. David was my Ph.D. advisor as well as a key consultant in the 1980s and early 1990s for research programs at Miles Institute for Preclinical Pharmacology in West Haven, CT, the U.S. research operation of Bayer AG, in the areas of Ca(2+) and K(+) channel ligands. The binding methodology developed in his laboratory was used to search for an endogenous ligand for L-type Ca(2+) channels. We did not find the substance that we were searching for, a genetically-determined, competitive inhibitor for the 1,4-dihydropyridine binding site, but instead isolated the endogenous ligand for the brain's own marijuana, anandamide. Devane, Mechoulam and coworkers first discovered that this compound was the endogenous ligand for delta-9-tetrahydrocannabinol, the active substance in cannabis. The endogenous endocannabinoid system is now the target of many exciting new approaches to drug discovery. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

PubMed

Kasten, Chelsea R; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L

2018-05-01

Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.

Combined cannabinoid therapy via an oromucosal spray.

PubMed

Perez, Jordi

2006-08-01

Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana.

PubMed

Weinstein, Aviv; Brickner, Orit; Lerman, Hedva; Greemland, Mazal; Bloch, Miki; Lester, Hava; Chisin, Roland; Mechoulam, Raphael; Bar-Hamburger, Rachel; Freedman, Nanette; Even-Sapir, Einat

2008-01-01

Twelve regular users of marijuana underwent two positron emission tomography (PET) scans using [18F] Fluorodeoxyglucose (FDG), one while subject to the effects of 17 mg THC, the other without THC. In both sessions, a virtual reality maze task was performed during the FDG uptake period. When subject to the effects of 17 mg THC, regular marijuana smokers hit the walls more often on the virtual maze task than without THC. Compared to results without THC, 17 mg THC increased brain metabolism during task performance in areas that are associated with motor coordination and attention in the middle and medial frontal cortices and anterior cingulate, and reduced metabolism in areas that are related to visual integration of motion in the occipital lobes. These findings suggest that in regular marijuana users, the immediate effects of marijuana may impact on cognitive-motor skills and brain mechanisms that modulate coordinated movement and driving.

Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant.

PubMed

Justinova, Zuzana; Munzar, Patrik; Panlilio, Leigh V; Yasar, Sevil; Redhi, Godfrey H; Tanda, Gianluigi; Goldberg, Steven R

2008-11-01

Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.

Cannabis and creativity: highly potent cannabis impairs divergent thinking in regular cannabis users.

PubMed

Kowal, Mikael A; Hazekamp, Arno; Colzato, Lorenza S; van Steenbergen, Henk; van der Wee, Nic J A; Durieux, Jeffrey; Manai, Meriem; Hommel, Bernhard

2015-03-01

Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with cannabis; however, the evidence is not conclusive. The aim of this study was to investigate the acute effects of cannabis on creativity. We examined the effects of administering a low (5.5 mg delta-9-tetrahydrocannabinol [THC]) or high (22 mg THC) dose of vaporized cannabis vs. placebo on creativity tasks tapping into divergent (Alternate Uses Task) and convergent (Remote Associates Task) thinking, in a population of regular cannabis users. The study used a randomized, double-blind, between-groups design. Participants in the high-dose group (n = 18) displayed significantly worse performance on the divergent thinking task, compared to individuals in both the low-dose (n = 18) and placebo (n = 18) groups. The findings suggest that cannabis with low potency does not have any impact on creativity, while highly potent cannabis actually impairs divergent thinking.

Cannabis in cancer care.

PubMed

Abrams, D I; Guzman, M

2015-06-01

Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Functional imaging studies in cannabis users.

PubMed

Chang, Linda; Chronicle, Edward P

2007-10-01

Cannabis remains the most widely used illegal drug in the United States. This update examines the available literature on neuroimaging studies of the brains of cannabis users. The majority of studies examining the acute effects of delta-9-tetrahydrocannabinol (THC) administration used PET methods and concluded that administration of THC leads to increased activation in frontal and paralimbic regions and the cerebellum. These increases in activation are broadly consistent with the behavioral effects of the drug. Although there is only equivocal evidence that chronic cannabis use might result in structural brain changes, blood-oxygenation-level-dependent-fMRI studies in chronic users consistently show alterations, or neuroadaptation, in the activation of brain networks responsible for higher cognitive functions. It is not yet certain whether these changes are reversible with abstinence. Given the high prevalence of cannabis use among adolescents, studies are needed to evaluate whether cannabis use might affect the developing brain. Considerable further work, employing longitudinal designs, is also required to determine whether cannabis use causes permanent functional alterations in the brains of adults.

Optimizing the "priming" effect: influence of prior exercise intensity and recovery duration on O2 uptake kinetics and severe-intensity exercise tolerance.

PubMed

Bailey, Stephen J; Vanhatalo, Anni; Wilkerson, Daryl P; Dimenna, Fred J; Jones, Andrew M

2009-12-01

It has been suggested that a prior bout of high-intensity exercise has the potential to enhance performance during subsequent high-intensity exercise by accelerating the O(2) uptake (Vo(2)) on-response. However, the optimal combination of prior exercise intensity and subsequent recovery duration required to elicit this effect is presently unclear. Eight male participants, aged 18-24 yr, completed step cycle ergometer exercise tests to 80% of the difference between the preestablished gas exchange threshold and maximal Vo(2) (i.e., 80%Delta) after no prior exercise (control) and after six different combinations of prior exercise intensity and recovery duration: 40%Delta with 3 min (40-3-80), 9 min (40-9-80), and 20 min (40-20-80) of recovery and 70%Delta with 3 min (70-3-80), 9 min (70-9-80), and 20 min (70-20-80) of recovery. Overall Vo(2) kinetics were accelerated relative to control in all conditions except for 40-9-80 and 40-20-80 conditions as a consequence of a reduction in the Vo(2) slow component amplitude; the phase II time constant was not significantly altered with any prior exercise/recovery combination. Exercise tolerance at 80%Delta was improved by 15% and 30% above control in the 70-9-80 and 70-20-80 conditions, respectively, but was impaired by 16% in the 70-3-80 condition. Prior exercise at 40%Delta did not significantly influence exercise tolerance regardless of the recovery duration. These data demonstrate that prior high-intensity exercise ( approximately 70%Delta) can enhance the tolerance to subsequent high-intensity exercise provided that it is coupled with adequate recovery duration (>or=9 min). This combination presumably optimizes the balance between preserving the effects of prior exercise on Vo(2) kinetics and providing sufficient time for muscle homeostasis (e.g., muscle phosphocreatine and H(+) concentrations) to be restored.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu Tangkui, E-mail: zhutangkui@sohu.com; Li, Miaoquan, E-mail: honeymli@nwpu.edu.cn

Effect of hydrogen content on the lattice parameter of Ti-6Al-4V alloy has been investigated by X-ray diffraction. The experimental results show that the solution of hydrogen in the Ti-6Al-4V alloy affects significantly on the lattice parameters of {alpha}, {beta} and {delta} phases, especially the {beta} phase. Furthermore, the critical hydrogen content of {delta} hydride formation for Ti-6Al-4V alloy is 0.385 wt.%. When the hydrogen content is lower than the critical hydrogen content, the {delta} hydride cannot precipitate and the lattice parameter ({alpha}) of {beta} phase linearly increases with the increasing of hydrogen content. When the hydrogen content is higher thanmore » the critical hydrogen content, the {delta} hydride precipitates and the lattice parameter ({alpha}) of {beta} phase varies inconspicuously with hydrogen content. In addition, the effects of lattice variations and {delta} hydride formation on microstructure are discussed. The {alpha}/{beta} interfaces of lamellar transformed {beta} phase become fuzzy with the increasing of hydrogen content because of the lattice expansion of {beta} phase. Compared with that of the Ti-6Al-4V alloy at low hydrogen content ({<=} 0.385 wt.%), the contrasts of primary {alpha} phase and transformed {beta} phase of Ti-6Al-4V alloy at high hydrogen content ({>=} 0.385 wt.%) were completely reversed due to the formation of {delta} hydride. - Research Highlights: {yields} A novel method for determining {delta} hydride in Ti-6Al-4V alloy is presented. {yields} The critical hydrogen content of {delta} hydride formation is 0.385 wt.%. {yields} The lattice parameter of {beta} phase can be expressed as follows: a=0.323(1+9.9x10{sup -2}C{sub H}) . {yields} Precipitation of {delta} hydride has a significant influence on the microstructure. {yields} The {alpha}/{beta} interfaces of transformed {beta} phase became fuzzy in the hydrogenated alloy.« less

Appraisal of the nitrogen-15 natural-abundance method for quantifying dinitrogen fixation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bremer, E.; van Kessel, C.

Several investigators have questioned the use of the {sup 15}N natural-abundance method of estimating N{sub 2} fixation because of variability in soil {delta}{sup 15}N and small differences between the {delta}{sup 15}N of soil N and atmospheric N. Investigations were conducted to compare the {sup 15}N natural-abundance and {sup 15}N-isotope-dilution methods for estimating N{sub 2} fixation of field-grown pea (Pisum sativum L.) and lentil (Lens culinaris Medik.). Spatial variability was assessed at three sites by determining the {delta}{sup 15}N of non-N{sub 2}-fixing plants. Seasonal variation in {delta}{sup 15}N for spring and winter wheat (Triticum aestivum L.), flax (Linum usitatissimum L.), barleymore » (Hordeum vulgare L.), rape (Brassica napus L.) and lentil was determined at one site. Comparisons between {delta}{sup 15}N and {sup 15}N-enriched isotope-dilution methods for estimating N{sub 2} fixation by lentil were conducted at several sites over a 3-yr period. Variability in {delta}{sup 15}N of the reference plant was site dependent: the {delta}{sup 15}N ranged from 2.8 to 9.3 at the first site, 3.4 to 8.8 at the second site, and 3.5 to 6.2 at the third site. The average {delta}{sup 15}N of four of the five non-N{sub 2}-fixing plants increased from 5.4 at 42 d after planting to 6.9 at the final harvest. The fifth non-N{sub 2}-fixing plant, rape, accumulated most of its N during the first 42 d after planting, and its {delta}{sup 15}N value declined from 8.1 at 42 d after planting to 7.3 at the final harvest. Estimates of N{sub 2} fixation were not significantly different in 18 out of 21 comparisons; in two comparisons in the {delta}{sup 15}N method and in one comparison the {sup 15}N-enriched method provided higher estimates of N{sub 2} fixation. Overall, both methods appeared to provide equally reliable estimates of N{sub 2} fixation for lentil.« less

Azimuthal decorrelation of jets widely separated in rapidity in pp collisions at $$\\sqrt{s} =$$ 7 TeV

DOE PAGES

Khachatryan, Vardan

2016-08-24

The decorrelation in the azimuthal angle between the most forward and the most backward jets (Mueller-Navelet jets) is measured in data collected in pp collisions with the CMS detector at the LHC atmore » $$\\sqrt{s} =$$ 7 TeV. The measurement is presented in the form of distributions of azimuthal-angle differences, $$\\Delta\\phi$$, between the Mueller-Navelet jets, the average cosines of $$(\\pi-\\Delta\\phi)$$, $$2(\\pi-\\Delta\\phi)$$, and $$3(\\pi-\\Delta\\phi)$$, and ratios of these cosines. The jets are required to have transverse momenta, $$p_{\\mathrm{T}}$$, in excess of 35 GeV and rapidities, $| y |$, of less than 4.7. The results are presented as a function of the rapidity separation, $$\\Delta{y}$$, between the Mueller-Navelet jets, reaching $$\\Delta{y}$$ up to 9.4 for the first time. Lastly, the results are compared to predictions of various Monte Carlo event generators and to analytical predictions based on the DGLAP and BFKL parton evolution schemes.« less

Azimuthal decorrelation of jets widely separated in rapidity in pp collisions at $$\\sqrt{s} =$$ 7 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khachatryan, Vardan

The decorrelation in the azimuthal angle between the most forward and the most backward jets (Mueller-Navelet jets) is measured in data collected in pp collisions with the CMS detector at the LHC atmore » $$\\sqrt{s} =$$ 7 TeV. The measurement is presented in the form of distributions of azimuthal-angle differences, $$\\Delta\\phi$$, between the Mueller-Navelet jets, the average cosines of $$(\\pi-\\Delta\\phi)$$, $$2(\\pi-\\Delta\\phi)$$, and $$3(\\pi-\\Delta\\phi)$$, and ratios of these cosines. The jets are required to have transverse momenta, $$p_{\\mathrm{T}}$$, in excess of 35 GeV and rapidities, $| y |$, of less than 4.7. The results are presented as a function of the rapidity separation, $$\\Delta{y}$$, between the Mueller-Navelet jets, reaching $$\\Delta{y}$$ up to 9.4 for the first time. Lastly, the results are compared to predictions of various Monte Carlo event generators and to analytical predictions based on the DGLAP and BFKL parton evolution schemes.« less

A positive cannabinoids workplace drug test following the ingestion of commercially available hemp seed oil.

PubMed

Struempler, R E; Nelson, G; Urry, F M

1997-01-01

A commercially available health food product of cold-pressed hemp seed oil ingested by one volunteer twice a day for 4 1/2 days (135 mL total). Urine specimens collected from the volunteer were subjected to standard workplace urine drug testing procedures, and the following concentrations of 11-nor-delta9- tetrahydrocannabinol carboxylic acid (9-THCA) were detected: 41 ng/mL 9-THCA at 45 h, 49 ng/mL at 69 h, and 55 ng/mL at 93 h. Ingestion was discontinued after 93 h, and the following concentrations were detected: 68 ng/mL at 108 h, 57 ng/mL at 117 h, 31 ng/mL at 126 h, and 20 ng/mL at 142 h. The first specimen that tested negative (50 ng/mL initial immunoassay test, 15 ng/mL confirmatory gas chromatographic-mass spectrometric test) was at 146 h, which was 53 h after the last hemp seed oil ingestion. Four subsequent specimens taken to 177 h were also negative. This study indicates that a workplace urine drug test positive for cannabinoids may arise from the consumption of commercially available cold-pressed hemp seed oil.

SU-F-T-238: Analyzing the Performance of MapCHECK2 and Delta4 Quality Assurance Phantoms in IMRT and VMAT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, SH; Tsai, YC; Lan, HT

2016-06-15

Purpose: Intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) have been widely investigated for use in radiotherapy and found to have a highly conformal dose distribution. Delta{sup 4} is a novel cylindrical phantom consisting of 1069 p-type diodes with true treatments measured in the 3D target volume. The goal of this study was to compare the performance of a Delta{sup 4} diode array for IMRT and VMAT planning with ion chamber and MapCHECK2. Methods: Fifty-four IMRT (n=9) and VMAT (n=45) plans were imported to Philips Pinnacle Planning System 9.2 for recalculation with a solid water phantom, MapCHECK2, and themore » Delta4 phantom. To evaluate the difference between the measured and calculated dose, we used MapCHECK2 and Delta{sup 4} for a dose-map comparison and an ion chamber (PTW 31010 Semiflex 0.125 cc) for a point-dose comparison. Results: All 54 plans met the criteria of <3% difference for the point dose (at least two points) by ion chamber. The mean difference was 0.784% with a standard deviation of 1.962%. With a criteria of 3 mm/3% in a gamma analysis, the average passing rates were 96.86%±2.19% and 98.42%±1.97% for MapCHECK2 and Delta{sup 4}, respectively. The student t-test of MapCHECK2/Delta{sup 4}, ion chamber/Delta{sup 4}, and ion chamber/MapCHECK2 were 0.0008, 0.2944, and 0.0002, respectively. There was no significant difference in passing rates between MapCHECK2 and Delta{sup 4} for the IMRT plan (p = 0.25). However, a higher pass rate was observed in Delta{sup 4} (98.36%) as compared to MapCHECK2 (96.64%, p < 0.0001) for the VMAT plan. Conclusion: The Pinnacle planning system can accurately calculate doses for VMAT and IMRT plans. The Delta{sup 4} shows a similar result when compared to ion chamber and MapCHECK2, and is an efficient tool for patient-specific quality assurance, especially for rotation therapy.« less

Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC{delta} in cell culture and animal models of Parkinson's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun

2011-11-15

The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 {mu}M) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the freemore » radical scavenger MnTBAP (10 {mu}M) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKC{delta}) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 {mu}M). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKC{delta}{sup D327A} and kinase dead PKC{delta}{sup K376R} or siRNA-mediated knockdown of PKC{delta} protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKC{delta} promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKC{delta} expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKC{delta} cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKC{delta}{sup D327A} protein protected against 6-OHDA-induced PKC{delta} activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKC{delta} is a key downstream event in dopaminergic degeneration, and these results may have important translational value for development of novel treatment strategies for PD.« less

The Crystal Structure of the Ivy delta4-16:0-ACP Desaturase Reveals Structural Details of the Oxidized Active Site and Potential Determinants of Regioselectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy,J.; Whittle, E.; Kumaran, D.

2007-01-01

The multifunctional acyl-acyl carrier protein (ACP) desaturase from Hedera helix (English ivy) catalyzes the {Delta}{sup 4} desaturation of 16:0-ACP and the{Delta}{sup 9} desaturation of 18:0-ACP and further desaturates{Delta}{sup 9}-16:1 or {Delta}{sup 9}-18:1 to the corresponding {Delta}{sup 4,9} dienes. The crystal structure of the enzyme has been solved to 1.95{angstrom} resolution, and both the iron-iron distance of 3.2{angstrom} and the presence of a {mu}-oxo bridge reveal this to be the only reported structure of a desaturase in the oxidized FeIII-FeIII form. Significant differences are seen between the oxidized active site and the reduced active site of the Ricinus communis (castor) desaturase;more » His{sup 227} coordination to Fe2 is lost, and the side chain of Glu{sup 224}, which bridges the two iron ions in the reduced structure, does not interact with either iron. Although carboxylate shifts have been observed on oxidation of other diiron proteins, this is the first example of the residue moving beyond the coordination range of both iron ions. Comparison of the ivy and castor structures reveal surface amino acids close to the annulus of the substrate-binding cavity and others lining the lower portion of the cavity that are potential determinants of their distinct substrate specificities. We propose a hypothesis that differences in side chain packing explains the apparent paradox that several residues lining the lower portion of the cavity in the ivy desaturase are bulkier than their equivalents in the castor enzyme despite the necessity for the ivy enzyme to accommodate three more carbons beyond the diiron site.« less

Captures of Ostrinia furnacalis (Lepidoptera: Crambidae) With Sex Pheromone Traps in NE China Corn and Soybeans.

PubMed

Chen, Ri-Zhao; Li, Lian-Bing; Klein, Michael G; Li, Qi-Yun; Li, Peng-Pei; Sheng, Cheng-Fa

2016-02-01

Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae), commonly referred to as the Asian corn borer, is the most important corn pest in Asia. Although capturing males with pheromone traps has recently been the main monitoring tool and suppression technique, the best trap designs remain unclear. Commercially available Delta and funnel traps, along with laboratory-made basin and water traps, and modified Delta traps, were evaluated in corn and soybean fields during 2013-2014 in NE China. The water trap was superior for capturing first-generation O. furnacalis (1.37 times the Delta trap). However, the basin (8.3 ± 3.2 moths/trap/3 d), Delta (7.9 ± 2.5), and funnel traps (7.0 ± 2.3) were more effective than water traps (1.4 ± 0.4) during the second generation. Delta traps gave optimal captures when deployed at ca. 1.57 × the highest corn plants, 1.36× that of average soybean plants, and at the field borders. In Delta traps modified by covering 1/3 of their ends, captures increased by ca. 15.7 and 8.1% in the first and second generations, respectively. After 35 d in the field, pheromone lures were still ca. 50% as attractive as fresh lures, and retained this level of attraction for ca. 25 more days. Increased captures (first and second generation: 90.9 ± 9.5%; 78.3 ± 9.3%) were obtained by adding a lure exposed for 5 d to funnel traps baited with a 35-d lure. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Experimental Determination of the Electric Dipole Moment Function of the X Pi-2 Hydroxyl Radical

NASA Technical Reports Server (NTRS)

Chackerian, C., Jr.; Goorvitch, D.; Abrams, M. C.; Davis, S. P.; Benidar, A.; Farrenq, R.; Guelachvili, G.; Strawa, Anthony W. (Technical Monitor)

1995-01-01

Laboratory infrared emission spectra of X 2piOH obtained with the Solar McMath FTS and the U. Paris (Orsay) FTS are used in an inversion procedure to experimentally determine the electric dipole moment function (EDMF) of the hydroxyl radical. The spectra produced at Kitt Peak show vibrational levels up to v = 10 and rotational lines in the range, -25.5 less than or equal to m less than or equal to 12.5. The following vibrational quantum number ranges were observed: for DELTA v = -1, v prime = 1 - 9, for DELTA v = -2, v prime = 2 - 10, and for DELTA v = - 3, v prime = 6 - 10. The spectra produced at Orsay show DELTA v = -1, with v prime = 1 - 4 and -22.5 less than or equal to m less than or equal to 9.5 as well as DELTA v = 0, with v prime= 1 - 3, and 9.5 less than or equal to m less than or equal to 25.5. The OH rovibrational wavefunctions used in the inversion procedure were calculated using a procedure which reproduces observed rotational constants with a high level of accuracy. Comparisons of our EDMF are made with previous experimental and theoretical work.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacKay,W.W.

For a ring like RHIC with two full Siberian snakes on opposite sides of the ring, the spin tune for a flat orbit will be 1/2 if the snake rotation axes are perpendicular, {Delta}{phi} = {phi}{sub 9}-{phi}{sub 3} = {pi}/2. Here {phi}{sup 9} and {phi}{sub 3} are respectively the direction of the rotation axes of the 9 o'clock and 3 o'clock snakes relative to the design trajectory as shown in Figure 1. If the two snakes are slightly detuned by the same amount such that the rotation axes are no longer perpendicular, then the deviation of the closed-orbit spin tunemore » {nu}{sub 0} from 1/2 is given by {Delta}{nu}{sub 0} {approx_equal} ({Delta}{mu}){sup 2}/4{pi} cosG{gamma}{pi} - 2{Delta}{phi}/{pi} {approx_equal} 2{Delta}{phi}/180{sup o} with G{gamma} at a half integer, and where {Delta}{mu} is the deviation of snake rotation angle from 180{sup o}. It should be noted that there is a sign ambiguity in {Delta}{mu}{sub 0} since a spin tune of 0.495 is also a spin tune of 0.505, depending on the direction taken along the stable spin axis. In order to understand the effect of energy scaling on the snake axis direction, I have integrated the trajectory and spin rotation through a model of a RHIC snake (bi9-snk7) and found the energy (U) dependence of the snake axis angle {phi}{sub 9} and rotation angle {mu} as shown. A {approx_equal} p{sup -2} scaling of errors is typical in helical snakes. To first order, the orbit excursion drops as p{sup -1} and the spin precessions about transverse fields increase as {gamma} giving an approximate cancellation with energy, so we do not expect much change during the field ramp. The next order term which comes in is primarily proportional to p{sup -2}; although naively one might expect a slight effect inversely proportional to the velocity since {gamma}/p {proportional_to} c/{nu} {approx_equal} 1 + 1/2{gamma}{sup 2}.« less

New insights into ETS-10 and titanate quantum wire: a comprehensive characterization.

PubMed

Jeong, Nak Cheon; Lee, Young Ju; Park, Jung-Hyun; Lim, Hyunjin; Shin, Chae-Ho; Cheong, Hyeonsik; Yoon, Kyung Byung

2009-09-16

The titanate quantum wires in ETS-10 crystals remain intact during ion exchange of the pristine cations (Na(+)(0.47) + K(+)(0.53)) with M(n+) ions (M(n+) = Na(+), K(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Pb(2+), Cd(2+), Zn(2+)) and during reverse exchange of the newly exchanged cations with Na(+). The binding energies of O(1s) and Ti(2p) decrease as the electronegativity of the cation decreases, and they are inversely proportional to the negative partial charge of the framework oxygen [-delta(O(f))]. At least five different oxygen species were identified, and their binding energies (526.1-531.9 eV) indicate that the titanate-forming oxides are much more basic than those of aluminosilicate zeolites (530.2-533.3 eV), which explains the vulnerability of the quantum wire to acids and oxidants. The chemical shifts of the five NMR-spectroscopically nonequivalent Si sites, delta(I(A)), delta(I(B)), delta(II(A)), delta(II(B)), and delta(III), shift downfield as -delta(O(f)) increases, with slopes of 2.5, 18.6, 133.5, 216.3, and 93.8 ppm/[-delta(O(f))], respectively. The nonuniform responses of the chemical shifts to -delta(O(f)) arise from the phenomenon that the cations in the 12-membered-ring channels shift to the interiors of the cages surrounded by four seven-membered-ring windows. On the basis of the above, we assign delta(I(A)), delta(I(B)), delta(II(A)), and delta(II(B)) to the chemical shifts arising from Si(12,12), Si(12,7), Si(7,12), and Si(7,7) atoms, respectively. The frequency of the longitudinal stretching vibration of the titanate quantum wire increases linearly and the bandwidth decreases nonlinearly with increasing -delta(O(f)), indicating that the titanate quantum wire resembles a metallic carbon nanotube. As the degree of hydration increases, the vibrational frequency shifts linearly to higher frequencies while the bandwidth decreases. We identified another normal mode of vibration of the quantum wire, which vibrates in the region of 274-280 cm(-1). In the dehydrated state, the band-gap energy and the first absorption maximum shift to lower energies as -delta(O(f)) increases, indicating the oxide-to-titanium(IV) charge-transfer nature of the transitions.

Azide and acetate complexes plus two iron-depleted crystal structures of the di-iron enzyme delta9 stearoyl-acyl carrier protein desaturase. Implications for oxygen activation and catalytic intermediates.

PubMed

Moche, Martin; Shanklin, John; Ghoshal, Alokesh; Lindqvist, Ylva

2003-07-04

Delta9 stearoyl-acyl carrier protein (ACP) desaturase is a mu-oxo-bridged di-iron enzyme, which belongs to the structural class I of large helix bundle proteins and that catalyzes the NADPH and O2-dependent formation of a cis-double bond in stearoyl-ACP. The crystal structures of complexes with azide and acetate, respectively, as well as the apoand single-iron forms of Delta9 stearoyl-ACP desaturase from Ricinus communis have been determined. In the azide complex, the ligand forms a mu-1,3-bridge between the two iron ions in the active site, replacing a loosely bound water molecule. The structure of the acetate complex is similar, with acetate bridging the di-iron center in the same orientation with respect to the di-iron center. However, in this complex, the iron ligand Glu196 has changed its coordination mode from bidentate to monodentate, the first crystallographic observation of a carboxylate shift in Delta9 stearoyl-ACP desaturase. The two complexes are proposed to mimic a mu-1,2 peroxo intermediate present during catalytic turnover. There are striking structural similarities between the di-iron center in the Delta9 stearoyl-ACP desaturase-azide complex and in the reduced rubrerythrin-azide complex. This suggests that Delta9 stearoyl-ACP desaturase might catalyze the formation of water from exogenous hydrogen peroxide at a low rate. From the similarity in iron center structure, we propose that the mu-oxo-bridge in oxidized desaturase is bound to the di-iron center as in rubrerythrin and not as reported for the R2 subunit of ribonucleotide reductase and the hydroxylase subunit of methane monooxygenase. The crystal structure of the one-iron depleted desaturase species demonstrates that the affinities for the two iron ions comprising the di-iron center are not equivalent, Fe1 being the higher affinity site and Fe2 being the lower affinity site.

TRANSMISSION ELECTRON MICROSCOPY STUDY OF HELIUM BEARING FUSION WELDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tosten, M; Michael Morgan, M

2008-12-12

A transmission electron microscopy (TEM) study was conducted to characterize the helium bubble distributions in tritium-charged-and-aged 304L and 21Cr-6Ni-9Mn stainless steel fusion welds containing approximately 150 appm helium-3. TEM foils were prepared from C-shaped fracture toughness test specimens containing {delta} ferrite levels ranging from 4 to 33 volume percent. The weld microstructures in the low ferrite welds consisted mostly of austenite and discontinuous, skeletal {delta} ferrite. In welds with higher levels of {delta} ferrite, the ferrite was more continuous and, in some areas of the 33 volume percent sample, was the matrix/majority phase. The helium bubble microstructures observed were similarmore » in all samples. Bubbles were found in the austenite but not in the {delta} ferrite. In the austenite, bubbles had nucleated homogeneously in the grain interiors and heterogeneously on dislocations. Bubbles were not found on any austenite/austenite grain boundaries or at the austenite/{delta} ferrite interphase interfaces. Bubbles were not observed in the {delta} ferrite because of the combined effects of the low solubility and rapid diffusion of tritium through the {delta} ferrite which limited the amount of helium present to form visible bubbles.« less

9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

PubMed

Asciak, C P; Domazet, Z

1975-02-20

1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

High growth fraction at 9 grays of radiotherapy is associated with a good prognosis for patients with cervical squamous cell carcinoma.

PubMed

Oka, K; Suzuki, Y; Nakano, T

2000-10-01

MIB-1, a murine monoclonal antibody, recognizes the Ki-67 antigen of routinely processed paraffin sections after microwave treatment. Cycling cells are positive for MIB-1 in their nucleus, and quiescent cells are negative for MIB-1. The MIB-1 labeling index represents the growth fraction of the cell population. A total of 150 cervical biopsy specimens were taken from 75 consecutive patients with cervical squamous cell carcinomas before radiotherapy (RT) and at 9 grays (Gy) of RT and were investigated to analyze the correlation between the MIB-1 labeling index or the deltaMIB-1 labeling index and patient prognosis or local disease control. The deltaMIB-1 index was calculated as the MIB-1 index at 9 Gy minus the MIB-1 index before RT. The mean MIB-1 index was 38% (range, 11-67%) before RT and 54% (range, 15-85%) at 9 Gy. The MIB-1 index at 9 Gy was related to prognosis, including overall survival (P = 0.025), disease free survival (P = 0. 024), and metastasis free survival (P = 0.045). Patients who had a deltaMIB-1 index > 20% showed a trend toward a higher disease free survival rate compared with patients who had a deltaMIB-1 index < 20% (P = 0.093). Neither the MIB-1 index nor the deltaMIB-1 index was associated with local disease control. The high growth fraction at 9 Gy is regarded as a predictive factor for a good prognosis in patients with cervical squamous cell carcinoma patients who undergo RT alone.

Fistuloclysis Improves Liver Function and Nutritional Status in Patients with High-Output Upper Enteric Fistula

PubMed Central

Wu, Yin; Ren, Jianan; Wang, Gefei; Zhou, Bo; Ding, Chao; Gu, Guosheng; Chen, Jun; Liu, Song; Li, Jieshou

2014-01-01

Background. We aimed to determine the efficacy of fistuloclysis in patients with high-output upper enteric fistula (EF). Methods. Patients were assigned into the fistuloclysis group (n = 35, receiving fistuloclysis plus total enteral nutrition (TEN)) and the control group (n = 60, receiving TEN). Laboratory variables were measured during the four-week treatment. Results. At baseline, variables were similar between the two groups. Delta value was defined as the changes from baseline to day 28. Compared with the control group, the fistuloclysis group showed greater improvements in liver function (Delta total bilirubin (TB): 20.3 ± 9.7 in the fistuloclysis group versus 15.6 ± 6.3 in the control group, P = 0.040; Delta direct bilirubin (DB): 12.5 ± 3.4 versus 10.0 ± 3.6, P = 0.011; Delta alkaline phosphatase (ALP): 98.4 ± 33.5 versus 57.6 ± 20.9, P < 0.001); nutritional status (Delta total protein: 21.8 ± 8.7 versus 10.7 ± 2.1, P < 0.001; Delta albumin: 11.3 ± 2.5 versus 4.2 ± 1.3, P < 0.001). In the fistuloclysis subgroups, biliary fistula patients had the maximum number of variables with the greatest improvements. Conclusions. Fistuloclysis improved hepatic and nutritional parameters in patients with high-output upper EF, particularly in biliary fistula patients. PMID:24719613

Fistuloclysis improves liver function and nutritional status in patients with high-output upper enteric fistula.

PubMed

Wu, Yin; Ren, Jianan; Wang, Gefei; Zhou, Bo; Ding, Chao; Gu, Guosheng; Chen, Jun; Liu, Song; Li, Jieshou

2014-01-01

Background. We aimed to determine the efficacy of fistuloclysis in patients with high-output upper enteric fistula (EF). Methods. Patients were assigned into the fistuloclysis group (n = 35, receiving fistuloclysis plus total enteral nutrition (TEN)) and the control group (n = 60, receiving TEN). Laboratory variables were measured during the four-week treatment. Results. At baseline, variables were similar between the two groups. Delta value was defined as the changes from baseline to day 28. Compared with the control group, the fistuloclysis group showed greater improvements in liver function (Delta total bilirubin (TB): 20.3 ± 9.7 in the fistuloclysis group versus 15.6 ± 6.3 in the control group, P = 0.040; Delta direct bilirubin (DB): 12.5 ± 3.4 versus 10.0 ± 3.6, P = 0.011; Delta alkaline phosphatase (ALP): 98.4 ± 33.5 versus 57.6 ± 20.9, P < 0.001); nutritional status (Delta total protein: 21.8 ± 8.7 versus 10.7 ± 2.1, P < 0.001; Delta albumin: 11.3 ± 2.5 versus 4.2 ± 1.3, P < 0.001). In the fistuloclysis subgroups, biliary fistula patients had the maximum number of variables with the greatest improvements. Conclusions. Fistuloclysis improved hepatic and nutritional parameters in patients with high-output upper EF, particularly in biliary fistula patients.

Contributions from inner and outer shell electron energies to reaction heats for C/sub 1/, C/sub 2/, and C/sub 3/ hydrocarbons

DOE Office of Scientific and Technical Information (OSTI.GOV)

George, P.; Bock, C.W.; Trachtman, M.

1979-04-01

The expectation energy values E/sub k/, V/sub ee/, V/sub nn/, V/sub en/, and E/sub T/ have been calculated for H/sub 2/ and the C/sub 1/, C/sub 2/, and C/sub 3/ hydrocarbons using a (9,5) basis set and the experimental geometries. Treating the theoretical reaction heat, ..delta..E/sub T/, as the resultant of the nuclear repulsion term, ..delta..V/sub nn/, and the net electron energy term, ..delta..E/sub elec/ = ..delta..E/sub k/ + ..delta..V/sub ee/ + ..delta..V/sub en/, the contribution of inner and outer shell electron energies to ..delta..E/sub elec/, and hence to ..delta..E/sub T/, has been calculated for a large number of hydrocarbonmore » reactions by evaluating the Coulson--Neilson energies eta/sub i/, where eta/sub i/ = E/sub elec/. For the vast majority of reactions, 67/84, the change in inner shell electron energy, (..delta sigma..eta/sub i/)/sub inner/, accounts for more than 10% of ..delta..E/sub elec/, in many cases being as high as 20-35%. Furthermore, in addition to these cases in which the change in inner shell electron energy serves to augment (significantly) the change in outer shell electron energy, there are other cases in which the change in inner shell electron energy either exceeds in magnitude the change in outer shell energy, or is even opposite in sign, indicative of inner and outer shell electrons acting contrariwise. Inner shell electron energies contribute to the reaction heats because they are structure dependent, like the more familiar orbital energies epsilon, but the dependence is of a different kind.« less

Development of markers for Delta9-Stearoyl-ACP-Desaturase (SAD) to screen for cold acclimation

USDA-ARS?s Scientific Manuscript database

Delta 9-Stearoyl-acyl carrier protein (ACP) desaturase (SAD) is an important enzyme of fatty acid biosynthesis in higher plants. Located in the plastid stroma, SAD catalyzes the desaturation of stearoyl-ACP to oleyl-ACP. SAD plays a key role in determining the ratio of saturated fatty acids to unsat...

78 FR 18519 - Abamectin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... equal to 20% avermectin delta-8,9-isomer) in or on cotton and strawberries. Syngenta Crop Protection Inc... A 1 ) and its delta-8,9-isomer) (referred to as ``abamectin'' in this document) in or on cotton, undelinted seed from 0.005 parts per million (ppm) to 0.015 ppm; cotton, gin by-products from 0.15 ppm to 1.0...

Purification of the bacteriocin bavaricin MN and characterization of its mode of action against Listeria monocytogenes Scott A cells and lipid vesicles.

PubMed

Kaiser, A L; Montville, T J

1996-12-01

Bavaricin MN was purified from Lactobacillus sake culture supernatant 135-fold with a final yield of 11%. Sequence analysis revealed bavaricin MN to be a 42-amino-acid peptide having a molecular weight of 4,769 and a calculated pI of 10.0. Computer analysis indicated that the C-terminal region may form an alpha-helical structure with an amphipathic nature deemed important in the interaction of bacteriocins with biological membranes. Bavaricin MN rapidly depleted the membrane potential (delta p) of energized Listeria monocytogenes cells in a concentration-dependent fashion. At a bavaricin MN concentration of 9.0 micrograms/ml, the delta p decreased by 85%. Both the electrical potential (delta psi) and Z delta pH components of the delta p were depleted, and this depletion was not dependent on a threshold level of proton motive force. In addition to studying the effect of bavaricin MN on the delta p of vegetative cells, bavaricin MN-induced carboxyfluorescein (CF) efflux from L. monocytogenes-derived lipid vesicles was also characterized. Bavaricin MN-induced CF leakage was also concentration dependent with an optimum of pH 6.0. The rate of CF efflux was 63% greater in lipid vesicles in which a delta psi was generated compared with that in lipid vesicles in the absence of a delta psi.

Biosynthesis of 10,12-dienoic fatty acids by a bifunctional Delta11 desaturase in Spodoptera littoralis.

PubMed

Serra, Montserrat; Piña, Benjami; Bujons, Jordi; Camps, Francisco; Fabriàs, Gemma

2006-08-01

In the biosynthetic pathway of Spodoptera littoralis sex pheromone, (E,E)-10,12-tetradecadienoic acid is produced from (Z)-11-tetradecenoic acid by desaturation and concomitant migration of the precursor double bond. With the aim of identifying the enzyme involved in this biotransformation, yeast Deltaelo1/Deltaole mutants, which are both elongase 1 and Delta9 desaturase-deficient, were transformed with the S. littoralis Delta11 desaturase gene using a Cu+2 inducible expression vector. The transformants produced a recombinant polyhistidine-tagged Delta11 desaturase that could be detected by immunoblotting from cell lysates. Lipid analysis revealed that besides producing large quantities of C11-monounsaturated fatty acids, mainly (Z)-11-hexadecenoic acid, (E,E)-10,12-tetradecadienoic acid and minor amounts of (E,Z)-10,12-hexadecadienoic acid were also produced, as well as very low quantities of another tetradecadienoate, which was tentatively identified as the (E,Z)-10,12-tetradecadienoic isomer. None of these dienes was detected with the Delta11 desaturase gene of Trichoplusia ni, which does not produce conjugated dienes as pheromone components. We conclude that the Delta11 desaturase of S. littoralis is a bifunctional enzyme with both Delta11 and Delta10,12 desaturation activities. The relationship between the substrate structure and the stereochemical outcome of the reaction is discussed.

Kinetics and mechanism of degradation of some 2-sulfanilamidopyrimidine derivatives. Part VI. The use of Hammett equation for kinetic investigation of 2-sulfanilamidopyrimidine derivatives hydrolysis.

PubMed

Zajac, M

1977-01-01

General, k, and specific, k1 and k2, first-order rate constants for the parallel reaction of hydrolysis catalized by H+ ions were estimated for sulfadiazine (I), sulfamerazine (II), sulfadimidine (III), sulfaperine (IV) and sulfamethoxydiazine (V), hydrolyzed in 1 mole/dm3 HCl at 333, 343, 355 and 363 K. General first-order rate constants for the spontaneous hydrolysis of I--V in borate buffer pH 9.20 at 403, 411 and 418 K were also determined. Thermodynamic parameters of the reaction (delta Ha, deltaH not equal to, deltaS not equal to, deltaG not equal to and log A) were calculated. The effect of substituents in positions 4, 5 and 6 of the pyrimidine ring on the rate of hydrolysis was interpreted in terms of Hammett equation.

The current status of artisanal cannabis for the treatment of epilepsy in the United States.

PubMed

Sulak, Dustin; Saneto, Russell; Goldstein, Bonni

2017-05-01

The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, including potential risks and benefits, challenges related to artisanal preparations, and cannabinoid dosing, are discussed. Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing thermochemical data

NASA Astrophysics Data System (ADS)

Holmes, John L.; Aubry, Christiane; Wang, Xian

2007-11-01

This paper describes, with examples, a critical assessment of thermochemical data for some small molecules and free radicals. The available heats of formation, [Delta]fH° (all 298 K values). for simple alkyl hydroperoxides and di-alkyl peroxides were compared and new data are provided. The [Delta]fH° values, all ±5 kJ/mol, are: CH3OOH, -135; CH3CH2OOH, -168; n-C3H7OOH, -189; s-C3H7OOH, -205; t-C4H9OOH, -240; CH3OOCH3, -132; CH3CH2OOCH3, -165; C2H5OOC2H5, -198; n-C3H7OOn-C3H7, -240; s-C3H7OOs-C3H7, -272; t-C4H9OOt-C4H9, -342. These are consistent with established O-O bond dissociation energies and with additivity considerations. [Delta]fH° values for the corresponding alkoxy radicals are also addressed. A similar survey was applied to the homologous n-alkyl aldehydes, C2 to C8, for which recommended [Delta]fH° values, all ±1.5 kJ/mol, are: -166.5, -189, -207.5, -227, -248, -268 and -289, respectively. Particular attention was given to [Delta]fH°(CH3CO) = -10.3 ± 1.8 kJ/mol. The current NIST WebBook datum, [Delta]fH°(CS) = 280.3 kJ/mol, is arguably the best value, being consistent with related thermochemical data. Finally the [Delta]fH° values for the allylic free radicals CH2CHCH2, 174 ± 3 kJ/mol, CH2CHCH(OH), 4.5 ± 4 kJ/mol, and (CH2CH)2C(OH), 37 ± 4 kJ/mol, derived from experimental data and results of computational chemistry are described, together with some related homolytic bond strengths.

Changes in nitrogen isotopic compositions during composting of cattle feedlot manure: effects of bedding material type.

PubMed

Kim, Young-Joo; Choi, Woo-Jung; Lim, Sang-Sun; Kwak, Jin-Hyeob; Chang, Scott X; Kim, Han-Yong; Yoon, Kwang-Sik; Ro, Hee-Myong

2008-09-01

Temporal changes in delta(15)N of cattle feedlot manure during its composting with either rice hull (RHM) or sawdust (SDM) as bedding materials were investigated. Regardless of the bedding material used, the delta(15)N of total N in the manure increased sharply from +7.6 per thousand to +9.9 per thousand and from +11.4 per thousand to +14.3 per thousand, respectively, in RHM or SDM, within 10 days from the commencement of composting. Such increases could be attributed primarily to N loss via NH(3) volatilization and denitrification based on the very high delta(15)N values (greater than +20 per thousand) of NH(4)(+) and NO(3)(-) in the co-composted manure. The delta(15)N of total N in RHM was substantially lower (by more than 3 per thousand) than that in SDM, suggesting that the delta(15)N of the composted manure was affected not only by N loss but also by the type of bedding material used. Specifically, the higher N concentration in the rice hull than in the saw dust could lead to a greater (15)N isotope dilution.

Cloning and characterization of unusual fatty acid desaturases from Anemone leveillei: identification of an acyl-coenzyme A C20 Delta5-desaturase responsible for the synthesis of sciadonic acid.

PubMed

Sayanova, Olga; Haslam, Richard; Venegas Caleron, Monica; Napier, Johnathan A

2007-05-01

The seed oil of Anemone leveillei contains significant amounts of sciadonic acid (20:3Delta(5,11,14); SA), an unusual non-methylene-interrupted fatty acid with pharmaceutical potential similar to arachidonic acid. Two candidate cDNAs (AL10 and AL21) for the C(20) Delta(5cis)-desaturase from developing seeds of A. leveillei were functionally characterized in transgenic Arabidopsis (Arabidopsis thaliana) plants. The open reading frames of both Delta(5)-desaturases showed some similarity to presumptive acyl-coenzyme A (CoA) desaturases found in animals and plants. When expressed in transgenic Arabidopsis, AL21 showed a broad range of substrate specificity, utilizing both saturated (16:0 and 18:0) and unsaturated (18:2, n-6 and 18:3, n-3) substrates. In contrast, AL10 did not show any activity in wild-type Arabidopsis. Coexpression of AL10 or AL21 with a C(18) Delta(9)-elongase in transgenic Arabidopsis plants resulted in the production of SA and juniperonic fatty acid (20:4Delta(5,11,14,17)). Thus, AL10 acted only on C(20) polyunsaturated fatty acids in a manner analogous to "front-end" desaturases. However, neither AL10 nor AL21 contain the cytochrome b(5) domain normally present in this class of enzymes. Acyl-CoA profiling of transgenic Arabidopsis plants and developing A. leveillei seeds revealed significant accumulation of Delta(5)-unsaturated fatty acids as acyl-CoAs compared to the accumulation of these fatty acids in total lipids. Positional analysis of triacylglycerols of A. leveillei seeds showed that Delta(5)-desaturated fatty acids were present in both sn-2 and sn-1 + sn-3 positions, although the majority of 16:1Delta(5), 18:1Delta(5), and SA was present at the sn-2 position. Our data provide biochemical evidence for the A. leveillei Delta(5)-desaturases using acyl-CoA substrates.

Identification of anthropogenic and natural inputs of sulfate and chloride into the karstic ground water of Guiyang, SW China: combined delta37Cl and delta34S approach.

PubMed

Liu, Cong-Qiang; Lang, Yun-Chao; Satake, Hiroshi; Wu, Jiahong; Li, Si-Liang

2008-08-01

Because of active exchange between surface and groundwater of a karstic hydrological system, the groundwater of Guiyang, the capital city of Guizhou Province, southwest China, has been seriously polluted by anthropogenic inputs of NO3-, SO4(2-), Cl-, and Na+. In this work, delta37Cl of chloride and delta34S variations of sulfate in the karstic surface/groundwater system were studied, with a main focus to identify contaminant sources, including their origins. The surface, ground, rain, and sewage water studied showed variable delta37Cl and delta34S values, in the range of -4.1 to +2.0 per thousand, and -20.4 to +20.9 per thousand for delta37Cl and delta34S (SO4(2-)), respectively. The rainwater samples yielded the lowest delta37Cl values among those observed to date for aerosols and rainwater. Chloride in the Guiyang area rain waters emanated from anthropogenic sources rather than being of marine origin, probably derived from HCl (g) emitted by coal combustion. By plotting 1/SO4(2-) vs delta34S and 1/Cl- vs delta37Cl, respectively, we were able to identify some clusters of data, which were assigned as atmospheric deposition (acid rain component), discharge from municipal sewage, paleo-brine components in clastic sedimentary rocks, dissolution of gypsum mainly in dolomite, oxidation of sulfide minerals in coal-containing clastic rocks, and possibly degradation of chlorine-containing organic matter. We conclude that human activities give a significant input of sulfate and chloride ions, as well as other contaminants, into the studied groundwater system through enhanced atmospheric deposition and municipal sewage, and that multiple isotopic tracers constitute a powerful tool to ascertain geochemical characteristics and origin of complex contaminants in groundwater.

The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

PubMed

Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

2009-12-01

Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

Fabrication of a nanometer thick nitrogen delta doped layer at the sub-surface region of (100) diamond

NASA Astrophysics Data System (ADS)

Chandran, Maneesh; Michaelson, Shaul; Saguy, Cecile; Hoffman, Alon

2016-11-01

In this letter, we report on the proof of a concept of an innovative delta doping technique to fabricate an ensemble of nitrogen vacancy centers at shallow depths in (100) diamond. A nitrogen delta doped layer with a concentration of ˜1.8 × 1020 cm-3 and a thickness of a few nanometers was produced using this method. Nitrogen delta doping was realized by producing a stable nitrogen terminated (N-terminated) diamond surface using the RF nitridation process and subsequently depositing a thin layer of diamond on the N-terminated diamond surface. The concentration of nitrogen on the N-terminated diamond surface and its stability upon exposure to chemical vapor deposition conditions are determined by x-ray photoelectron spectroscopy analysis. The SIMS profile exhibits a positive concentration gradient of 1.9 nm/decade and a negative gradient of 4.2 nm/decade. The proposed method offers a finer control on the thickness of the delta doped layer than the currently used ion implantation and delta doping techniques.

Changes in fatty acid composition in plant tissues expressing a mammalian delta9 desaturase.

PubMed

Moon, H; Hazebroek, J; Hildebrand, D F

2000-05-01

Plant tissues expressing a mammalian stearoyl-CoA delta9 desaturase were reported to accumulate delta9 hexadecenoic acid (16:1), normally very minor in most plant tissues. The transgenic plants were thoroughly analyzed for alterations of individual lipids in different subcellular sites. Western blot analysis indicated that the animal desaturase was targeted to the microsomes. The delta9 16:1 was incorporated into both the sn-1 and sn-2 positions of all the major membrane lipids tested, indicating that the endoplasmic reticulum acyltransferases do not exclude unsaturated C16 fatty acids from the sn-2 position. In addition to increases in monounsaturated and decreases in saturated fatty acids, accumulation of 16:1 was accompanied by a reduction in 18:3 in all the lipids tested except phosphatidylglycerol, and increases in 18:2 in phospholipids. Total C16 fatty acid content in the galactolipids of the transgenics was significantly higher than that in the control, but those in the phospholipids were unchanged. In transgenics, delta11 18:1 was detected in the sn-1 position of the lipids tested except phosphatidylinositol and phosphatidylserine. Introduction of the animal desaturase, controlled by a seed-specific phaseolin promoter, into soybean somatic embryo resulted in a significant reduction in saturated fatty acids. Such effects were greater in cotyledons than hypocotyl-radicles. This study demonstrated that the animal desaturase can be used to decrease the levels of saturated fatty acids in a crop plant.

Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

PubMed

Berndt, T J; Tucker, R R; Kent, P D; Streiff, P C; Tyce, G M; Knox, F G

1999-12-01

The phosphaturic response to parathyroid hormone (PTH) is blunted during acute respiratory alkalosis. The objective of the present study was to determine the effect of dopamine on the blunted phosphaturic response to PTH during acute respiratory alkalosis. The phosphaturic response to PTH was determined in thyroparathyroidectomized (TPTX) normocapnic and respiratory alkalotic rats in the absence and presence of the infusion of exogenous dopamine (25 microg/kg/min) or of 3,4-dihydroxyphenylalanine (L-DOPA, 250 microg/kg/min) to increase endogenous dopamine synthesis. In normocapnic rats, PTH infusion (33 U/kg plus 1 U/kg/min) significantly increased the fractional excretion of phosphate (FE(Pi)), from 1.5%+/-0.5% to 28.4%+/-4.0%, (deltaFE(Pi) 26.9%+/-4.1%, n = 11, P<.05); in respiratory alkalotic rats, the increase was from 0.4%+/-0.1% to 11.4%+/-1.7% (deltaFE(Pi) 11.0%+/-1.8%, n = 13, P<.05). However, the phosphaturic response to PTH was attenuated in respiratory alkalotic rats (deltaFE(Pi) 26.9%+/-4.1% vs 11.0%+/-1.9%, P<.05). In normocapnic rats, in the presence of dopamine or L-DOPA infusions, PTH infusion significantly increased the FE(Pi) from 6.1%+/-2.3% to 33.4%+/-8.0% (deltaFE(Pi) 27.3%+/-7.0%, n = 5) and from 3.2%+/-0.6% to 32.5%+/-3.3% (deltaFE(Pi) 29.3%+/-3.2%, n = 7), respectively. In respiratory alkalotic rats, in the presence of dopamine infusion, PTH significantly increased the FE(Pi), from 0.6%+/-0.2% to 19.3%+/-3.3% (deltaFE(Pi) 18.7%+/-3.3%, n = 6); in the presence of L-DOPA infusion it increased from 1.0%+/-0.3% to 20.5%+/-2.8% (deltaFE(Pi) 19.5%+/-2.9%, n = 8, P<.05 as compared with PTH alone). Thus the phosphaturic effect of PTH that was attenuated in respiratory alkalotic rats was enhanced by stimulation of endogenous dopamine synthesis by the infusion of L-DOPA.

Raman spectroscopy and melting of nitrogen between 290 and 900 K and 2. 3 and 18 GPa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zinn, A.S.; Schiferl, D.; Nicol, M.F.

1987-07-15

Raman spectroscopy was used to study the melting of nitrogen from 290 to 900 K at pressures from 2.3 to 18 GPa. This work, which extends the melting by a factor of 9 over previously published results was made possible by new developments in high-temperature diamond-anvil cells. The ..beta../delta phase boundary was also determined, and the ..beta..--delta--fluid triple point was found to be at 578 +- 10 K and 9.9 +- 0.5 GPa. The Raman frequencies of the vibron in fluid N/sub 2/ and the ..nu../sub 2/ vibron in delta-N/sub 2/ were found to have the same pressure dependence andmore » be independent of temperature to a good approximation. A temperature-independent pressure scale, useful to at least 900 K is approximated by P/GPa = 0.4242 ..nu../cm/sup -1/ -987.8, where ..nu.. is the frequency of either the ..nu../sub 2/ vibron in delta-N/sub 2/ or the vibron in fluid-N/sub 2/.« less

Sarcoplasmic reticulum calcium release compared in slow-twitch and fast-twitch fibres of mouse muscle.

PubMed

Baylor, S M; Hollingworth, S

2003-08-15

Experiments were carried out to compare the amplitude and time course of Ca2+ release from the sarcoplasmic reticulum (SR) in intact slow-twitch and fast-twitch mouse fibres. Individual fibres within small bundles were injected with furaptra, a low-affinity, rapidly responding Ca2+ indicator. In response to a single action potential at 16 degrees C, the peak amplitude and half-duration of the change in myoplasmic free [Ca2+] (Delta[Ca2+]) differed significantly between fibre types (slow-twitch: peak amplitude, 9.4 +/- 1.0 microM (mean +/- S.E.M.); half-duration, 7.7 +/- 0.6 ms; fast-twitch: peak amplitude 18.5 +/- 0.5 microM; half-duration, 4.9 +/- 0.3 ms). SR Ca2+ release was estimated from Delta[Ca2+] with a computational model that calculated Ca2+ binding to the major myoplasmic Ca2+ buffers (troponin, ATP and parvalbumin); buffer concentrations and reaction rate constants were adjusted to reflect fibre-type differences. In response to an action potential, the total concentration of released Ca2+ (Delta[CaT]) and the peak rate of Ca2+ release ((d/dt)Delta[CaT]) differed about 3-fold between the fibre types (slow-twitch: Delta[CaT], 127 +/- 7 microM; (d/dt)Delta[CaT], 70 +/- 6 microM ms-1; fast-twitch: Delta[CaT], 346 +/- 6 microM; (d/dt)Delta[CaT], 212 +/- 4 microM ms-1). In contrast, the half-duration of (d/dt)Delta[CaT] was very similar in the two fibre types (slow-twitch, 1.8 +/- 0.1 ms; fast-twitch, 1.6 +/- 0.0 ms). When fibres were stimulated with a 5-shock train at 67 Hz, the peaks of (d/dt)Delta[CaT] in response to the second and subsequent shocks were much smaller than that due to the first shock; the later peaks, expressed as a fraction of the amplitude of the first peak, were similar in the two fibre types (slow-twitch, 0.2-0.3; fast-twitch, 0.1-0.3). The results support the conclusion that individual SR Ca2+ release units function similarly in slow-twitch and fast-twitch mammalian fibres.

Review of the neurological benefits of phytocannabinoids.

PubMed

Maroon, Joseph; Bost, Jeff

2018-01-01

Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. In 1980, Cunha et al . reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes.

Dynamic stretching and golf swing performance.

PubMed

Moran, K A; McGrath, T; Marshall, B M; Wallace, E S

2009-02-01

The aim of the present study was to examine the effect of dynamic stretching, static stretching and no stretching, as part of a general warm-up, on golf swing performance with a five-iron. Measures of performance were taken 0 min, 5 min, 15 min and 30 min after stretching. Dynamic stretching produced significantly greater club head speeds than both static stretching (Delta=1.9m.s (-1); p=0.000) and no stretching (Delta=1.7 m.s (-1); p=0.000), and greater ball speeds than both static stretching (Delta=3.5m.s (-1); p=0.003) and no stretching (Delta=3.3m.s (-1); p=0.001). Dynamic stretching produced significantly straighter swing-paths than both static stretching (Delta=-0.61 degrees , p=0.000) and no stretching (Delta=-0.72 degrees , p=0.01). Dynamic stretching also produced more central impact points than the static stretch (Delta=0.7 cm, p=0.001). For the club face angle, there was no effect of either stretch or time. For all of the variables measured, there was no significant difference between the static stretch and no stretch conditions. All of the results were unaffected by the time of measurement after stretching. The results indicate that dynamic stretching should be used as part of a general warm-up in golf.

YALE NATURAL RADIOCARBON MEASUREMENTS. PART VI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuiver, M.; Deevey, E.S.

1961-01-01

Most of the measurements made since publication of Yale V are included; some measurements, such as a series collected in Greenland, are withneld pending additional information or field work that will make better interpretations possible. In addition to radiocarbon dates of geologic and/or archaeologic interest, recent assays are given of C/sup 14/ in lake waters and other lacustrine materials, now normalized for C/sup 13/ content. The newly accepted convention is followed in expressing normalized C/sup 14/ values as DELTA = delta C/sup 14/ (2 delta C/sup 13/ + 50)STAl + ( delta C/sup 14//1000)! where DELTA is the per milmore » deviation of the C/sup 14/ if the sample from any contemporary standard (whether organic or a carbonate) after correction of sample and/or standard for real age, for the Suess effect, for normal isotopic fractionation, and for deviations of C/sup 14/ content of the age- and pollution- corrected l9th-century wood standard from that of 95% of the NBS oxalic acid standard; delta C/sup 14/ is the measured deviation from 95% of the NBS standard, and delta C/sup 13/ is the deviation from the NBS limestone standard, both in per mil. These assays are variously affected by artificial C/sup 14/ resulting from nuclear tests. (auth)« less

Functional characterisation of two cytochrome b5-fusion desaturases from Anemone leveillei: the unexpected identification of a fatty acid Delta6-desaturase.

PubMed

Whitney, Heather M; Michaelson, Louise V; Sayanova, Olga; Pickett, John A; Napier, Johnathan A

2003-10-01

The Ranunculaceae are known to accumulate a wide range of unusual fatty acids in their seed lipids, and this variability has been advocated as a taxonomic marker. The Anemone species, Anemone leveillei L. and Anemone rivularis Buch.-Ham., have previously been reported to accumulate Delta5-desaturated fatty acids in their seed tissue [K. Aitzetmüller (1995) Plant Syst Evol 9:229-240]. Two cDNAs, AL1 and AL2, with similarity to plant cytochrome b5-fusion "front-end" desaturases were isolated from developing seeds of A. leveillei and their function identified by expression in Saccharomyces cerevisiae. AL2 was characterised as a sphingolipid long-chain-base Delta8-desaturase, while AL1 acted as a fatty acid desaturase. However, AL1 did not produce Delta5-desaturated fatty acids as expected; instead, when expressed in transgenic S. cerevisiae or Arabidopsis thaliana this enzyme was functionally characterised as a Delta6-desaturase. Northern analysis confirmed the expression of this gene in seed tissue and leaf tissue of A. leveillei, though Delta6-desaturated fatty acids were found to accumulate only in the leaf tissue. The unexpected characterisation of a Delta6-desaturase in A. leveillei has implications for the use of fatty acids in chemotaxonomic studies. This is also the first report of a higher-plant Delta6-desaturase from a family other than the Boraginaceae.

Influence of internal biogas production on hydrodynamic behavior of anaerobic fluidized-bed reactors.

PubMed

Wu, Chun-Sheng; Huang, Ju-Sheng; Chou, Hsin-Hsien

2006-01-01

Predictive models for describing the hydrodynamic behavior (bed-expansion and bed-pressure gradient) of a three-phase anaerobic fluidized bed reactor (AFBR) was developed according to wake theory together with more realistic dynamic bed-expansion experiments (with and without internal biogas production). A reliable correlation equation for the parameter k (mean volume ratio of wakes to bubbles) was also established, which is of help in estimating liquid hold up of fluidized beds. The experimental expansion ratio of three-phase fluidized beds (E(GLS)) was approximately 18% higher than that of two-phase fluidized beds (E(LS)); whereas the experimental bed-pressure gradient of the former [(-DeltaP/H)(GLS)] was approximately 9.3% lower than that of the latter [(-DeltaP/H)(LS)]. Both the experimental and modeling results indicated that a higher superficial gas velocity (u(g)) gave a higher E(GLS) and a higher E(GLS) to E(LS) ratio as well as a lower (-DeltaP/H)(GLS) and a lower (-DeltaP/H)(GLS) to (-DeltaP/H)(LS) ratio. As for the operation stability of the AFBR, the sensitivity of u(g) to expansion height (H(GLS)) and (-DeltaP/H)(GLS) is between the sensitivity of superficial liquid velocity and biofilm thickness. The model predictions of E(GLS), (-DeltaP)(GLS), and (-DeltaP/H)(GLS) agreed well the experimental measurements. Accordingly, the predictive models accounting for internal biogas production described fairly well the hydrodynamic behavior of the AFBR.

Color characteristics of low-chroma and high-translucence dental resin composites by different measuring modes.

PubMed

Lee, Y K; Lim, B S; Kim, C W; Powers, J M

2001-01-01

The objective of the described research was the evaluation of the effects of the differences in the color-measuring geometry (SCE, SCI) and the standard illuminant on the color and color change after polymerization and thermocycling of resin composites. White, translucent, and conventional shades of two brands of resin composites were measured before and after polymerization and after thermocycling according to the CIE L*a*b* color scale on a reflection spectrophotometer with SCE and SCI geometry under the standard illuminants A, D65, and C. Under both SCE and SCI modes, the color differences (DeltaE*) of specimens between the values measured under illuminants A and D65 or A and C were larger than those between D65 and C in unpolymerized, polymerized, and thermocycled conditions. With SCE geometry, DeltaE* after polymerization of the white shade group was 8.7-9.8 under D65, and was higher than the conventional shade group (p < 0.05) in both materials. With SCE geometry, DeltaE* between polymerized and thermocycled white, translucent shade was 4.4-7.1 under D65. With SCI geometry, the results were in general agreement with those of SCE mode. After polymerization, DeltaE* measured under illuminant A was generally higher than that under D65 or C (p < 0.01). After thermocycling, the color change was different depending on the color-measuring geometry and standard illuminant. Copyright 2001 John Wiley & Sons, Inc.

Analysis of cannabis in oral fluid specimens by GC-MS with automatic SPE.

PubMed

Choi, Hyeyoung; Baeck, Seungkyung; Kim, Eunmi; Lee, Sooyeun; Jang, Moonhee; Lee, Juseon; Choi, Hwakyung; Chung, Heesun

2009-12-01

Methamphetamine (MA) is the most commonly abused drug in Korea, followed by cannabis. Traditionally, MA analysis is carried out on both urine and hair samples and cannabis analysis in urine samples only. Despite the fact that oral fluid has become increasingly popular as an alternative specimen in the field of driving under the influence of drugs (DUID) and work place drug testing, its application has not been expanded to drug analysis in Korea. Oral fluid is easy to collect and handle and can provide an indication of recent drug abuse. In this study, we present an analytical method using GC-MS to determine tetrahydrocannabinol (THC) and its main metabolite 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in oral fluid. The validated method was applied to oral fluid samples collected from drug abuse suspects and the results were compared with those in urine. The stability of THC and THC-COOH in oral fluid stored in different containers was also investigated. Oral fluid specimens from 12 drug abuse suspects, submitted by the police, were collected by direct expectoration. The samples were screened with microplate ELISA. For confirmation they were extracted using automated SPE with mixed-mode cation exchange cartridge, derivatized and analyzed by GC-MS using selective ion monitoring (SIM). The concentrations ofTHC and THC-COOH in oral fluid showed a large variation and the results from oral fluid and urine samples from cannabis abusers did not show any correlation. Thus, detailed information about time interval between drug use and sample collection is needed to interpret the oral fluid results properly. In addition, further investigation about the detection time window ofTHC and THC-COOH in oral fluid is required to substitute oral fluid for urine in drug testing.

Differential effects of presynaptic versus postsynaptic adenosine A2A receptor blockade on Δ9-tetrahydrocannabinol (THC) self-administration in squirrel monkeys.

PubMed

Justinová, Zuzana; Redhi, Godfrey H; Goldberg, Steven R; Ferré, Sergi

2014-05-07

Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynaptic A2A receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2A receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously self-administer THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2A receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.

Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms.

PubMed

Morrison, Paul D; Nottage, Judith; Stone, James M; Bhattacharyya, Sagnik; Tunstall, Nigel; Brenneisen, Rudolf; Holt, David; Wilson, Daniel; Sumich, Alex; McGuire, Philip; Murray, Robin M; Kapur, Shitij; Ffytche, Dominic H

2011-03-01

The main ingredient in cannabis, Δ(9)-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence. In a within-subjects design, participants (n=16) were given intravenous THC (1.25 mg) or placebo under double-blind conditions, during EEG recordings. Using fast-Fourier transform, EEG data were analyzed for power and coherence in the delta (1-3.5 Hz), theta (3.5-7 Hz), alpha (8-13 Hz), beta (14-25 Hz), low-gamma (30-40 Hz), and high-gamma (60-70 Hz) bands during engagement in the n-back test of working memory (WM). Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001) and slowed WM performance (p<0.05). Under THC, theta power was specifically reduced, (p<0.001) regardless of WM load; however, the reduction showed no relationship with psychotic symptoms or WM impairment. Coherence between bi-frontal electrodes in the theta band was also reduced by THC (p<0.05) and these reductions correlated with the change-in positive psychotic symptoms (rho=0.79, p<0.001). Bi-frontal specificity was suggested by the absence of a relationship between psychotic symptoms and fronto-parietal coherence. The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.

Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.

PubMed

Hindocha, Chandni; Freeman, Tom P; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K; Morgan, Celia J A; Curran, H Valerie

2015-03-01

Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users

PubMed Central

Hindocha, Chandni; Freeman, Tom P.; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K.; Morgan, Celia J.A.; Curran, H. Valerie

2015-01-01

Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. PMID:25534187

How Many Ultra-Low Delta-v Near Earth Objects Remain Undiscovered? Implications for missions.

NASA Astrophysics Data System (ADS)

Elvis, Martin; Ranjan, Sukrit; Galache, Jose Luis; Murphy, Max

2015-08-01

The past decade has witnessed considerable growth of interest in missions to Near-Earth Objects (NEOs). NEOs are considered prime targets for manned and robotic missions, for both scientific objectives as well as in-situ resource utilization including harvesting of water for propellant and life support and mining of high-value elements for sale on Earth. Appropriate targets are crucial to such missions. Hence, ultra-low delta-v mission targets are strongly favored. Some mission architectures rely on the discovery of more ultra-low delta-v NEOs. In fact the approved and executed NEO missions have all targeted asteroids with ultra-low LEO to asteroid rendezvous delta-v <5.5 km/s.In this paper, we estimate the total NEO population as a function of delta-v, and how many remain to be discovered in various size ranges down to ~100m. We couple the NEOSSat-1 model (Greenstreet et al., 2012) to the NEO size distribution derived from the NEOWISE survey (Mainzer et al., 2011b) to compute an absolute NEO population model. We compare the Minor Planet Center (MPC) catalog of known NEOs to this NEO population model. We compute the delta-v from LEO to asteroid rendezvous orbits using a modified Shoemaker-Helin (S-H) formalism that empirically removes biases found comparing S-H with the results from NHATS. The median delta-v of the known NEOs is 7.3 km/s, the median delta-v predicted by our NEO model is 9.8 km/s, suggesting that undiscovered objects are biased to higher delta-v. The survey of delta-v <10.3 km/s NEOs is essentially complete for objects with diameter D >300 m. However, there are tens of thousands of objects with delta-v <10.3 km/s to be discovered in the D = 50 - 300 m size class (H = 20.4 - 24.3). Our work suggests that there are 100 yet-undiscovered NEOs with delta-v < 5:8 km/s, and 1000 undiscovered NEOs with v < 6.3 km/s. We conclude that, even with complete NEO surveys, the selection of good (i.e. ultra-low delta-v) mission targets is limited given current propulsion technology. Visiting the full range of NEO sub-types will likely require improved propulsion systems.

Constraining Holocene Evolution of Shelf Bayhead Delta Deposits Offshore Mississippi, USA

NASA Astrophysics Data System (ADS)

Hollis, R. J.; Wallace, D. J.; Miner, M. D.

2017-12-01

The slowly subsiding inner shelf of Mississippi-Alabama (MS-AL) has a complex network of Late Quaternary paleofluvial and deltaic deposits driven by fluctuating sea levels. Since the Last Glacial Maximum, sea-level rise (SLR) has lead to transgressive reworking of these lithosomes. In rare instances, typically when the rate of relative sea-level rise was particularly rapid or sediment supply was high, these deposits are preserved. Results from studies in Texas and Alabama suggest bayhead deltas (or upper-estuarine units) backstepped kilometers landward in response to periods of rapid sea-level rise (i.e. 9.8-9.5 ka, 8.9-8.5 ka, 8.4-8.0 ka, 7.9-7.5 ka, and 7.4-6.8 ka). Bayhead delta backstepping depends on relative SLR rates, accommodation space, shelf slope, wave climate and sediment supply. While at least one preserved bayhead delta deposit has been identified on the inner shelf of MS-AL, the flooding and abandonment chronology is currently unknown. The previously quantified sandy bayhead delta deposit (>100.4 x106 m3) is roughly twice the combined volume of the subaerial Petit Bois barrier island, located two miles to the north, and the three western offshore shelf sand shoals (55.9 x106 m3). The sediment supply needed for the shoal's genesis requires further exploration and likely has many contributors, but transgressive ravinement of the sandy bayhead delta seems like a logical source. This study builds on previous work that has extensively mapped the stratigraphy of the eastern MS-AL inner shelf using geophysical and core data by adding a robust number of radiocarbon ages and macro-/micro- faunal analysis from new cores as a proxy for depositional environments. This source-to-sink approach helps to detail the evolution of ancient Pascagoula/Escatawpa, La Batre and Fowl paleo rivers, and their roles in the formation of the large inner shelf, shore-oblique shoals as well as Petit Bois Island. Correlating the new ages with previously published high-resolution sea level curves will be a valuable resource toward predicting future barrier island responses with accelerated SLR in the Gulf of Mexico by understanding the Holocene evolution of Petit Bois Island, adjacent bayhead deltas, and offshore sand shoals.

Distribution of hexadecenoic, octadecenoic and octadecadienoic acid isomers in human tissue lipids.

PubMed

Adlof, R O; Emken, E A

1986-09-01

The trans 16:1, 18:1 and 18:2 fatty acid composition of various human organ lipids was studied to determine if isomers accumulated in specific tissues. "Trans" isomers are defined as those fatty acids containing one or more trans double bonds. Adipose, kidney, brain, heart and liver tissue lipids were analyzed. Gas chromatography with a 100-SP2560 capillary column was used to characterize the various positional and/or geometrical isomers. The distribution of trans 16:1 and 18:1 isomers ranged from 0.3% in the brain to 4.0% in adipose tissue, while trans 18:2 isomers ranged from 0.0% in the brain to 0.4% in adipose tissue. No trans 18:3 isomers were detected. Positional isomer ratios for cis 16:1 (delta 9 vs delta 7) and cis 18:1 (delta 11 vs delta 9) were also determined. Since these ratios are reproducible from one individual to the next, they might be useful for diagnosis of human metabolic disorders.

Unlocking the ice house: Oligocene-Miocene oxygen isotopes, eustasy, and margin erosion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, K.G.; Wright, J.D.; Fairbanks, R.G.

1991-04-10

Benthic foraminiferal {delta}{sup 18}O records place limits on the history of glaciation, suggesting the presence of ice sheets at least intermittently since the earliest Oligocene. The best indicator of ice growth is a coeval increase in global benthic and western equatorial planktonic {delta}{sup 18}O records. Although planktonic isotope records from the western equatorial regions are limited, subtropical planktonic foraminifera may also record such ice volume changes. It is difficult to apply these established principles to the Cenozoic {delta}{sup 18}O record because of the lack of adequate data and problems in stratigraphic correlations that obscure isotope events. The authors improved Oligocenemore » to Miocene correlations of {delta}{sup 18}O records and erected eight oxygen isotope zones (Oi1-Oi2, Mi1-Mi6). Benthic foraminiferal {delta}{sup 18}O increases which can be linked with {delta}{sup 18}O increases in subtropical planktonic foraminifera and with intervals of glacial sedimentation on or near Antarctica. These new correlations of middle Miocene benthic and western equatorial planktonic {delta}{sup 18}O records show remarkable agreement in timing and amplitude. They interpret benthic-planktonic covariance to reflect substantial ice volume increases near the bases of Zones Mi2 (circa 16.1 Ma), Mi3 (circa 13.6 Ma), and possibly Mi5 (circa 11.3 Ma). Possible glacioeustatic lowerings are associated with the {delta}{sup 18}O increases which culminated with the bases of Zone Mi4 (circa 12.6 Ma) and Mi6 (circa 9.6 Ma), although low-latitude planktonic {delta}{sup 18}O records are required to test this. These inferred glacioeustatic lowerings can be linked to seismic and rock disconformities.« less

Inversion and Prediction of Consolidation Settlement Characteristics of the Fluvial Sediments Based on Void Ratio Variation in the Northern Modern Yellow River Subaqueous Delta, China

NASA Astrophysics Data System (ADS)

Liu, Xiao; Liu, Jie; Feng, Xiuli

2018-06-01

The modern Yellow River delta is formed near the estuary of the Yellow River with the characteristics of short formation time, efficient sedimentation rate and loose structure which make sediments prone to be compacted and consolidate under the geostatic stress and overburden stress. It is one of the key areas with land subsidence disasters in China, bringing a series of safety hazards to production and living. Based on the data of massive surface cores and ten drill holes ranging from 12 to 40 m obtained from the northern modern Yellow River subaqueous delta, the inversion method suitable for the calculation of consolidation settlement characteristics of the modern Yellow River subaqueous delta is discussed, and the consolidation settlement characteristics of the delta sediments are inversed and predicted in this paper. The actual void ratio of the delta sediments at the depth from 3 to 15 m shows a significant power function relationship with the depth, while the void ratio of the sediments below 15 m changes little with depth. The pre-consolidation settlement (from deposition to sampling) of the delta sediments is between 0.91 and 1.96 m, while the consolidation settlement of unit depth is between 9.6 and 14.0 cm m-1. The post-consolidation settlement (from sampling to stable) of the subaqueous delta sediments is between 0.65 and 1.56 m in the later stage, and the consolidation settlement of unit depth is between 7.6 and 13.1 cm m-1 under the overburden stress. The delta sediments with a buried depth of 3 to 7 m contribute the most to the possible consolidation settlement in the later stage.

Dynamic Towed Array Models and State Estimation for Underwater Target Tracking

DTIC Science & Technology

2013-09-01

adjusting the value of 2q impacts how much non-linear acceleration the model can handle. In [22] it is shown that the best value for 2q is generated...partial_brng_x1 = (-deltaY) / ((deltaY)^2 + (deltaX)^2); partial_brng_x3 = (deltaX) / ((deltaY)^2 + (deltaX)^2); H11 = partial_brng_x1; H13 ...freq_recHat]; H11 = -deltaY/Rng^2; H13 = deltaX/Rng^2; Mult = xhat(5)/Sound_Spd; T1 = Mult*deltaY/Rng^3; T2 = ((deltaVx)*(deltaY)-(deltaVy

[Can the scattering of differences from the target refraction be avoided?].

PubMed

Janknecht, P

2008-10-01

We wanted to check how the stochastic error is affected by two lens formulae. The power of the intraocular lens was calculated using the SRK-II formula and the Haigis formula after eye length measurement with ultrasound and the IOL Master. Both lens formulae were partially derived and Gauss error analysis was used for examination of the propagated error. 61 patients with a mean age of 73.8 years were analysed. The postoperative refraction differed from the calculated refraction after ultrasound biometry using the SRK-II formula by 0.05 D (-1.56 to + 1.31, S. D.: 0.59 D; 92 % within +/- 1.0 D), after IOL Master biometry using the SRK-II formula by -0.15 D (-1.18 to + 1.25, S. D.: 0.52 D; 97 % within +/- 1.0 D), and after IOL Master biometry using the Haigis formula by -0.11 D (-1.14 to + 1.14, S. D.: 0.48 D; 95 % within +/- 1.0 D). The results did not differ from one another. The propagated error of the Haigis formula can be calculated according to DeltaP = square root (deltaL x (-4.206))(2) + (deltaVK x 0.9496)(2) + (DeltaDC x (-1.4950))(2). (DeltaL: error measuring axial length, DeltaVK error measuring anterior chamber depth, DeltaDC error measuring corneal power), the propagated error of the SRK-II formula according to DeltaP = square root (DeltaL x (-2.5))(2) + (DeltaDC x (-0.9))(2). The propagated error of the Haigis formula is always larger than the propagated error of the SRK-II formula. Scattering of the postoperative difference from the expected refraction cannot be avoided completely. It is possible to limit the systematic error by developing complicated formulae like the Haigis formula. However, increasing the number of parameters which need to be measured increases the dispersion of the calculated postoperative refraction. A compromise has to be found, and therefore the SRK-II formula is not outdated.

Stable isotope analyses of the peralkaline volcanics Gregory Rift Valley, Kenya

NASA Technical Reports Server (NTRS)

Black, S.; Macdonald, R.; Fallick, A. E.; Kelly, M.

1993-01-01

Delta O-18 analyses of the Naivasha rhyolites, basalts, Menengai trachytes and the Yatta phonolite are presented together with D/H analyses of the Naivasha rhyolites. Delta O-18 results vary from 5.7 to 8.9 per mill which is within the reported range of delta O-18 analyses for continental volcanics. Closure temperatures calulated from the basalts and rhyolites show equilibration to be at magmatic temperatures. D/H values range from -40 to -148 per mill indicating that the rhyolites have undergone large scale degasssing.

Delta modulation

NASA Technical Reports Server (NTRS)

Schilling, D. L.

1971-01-01

The conclusions of the design research of the song adaptive delta modulator are presented for source encoding voice signals. The variation of output SNR vs input signal power/when 8, 9, and 10 bit internal arithmetic is employed. Voice intelligibility tapes to test the 10-bit system are used. An analysis of a delta modulator is also presented designed to minimize the in-band rms error. This is accomplished by frequency shaping the error signal in the modulator prior to hard limiting. The result is a significant increase in the output SNR measured after low pass filtering.

Nuclear Microprobe using Elastic Recoil Detection (ERD) for Hydrogen Profiling in High Temperature Protonic Conductors

NASA Technical Reports Server (NTRS)

Berger, Pascal; Sayir, Ali; Berger, Marie-Helene

2004-01-01

The interaction between hydrogen and various high temperature protonic conductors (HTPC) has not been clearly understood due to poor densification and unreacted secondary phases. the melt-processing technique is used in producing fully dense simple SrCe(0.9)Y (0.10) O(3-delta) and complex Sr3Ca(1+x)Nb(2+x)O(9-delta) perovskites that can not be achieved by solid-state sintering. the possibilities of ion beam analysis have been investigated to quantify hydrogen distribution in HTPC perovskites subjected to water heat treatment. Nuclear microprobe technique is based on the interactions of a focused ion beam of MeV light ions (H-1, H-2, He-3, He-4,.) with the sample to be analyzed to determine local elemental concentrations at the cubic micrometer scale, the elastic recoil detection analysis technique (ERDA) has been carried out using He-4(+) microbeams and detecting the resulting recoil protons. Mappings of longitudinal sections of water treated SrCeO3 and Sr(Ca(1/3)Nb(2/3))O3 perovskites have been achieved, the water treatment strongly alters the surface of simple SrCe(0.9)Y(0.10)O(3-delta) perovskite. From Rutherford Back Scattering measurements (RBS), both Ce depletion and surface re-deposition is evidenced. the ERDA investigations on water treated Sr3Ca(1+x)Nb(2+x)O(9-delta) perovskite did not exhibit any spatial difference for the hydrogen incorporation from the surface to the centre. the amount of hydrogen incorporation for Sr3Ca(1+x)Nb(2+x)O(9-delta) was low and required further development of two less conventional techniques, ERDA in forward geometry and forward elastic diffusion H-1(p,p) H-1 with coincidence detection.

In-Situ Oxygen Isotopic Composition of Tagish Lake: An Ungrouped Type 2 Carbonaceous Chondrite

NASA Technical Reports Server (NTRS)

Zolensky, Michael E.; Engrand, Cecile; Gounelle, Matthieu; Zolensky, Mike E.

2001-01-01

We have measured the oxygen isotopic composition of several components of Tagish Lake by ion microprobe. This meteorite constitutes the best preserved sample of C2 matter presently available for study. It presents two different lithologies (carbonate-poor and -rich) which have fairly comparable oxygen isotopic composition, with regard to both the primary or secondary minerals. For the olivine and pyroxene grains, their delta O-18 values range from - 10.5% to + 7.4% in the carbonate-poor lithology, with a mean Delta O-17 value of - 3.7 2.4%. In the carbonate-rich lithology, delta O-18 varies from - 7.9% to + 3.3%, and the mean Delta O-17 value is - 4.7 +/- 1.4%. Olivine inclusions (Fo(sub >99)) with extreme O-16-enrichment were found in both lithologies: delta O-18 = - 46.1 %, delta O-187= - 48.3% and delta O-18 = - 40.6%, delta O-17 = - 41.2% in the carbonate-rich lithology; delta O-18 = - 41.5%, delta O-17 = -43.4%0 in the carbonate-poor lithology. Anhydrous minerals in the carbonate-poor lithology are slightly more O-16-rich than in the carbonate-rich one. Four low-iron manganese-rich (LIME) olivine grains do not have an oxygen isotopic composition distinct from the other "normal" olivines. The phyllosilicate matrix presents the same range of oxygen isotopic compositions in both lithologies: delta O-18 from approximately 11 % to approximately 6%, with an average Delta. O-17 approximately 0%. Because the bulk Tagish Lake oxygen isotopic composition given by Brown et al. is on the high end of our matrix analyses, we assume that this "bulk Tagish Lake" composition probably only represents that of the carbonate-rich lithology. Calcium carbonates have delta O-18 values up to 35%, with Delta O-17 approximately 0.5%0. Magnetite grains present very high Delta O-17 values approximately + 3.4%0 +/- 1.2%. Given our analytical uncertainties and our limited carbonate data, the matrix and the carbonate seem to have formed in isotopic equilibrium. In that case, their large isotopic fractionation would argue for a low temperature (CM-like, T approximately 0 deg) formation. Magnetite probably formed during a separate event. Tagish Lake magnetite data is surprisingly compatible with that of R-chondrites and unequilibrated ordinary (LL3) chondrites. Our oxygen isotope data strongly supports the hypothesis of a single precursor for both lithologies. Drastic mineralogical changes between the two lithologies not being accompanied with isotopic fractionation seem compatible with the alteration model presented by Young et aI. Tagish Lake probably represents the first well preserved large sample of the C2 matter that dominates interplanetary matter since the formation of the solar system.

SU-F-T-586: Pre-Treatment QA of InCise2 MLC Plans On a Cyberknife-M6 Using the Delta4 System in SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidhalter, D; Henzen, D; Malthaner, M

Purpose: Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). Methods: In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed usingmore » a 10×10 cm{sup 2} field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. Results: All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. Conclusion: Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.« less

Effect of different high-palladium metal-ceramic alloys on the color of opaque and dentin porcelain.

PubMed

Stavridakis, Minos M; Papazoglou, Efstratios; Seghi, Robert R; Johnston, William M; Brantley, William A

2004-08-01

The color of dental porcelain depends on the type of metal substrate. Little research has been done to document the effects of different types of high-palladium alloys on the color of dental porcelain. The purpose of this in vitro study was to evaluate the effects of different high-palladium alloys on the resulting color of dentin porcelain, as well as on that of opaque porcelain after simulated dentin and glazing firing cycles. Three Pd-Cu-Ga alloys, Spartan Plus (S), Liberty (B), and Freedom Plus (F), and 5 Pd-Ga alloys, Legacy (L), IS 85 (I), Protocol (P), Legacy XT (X), and Jelenko No.1 (N), were examined. A Pd-Ag alloy, Super Star (T), was included for comparison to the high-palladium alloys, and the Au-Pd alloy, Olympia (O), served as the control. Six cast discs (16 x 1 mm) were prepared from each of the alloys. Shade B1 opaque porcelain (Vita-Omega) was applied at a final thickness of 0.1 mm. After 2 opaque porcelain firing cycles, the surfaces were airborne-particle abraded, and the specimens were divided into 2 groups. In the first group, 0.9 mm of B1 dentin porcelain was applied. The other group of specimens with only opaque porcelain underwent the same dentin porcelain and glazing firing cycles. Color differences (DeltaE) were determined with a colorimeter between the control and each experimental group, after the second opaque porcelain, second dentin porcelain, and glazing firing cycles. One-way analysis of variance and Dunnett's multiple range test were performed on the DeltaE data (alpha=.05). After the application of dentin porcelain, the 3 Pd-Cu-Ga alloys showed significantly different (P<.05) DeltaE values (S=2.3 +/- 0.5, B=1.4 +/- 0.3, and F=1.3 +/- 0.7) than the control group. After the glazing cycle of this group, the 3 Pd-Cu-Ga alloys and the Pd-Ag alloy exhibited significantly different (P<.05) DeltaE values (S=2.8 +/- 0.8, B=2.2 +/- 0.3, F=1.9 +/- 1.0, and T=1.4 +/- 0.5) than the control group. After the simulated dentin porcelain firing cycles, the specimens with only opaque porcelain exhibited significantly different (P<.05) DeltaE values (S=5.2 +/- 1.4, B=5.4 +/- 0.6, and F=3.9 +/- 0.2) than the control group. The color difference between the 3 Pd-Cu-Ga alloys with only opaque porcelain and the control group increased more after the simulated glazing cycle (S=6.6 +/- 1.5, B=6.3 +/- 0.5, and F=4.6 +/- 0.1). The observed color differences between the Pd-Ga alloys and the control group were not statistically significant at any point. The Pd-Cu-Ga alloys with only opaque porcelain, after the simulated dentin porcelain and glazing firing cycles, exhibited clinically unacceptable color differences. The application of dentin porcelain to the Pd-Cu-Ga alloys resulted in clinically acceptable color differences. The application of dentin porcelain to the Pd-Ag alloy, after the glazing firing cycle, resulted in clinically acceptable color differences (approximately 2.8 to 3.7 DeltaE CIELAB units). The Pd-Ag alloy specimens with only opaque porcelain did not exhibit significant color differences from the control group, whereas significant color differences from the control group after the dentin porcelain and glazing firing cycles were still clinically acceptable.

Delta Airlines LOFT training

NASA Technical Reports Server (NTRS)

Whitehead, J.

1981-01-01

A LOFT program was developed as part of the DC-9 training program which serves as a prototype for much of Delta's other aircraft training programs. The LOFT used differs little from the ideology presented in the Advisory Circular. Difficulty and experienced concerns regarding the effectiveness of LOFT as a complete training vehicle are explored.

Isotopic composition of sulphates from meteoric precipitation as an indicator of pollutant origin in Wrocław (SW Poland).

PubMed

Gorka, Maciej; Jedrysek, Mariusz-Orion; Strapoc, Dariusz

2008-06-01

This paper describes the results of isotopic analyses of (i) hydrogen and oxygen in water (delta DH2O and delta18OH2O ) and (ii) sulphur and oxygen in sulphates (delta34Ssulphate and delta18Osulphate) from atmospheric precipitation collected within a one-year period between 25 May 2004 and 25 May 2005 in Wrocław (SW Poland). The resulting equation of Local Meteoric Water Line for Wrocław is delta D=6.373xdelta18O-0.047, (r2=0.97, n=32). The delta34Ssulphate varies from 1.1 to 4.2 per thousand (with an average of 2.5 per thousand), delta18Osulphate varies from 9.0 to 16.7 per thousand (with an average of 13.8 per thousand) and delta18OH2O varies from-0.8 to-16.3 per thousand (with an average of-8.2 per thousand). The above results indicate two main sources of sulphates in Wrocław precipitation: (i) low-temperature secondary sulphates forming in situ in Wrocław from the atmospheric SO2 as well as precipitation water (heterogeneous and homogeneous pathways oxidation) and (ii) high-temperature primary sulphates forming in rapid high-temperature hydratation of SO3- in an immediate proximity of industrial chimneys. We hypothesise that the secondary low-temperature type of sulphates is probably formed from the local sulphur and oxygen reservoirs, whereas the primary high-temperature type is allochthonous and it is probably transported from industrial areas located outside of Wrocław.

Reliability of conventional shade guides in teeth color determination.

PubMed

Todorović, Ana; Todorović, Aleksandar; Gostović, Aleksandra Spadijer; Lazić, Vojkan; Milicić, Biljana; Djurisić, Slobodan

2013-10-01

Color matching in prosthodontic therapy is a very important task because it influences the esthetic value of dental restorations. Visual shade matching represents the most frequently applied method in clinical practice. Instrumental measurements provide objective and quantified data in color assessment of natural teeth and restorations. In instrumental shade analysis, the goal is to achieve the smallest deltaE value possible, indicating the most accurate shade match. The aim of this study was to evaluate the reliability of commercially available ceramic shade guides. VITA Easyshade spectrophotometer (VITA, Germany) was used for instrumental color determination. Utilizing this device, color samples of ten VITA Classical and ten VITA 3D - Master shade guides were analyzed. Each color sample from all shade guides was measured three times and the basic parameters of color quality were examined: deltaL, deltaC, deltaH, deltaE, deltaElc. Based on these parameters spectrophotometer marks the shade matching as good, fair or adjust. After performing 1,248 measurements of ceramic color samples, frequency of evaluations adjust, fair and good were statistically significantly different between VITA Classical and VITA 3D Master shade guides (p = 0.002). There were 27.1% cases scored as adjust, 66.3% as fair and 6.7% as good. In VITA 3D - Master shade guides 30.9% cases were evaluated as adjust, 66.4% as fair and 2.7% cases as good. Color samples from different shade guides, produced by the same manufacturer, show variability in basic color parameters, which once again proves the lack of precision and nonuniformity of the conventional method.

Tequila authenticity assessment by headspace SPME-HRGC-IRMS analysis of 13C/12C and 18O/16O ratios of ethanol.

PubMed

Aguilar-Cisneros, Blanca O; López, Mercedes G; Richling, Elke; Heckel, Frank; Schreier, Peter

2002-12-18

By use of headspace SPME sampling and a PLOT column, on-line capillary gas chromatography-isotope ratio mass spectrometry was employed in the combustion (C) and the pyrolysis (P) modes (HRGC-C/P-IRMS) to determine the delta(13)C(VPDB) and delta(18)O(VSMOW) values of ethanol in authentic (n = 14) and commercial tequila samples (n = 15) as well as a number of other spirits (n = 23). Whereas with delta(13)C(VPDB) values ranging from -12.1 to -13.2 per thousand and from -12.5 to -14.8 per thousand similar variations were found for 100% agave and mixed tequilas, respectively, the delta(18)O(VSMOW) data differed slightly within these categories: ranges from +22.1 to +22.8 per thousand and +20.8 to +21.7 per thousand were determined for both the authentic 100% agave and mixed products, respectively. The data recorded for commercial tequilas were less homogeneous; delta(13)C(VPDB) data from -10.6 to -13.9 per thousand and delta(18)O(VSMOW) values from +15.5 to +22.7 per thousand were determined in tequilas of both categories. Owing to overlapping data, attempts to differentiate between white, rested, and aged tequilas within each of the two categories failed. In addition, discrimination of tequila samples from other spirits by means of delta(13)C(VPDB) and delta(18)O(VSMOW) data of ethanol was restricted to the products originating from C(3) as well as C(4)/CAM raw materials.

Assessment and potential sources of metals in the surface sediments of the Yellow River Delta, Eastern China.

PubMed

Cheng, Qingli; Lou, Guangyan; Huang, Wenhai; Li, Xudong

2017-07-01

The Yellow River Delta is the most intact estuary wetland in China and suffers from great pressure of metals. Seventy-seven surface sediment samples were collected in the delta, and contents of Cu, Pb, Cd, Cr, Zn, Ni, and Mn were analyzed by inductively coupled plasma spectrometry and those of Hg and As by atomic fluorescence spectrometry. The results showed that means of metal contents (ppm, dry weight) were as follows: Hg, 0.04; Cr, 61.72; Cu, 20.97; Zn, 60.73; As, 9.47; Pb, 21.91; Cd, 0.12; Ni, 27.24; and Mn, 540.48. 43.8% of Hg and 14.3% of Cd were from the allogenic source while others from the authigenic source. The results of the geoaccumulation indexes appeared that 6.5% of sites from the estuarine and the Gudao areas were moderately polluted by Hg. All ecological risk index values of Hg and 37.7% of Cd were more than 40, which were the main factors of strongly and moderately potential ecological risks of 37.7% of sites in the delta. High Cd contents may be due to the alkaline conditions of the delta and the unreasonable management of the farmland, while the abnormal distribution of Hg to the wet or dry deposition and the erosion of the seawater. It was suggested to monitor Hg content in the atmosphere of the Yellow River Delta. The results were expected to update the pollution status of metals in the delta and created awareness of preserving the sound condition of the Yellow River Delta.

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China.

PubMed

Wang, Dayan; Yang, Lei; Zhu, Wenfei; Zhang, Ye; Zou, Shumei; Bo, Hong; Gao, Rongbao; Dong, Jie; Huang, Weijuan; Guo, Junfeng; Li, Zi; Zhao, Xiang; Li, Xiaodan; Xin, Li; Zhou, Jianfang; Chen, Tao; Dong, Libo; Wei, Hejiang; Li, Xiyan; Liu, Liqi; Tang, Jing; Lan, Yu; Yang, Jing; Shu, Yuelong

2016-06-15

Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened. Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Two Outbreak Sources of Influenza A (H7N9) Viruses Have Been Established in China

PubMed Central

Wang, Dayan; Yang, Lei; Zhu, Wenfei; Zhang, Ye; Zou, Shumei; Bo, Hong; Gao, Rongbao; Dong, Jie; Huang, Weijuan; Guo, Junfeng; Li, Zi; Zhao, Xiang; Li, Xiaodan; Xin, Li; Zhou, Jianfang; Chen, Tao; Dong, Libo; Wei, Hejiang; Li, Xiyan; Liu, Liqi; Tang, Jing; Lan, Yu; Yang, Jing

2016-01-01

ABSTRACT Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened. IMPORTANCE Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China. PMID:27030268

A dynamic soil chamber system coupled with a tunable diode laser for online measurements of delta-13C, delta-18O, and efflux rate of soil respired CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powers, Heath H; Mcdowell, Nate; Hanson, David

2009-01-01

High frequency observations of the stable isotopic composition of CO(2) effluxes from soil have been sparse due in part to measurement challenges. We have developed an open-system method that utilizes a flow-through chamber coupled to a tunable diode laser (TDL) to quantify the rate of soil CO(2) efflux and its delta(13)C and delta(18)O values (delta(13)C(R) and delta(18)O(R), respectively). We tested the method first in the laboratory using an artificial soil test column and then in a semi-arid woodland. We found that the CO(2) efflux rates of 1.2 to 7.3 micromol m(-2) s(-1) measured by the chamber-TDL system were similar tomore » measurements made using the chamber and an infrared gas analyzer (IRGA) (R(2) = 0.99) and compared well with efflux rates generated from the soil test column (R(2) = 0.94). Measured delta(13)C and delta(18)O values of CO(2) efflux using the chamber-TDL system at 2 min intervals were not significantly different from source air values across all efflux rates after accounting for diffusive enrichment. Field measurements during drought demonstrated a strong dependency of CO(2) efflux and isotopic composition on soil water content. Addition of water to the soil beneath the chamber resulted in average changes of +6.9 micromol m(-2) s(-1), -5.0 per thousand, and -55.0 per thousand for soil CO(2) efflux, delta(13)C(R) and delta(18)O(R), respectively. All three variables initiated responses within 2 min of water addition, with peak responses observed within 10 min for isotopes and 20 min for efflux. The observed delta(18)O(R) was more enriched than predicted from temperature-dependent H(2)O-CO(2) equilibration theory, similar to other recent observations of delta(18)O(R) from dry soils (Wingate L, Seibt U, Maseyk K, Ogee J, Almeida P, Yakir D, Pereira JS, Mencuccini M. Global Change Biol. 2008; 14: 2178). The soil chamber coupled with the TDL was found to be an effective method for capturing soil CO(2) efflux and its stable isotope composition at high temporal frequency.« less

Cannabinoids for pediatric epilepsy? Up in smoke or real science?

PubMed Central

2015-01-01

Public interest in the use of “medical marijuana” for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in “medical marijuana” in general. Physicians and pediatricians must balance their patients’ desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological disease and specifically epilepsy is explored. The potential for adverse effects and particularly of neurotoxicity is addressed. Finally, public health and sociocultural implications are touched upon. Specific recommendations for interested physicians are provided including advocacy for patients and for a change in the “scheduling” of cannabis in order to better foster much-needed high-quality scientific research in this important area. PMID:26835389

The clinical pharmacology and dynamics of marihuana cigarette smoking.

PubMed

Perez-Reyes, M; Owens, S M; Di Guiseppi, S

1981-01-01

We have studied the dynamics of marihuana smoking, the plasma concentration of delta 9-tetrahydrocannabinol (THC), and the pharmacologic effects produced by the sequential smoking of two 1% marihuana cigarettes at a 2-hour interval. Three males and three females, experienced marihuana smokers, participated in the study. The results indicate that each subject smoked his or her two cigarettes at a similar rate. The THC plasma concentrations produced by the smoking of the second cigarette were slightly lower than those produced by the first cigarette. The levels of the psychologic "high" caused by the two cigarettes were similar. However, the first cigarette accelerated the heart twice as much as the second cigarette. Between males and females there were marked differences in the rate at which the cigarettes were smoked. In particular, males took more puffs, took them more often, and consumed the cigarettes more rapidly than females. The plasma concentrations of THC, the self-reported psychologic effects, and the heart rate acceleration produced by the smoking of the two cigarettes were identical between the sexes.

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

PubMed Central

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

What place for ▾ cannabis extract in MS?

PubMed

2012-12-01

Multiple sclerosis (MS) is a neurological condition that is estimated to affect around 60,000 people in England and Wales, with a lifetime risk in the UK of 1 in 1,000.(1,2) Spasticity (an increase in muscle tone) is a common symptom of MS, resulting in muscle spasms, immobility, disturbed sleep and pain.(3,4) Complex drug combinations are sometimes necessary to manage symptoms of MS, but these are often only partially effective and associated with unacceptable side effects.(5) Cannabis extract containing delta9-tetrahydrocannabinol (dronabinol) and cannabidiol are the principal extracts from the cannabis plant present in a licensed preparation (▾Sativex - GW Pharma Ltd), the first cannabinoid preparation to be approved for medical use. Sativex has been licensed "for symptom improvement in adult patients with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy".(6) Here we review the evidence for cannabis extract and its place in the treatment of the condition.

Catalyzing action towards the sustainability of deltas: deltas as integrated socio-ecological systems and sentinels of regional and global change

NASA Astrophysics Data System (ADS)

Foufoula-Georgiou, E.; Tessler, Z. D.; Brondizio, E.; Overeem, I.; Renaud, F.; Sebesvari, Z.; Nicholls, R. J.; Anthony, E.

2016-12-01

Deltas are highly dynamic and productive environments: they are food baskets of the world, home to biodiverse and rich ecosystems, and they play a central role in food and water security. However, they are becoming increasingly vulnerable to risks arising from human activities, land subsidence, regional water management, global sea-level rise, and climate extremes. Our Belmont Forum DELTAS project (BF-DELTAS: Catalyzing actions towards delta sustainability) encompasses an international network of interdisciplinary research collaborators with focal areas in the Mekong, Ganges Brahmaputra, and the Amazon deltas. The project is organized around five main modules: (1) developing an analytical framework for assessing delta vulnerability and scenarios of change (Delta-SRES), (2) developing an open-acess, science-based integrative modeling framework for risk assessment and decision support (Delta-RADS), (3) developing tools to support quantitative mapping of the bio-physical and socio-economic environments of deltas and consolidate bio-physical and social data within shared data repositories (Delta-DAT), (4) developing Global Delta Vulnerability Indices (Delta-GDVI) that capture current and projected scenarios for major deltas around the world , and (5) collaborating with regional stakeholders to put the science, modeling, and data into action (Delta-ACT). In this talk, a research summary will be presented on three research domains around which significant collaborative work was developed: advancing biophysical classification of deltas, understanding deltas as coupled socio-ecological systems, and analyzing and informing social and environmental vulnerabilities in delta regions.

Soil Organic Carbon Storage in Five Different Arctic Permafrost Environments

NASA Astrophysics Data System (ADS)

Fuchs, M.; Grosse, G.; Jones, B. M.; Maximov, G.; Strauss, J.

2016-12-01

Arctic river deltas and ice-rich permafrost regions are highly dynamic environments which will be strongly affected by future climate change. Rapid thaw of permafrost (thermokarst and thermo-erosion) may cause significant mobilization of organic carbon, which is assumed to be stored in large amounts in Arctic river deltas and ice-rich permafrost. This study presents and compares new data on organic carbon storage in thermokarst landforms and Arctic river delta deposits for the first two meters of soils for five different study areas in Alaska and Siberia. The sites include the Ikpikpuk river delta (North Alaska), Fish Creek river delta (North Alaska), Teshekpuk Lake Special Area (North Alaska), Sobo-Sise Island (Lena river delta, Northeast Siberia), and Bykovsky Peninsula (Northeast Siberia). Samples were taken with a SIPRE auger along transects covering the main geomorphological landscape units in the study regions. Our results show a high variability in soil organic carbon storage among the different study sites. The studied profiles in the Teshekpuk Lake Special Area - dominated by drained thermokarst lake basins - contained significantly more carbon than the other areas. The Teshekpuk Lake Special Area contains 44 ± 9 kg C m-2 (0-100 cm, mean value of profiles ± Std dev) compared to 20 ± 7 kg C m-2 kg for Sobo-Sise Island - a Yedoma dominated island intersected by thaw lake basins and 24 ± 6 kg C m-2 for the deltaic dominated areas (Fish Creek and Ikpikpuk). However, especially for the Ikpikpuk river delta, a significant amount of carbon (25 ± 9 kg C m-2) is stored in the second meter of soil (100-200cm). This study shows the importance of including deltaic and thermokarst-affected landscapes as considerable carbon pools, but indicates that these areas are heterogeneous in terms of organic carbon storage and cannot be generalized. As a next step, the site-level carbon stocks will be upscaled to the landscape level using remote sensing-based land cover classifications to calculate the carbon storage potential for Arctic deltas and larger thermokarst regions, to estimate mobilization potentials from thermokarst and thermo-erosion, and to provide input data for future permafrost carbon feedback models.

Na{sub 6}B{sub 13}O{sub 22.5}, a new noncentrosymmetric sodium borate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penin, N.; Touboul, M.; Nowogrocki, G.

2005-03-15

Na{sub 6}B{sub 13}O{sub 22.5} (B/Na=2.17) single crystals were obtained by heating, melting and appropriately cooling borax, Na{sub 2}[B{sub 4}O{sub 5}(OH){sub 4}].8H{sub 2}O. Its formula has been determined by the resolution of the structure from single-crystal X-ray diffraction data. The compound crystallizes in the noncentrosymmetric orthorhombic Iba2 space group, with the following unit cell parameters: a=33.359(11)A, b=9.554(3)A, c=10.644(4)A; V=3392.4(19)A{sup 3}; Z=8. The crystal structure was solved from 3226 reflections until R{sub 1}=0.0385. It exhibits a three-dimensional framework built up from BO{sub 3} triangles ({delta}) and BO{sub 4} tetrahedra (T). Two kinds of borate groups can be considered forming two different doublemore » B{sub 3}O{sub 3} rings: two B{sub 4}O{sub 9} (linkage by two boron atoms) and one B{sub 5}O{sub 11} (linkage by one boron atom); the shorthand notation of the new fundamental building block (FBB) existing in this compound is: 13: {infinity}{sup 3} [(5: 3{delta}+2T)+2(4: 2{delta}+2T)]. The discovery of this new borate questions the real number of Na{sub 2}B{sub 4}O{sub 7} varieties. The existence of Na{sub 6}B{sub 13}O{sub 22.5} (B/Na=2.17) and of another recently discovered borate, Na{sub 3}B{sub 7}O{sub 12} (B/Na=2.33; FBB 7: {infinity}{sup 3} [(3: 2{delta}+T)+(3: {delta}+2T)+(1: {delta})], with a composition close to the long-known borate {alpha}-Na{sub 2}B{sub 4}O{sub 7} (B/Na=2; FBB 8: {infinity}{sup 3} [(5: 3{delta}+2T)+(3: 2{delta}+T)], may explain the very complex equilibria reported in the Na{sub 2}O-B{sub 2}O{sub 3} phase diagram, especially in this range of composition.« less

[Effect of hydrochloric acid on cavernous pressure in the duodenogastroesphageal zone in patients with duodenal ulcer associated with Helicobacter pylori].

PubMed

Maev, I V; Gorban', V V; Salova, L M

2008-01-01

Endoscopic manometrografy was performed in 128 patients 40,7 +/- 1,7 years old with duodenal ulcer (DU). In patients with increased basal acid outflow (BAO > 10 MM/per hour vs. BAO < 7 MM/per hour) was increased pressure (mm Hg) in duodenum (11,8 +/- 1,0 vs. 9,2 +/- 0,5) and gastric antrum (11,4 +/- 0,6 vs. 9,3 +/- 0,4), decreased pylorus tone (18,5 +/- 2,4 vs. 30,6 +/- 2,2) and pressure gradient (deltaP) between low esophageal sphincter (LES) and duodenum (3,9 +/- 1,3 vs. 6,4 +/- 0,3). Acid infusion of duodenum with 0.1N HCL in 39 patients with DU was accompanied with the sensation of pain in 87,2% patients with active duodenal ulcers and increased pressure in duodenum (from 9,7 +/- 1,1 to 13,1 +/- 1,2) and gastric antrum (from 8,6 +/- 1,3 to 12,8 +/- 1,4). In 47 Hp-positive patients versus 26 Hp-negative patients was detected increased deltaP duodenum-gastric antrum (2,1 +/- 1,1 vs.- 0,6 +/- 0,43), decreased deltaP LES-duodenum (3,4 +/- 1,5 vs. 8,3 +/- 1,6), deltaP LES-gastric body (9,8 +/- 1,2 vs. 14,3 +/- 1,3) and significantly esophagitis (0,64 +/- 0,09 vs. 0,38 +/- 0,11 score, p < 0,05).

Identification of novel alpha-methoxylated phospholipid fatty acids in the Caribbean sponge Erylus goffrilleri.

PubMed

Carballeira, Néstor M; Oyola, Delise; Vicente, Jan; Rodriguez, Abimael D

2007-11-01

The phospholipid fatty acid composition of the Caribbean sponge Erylus goffrilleri is described for the first time. A total of 70 fatty acids with chain lengths between 13 and 29 carbons were identified in the sponge. Methyl-branched fatty acids predominated in E. goffrilleri suggesting the presence of a considerable number of bacterial symbionts. The novel fatty acids (5Z,9Z)-2-methoxy-5,9-hexadecadienoic acid, (5Z,9Z)-2-methoxy-5,9-octadecadienoic acid, (5Z,9Z)-2-methoxy-5,9-nonadecadienoic acid, and (5Z,9Z)-2-methoxy-5,9-eicosadienoic acid are described for the first time in the literature. In addition, the iso-methyl-branched fatty acids (9Z)-2-methoxy-15-methyl-9-hexadecenoic acid and (5Z,9Z)-2-methoxy-15-methyl-5,9-hexadecadienoic acid, also identified in E. goffrilleri, were identified for the first time in nature. Based on the identified metabolites it is proposed that the unprecedented biosynthetic sequence: i-17:1Delta9 --> 2-OMe-i-17:1Delta9 --> 2-OMe-i-17:2Delta5,9 might be responsible for the biosynthesis of the novel iso-alpha-methoxylated fatty acids in E. goffrilleri.

Forest statistics for Mississippi Delta counties - 1987

Treesearch

John F. Kelly; F. Dee Hines

1987-01-01

The 1987 survey of the 14 counties in the Mississippi Delta unit indicated the following changes since the previous survey in 1977:Timber area, now covering 1,388.3 thousand acres, has decreased 6 percent.Forest industry-owned timberland decreased 127.9 thousand acres, or 49 percent; other public land increased 70.3 thousand...

Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype.

PubMed

Spring, K; Cross, S; Li, C; Watters, D; Ben-Senior, L; Waring, P; Ahangari, F; Lu, S L; Chen, P; Misko, I; Paterson, C; Kay, G; Smorodinsky, N I; Shiloh, Y; Lavin, M F

2001-06-01

ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Atm-DeltaSRI, was designed as a model of one of the most common deletion mutations (7636del9) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-DeltaSRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-DeltaSRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-DeltaSRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-DeltaSRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-DeltaSRI animals. Thus, expression of mutant protein in Atm-DeltaSRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations.

Managing per Member per Month (PMPM). Findings Regarding Variation and Drivers of Cost

DTIC Science & Technology

2011-01-25

BenGrpDiag Desc RVU/100 Vst /100 RVU/100 Vst /100 Delta Pct 8 AD 7242 LUMBAGO 41.98 26.27 63.37 40.88 21.39 50.9% 71946 JOINT...Conference 30 All Enrollee AD MDC-19 MH Top 25 Primary Diagnosis with increases 2006 2009 MDC Adj BenGrpDiag Desc RVU/100 Vst /100 RVU/100 Vst /100 Delta Pct 19...Diagnosis with increases MDC Adj BenGrp Diag Desc RVU/100 Vst /100 RVU/100 Vst /100 Delta Pct 23 AD V705 HEALTH EXAMINATION OF DEFINED NATURE 300.25

Cyclic catalytic upgrading of chemical species using metal oxide materials

NASA Technical Reports Server (NTRS)

White, James H. (Inventor); Schutte, Erick J. (Inventor); Rolfe, Sara L. (Inventor)

2010-01-01

Processes are disclosure which comprise alternately contacting an oxygen-carrying catalyst with a reducing substance, or a lower partial pressure of an oxidizing gas, and then with the oxidizing gas or a higher partial pressure of the oxidizing gas, whereby the catalyst is alternately reduced and then regenerated to an oxygenated state. In certain embodiments, the oxygen-carrying catalyst comprises at least one metal oxide-containing material containing a composition having one of the following formulas: (a) Ce.sub.xB.sub.yB'.sub.zB''O.sub..delta., wherein B=Ba, Sr, Ca, or Zr; B'=Mn, Co, or Fe; B''=Cu; 0.01

Cyclic catalytic upgrading of chemical species using metal oxide materials

DOEpatents

White, James H.; Schutte, Erick J.; Rolfe, Sara L.

2010-11-02

Processes are disclosure which comprise alternately contacting an oxygen-carrying catalyst with a reducing substance, or a lower partial pressure of an oxidizing gas, and then with the oxidizing gas or a higher partial pressure of the oxidizing gas, whereby the catalyst is alternately reduced and then regenerated to an oxygenated state. In certain embodiments, the oxygen-carrying catalyst comprises at least one metal oxide-containing material containing a composition having one of the following formulas: (a) Ce.sub.xB.sub.yB'.sub.zB''O.sub..delta., wherein B=Ba, Sr, Ca, or Zr; B'=Mn, Co, or Fe; B''=Cu; 0.01

Pressure dependence of the photocycle kinetics of bacteriorhodopsin.

PubMed Central

Klink, B U; Winter, R; Engelhard, M; Chizhov, I

2002-01-01

The pressure dependence of the photocycle kinetics of bacteriorhodopsin from Halobacterium salinarium was investigated at pressures up to 4 kbar at 25 degrees C and 40 degrees C. The kinetics can be adequately modeled by nine apparent rate constants, which are assigned to irreversible transitions of a single relaxation chain of nine kinetically distinguishable states P(1) to P(9). All states except P(1) and P(9) consist of two or more spectral components. The kinetic states P(2) to P(6) comprise only the two fast equilibrating spectral states L and M. From the pressure dependence, the volume differences DeltaV(o)(LM) between these two spectral states could be determined that range from DeltaV(o)(LM) = -11.4 +/- 0.7 ml/mol (P(2)) to DeltaV(o)(LM) = 14.6 +/- 2.8 mL/mol (P(6)). A model is developed that explains the dependence of DeltaV(o)(LM) on the kinetic state by the electrostriction effect of charges, which are formed and neutralized during the L/M transition. PMID:12496115

Color stability and degree of cure of direct composite restoratives after accelerated aging.

PubMed

Sarafianou, Aspasia; Iosifidou, Soultana; Papadopoulos, Triantafillos; Eliades, George

2007-01-01

This study evaluated the color changes and amount of remaining C = C bonds (%RDB) in three dental composites after hydrothermal- and photoaging. The materials tested were Estelite sigma, Filtek Supreme and Tetric Ceram. Specimens were fabricated from each material and subjected to L* a* b* colorimetry and FTIR spectroscopy before and after aging. Statistical evaluation of the deltaL,* deltaa,* deltab,* deltaE and %deltaRDB data was performed by one-way ANOVA and Tukey's test. The %RDB data before and after aging were statistically analyzed using two-way ANOVA and Student-Newman-Keuls test. In all cases an alpha = 0.05 significance level was used. No statistically significant differences were found in deltaL*, deltaa*, deltaE and %deltaRDB among the materials tested. Tetric Ceram demonstrated a significant difference in deltab*. All the materials showed visually perceptible (deltaE >1) but clinically acceptable values (deltaE < 3.3). Within each material group, statistically significant differences in %RDB were noticed before and after aging (p < 0.05). Filtek Supreme presented the lowest %RDB before aging, with Tetric Ceram presenting the lowest %RDB after aging (p < 0.05). The %deltaRDB mean values were statistically significantly different among all the groups tested. No correlation was found between deltaE and %deltaRDB.

Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis.

PubMed

Brunt, Tibor M; van Genugten, Marianne; Höner-Snoeken, Kathrin; van de Velde, Marco J; Niesink, Raymond J M

2014-06-01

In The Netherlands, pharmaceutical-grade cultivated cannabis is distributed for medicinal purposes as commissioned by the Ministry of Health. Few studies have thus far described its therapeutic efficacy or subjective (adverse) effects in patients. The aims of this study are to assess the therapeutic satisfaction within a group of patients using prescribed pharmaceutical-grade cannabis and to compare the subjective effects among the available strains with special focus on their delta-9-tetrahydrocannabinol and cannabidiol content. In a cross-sectional and natural design, users of pharmaceutical-grade cannabis were investigated with questionnaires. Medical background of the patients was asked as well as experienced therapeutic effects and characteristics of cannabis use. Subjective effects were measured with psychometric scales and used to compare among the strains of cannabis used across this group of patients. One hundred two patients were included; their average age was 53 years and 76% used it for more than a year preceding this study. Chronic pain (53%; n = 54) was the most common medical indication for using cannabis followed by multiple sclerosis (23%; n = 23), and 86% (n = 88) of patients (almost) always experienced therapeutic satisfaction when using pharmaceutical cannabis. Dejection, anxiety, and appetite stimulation were found to differ among the 3 strains of cannabis. These results show that patients report therapeutic satisfaction with pharmaceutical cannabis, mainly pain alleviation. Some subjective effects were found to differ among the available strains of cannabis, which is discussed in relation to their different tetrahydrocannabinol/cannabidiol content. These results may aid in further research and critical appraisal for medicinally prescribed cannabis products.

Stability of Tetrahydrocannabinol and Cannabidiol in Prepared Quality Control Medible Brownies.

PubMed

Wolf, Carl E; Poklis, Justin L; Poklis, Alphonse

2017-03-01

The legalization of marijuana in the USA for both medicinal and recreational use has increased in the past few years. Currently, 24 states have legalized marijuana for medicinal use. The US Drug Enforcement Administration has classified marijuana as a Schedule I substance. The US Food and Drug Administration does not regulate formulations or packages of marijuana that are currently marketed in states that have legalized marijuana. Marijuana edibles or "medibles" are typically packages of candies and baked goods consumed for medicinal as well as recreational marijuana use. They contain major psychoactive drug in marijuana, delta-9-tetrahydrocannabinol (THC) and/or cannabidiol (CBD), which has reputed medical properties. Presented is a method for the preparation and application of THC and CBD containing brownies used as quality control (QC) material for the analysis of marijuana or cannabinoid baked medibles. The performance parameters of the assay including possible matrix effects and cannabinoid stability in the brownie QC over time are presented. It was determined that the process used to prepare and bake the brownie control material did not degrade the THC or CBD. The brownie matrix was found not to interfere with the analysis of a THC or a CBD. Ten commercially available brownie matrixes were evaluated for potential interferences; none of them were found to interfere with the analysis of THC or CBD. The laboratory baked medible QC material was found to be stable at room temperature for at least 3 months. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Visible and near-infrared Ge-H vibrational overtones in GeH/sub 4/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernheim, R.A.; Allbee, D.C.; Lampe, F.W.

1988-04-07

Absorption spectra in the 11,000-18,000-cm/sup -1/ range have been recorded for gaseous GeH/sub 4/ by intracavity photoacoustic detection with CW dye lasers. The observed transitions correspond to ..delta..v = 6-9 overtones of the Ge-H local mode stretch and show band contours arising from rotational structure at sample pressures of 1 atm. The local mode Ge-H stretch can be characterized by omega/sub e/ = 2178.3 +- 0.3 cm/sup -1/ and omega/sub e/chi/sub e/ = 33.7 +- 0.1 cm/sup -1/. In addition, the ..delta..v = 5-8 + v/sub 4/ combinations were observed. Evidence for chemical reaction induced by the ..delta..v = 9more » excitation is also found.« less

Involvement of formate as an interspecies electron carrier in a syntrophic acetate-oxidizing anaerobic microorganism in coculture with methanogens.

PubMed

Hattori, S; Luo, H; Shoun, H; Kamagata, Y

2001-01-01

To determine whether formate is involved in interspecies electron transfer between substrate-oxidizing bacteria and hydrogenotrophic microorganisms under anaerobic conditions, a syntrophic acetate-oxidizing bacterium Thermacetogenium phaeum strain PB was cocultured either with a formate /H2-utilizing methanogen strain TM (designated as PB/TM coculture), or an H2-utilizing methanogen strain deltaH (designated as PB/deltaH coculture). Acetate oxidation and subsequent methanogenesis in PB/TM coculture were found to be significantly faster than in PB/deltaH coculture. Formate dehydrogenase and hydrogenase were both detected in strains PB and TM. H2 partial pressures in the PB/TM coculture were kept lower (20 to 40 Pa) than those of the PB/deltaH coculture (40 to 60 Pa) during the exponential growth phase. Formate was also detected in both PB/TM and PB/deltaH cocultures, and the concentration of formate was maintained at a lower level in the PB/TM coculture (5 to 9 microM) than in the PB/deltaH coculture. Thermodynamic calculations revealed that the concentrations of both H2 and formate severely affect the syntrophic oxidation of acetate. These results strongly indicate that not only H2 but also formate may be involved in interspecies electron transfer.

Experimental investigation of channel avulsion frequency on river deltas under rising sea levels

NASA Astrophysics Data System (ADS)

Silvestre, J.; Chadwick, A. J.; Steele, S.; Lamb, M. P.

2017-12-01

River deltas are low-relief landscapes that are socioeconomically important; they are home to over half a billion people worldwide. Many deltas are built by cycles of lobe growth punctuated by abrupt channel shifts, or avulsions, which often reoccur at a similar location and with a regular frequency. Previous experimental work has investigated the effect of hydrodynamic backwater in controlling channel avulsion location and timing on deltas under constant sea level conditions, but it is unclear how sea-level rise impacts avulsion dynamics. We present results from a flume experiment designed to isolate the role of relative sea-level rise on the evolution of a backwater-influenced delta. The experiment was conducted in the river-ocean facility at Caltech, where a 7m long, 14cm wide alluvial river drains into a 6m by 3m "ocean" basin. The experimental delta grew under subcritical flow, a persistent backwater zone, and a range of sea level rise rates. Without sea level rise, lobe progradation produced in-channel aggradation and periodic avulsions every 3.6 ± 0.9 hours, which corresponded to when channels aggraded to approximately one-half of their flow depth. With a modest rate of sea-level rise (0.25 mm/hr), we observed enhanced aggradation in the backwater zone, causing channels to aggrade more quickly and avulse more frequently (every 2.1 ± 0.6 hours). In future work, we expect further increases in the rate of relative sea-level rise to cause avulsion frequency to decrease as the delta drowns and the backwater zone retreats upstream. Experimental results can serve as tests of numerical models that are needed for hazard mitigation and coastal sustainability efforts on drowning deltas.

Deficient production of hexadecenoic acid in the skin is associated in part with the vulnerability of atopic dermatitis patients to colonization by Staphylococcus aureus.

PubMed

Takigawa, Hirofumi; Nakagawa, Hidemi; Kuzukawa, Michiya; Mori, Hajime; Imokawa, Genji

2005-01-01

As one of the major skin fatty acids, cis-6-hexadecenoic acid (C16:1Delta6) exhibits a specific antibacterial activity and might play a specific role in the defense mechanism against Staphylococcus aureus, in healthy subjects whereas S. aureus frequently colonizes the skin of patients with atopic dermatitis (AD). Fatty acid composition of sebum at the recovery level was analyzed by gas chromatography and S. aureus colonizing the skin was assessed by the 'cup-scrub' method (9 patients and 10 healthy controls). To evaluate in vivo effect of C16:1Delta6 on colonization, C16:1Delta6 was applied for 2 weeks on the upper arm skin of another group of AD patients (11 patients). Analysis of sebum lipids revealed that there is a significant lower free C16:1Delta6 content in nonlesional skin from AD patients compared with healthy controls. This lower content is also accompanied by a significantly lower level of C16:1Delta6 in the total fatty acid composition of sebum (analyzed following hydrolysis). The lower level of free C16:1Delta6 correlated significantly (R(2) = 0.41, p < 0.01) with the numbers of S. aureus colonizing nonlesional skin. Topical application of free C16:1Delta6 on the skin of AD patients for 2 weeks abolished the markedly increased bacterial count in 6 out of the 8 AD patients tested. Free C16:1Delta6 may be involved in the defense mechanism against S. aureus in healthy skin and this deficit triggers the susceptibility of the skin to colonization by S. aureus in AD. Copyright 2005 S. Karger AG, Basel.

Rapid-mix and chemical quench studies of ferredoxin-reduced stearoyl-acyl carrier protein desaturase.

PubMed

Lyle, Karen S; Haas, Jeffrey A; Fox, Brian G

2003-05-20

Stearoyl-ACP Delta9 desaturase (Delta9D) catalyzes the NADPH- and O(2)-dependent insertion of a cis double bond between the C9 and C10 positions of stearoyl-ACP (18:0-ACP) to produce oleoyl-ACP (18:1-ACP). This work revealed the ability of reduced [2Fe-2S] ferredoxin (Fd) to act as a catalytically competent electron donor during the rapid conversion of 18:0-ACP into 18:1-ACP. Experiments on the order of addition for substrate and reduced Fd showed high conversion of 18:0-ACP to 18:1-ACP (approximately 95% per Delta9D active site in a single turnover) when 18:0-ACP was added prior to reduced Fd. Reactions of the prereduced enzyme-substrate complex with O(2) and the oxidized enzyme-substrate complex with reduced Fd were studied by rapid-mix and chemical quench methods. For reaction of the prereduced enzyme-substrate complex, an exponential burst phase (k(burst) = 95 s(-1)) of product formation accounted for approximately 90% of the turnover expected for one subunit in the dimeric protein. This rapid phase was followed by a slower phase (k(linear) = 4.0 s(-1)) of product formation corresponding to the turnover expected from the second subunit. For reaction of the oxidized enzyme-substrate complex with excess reduced Fd, a slower, linear rate (k(obsd) = 3.4 s(-1)) of product formation was observed over approximately 1.5 turnovers per Delta9D active site potentially corresponding to a third phase of reaction. An analysis of the deuterium isotope effect on the two rapid-mix reaction sequences revealed only a modest effect on k(burst) ((D)k(burst) approximately 1.5) and k(linear) (D)k(linear) approximately 1.4), indicating C-H bond cleavage does not contribute significantly to the rate-limiting steps of pre-steady-state catalysis. These results were used to assemble and evaluate a minimal kinetic model for Delta9D catalysis.

The accent method of voice therapy: effect of accentuations on FO, SPL, and airflow.

PubMed

Kotby, M N; Shiromoto, O; Hirano, M

1993-12-01

The effect of the increased flow rate (delta U) in response to the Accent Method exercises on fundamental frequency (FO) and sound pressure level (SPL) was studied in three subjects (professionally trained, trained, and untrained in this method). In all the subjects, the rhythmic accentuated exercises produced a variable degree of increase in FO (delta FO) and SPL (delta SPL). The professionally trained subject showed greater delta FO and delta SPL in response to the delta U in the fastest tempo, which requires higher skills. Both trained subjects showed a greater correlation between delta U and both delta SPL and delta FO, as well as between delta FO and delta SPL, as compared to the untrained subject. The effects of the accentuated exercises on FO and SPL in response to the increased airflow rate (delta U) thus appear to demonstrate the treating effectiveness of the Accent Method.

Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Jun; Department of Physiology, Third Military Medical University, Chongqing 400038; Song, Min

2009-07-31

In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{submore » {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.« less

Specific inspiratory muscle warm-up enhances badminton footwork performance.

PubMed

Lin, Hua; Tong, Tom Kwokkeung; Huang, Chuanye; Nie, Jinlei; Lu, Kui; Quach, Binh

2007-12-01

The effects of inspiratory muscle (IM) warm-up on IM function and on the maximum distance covered in a subsequent incremental badminton-footwork test (FWmax) were examined. Ten male badminton players were recruited to perform identical tests in three different trials in a random order. The control trial did not involve an IM warm-up, whereas the placebo and experimental trials did involve an IM warm-up consisting of two sets of 30-breath manoeuvres with an inspiratory pressure-threshold load equivalent to 15% (PLA) and 40% (IMW) maximum inspiratory mouth pressure, respectively. In the IMW trial, IM function was improved with 7.8%+/-4.0% and 6.9%+/-3.5% increases from control found in maximal inspiratory pressure at zero flow (P0) and maximal rate of P0 development (MRPD), respectively (p<0.05). FWmax was enhanced 6.8%+/-3.7%, whereas the slope of the linear relationship of the increase in the rating of perceived breathlessness for every minute (RPB/min) was reduced (p<0.05). Reduction in blood lactate ([La-]b) accumulation was observed when the test duration was identical to that of the control trial (P<0.05). In the PLA trial, no parameter was changed from control. For the changes (Delta) in parameters in IMW (n=10), negative correlations were found between DeltaP0 and DeltaRPB/min (r2=0.58), DeltaMRPD and DeltaRPB/min (r2=0.48), DeltaRPB/min, and DeltaFWmax (r2=0.55), but not between Delta[La-]b accumulation and DeltaFWmax. Such findings suggest that the IM-specific warm-up improved footwork performance in the subsequent maximum incremental badminton-footwork test. The improved footwork was partly attributable to the reduced breathless sensation resulting from the enhanced IM function, whereas the contribution of the concomitant reduction in [La-]b accumulation was relatively minor.

Towards an understanding of the molecular mechanism of solvation of drug molecules: a thermodynamic approach by crystal lattice energy, sublimation, and solubility exemplified by paracetamol, acetanilide, and phenacetin.

PubMed

Perlovich, German L; Volkova, Tatyana V; Bauer-Brandl, Annette

2006-10-01

Temperature dependencies of saturated vapor pressure for the monoclinic modification of paracetamol (acetaminophen), acetanilide, and phenacetin (acetophenetidin) were measured and thermodynamic functions of sublimation calculated (paracetamol: DeltaGsub298=60.0 kJ/mol; DeltaHsub298=117.9+/-0.7 kJ/mol; DeltaSsub298=190+/-2 J/mol.K; acetanilide: DeltaGsub298=40.5 kJ/mol; DeltaHsub298=99.8+/-0.8 kJ/mol; DeltaSsub298=197+/-2 J/mol.K; phenacetin: DeltaGsub298=52.3 kJ/mol; DeltaHsub298=121.8+/-0.7 kJ/mol; DeltaSsub298=226+/-2 J/mol.K). Analysis of packing energies based on geometry optimization of molecules in the crystal lattices using diffraction data and the program Dmol3 was carried out. Parameters analyzed were: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy; (b) contributions of fragments of the molecules to the packing energy. The fraction of hydrogen bond energy in the packing energy increases as: phenacetin (17.5%)

Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers

PubMed Central

Oh, D Alexander; Parikh, Neha; Khurana, Varun; Cognata Smith, Christina; Vetticaden, Santosh

2017-01-01

Dronabinol is a pharmaceutical tetrahydrocannabinol originally developed as an oral capsule. A dronabinol oral solution was recently approved, and the effects of food on absorption and bioavailability of the oral solution versus capsules were compared in an open-label, single-dose, 3-period crossover study. Healthy volunteers were randomized to either dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted). Dosing was separated by a 7-day washout period. Plasma pharmacokinetics were evaluated for dronabinol and its major metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-Δ9-THC). Pharmacokinetic data were available for analysis in 54 volunteers. In the fed state, initial dronabinol absorption was faster with oral solution versus capsule (mean time to the first measurable concentration, 0.15 vs 2.02 hours, respectively), with 100% and 15% of volunteers, respectively, having detectable plasma dronabinol levels 30 minutes postdose. There was less interindividual variability in plasma dronabinol concentration during early absorption with oral solution versus capsule. Compared with the fasted state, mean area under the plasma concentration–time curve from time zero to the last measurable concentration (AUC0−t) increased by 2.1- and 2.4-fold for dronabinol oral solution and capsule, respectively, when taken with food. Mean time to maximum plasma concentration was similarly delayed for dronabinol oral solution with food (7.7 hours) and capsule with food (5.6 hours) versus capsule with fasting (1.7 hours). Under fed conditions, AUC0−t and area under the plasma concentration–time curve from time zero to infinity were similar for the oral solution versus capsule based on 11-OH-Δ9-THC levels. An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients, given its rapid and lower interindividual absorption variability versus dronabinol capsule. PMID:28138268

Evaluation of chlorhexidine gluconate mouthrinse-induced staining using a digital colorimeter: an in vivo study.

PubMed

Bagis, Bora; Baltacioglu, Esra; Özcan, Mutlu; Ustaomer, Seda

2011-03-01

To investigate the persistence of staining after the use of chlorhexidine gluconate mouthrinse. Twenty-four subjects (nine women and 15 men) who underwent periodontal therapy and were prescribed the use of 0.2% chlorhexidine gluconate mouthrinse participated in this study. Color values of maxillary central incisors, canines, and first molars were recorded at baseline; 3 days; and 1, 2, and 3 weeks of twice-daily chlorhexidine gluconate use with a digital intraoral colorimeter according to the CIE L*a*b* coordinates. While color-change (Delta E) values showed significant differences (P=.020) at different time points (10.1, 8.9, 8.9, 9.4, after 3 days and 1, 2, and 3 weeks, respectively), the duration of chlorhexidine gluconate use did not significantly affect the results (P=.873) (two-way ANOVA, Tukey test). No significant difference was found among Delta L* (P=.070), Delta a* (P=.169), and Delta b* (P=.691) values at any time point (one-way ANOVA). Measurements of baseline to day 3 differences showed significantly higher Delta E values than those at other time points (P<.05), but this change remained nonsignificant after 1, 2, and 3 weeks of chlorhexidine gluconate use (P>.05) (Tukey test). The highest visible staining occurred on the first molars at all time points (83%, 79%, 79%, and 96% after 3 days and 1, 2, and 3 weeks, respectively) compared to the other teeth evaluated. The staining effect of chlorhexidine gluconate mouthrinse on natural dentition should be expected to be the highest in the first few days of use.

KSC-07pd1514

NASA Image and Video Library

2007-06-15

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 17-B at Cape Canaveral Air Force Station, the second stage of the Delta II launch vehicle for the Dawn spacecraft is lowered into the hole toward the Delta first stage below. The two stages will be mated. The Delta II-Heavy, manufactured by the United Launch Alliance, is scheduled to launch the Dawn spacecraft on its 4-year flight to the asteroid belt. The Delta II-Heavy is the strongest rocket in the Delta II class. It will use three stages and nine solid-fueled booster rockets to propel Dawn on its way. A 9.5-foot payload fairing will protect the spacecraft from the heat and stresses of launch. Dawn's goal is to characterize the conditions and processes of the solar system's earliest epoch by investigating in detail the largest protoplanets that have remained intact since their formations: asteroid Vesta and the dwarf planet Ceres. They reside in the extensive zone between Mars and Jupiter together with many other smaller bodies, called the asteroid belt. Dawn is scheduled to launch July 7. Photo credit: NASA/Jack Pfaller

Thermodynamic properties of {Delta}H{sub f 298}{degree}, S{sub 298}{degree}, and C{sub p}(T) for 2-fluoro-2-methylpropane, {Delta}H{sub f 298}{degree} of fluorinated ethanes, and group additivity for fluoroalkanes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, Takahiro; Bozzelli, J.W.

1999-09-09

G2(MP2) composite calculations are performed to obtain thermodynamic properties ({Delta}H{sub f 298}{degree}, S{sub 298}{degree} and C{sub p}(T)'s) of 2-fluoro-2-methylpropane. {Delta}H{sub f 298}{degree} is calculated from the G2(MP2) calculated enthalpy of reaction ({Delta}H{sub rxn 298}{degree}) and use of isodesmic reactions. Standard entropy (S{sub 298}{degree} in cal/(mol{center{underscore}dot}K)) and heat capacities (C{sub p}(T)'s in cal/(mol{center{underscore}dot}K)) are calculated using the rigid-rotor--harmonic-oscillator approximation with direct integration over energy levels of the intermolecular rotation potential energy curve. These thermodynamic properties are used to estimate data for the C/C3/F group. Enthalpies of formation ({Delta}H{sub f 298}{degree} in kcal/mol) for 1,2-difluoroethane ({minus}102.7), 1,1,2-trifluoroethane ({minus}156.9), 1,1,2,2- and 1,1,1,2-tetrafluoroethane (209.6more » and 213.3), and pentafluoroethane ({minus}264.1), are calculated using total energies obtained from G2(MP2) composite ab initio methods. Isodesmic reactions with existing literature values of {Delta}H{sub f 298}{degree} for ethane, 1-fluoroethane, 1,1-difjuoroethane and 1,1,1-trifluoroethane are used. Fluorine/fluorine interaction terms, F/F, 2F/F, 3F/F, 2F/2F, and 3F/2F, where ``/'' indicates interaction for alkane compounds, for {Delta}H{sub f 298}{degree} are reevaluated based on {Delta}H{sub f 298}{degree} of the above five fluoroethanes. Thermodynamic properties ({Delta}H{sub f 298}{degree}, S{sub 298}{degree} and C{sub p}(T)'s (300 {le} T/K {le} 1500)) for fluorinated carbon groups, C/C3F, C/C2/F/H, C/C2/F2, are calculated using data from ab initio methods and existing literature data. Fluorine-methyl (alkyl) group additivity corrections for gauche interactions are also evaluated.« less

A coral-based reconstruction of Intertropical Convergence Zone variablity over Central America since 1707

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linsley, B.K.; Dunbar, R.B.; Mucciarone, D.A.

1994-05-15

Seasonal movements of the Intertropical Convergence Zone (ITCZ) control precipitation patterns and cloud cover throughout the tropics. In this study the authors have reconstructed seasonal and interannual variability of the eastern Pacific ITCZ from 1984 to 1707 using subseasonal {delta}{sup 18}O analyses on a massive coral from Secas Island (7{degrees}59{prime}N, 82{degrees}3{prime}W) in the Gulf of Chiriqui, Panama. The land area that drains into the Gulf of Chiriqui has served to amplify the rainfall effect on nearshore surface waters and coral {delta}{sup 18}O{sub ppt} composition. During the protracted wet season in Panama, the {delta}{sup 18}O of precipitation ({delta}{sup 18}O{sub ppt}) ismore » reduced on average by 10{per_thousand} and sea surface salinity (SSS) along the western coast is reduced up to 11{per_thousand}. Calibration of the coral {delta}{sup 18}O{sub ppt} from Secas Island against instrumental sea surface temperature (SST), SSS, precipitation and {delta}{sup 18}O{sub ppt} data indicate that seasonal rainfall induced variations in seawater {delta}{sup 18}O are responsible for {approximately}80% of the annual {delta}{sup 18}O variance. The regularity of the reconstructed seasonal ITCZ cycle indicates that over the length of the record the zone of maximum rainfall in the eastern Pacific has always expanded north to at least Panama in every northern hemisphere summer. Significant interannual and interdecadal {delta}{sup 18}O oscillations occur at average periods near 9, 3-7 (ENSO band), 17 and 33 years (listed in order of decreasing variance). As the Gulf of Chiriqui coral {delta}{sup 18}O time series is the first paleoclimatic record of past variations in the ITCZ, other seasonal-resolution reconstructions of the past behavior of the ITCZ are required to test whether the interannual and long-term variability observed in the eastern Pacific ITCZ is more than regional in scale. 79 refs., 13 figs., 2 tabs.« less

Carbon and nitrogen isotopic compositions of particulate organic matter and biogeochemical processes in the eutrophic Danshuei Estuary in northern Taiwan.

PubMed

Liu, Kon-Kee; Kao, Shuh-Ji; Wen, Liang-Saw; Chen, Kuan-Lun

2007-08-15

The Danshuei Estuary is distinctive for the relatively short residence time (1-2 d) of its estuarine water and the very high concentration of ammonia, which is the dominant species of dissolved inorganic nitrogen in the estuary, except near the river mouth. These characteristics make the dynamics of nitrogen cycling distinctively different from previously studied estuaries and result in unusual isotopic compositions of particulate nitrogen (PN). The delta(15)N(PN) values ranging from -16.4 per thousand to 3.8 per thousand lie in the lower end of nitrogen isotopic compositions (-16.4 to +18.7 per thousand) of suspended particulate matter observed in estuaries, while the delta(13)C values of particulate organic carbon (POC) and the C/N (organic carbon to nitrogen) ratios showed rather normal ranges from -25.5 per thousand to -19.0 per thousand and from 6.0 to 11.3, respectively. There were three major types of particulate organic matter (POM) in the estuary: natural terrigenous materials consisting mainly of soils and bedrock-derived sediments, anthropogenic wastes and autochthonous materials from the aquatic system. During the typhoon induced flood period in August 2000, the flux-weighted mean of delta(13)C(POC) values was -24.4 per thousand, that of delta(15)N(PN) values was +2.3 per thousand and that of C/N ratio was 9.3. During non-typhoon periods, the concentration-weighted mean was -23.6 per thousand for delta(13)C(POC), -2.6 per thousand for delta(15)N(PN) and 8.0 for C/N ratio. From the distribution of delta(15)N(PN) values of highly polluted estuarine waters, we identified the waste-dominated samples and calculated their mean properties: delta(13)C(POC) value of -23.6+/-0.7 per thousand, delta(15)N(PN) value of -3.0+/-0.1 per thousand and C/N ratio of 8.0+/-1.4. Using a three end-member mixing model based on delta(15)N(PN) values and C/N ratios, we calculated contributions of the three major allochthonous sources of POC, namely, wastes, soils and bedrock-derived sediments, to the estuary. Their contributions were, respectively, 83%, 12% and 5% under non-typhoon conditions, and 9%, 63% and 28% under typhoon conditions. The autochthonous POM had the most varied isotopic compositions, encompassing the full ranges of delta(13)C(POC) (-25.5 to -19.1 per thousand), delta(15)N(PN) (-16.4-3.8 per thousand) and C/N ratio (6.0-11.3). The heavy end of the carbon isotopic composition reflected the typical marine condition and the lower end the estuarine condition, which probably had elevated concentrations of dissolved inorganic carbon with low delta(13)C values due to input from decomposition of organic matter. The lack of isotopically heavy PN, as found in larger estuaries, was attributed to isotopically light starting materials, namely, anthropogenic wastes, the slow phytoplankton growth within the estuary and the rather short residence time; the latter two factors made (15)N enrichment during ammonia consumption very limited. The most isotopically light PN likely originated from phytoplankton incorporating (15)N-depleted nitrate near the river mouth, where ammonia inhibition of nitrate uptake probably stopped.

Tides and deltaic morphodynamics

NASA Astrophysics Data System (ADS)

Plink-Bjorklund, Piret

2016-04-01

Tide-dominated and tide-influenced deltas are not widely recognized in the ancient record, despite the numerous modern and Holocene examples, including eight of the twelve modern largest deltas in the world, like the Ganges-Brahmaputra, Amazon, Chang Jiang, and Irrawadi. Furthermore, tide-dominated or tide-influenced deltas are suggested to be more common in inner-shelf or embayment settings rather than close to or at a shelf edge, primarily because wave energy is expected to be higher and tidal energy lower in outer shelf and shelf-edge areas. Thus, most shelf-edge deltas are suggested to be fluvial or wave dominated. However, there are ancient examples of tide-influenced shelf-edge deltas, indicating that the controls on tidal morphodynamics in deltas are not yet well understood. This paper asks the following questions: (1) How do tides influence delta deposition, beyond creating recognizable tidal facies? (2) Does tidal reworking create specific geometries in delta clinoforms? (3) Does tidal reworking change progradation rates of deltas? (4) Is significant tidal reworking of deltas restricted to inner-shelf deltas only? (5) What are the conditions at which deltas may be tidally influenced or tide-dominated in outer-shelf areas or at the shelf edge? (6) What are the main morphodynamic controls on the degree of tidal reworking of deltas? The paper utilizes a dataset of multiple ancient and modern deltas, situated both on the shelf and shelf edge. We show that beyond the commonly recognized shore-perpendicular morphological features and the recognizable tidal facies, the main effects of tidal reworking of deltas are associated with delta clinoform morphology, morphodynamics of delta lobe switching, delta front progradation rates, and the nature of the delta plain. Strong tidal influence is here documented to promote subaqueous, rapid progradation of deltas, by efficiently removing sediment from river mouth and thus reducing mouth bar aggradation and fluvial delta plain construction rates. Such subaqueous progradation of the delta front is decoupled from shoreline progradation. The delta plain of such tide-dominated deltas consists of a few distributary channels and tidal flats on top of the emerged tidal bars. The delta front clinoforms become gentler and longer, as ebb tidal currents together with river effluent efficiently transport sediment to the basin. Tide-dominated deltas tend to maintain a funnel shape and show low lobe switching rates, compared to fluvial-dominated and tide-influenced deltas. The funnel and thus river mouth position is further stabilized by fine-grained sediment accumulation on marginal tidal flats due to the flood current sediment transport. However, all these effect weaken as the deltas prograde to the shelf edge, due to the loss of vertical (and lateral) restriction and tidal amplification. Here significant tidal reworking tends to be restricted to topographic irregularities, caused by incision, delta-lobe or mouth bar deposition and avulsions, or tectonic processes. The role of such topographic restrictions is twofold, by reducing wave energy and amplifying tidal energy.

Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visel, Axel; Zhu, Yiwen; May, Dalit

2010-01-01

Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation propertiesmore » of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.« less

Redundant role of protein kinase C delta and epsilon during mouse embryonic development.

PubMed

Carracedo, Sergio; Sacher, Frank; Brandes, Gudrun; Braun, Ursula; Leitges, Michael

2014-01-01

Protein Kinase C delta and epsilon are mediators of important cellular events, such as cell proliferation, migration or apoptosis. The formation of blood vessels, i.e., vasculo- and angiogenesis, is a process where these isoforms have also been shown to participate. However, mice deficient in either Protein Kinase C delta or epsilon are viable and therefore their individual contribution to the formation of the vasculature appeared so far dispensable. In this study, we show that double null mutation of Protein Kinase C delta and epsilon causes embryonic lethality at approximately E9.5. At this stage, whole mount staining of the endothelial marker CD31 in double null embryos revealed defective blood vessel formation. Moreover, culture of double deficient mouse allantois showed impaired endothelial cell organization, and analyses of double deficient embryo sections showed dilated vessels, decreased endothelial-specific adherent junctions, and decreased contact of endothelial cells with mural cells. Protein kinase C delta and epsilon also appeared essential for vascular smooth muscle cell differentiation, since α-smooth muscle actin, a classical marker for vascular smooth muscle cells, was almost undetectable in double deficient embryonic aorta at E9.5. Subsequent qPCR analyses showed decreased VE-cadherin, Vegfr2, Cd31, Cdh2, Ets1, and Fli-1, among other angiogenesis related transcripts in double deficient embryos. Taken together, these data suggest for the first time an in vivo redundant role between members of the novel Protein Kinase C subfamily that allows for mutual compensation during mouse embryonic development, with vasculogenesis/angiogenesis as an obvious common function of these two Protein Kinase Cs. Protein Kinase C delta and epsilon might therefore be useful targets for inhibiting vasculo- and/or angiogenesis.

Biosynthesis of polyunsaturated fatty acids in the developing brain. I. Metabolic transformations of intracranially administered 1-/sup 14/C linolenic acid. [Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhopeshwarkar, G.A.; Subramanian, C.

1971-01-01

Thirteen-day old rats were given intracranial injections of 1-/sup 14/C linolenic acid (all cis 9, 12, 15 octadecatrienoic acid) and were sacrificed after 8 hr. Analysis of brain fatty acids showed that 16 : 0, 18 : 0, 18 : 1, 18 : 3, 20 : 3, 20 : 4, 20 : 5, 22 : 5 and 22 : 6 were labeled. The total fatty acid methyl esters were separated into classes according to degree of unsaturation on a AgNO/sub 3/ : SiO/sub 2/ impregnated plate. The bands were scraped off and the eluted fatty acds were first analyzed bymore » radio-gas liquid chromatography and then subjected to reductive ozonolysis to determine double bond position. The saturated acids, 16 : 0 and 18 : 0, as well as the monounsaturated 18 : 1, must have been formed from radioactive acetate produced by ..beta.. oxidation of the injected linolenate. Among the polyunsaturated fatty acids, the triene fraction was characterized and identified as 18 : 3 ..omega..3 (..delta../sup 9/,/sup 12/,/sup 15/), the starting material, and 20 : 3 ..omega..3 (..delta../sup 11/,/sup 14/,/sup 17/); the tetraene fraction was identified as 20 : 4 ..omega..3 (..delta../sup 8/,/sup 11/,/sup 14/,/sup 17/); the pentaene fraction was identified as 20 : 5 ..omega..3 (..delta../sup 5/,/sup 8/,/sup 11/,/sup 14/,/sup 17/) and 22 : 5 ..omega..3 (..delta../sup 7/,/sup 10/,/sup 13/,/sup 16/,/sup 19/); and, finally, the hexaene fraction was shown to be 22 : 6 ..omega..3 (..delta../sup 4/,/sup 7/,/sup 10/,/sup 13/,/sup 16/,/sup 19/). The biosynthesis of these ..omega..3 family fatty acids in the brain in situ is discussed.« less

Detection of Human Sewage in Urban Stormwater Using DNA Based Methods and Stable Isotope Analysis

NASA Astrophysics Data System (ADS)

McLellan, S. L.; Malet, N.; Sauer, E.; Mueller-Spitz, S.; Borchardt, M.

2008-12-01

Urban stormwater is a major source of fecal indicator bacteria in the Milwaukee River Basin, a major watershed draining to Lake Michigan. Much of the watershed is in highly urbanized areas and Escherichia coli (E. coli) levels have been found to be 20,000 CFU per 100 ml in the estuary leading to Lake Michigan. Aging infrastructure and illicit cross connections may allow sewage to infiltrate the stormwater system and could contribute both fecal indicator bacteria and human pathogens to these waters. We conducted extensive sampling of stormwater outfalls in the lower reaches of three major tributaries. Three outfalls along the heavily urbanized Kinnickinnick (KK) were found to have geometric mean E. coli and enterococci levels of 16,200 and 28,700 CFU/100 ml, respectively. Four outfalls along the Menomonee River, draining both suburban and urban areas, had geometric mean E. coli and enterococci levels of 14,700 and 12,800 CFU/100 ml, respectively. These seven outfalls had more than 60% of the samples positive for human specific Bacteroides genetic marker (n=46), suggesting the presence of human sources. In addition, two outfalls on Lincoln Creek, a smaller tributary of the Milwaukee River, had geometric mean E. coli and enterococci levels of 16,700 and 14,900 CFU per 100 ml, respectively. The human specific Bacteroides marker was positive in nearly 90% of the samples (n=24). Subsequent virus testing at one of these outfalls confirmed human pathogens were present with adenovirus detected at 1.3 x 10E3 genomic equivalents (ge)/L, enterovirus at 1.9 x 10E4 ge/L and G1 norovirus at 1.5 x 10E3 ge/L; these values are similar to concentrations found in sewage. Stable isotope studies were conducted in the three tributaries to investigate the relationship between delta C and delta N isotopic composition and microbiological quality of this urban freshwater system. This work is based on the premise that the organic matter of the stormwater will have a stable isotopic signature related to the mixed organic matter sources in polluted stormwater runoff, and that this signal will distinct from untreated sanitary sewage. Stable isotope signatures of stormwater and untreated sewage were determined and compared with the rivers. Isotopic values of stormwater was delta 15N = 1.1 ± 2 %; delta 13C = -25.5 ± 3 % and sewage was delta 15N = -1.9 ± 0.2 %; delta 13C = -23.6 ± 0.3. Suspended particular organic matter (SPOM) of Milwaukee River showed depleted delta 13C (-28.6 ± 1.6 %) and enriched delta 15N (7.7 ± 1.9 %) values. SPOM of the KK River exhibited the most depleted delta 15N (0.2 ± 1.6 %) and enriched delta 13C (-24.8 ± 1.8 %) isotopic values. Menomonee River SPOM showed intermediate isotopic values. The delta 13C values of each river and the estuary enriched significantly throughout the summer storm periods. The isotope signals in the KK and Menomonee were indicative of stormwater runoff and sewage contamination. These results suggest that unrecognized sewage inputs are chronically present and may be delivered through urban stormwater systems. DNA based methods combined with isotope analysis may provide a useful tool for urban watershed assessments and to identify sewage inputs. Delineating the relative contribution of stormwater and sewage to overall degraded water quality might give the first indication of the impact of these sources on the Michigan Lake waters.

Estimating changes in mean body temperature for humans during exercise using core and skin temperatures is inaccurate even with a correction factor.

PubMed

Jay, Ollie; Reardon, Francis D; Webb, Paul; Ducharme, Michel B; Ramsay, Tim; Nettlefold, Lindsay; Kenny, Glen P

2007-08-01

Changes in mean body temperature (DeltaT(b)) estimated by the traditional two-compartment model of "core" and "shell" temperatures and an adjusted two-compartment model incorporating a correction factor were compared with values derived by whole body calorimetry. Sixty participants (31 men, 29 women) cycled at 40% of peak O(2) consumption for 60 or 90 min in the Snellen calorimeter at 24 or 30 degrees C. The core compartment was represented by esophageal, rectal (T(re)), and aural canal temperature, and the shell compartment was represented by a 12-point mean skin temperature (T(sk)). Using T(re) and conventional core-to-shell weightings (X) of 0.66, 0.79, and 0.90, mean DeltaT(b) estimation error (with 95% confidence interval limits in parentheses) for the traditional model was -95.2% (-83.0, -107.3) to -76.6% (-72.8, -80.5) after 10 min and -47.2% (-40.9, -53.5) to -22.6% (-14.5, -30.7) after 90 min. Using T(re), X = 0.80, and a correction factor (X(0)) of 0.40, mean DeltaT(b) estimation error for the adjusted model was +9.5% (+16.9, +2.1) to -0.3% (+11.9, -12.5) after 10 min and +15.0% (+27.2, +2.8) to -13.7% (-4.2, -23.3) after 90 min. Quadratic analyses of calorimetry DeltaT(b) data was subsequently used to derive best-fitting values of X for both models and X(0) for the adjusted model for each measure of core temperature. The most accurate model at any time point or condition only accounted for 20% of the variation observed in DeltaT(b) for the traditional model and 56% for the adjusted model. In conclusion, throughout exercise the estimation of DeltaT(b) using any measure of core temperature together with mean skin temperature irrespective of weighting is inaccurate even with a correction factor customized for the specific conditions.

Isomers of hexadecenoic and hexadecadienoic acids in Androsace septentrionalis (Primulaceae) seed oil.

PubMed

Tsevegsuren, N; Aitzetmuller, K; Vosmann, K

2003-11-01

Seeds of Androsace septentrionalis of the genus Androsace (tribus Primuleae) from the plant family Primulaceae were studied for their oil content and FA composition. The seed oil of A. septentrionalis was found to contain two unusual FA rarely occurring in plants: 11-cis-hexadecenoic acid (16:1delta11c or 16:1n-5) and 9-cis,12-cis-hexadecadienoic acid (16:2delta9c,12c or 16:2n-4). It also contained an unusually high amount (21.4%) of 9-cis-hexadecenoic acid (palmitoleic acid; 16:1delta9c or 16:1n-7), i.e., at a level higher than that of oleic acid, in addition to common FA. Compared with most plant seed oils, at 3.8% the level of 18:1delta11c (or 18:1n-7) also was elevated. The nonidentity of the Androsace 16:2-acid with the 16:2-acid, which is very typical for Ranunculus spp., as well as its identity with the 16:2-acid typically found in Asclepiadaceae was established by co-chromatography. The structure and composition of the constituent FA of A. septentrionalis were also determined by various chromatographic methods (TLC, Ag+-TLC, capillary GLC) and spectroscopic methods (IR, GC-MS). The significant deviation of the Androsace FA pattern from that of other Primuleae, indicating a separate phylogenetic position of Androsace, is discussed.

Review of the neurological benefits of phytocannabinoids

PubMed Central

Maroon, Joseph; Bost, Jeff

2018-01-01

Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS. Methods: In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts. Results: Recent neurological uses include adjunctive treatment for malignant brain tumors, Parkinson's disease, Alzheimer's disease, multiple sclerosis, neuropathic pain, and the childhood seizure disorders Lennox-Gastaut and Dravet syndromes. In addition, psychiatric and mood disorders, such as schizophrenia, anxiety, depression, addiction, postconcussion syndrome, and posttraumatic stress disorders are being studied using phytocannabinoids. Conclusions: In this review we will provide animal and human research data on the current clinical neurological uses for CBD individually and in combination with Δ9-THC. We will emphasize the neuroprotective, antiinflammatory, and immunomodulatory benefits of phytocannabinoids and their applications in various clinical syndromes. PMID:29770251

Plant delta 15N correlates with the transpiration efficiency of nitrogen acquisition in tropical trees.

PubMed

Cernusak, Lucas A; Winter, Klaus; Turner, Benjamin L

2009-11-01

Based upon considerations of a theoretical model of (15)N/(14)N fractionation during steady-state nitrate uptake from soil, we hypothesized that, for plants grown in a common soil environment, whole-plant delta(15)N (deltaP) should vary as a function of the transpiration efficiency of nitrogen acquisition (F(N)/v) and the difference between deltaP and root delta(15)N (deltaP - deltaR). We tested these hypotheses with measurements of several tropical tree and liana species. Consistent with theoretical expectations, both F(N)/v and deltaP - deltaR were significant sources of variation in deltaP, and the relationship between deltaP and F(N)/v differed between non-N(2)-fixing and N(2)-fixing species. We interpret the correlation between deltaP and F(N)/v as resulting from variation in mineral nitrogen efflux-to-influx ratios across plasma membranes of root cells. These results provide a simple explanation of variation in delta(15)N of terrestrial plants and have implications for understanding nitrogen cycling in ecosystems.

Research of the (E/Z)-isomerization of carotenoids in Pécs since the 1970s.

PubMed

Molnár, Péter

2009-03-15

Geometrical configuration of the polyene chain of approximately 40 mono- and di-cis carotenoids was determined from 1970 through 1990. Subsequently, the kinetic, equilibrium and thermodynamic parameters (k, K, A, E(A), DeltaH(#), DeltaG(#), DeltaS(#)) of the reversible thermal isomerization of several symmetrical and unsymmetrical carotenoids were calculated. The rate of the iodine-catalyzed photoisomerization of (all-E)-, (9Z)- and (13Z)-zeaxanthin was compared and the 'specific rate' (per unit light energy at given wavelengths) of the iodine-catalyzed photoisomerization for several (13Z)-carotenoids was investigated. As the missing links of the biosynthetic pathway of paprika-carotenoids, carotenoids containing new end groups were isolated; their sterically unhindered mono-cis isomers were also prepared and their geometrical configuration was determined. The investigation concentrated on the substrate specificity of the enzyme violaxanthin-deepoxidase, the light-induced formation of (13Z)-violaxanthin in green leaves, the binding of xanthophylls to the bulk light-harvesting complex (LHC) of photosystem II in higher plants, the biochemical basis of color as an aesthetic quality in Citrus-fruits and the (9Z)-epoxycarotenoid cleavage enzyme activity for ABA biosynthesis. Recently (9Z)-capsanthin-5,6-epoxide and capsoneoxanthin, two novel carotenoids have been isolated from natural sources.

An analysis of the errors associated with the determination of atmospheric temperature from atmospheric pressure and density data

NASA Technical Reports Server (NTRS)

Minzner, R. A.

1976-01-01

A graph was developed for relating delta T/T, the relative uncertainty in atmospheric temperature T, to delta p/p, the relative uncertainty in the atmospheric pressure p, for situations, when T is derived from the slope of the pressure-height profile. A similar graph relates delta T/T to delta roh/rho, the relative uncertainty in the atmospheric density rho, for those cases when T is derived from the downward integration of the density-height profile. A comparison of these two graphs shows that for equal uncertainties in the respective basic parameters, p or rho, smaller uncertainties in the derived temperatures are associated with density-height rather than with pressure-height data. The value of delta T/T is seen to depend not only upon delta p or delta rho, and to a small extent upon the value of T or the related scale height H, but also upon the inverse of delta h, the height increment between successive observations of p or rho. In the case of pressure-height data, delta T/T is dominated by 1/delta h for all values of delta h; for density-height data, delta T/T is dominated by delta rho/rho for delta h smaller than about 5 km. In the case of T derived from density-height data, this inverse relationship between delta T/T and delta h applies only for large values of delta h, that is, for delta h 35 km. No limit exists in the fineness of usable height resolution of T which may be derived from densities, while a fine height resolution in pressure-height data leads to temperature with unacceptably large uncertainties.

75 FR 20598 - Public Buildings Service; Prospect Island, Sacramento Delta, Solano County, CA; Transfer of Property

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-20

... GENERAL SERVICES ADMINISTRATION [Wildlife Order 188; 9-I-CA-1674] Public Buildings Service; Prospect Island, Sacramento Delta, Solano County, CA; Transfer of Property Pursuant to section 2 of Public Law 537, 80th Congress, approved May 19, 1948 (16 U.S.C. 667c), notice is hereby given that: 1. The...

Force Measurement on the GLAST Delta II Flight

NASA Technical Reports Server (NTRS)

Gordon, Scott; Kaufman, Daniel

2009-01-01

This viewgraph presentation reviews the interface force measurement at spacecraft separation of GLAST Delta II. The contents include: 1) Flight Force Measurement (FFM) Background; 2) Team Members; 3) GLAST Mission Overview; 4) Methodology Development; 5) Ground Test Validation; 6) Flight Data; 7) Coupled Loads Simulation (VCLA & Reconstruction); 8) Basedrive Simulation; 9) Findings; and 10) Summary and Conclusions.

PPARbeta/delta agonists modulate platelet function via a mechanism involving PPAR receptors and specific association/repression of PKCalpha--brief report.

PubMed

Ali, Ferhana Y; Hall, Matthew G; Desvergne, Béatrice; Warner, Timothy D; Mitchell, Jane A

2009-11-01

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is a nuclear receptor found in platelets. PPARbeta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPARbeta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPARbeta/delta receptors and their intracellular signaling pathways in platelets are not known. We have used mice lacking PPARbeta/delta (PPARbeta/delta(-/-)) to show the effects of the PPARbeta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPARbeta/delta, however GW501516 had no PPARbeta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKCalpha, which can mediate platelet activation, was bound and repressed by PPARbeta/delta after platelets were treated with GW501516. These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk.

DELTAS: A new Global Delta Sustainability Initiative (Invited)

NASA Astrophysics Data System (ADS)

Foufoula-Georgiou, E.

2013-12-01

Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh, Vietnam, and Canada. Key components of the DELTAS Sustainability Initiative are: integrated research on deltas as coupled socio-ecological systems undergoing change (Delta-SRES), a global delta data depository (Delta-DAT), a suite of open access delta risk assessment and decision support modeling tools (Delta-RADS), and the coordinated demonstration of these activities in deltas around the world (Delta-ACT).

Tuning metal-to-metal charge transfer of mixed-valence complexes containing ferrocenylpyridine and rutheniumammines via solvent donicity and substituent effects.

PubMed

Chen, Y J; Kao, C H; Lin, S J; Tai, C C; Kwan, K S

2000-01-24

A homogeneous series of heterobimetallic complexes of [R-Fc(4-py)Ru(NH3)5](PF6)2 (R = H, Et, Br, acetyl; Fc(4-py) = 4-ferrocenylpyridine) have been prepared and characterized. The mixed-valence species generated in situ using ferrocenium hexafluorophosphate as the oxidant show class II behavior, and the oxidized sites are ruthenium centered. deltaE(1/2), E(1/2)(Fe(III)/Fe(II)) - E(1/2)(Ru(III)/Ru(II)), an upper limit for deltaGo that is an energetic difference between the donor and acceptor sites, changes sharply and linearly with Gutmann solvent donor number (DN) and Hammett substituent constants (sigma). The solvent-dependent and substituent-dependent intervalence transfer bands were found to vary almost exclusively with deltaE(1/2). The activation energy for the optical electron transfer versus deltaE(1/2) plot yields a common nuclear reorganization energy (lambda) of 0.74 +/- 0.04 eV for this series. The equation that allows one to incorporate the effect of both solvent donicity and substituents on optical electron transfer is Eop = lambda + deltaGo, where deltaGo = (deltaGo)intrinsic + (deltaGo)solvent donicity + (deltaGo)substituent effect (deltaGo )intinnsic with a numerical value of 0.083 +/- 0.045 eV was obtained from the intercept of the deltaE(1/2) of [H-Fc(4-py)Ru(NH3)5]2+,3+,4+ versus DN plot. (deltaGo)solvent donicity was obtained from the average slopes of the deltaE(1/2) of [R-Fc-(4-py)Ru(NH3)5]2+,3+,4+ versus DN plot, and (deltaGo)substituent effect was obtained from the average slopes of the corresponding deltaE(1/2) versus sigma plot. The empirical equation allows one to finely tune Eop of this series to Eop = 0.82 + 0.019(DN) + 0.44sigma eV at 298 K, and the discrepancy between the calculated and experimental data is less than 6%.

Controls on delta formation, area, and topset slope: New predictive relationships developed using a global delta dataset

NASA Astrophysics Data System (ADS)

Caldwell, R. L.; Edmonds, D. A.; Baumgardner, S. E.; Paola, C.; Roy, S.; Nienhuis, J.

2017-12-01

River deltas are irreplaceable natural and societal resources, though they are at risk of drowning due to sea-level rise and decreased sediment delivery. To enhance hazard mitigation efforts in the face of global environmental change, we must understand the controls on delta growth. Previous empirical studies of delta growth are based on small datasets and often biased towards large, river-dominated deltas. We are currently lacking relationships that predict delta formation, area, or topset slope across the full breadth of global deltas. To this end, we developed a global dataset of 5,229 rivers (with and without deltas) paired with nine upstream (e.g., sediment discharge) and four downstream (e.g., wave height) environmental variables. Using Google Earth imagery, we identify all coastal river mouths (≥ 50 m wide) connected to an upstream catchment, and define deltas as river mouths that split into two or more distributary channels, end in a depositional protrusion from the shoreline, or do both. Delta area is defined as the area of the polygon connecting the delta node, two lateral shoreline extent points, and the basinward-most extent of the delta. Topset slope is calculated as the average, linear slope from the delta node elevation (extracted from SRTM data) to the main channel mouth, and shoreline and basinward extent points. Of the 5,229 rivers in our dataset, 1,816 (35%) have a delta. Using 495 rivers (those with data available for all variables), we build an empirically-derived relationship that predicts delta formation with 76% success. Delta formation is controlled predominantly by upstream water and sediment discharge, with secondary control by downstream waves and tides that suppress delta formation. For those rivers that do form deltas, we show that delta area is best predicted by sediment discharge, bathymetric slope, and drainage basin area (R2 = 0.95, n = 170), and exhibits a negative power-law relationship with topset slope (R2 = 0.85, n = 1,342). Topset slope is best predicted by grain size and wave height (R2 = 0.50, n = 358). These empirical relationships can aid in forecasting delta response to continued global environmental change.

Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck).

PubMed

Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco

2010-03-24

To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

Delta and theta power spectra of night sleep EEG are higher in breast-feeding mothers than in non-pregnant women.

PubMed

Nishihara, Kyoko; Horiuchi, Shigeko; Eto, Hiromi; Uchida, Sunao; Honda, Makoto

2004-09-23

The power spectra of night sleep EEGs of 12 breast-feeding 9-13 week postpartum mothers were analyzed and compared with those of 12 non-pregnant women. The power spectra in the delta and theta frequency range during NREM sleep for breast-feeding mothers were significantly higher than those for non-pregnant women. In addition, the all-night sleep patterns of the mothers were classified into two groups - interrupted sleep due to taking care of their infants and non-interrupted sleep - in order to observe the influence of partial sleep deprivation. The power spectra in the delta and theta frequency range were not significantly different between them. This result suggests that increased delta and theta power spectra during postpartum sleep do not result from partial sleep deprivation. The role of prolactin in breast-feeding mothers' sleep is also discussed.

Characterization of interaction between doxycycline and human serum albumin by capillary electrophoresis-frontal analysis.

PubMed

Sun, Hanwen; He, Pan

2009-06-01

The binding of doxycycline to HSA under simulated physiological conditions (pH 7.4, 67 mM phosphate, I=0.17, drug concentration 100 microM, HSA concentration up to 475 microM, 36.5 degrees C) was studied by CE-frontal analysis. The number of primary binding sites, binding constant and physiological protein-binding percentage were 1.9, 1.51 x 10(3) M(-1) and 59.80%, respectively. In addition, the thermodynamic parameters including enthalpy change (DeltaH), entropy change (DeltaS) and free energy change (DeltaG) of the reaction were obtained in order to characterize the acting forces between doxycycline and HSA. Furthermore, to better understand the nature of doxycycline-HSA binding and to get information about potential interaction with other drugs, displacement experiments were performed. The results showed that doxycycline binds at site II of HSA.

O2/1 Delta/ emission in the day and night airglow of Venus

NASA Technical Reports Server (NTRS)

Connes, P.; Noxon, J. F.; Traub, W. A.; Carleton, N. P.

1979-01-01

An intense airglow from O2(1 Delta) at 1.27 microns on both the light and the dark sides of Venus has been detected by using a ground-based high-resolution Fourier-transform spectrometer. Both dayglow and nightglow are roughly 1,000 times brighter than the visible O2 nightglow found by Veneras 9 and 10 in 1975. The column emission rate of O2(1 Delta) from Venus is close to the rate at which fresh O atoms are produced from photolysis of CO2 on the day side. Formation of O2(1 Delta) is thus a major step in the removal of O atoms from the atmosphere, and dynamical processes must carry these atoms to the night side fast enough to yield a maximum density near 90 km, which is almost constant over the planet.

Multimode delta Scuti stars in the open cluster NGC 7062

NASA Astrophysics Data System (ADS)

Freyhammer, L. M.; Arentoft, T.; Sterken, C.

2001-03-01

The central field of NGC 7062 was observed intensively with the main goal of finding delta Scuti stars suitable for use in asteroseismological tests of stellar structure and evolution theory. BV time series photometry was obtained for this northern open cluster, which has a large population of stars inside the delta Scuti instability strip, making it a probable host of several such variables. We report findings of 15 pulsating stars, including at least 13 delta Scuti stars. Ten variables oscillate in two or more frequencies. Only one of these variables was known before, for which we detected 9 frequencies. Five probable variables are mentioned, and period analysis is given for all 20 stars. Based on observations obtained at the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisíca de Canarias.

Measurement of sulfur isotope compositions by tunable laser spectroscopy of SO2.

PubMed

Christensen, Lance E; Brunner, Benjamin; Truong, Kasey N; Mielke, Randall E; Webster, Christopher R; Coleman, Max

2007-12-15

Sulfur isotope measurements offer comprehensive information on the origin and history of natural materials. Tunable laser spectroscopy is a powerful analytical technique for isotope analysis that has proven itself readily adaptable for in situ terrestrial and planetary measurements. Measurements of delta(34)S in SO2 were made using tunable laser spectroscopy of combusted gas samples from six sulfur-bearing solids with delta(34)S ranging from -34 to +22 per thousand (also measured with mass spectrometry). Standard deviation between laser and mass spectrometer measurements was 3.7 per thousand for sample sizes of 200 +/- 75 nmol SO(2). Although SO(2)(g) decreased 9% over 15 min upon entrainment in the analysis cell from wall uptake, observed fractionation was insignificant (+0.2 +/- 0.6 per thousand). We also describe a strong, distinct (33)SO(2) rovibrational transition in the same spectral region, which may enable simultaneous delta(34)S and Delta(33)S measurements.

Stepwise morphological evolution of the active Yellow River (Huanghe) delta lobe (1976-2013): Dominant roles of riverine discharge and sediment grain size

NASA Astrophysics Data System (ADS)

Wu, Xiao; Bi, Naishuang; Xu, Jingping; Nittrouer, Jeffrey A.; Yang, Zuosheng; Saito, Yoshiki; Wang, Houjie

2017-09-01

The presently active Yellow River (Huanghe) delta lobe has been formed since 1976 when the river was artificially diverted. The process and driving forces of morphological evolution of the present delta lobe still remain unclear. Here we examined the stepwise morphological evolution of the active Yellow River delta lobe including both the subaerial and the subaqueous components, and illustrated the critical roles of riverine discharge and sediment grain size in dominating the deltaic evolution. The critical sediment loads for maintaining the delta stability were also calculated from water discharge and sediment load measured at station Lijin, the last gauging station approximately 100 km upstream from the river mouth. The results indicated that the development of active delta lobe including both subaerial and subaqueous components has experienced four sequential stages. During the first stage (1976-1981) after the channel migration, the unchannelized river flow enhanced deposition within the channel and floodplain between Lijin station and the river mouth. Therefore, the critical sediment supply calculated by the river inputs obtained from station Lijin was the highest. However, the actual sediment load at this stage (0.84 Gt/yr) was more than twice of the critical sediment load ( 0.35 Gt/yr) for sustaining the active subaerial area, which favored a rapid seaward progradation of the Yellow River subaerial delta. During the second stage (1981-1996), the engineering-facilitated channelized river flow and the increase in median grain size of suspended sediment delivered to the sea resulted in the critical sediment load for keeping the delta stability deceasing to 0.29 Gt/yr. The active delta lobe still gradually prograded seaward at an accretion rate of 11.9 km2/yr at this stage as the annual sediment load at Lijin station was 0.55 Gt/yr. From 1996 to 2002, the critical sediment load further decreased to 0.15 Gt/yr with the sediment grain size increased to 22.5 μm; however, the delta suffered net erosion because of the insufficient sediment supply (0.11 Gt/yr). In the most recent stage (2002 - 2013), the intensive scouring of the lower river channel induced by the dam regulation provided relatively coarser sediment, which effectively reduced the critical sediment load to 0.06 Gt/yr, much lower than the corresponding sediment load at Lijin station ( 0.16 Gt/yr). Consequently, the subaerial Yellow River delta transitioned to a slight accretion phase. Overall, the evolution of the active Yellow River delta is highly correlated to riverine water and sediment discharge. The sediment supply for keeping the subaerial delta stability is inconstant and varying with the river channel morphology and sediment grain size. We conclude that the human-impacted riverine sediment discharge and grain-size composition play dominant roles in the stepwise morphological evolution of the active delta lobe.

Welcome to CALFED Bay-Delta Program

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Spectral contaminant identifier for off-axis integrated cavity output spectroscopy measurements of liquid water isotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brian Leen, J.; Berman, Elena S. F.; Gupta, Manish

Developments in cavity-enhanced absorption spectrometry have made it possible to measure water isotopes using faster, more cost-effective field-deployable instrumentation. Several groups have attempted to extend this technology to measure water extracted from plants and found that other extracted organics absorb light at frequencies similar to that absorbed by the water isotopomers, leading to {delta}{sup 2}H and {delta}{sup 18}O measurement errors ({Delta}{delta}{sup 2}H and {Delta}{delta}{sup 18}O). In this note, the off-axis integrated cavity output spectroscopy (ICOS) spectra of stable isotopes in liquid water is analyzed to determine the presence of interfering absorbers that lead to erroneous isotope measurements. The baseline offsetmore » of the spectra is used to calculate a broadband spectral metric, m{sub BB}, and the mean subtracted fit residuals in two regions of interest are used to determine a narrowband metric, m{sub NB}. These metrics are used to correct for {Delta}{delta}{sup 2}H and {Delta}{delta}{sup 18}O. The method was tested on 14 instruments and {Delta}{delta}{sup 18}O was found to scale linearly with contaminant concentration for both narrowband (e.g., methanol) and broadband (e.g., ethanol) absorbers, while {Delta}{delta}{sup 2}H scaled linearly with narrowband and as a polynomial with broadband absorbers. Additionally, the isotope errors scaled logarithmically with m{sub NB}. Using the isotope error versus m{sub NB} and m{sub BB} curves, {Delta}{delta}{sup 2}H and {Delta}{delta}{sup 18}O resulting from methanol contamination were corrected to a maximum mean absolute error of 0.93 per mille and 0.25 per mille respectively, while {Delta}{delta}{sup 2}H and {Delta}{delta}{sup 18}O from ethanol contamination were corrected to a maximum mean absolute error of 1.22 per mille and 0.22 per mille . Large variation between instruments indicates that the sensitivities must be calibrated for each individual isotope analyzer. These results suggest that the properly calibrated interference metrics can be used to correct for polluted samples and extend off-axis ICOS measurements of liquid water to include plant waters, soil extracts, wastewater, and alcoholic beverages. The general technique may also be extended to other laser-based analyzers including methane and carbon dioxide isotope sensors.« less

[Difference in ionic specificity of ATP synthesis in extremely alkalophilic sulfate-reducing and acetogenic bacteria].

PubMed

Pitriuk, A V; Pusheva, M A

2001-01-01

Ionic specificity of oxidative phosphorylation was studied in Natroniella acetigena and Desulfonatronum lacustre, which are new alkaliphilic anaerobes that were isolated from soda lakes and have a pH growth optimum of 9.5-9.7. The ability of their cells to synthesize ATP in response to the imposition of artificial delta pH+ and delta pNa+ gradients was studied. As distinct from other marine and freshwater sulfate reducers and extremely alkaliphilic anaerobes, D. lacustre uses a Na(+)-translocating ATPase for ATP synthesis. The alkaliphilic acetogen N. acetigena, which develops at a much higher Na+ concentration in the medium, generated primary delta pH+ for ATP synthesis. Thus, the high Na+ concentrations and alkaline pH values typical of soda lakes do not predetermine the type of bioenergetics of their inhabitants.

Natural and anthropogenic influences on depositional architecture of the Ural Delta, Kazakhstan, northern Caspian Sea, during the past 70 years

NASA Astrophysics Data System (ADS)

Scarelli, Frederico M.; Cantelli, Luigi; Barboza, Eduardo G.; Gabbianelli, Giovanni

2017-05-01

This paper focuses on the Ural Delta in the northern zone of the Caspian Sea, an area with particular characteristics, where intense influence from anthropogenic and natural factors exists, which acts on the fragile delta system. We built a database to integrate the data from the published sources, bathymetric survey, and recent images in the geographical information system (GIS) environment. The results were linked to the Caspian Sea level (CSL) curve, which had many variations, changing the Ural Delta system's dynamics and in its architecture. In addition, the anthropogenic changes contribute to shaping the actual Ural Delta architecture. Through the link between the results and CSL, we reconstructed an evolution model for the Ural Delta system for the last century and identified three different architectures for the Ural Delta, determined by the energy that acted on the system in the last century and by the anthropogenic changes. This work identifies six different delta phases, which are shaped by CSL changes during the last 70 years and by anthropogenic changes. The delta phases recognized are: i) a Lobate Delta phase, shaped during high CSL before 1935; ii) Natural Elongate Delta 1935-1950 formed during rapid CSL fall; iii) Anthropogenic Elongate Delta 1950-1966, formed during rapid CSL fall and after the Ural-Caspian Sea canal construction, which modified the sedimentary deposition on the delta; iv) Anthropogenic Elongate Delta 1966-1982 shaped during low CSL phase; v) Anthropogenic Elongate Delta 1982-1996 formed during a rapid CSL rise phase; and vi) Anthropogenic Elongate Delta 1996-2009 shaped during high CSL that represent the last phase and actual Ural Delta architecture.

Thermodynamics of phenanthrene partition into solid organic matter from water.

PubMed

Chen, Bao-liang; Zhu, Li-zhong; Tao, Shu

2005-01-01

The thermodynamic behavior of organic contaminants in soils is essential to develop remediation technologies and assess risk from alternative technologies. Thermodynamics of phenanthrene partition into four solids(three soils and a bentonite) from water were investigated. The thermodynamics parameters (deltaH, deltaG degrees, deltaS degrees) were calculated according to experimental data. The total sorption heats of phenanthrene to solids from water ranged from -7.93 to -17.1 kJ/mol, which were less exothermic than the condensation heat of phenanthrene-solid (i.e., -18.6 kJ/mol). The partition heats of phenanthrene dissolved into solid organic matter ranged from 23.1 to 32.2 kJ/mol, which were less endothermic than the aqueous dissolved heat of phenanthrene (i.e., 40.2 kJ/mol), and were more endothermic than the fusion heat of phenanthrene-solid (i.e., 18.6 kJ/mol). The standard free energy changes, deltaG degrees, are all negative which suggested that phenanthrene sorption into solid was a spontaneous process. The positive values of standard entropy changes, deltaS degrees, show a gain in entropy for the transfer of phenanthrene at the stated standard state. Due to solubility-enhancement of phenanthrene, the partition coefficients normalized by organic carbon contents decrease with increasing system temperature (i.e., ln Koc = -0.284 ln S + 9.82 (n = 4, r2 = 0.992)). The solubility of phenanthrene in solid organic matter increased with increasing temperatures. Transports of phenanthrene in different latitude locations and seasons would be predicted according to its sorption thermodynamics behavior.

Distribution, abundance, and age ratios of Wrangel Island lesser snow geese Anser caerulescens during autumn migration on the Yukon-Kuskokwim Delta, Alaska

USGS Publications Warehouse

Ely, Craig R.; Takekawa, John Y.; Wege, M.L.

1993-01-01

We monitored the distribution, abundance, and productivity of Lesser Snow Geese on the Yukon-Kuskokwim (Y-K) Delta, Alaska during September and October 1991, when the geese were en route from their nesting grounds on Wrangel Island, Russia to wintering areas along the Pacific Coast. Adult geese in brood flocks were captured on Wrangel Island and fitted with either satellite platform transmitting terminal (PTT) transmitters (29 birds) or conventional very high frequency (VHF) radio transmitters (68 birds). All geese with active PTTs used the Y-K Delta. Geese marked with PTTs and VHF transmitters were first detected on the Y-K Delta on 19 and 25 September, respectively, and stayed 8-9 days (range 1 to 25 days) Geese with PTTs used the same areas as unmarked geese and geese with VHF radios, except for the south Delta where only satellite data were obtained. Flocks averaged 1122 birds, and did not vary significantly in size during the study. Population estimates from two independent methods ranged from 58,000 to 88,000 geese during October. Productivity of the Wrangel Island population, as determined from the proportion of young in flocks using the Y-K Delta, has varied from 0.5 to 42.1% with a mean of 29%, since 1975. Age-ratio estimates from the Y-K Delta were highly correlated with, and not significantly different from, those from autumn staging and wintering areas further south, which may indicate that immatures in this population of geese suffer little mortality during the second half of their autumn migration.

Ratio of entropy to enthalpy in thermal transitions in biological tissues.

PubMed

Jacques, Steven L

2006-01-01

Thermal transitions in biological tissues that have been reported in the literature are summarized in terms of the apparent molar entropy (DeltaS) and molar enthalpy (DeltaH) involved in the transition. A plot of DeltaS versus DeltaH for all the data yields a straight line, consistent with the definition of free energy, DeltaG=DeltaH+TDeltaS. Various bonds may be involved in cooperative bond breakage during thermal transitions; however, for the sake of description, the equivalent number of cooperative hydrogen bonds can be cited. Most of the tissue data behave as if 10 to 20 hydrogen bonds are cooperatively broken during coagulation, with one transition, the expression of heat shock protein, involving 90 cooperative hydrogen bonds. The data are consistent with DeltaS=a+bDeltaH, where a=-327.5 J(mol K) and b=31.47 x 10(-4) K(-1). If each additional hydrogen bond adds 19 x 10(3) Jmol to DeltaH, then each additional bond adds 59.8 J(mol K) to DeltaS. Hence, the dynamics of irreversible thermal transitions can be described in terms of one free parameter, the apparent number of cooperative hydrogen bonds broken during the transition.

Investigations into the \\delta 15N and \\delta 13C of POM, Primary Producers, and Filter Feeders in the Florida Keys Coral Reef Tract

NASA Astrophysics Data System (ADS)

Lamb, K. A.; Swart, P. K.

2004-12-01

In order to examine the possible influences of anthropogenic wastes on the Florida Keys coral reef tract, water column particulate organic matter \\(POM\\), primary producers, and filter feeders were sampled from within the coastal waters of the reef tract, and analyzed for \\delta 15N and \\delta 13C isotopic composition. The POM was found to have a mean \\delta 15N value of +4.13\\permil (\\pm 1.03\\permil\\) and a mean \\delta 13C value of -19.93\\permil (\\pm 0.58\\permil). The \\delta 13C values for POM across the entire reef tract were heavier inshore \\(avg \\delta 13C = -18.29\\permil \\(\\pm 1.04\\permil\\)\\) and became lighter offshore \\(avg \\delta 13C = -21.41\\permil \\(\\pm 0.89\\permil\\)\\), which is consistent with influences from benthic algae/seagrass closer to shore in contrast to open-marine influences offshore. The \\delta 15N values for POM were neither temporally nor spatially interrelated, as the data showed no clear trend moving in either the inshore or offshore direction. Instead, our \\delta 15N values for POM reflect a combined influence from nitrogen fixation \\(\\approx0\\permil\\), zooplankton and other suspended particles, and not anthropogenic wastes \\(>+10\\permil\\), as other authors claim. The mean isotopic composition of various primary producers suggests a nitrogen fixation source of nutrients to the reef system (Halimeda sp. (\\delta 15N = 2.43\\permil; \\delta 13C = -18.04\\permill), Dictyota sp. (\\delta 15N = +2.86\\permil; \\delta 13C = -16.30\\permil), Thalassia sp. (\\delta 15N = 2.39\\permil; \\delta 13C = -10.32\\permil)), while filter feeders were found to have a mean isotopic composition more similar to POM values (sponge \\delta 15N = 4.95\\permil; \\delta 13C = -18.02\\permil). Our data simply do not appear to show evidence of anthropogenic influence on the Florida Keys reef tract. Further more, we suggest that \\delta 15N values of +4\\permil, which have recently been suggested to indicate anthropogenic influences are not, in fact, indicative of sewage.

Spatial and seasonal variations in stream water delta34S-dissolved organic matter in northern Sweden.

PubMed

Giesler, Reiner; Björkvald, Louise; Laudon, Hoalmar; Mörth, Carl-Magnus

2009-01-15

The discharge of terrestrial dissolved organic matter (DOM) by streams is an important cross-system linkage that strongly influences downstream aquatic ecosystems. Isotopic tracers are important tools that can help to unravel the source of DOM from different terrestrial compartments in the landscape. Here we demonstrate the spatial and seasonal variation of delta34S of DOM in 10 boreal streams to test if the tracer could provide new insights into the origin of DOM. We found large spatial and seasonal variations in stream water delta34S-DOM values ranging from -5.2 per thousand to +9.6 per thousand with an average of +4.0 +/- 0.6 (N = 62; average and 95% confidence interval). Large seasonal variations were found in stream water delta34S-DOM values: for example, a shift of more than 10 per thousand during the spring snowmelt in a wetland-dominated stream. Spatial differences were also observed during the winter base flow with higher delta34S-DOM values in the fourth-order Krycklan stream at the outlet of the 68 km2 catchment compared to the small (< 1 km2) headwater streams. Our data clearly show that the delta34S-DOM values have the potential to be used as a tracer to identify and generate new insights about terrestrial DOM sources in the boreal landscape.

[Distribution and sources of polycyclic aromatic hydrocarbons in sediments from rivers of Pearl River Delta and its nearby South China Sea].

PubMed

Luo, Xiao-Jun; Chen, She-Jun; Mai, Bi-Xian; Zeng, Yong-Ping; Sheng, Guo-Ying; Fu, Jia-Mo

2005-07-01

Polycyclic aromatic hydrocarbons (PAHs) are measured in surface sediments from rivers and estuary of Pearl River Delta and its nearby South China Sea. Total PAH concentration varied from 255.9 - 16 670.3 ng/g and a moderate to low level compare to relevant areas worldwide. The order of PAHs concentration in sediments was: rivers of Pearl River Delta > estuary > South China Sea, and the most significant PAH contamination was at Guangzhou channel of Zhujiang river. A decrease trend for PAHs concentration with distance from estuary to open sea can be sees in South China Sea. Coal and biomass combustion is the major source of PAHs in nearshore of South China Sea, and petroleum combustion is the main source of pyrolytic PAHs in rivers and estuary of Pearl River Delta according to PAHs diagnostic ratios. Petroleum PAHs are revealed have a high contribution to PAHs in Xijiang River, estuary and some stations in Zhujiang River. A comparison of data from study in 1997 with data from present study indicates that there is no clear change in the PAH concentration over time but the source of PAHs in Pearl River Delta have been change from a main coal combustion to petroleum combustion and being reflect in the sediments in rivers and estuary of Pearl River Delta where there have high sedimentation rate.

Evaluation of polymerization-dependent changes in color and translucency of resin composites using two formulae.

PubMed

Paravina, Rade D; Kimura, Mikio; Powers, John M

2005-09-01

The aim of this study was to evaluate polymerization-dependent changes in the color and translucency parameter (TP) of resin composites and to compare results obtained using two color-difference metric formulae, CIELAB and CIEDE 2000. Twenty-eight shades of commercial resin composites were analyzed. Specimens (n = 5) were made as discs, 11 mm in diameter and 2-mm thick, using cylindrical molds. Data were collected before and after composite polymerization, using a spectrophotometer. In regard to in vitro color changes of composites (DeltaE*) a DeltaE76 of 3.7 or greater was considered to be an unacceptable color change. Data were analyzed by analysis of variance, and Fisher's protected least significant difference (PLSD) intervals for comparison of means were calculated at the 0.05 level of significance. Mean polymerization-dependent differences in color were DeltaE00 = 4.48 (2.11) and DeltaE76 = 5.51 (2.68). The DeltaTP00 range was 2.57, while the DeltaTP76 range was 2.89. Mean polymerization-dependent differences in translucency were DeltaTP00 = 0.84 (0.77) and DeltaTP76 = 0.87 (0.76). Analysis of variance showed significant differences among composites, shades, and their interactions (P < 0.0001; power = 1.0). Regression equations and r values for the two color-difference formulae and all evaluated TP values showed very strong correlation. In conclusion, within the limitations of this study, polymerization-dependent changes in color and translucency were highly varied. The majority of shades showed polymerization-dependent differences in color higher than the DeltaE76 = 3.7. The TP generally increased after light polymerization by light activation. The very strong correlation (r > 0.97) between the two color-difference formulae indicates that the limitations of the CIELAB system do not appear to be a problem when evaluating composites; however, recorded differences between DeltaE76 and DeltaE00 values stress the importance of data conversion.

Developing a Truly Global Delta Database to Assess Delta Morphology and Morphodynamics

NASA Astrophysics Data System (ADS)

Caldwell, R. L.; Edmonds, D. A.; Baumgardner, S. E.; Whaling, A.

2015-12-01

Delta morphology reflects the interplay of various environmental parameters, though these relationships have only been tested on small datasets with 30-50 deltas. These datasets are biased toward the largest deltas, which typically have compound morphologies, form on passive margins, and may not be representative of the full breadth in delta morphology. With the goal of building more robust predictions of delta morphology to enhance hazard mitigation and resiliency planning, we have developed a truly global delta database including every delta on the world's marine coastlines. Using Google Earth imagery, we first identified all fluvial river mouths (≥ 50 m wide) connected to an upstream catchment. Deltas are defined geomorphically as river mouths that split into two or more active or relict distributary channels, end in a depositional protrusion from the shoreline, or do both. In our database we identified 5,801 river mouths, and 1,426 of those coastal rivers (~25%) have a geomorphic delta. ~75% of deltas exhibit an active or relict distributary network, while the remaining ~25% are single channel deltas with a basinward protrusion. Preliminary morphometric analysis (ratio of shore-parallel width, W, to shore-perpendicular length, L) on a subset of 159 deltas suggests W:L values range from 0.52 (elongate) to 23.6 (broad/cuspate). The median W:L value is 2.68, suggesting the majority of deltas are roughly semi-circular (W:L = 2), and the distribution is heavily skewed to the broad/cuspate deltas (~28% are >4 times wider than they are long). Preliminary comparison to downstream significant wave height data shows that the 'wider' deltas relate to higher wave heights (R2 = 0.42), though the data are scattered. Ultimately, the database will include additional measured morphometrics, including number of channel mouths and delta area, and morphodynamic data derived from serial Landsat imagery.

Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

PubMed Central

Franco, Christopher B.; Scripture-Adams, Deirdre D.; Proekt, Irina; Taghon, Tom; Weiss, Angela H.; Yui, Mary A.; Adams, Stephanie L.; Diamond, Rochelle A.; Rothenberg, Ellen V.

2006-01-01

PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment. PMID:16880393

Isotopic evidence for breastfeeding and possible adult dietary differences from Late/Sub-Roman Britain.

PubMed

Fuller, B T; Molleson, T I; Harris, D A; Gilmour, L T; Hedges, R E M

2006-01-01

Historical documents indicate that breastfeeding and weaning practices have fluctuated in England through history. In order to obtain evidence for general breastfeeding patterns in Late/Sub-Roman Britain, stable carbon and nitrogen isotope values were measured in juvenile and adult skeletons (n = 87) from the cemetery of Queenford Farm, Dorchester-on-Thames, Oxfordshire. As the site contained few individuals between 0-1.5 years of age, it was not possible to determine the initial timing for the introduction of weaning foods. Between ages 2-4 years, the mean +/- SD delta(13)C results (-20.2 +/- 0.3 per thousand) are significantly more negative (t = -4.03, P < 0.001) compared to adult females (-19.7 +/- 0.3 per thousand). This is interpreted as evidence of a different diet being fed to children during weaning. After age 2, the delta(15)N values gradually decline, indicating complete cessation of breastfeeding by 3-4 years. Among adults, stature (males = 1.68 +/- 0.06 m; females = 1.58 +/- 0.07 m) and sexual dimorphism (106) were low, suggesting that the population was possibly under environmental stress. The delta(13)C results for adults are similar, but females show a small but statistically significantly (t = -2.86, P < 0.01) lower mean delta(15)N value (9.9 +/- 0.9 per thousand) compared to males (10.6 +/- 0.5 per thousand). These lower female delta(15)N values possibly reflect the different physiology of the sexes (pregnancy and/or lactation) or the reduced consumption of animal/fish protein by women, and this may have been influenced by individual preference, family needs, or societal values of the era.

Adolescent Changes in Homeostatic Regulation of EEG Activity in the Delta and Theta Frequency Bands during NREM Sleep

PubMed Central

Campbell, Ian G.; Darchia, Nato; Higgins, Lisa M.; Dykan, Igor V.; Davis, Nicole M.; de Bie, Evan; Feinberg, Irwin

2011-01-01

Study Objectives: Slow wave EEG activity in NREM sleep decreases by more than 60% between ages 10 and 20 years. Slow wave EEG activity also declines across NREM periods (NREMPs) within a night, and this decline is thought to represent the dynamics of sleep homeostasis. We used longitudinal data to determine whether these homeostatic dynamics change across adolescence. Design: All-night sleep EEG was recorded semiannually for 6 years. Setting: EEG was recorded with ambulatory recorders in the subjects' homes. Participants: Sixty-seven subjects in 2 cohorts, one starting at age 9 and one starting at age 12 years. Measurements and Results: For NREM delta (1-4 Hz) and theta (4-8 Hz) EEG, we tested whether the proportion of spectral energy contained in the first NREMP changes with age. We also tested for age changes in the parameters of the process S exponential decline. For both delta and theta, the proportion of energy in the first NREMP declined significantly across ages 9 to 18 years. Process S parameters SWA0 and TWA0, respectively, represent slow wave (delta) activity and theta wave activity at the beginning of the night. SWA0 and TWA0 declined significantly (P < 0.0001) across ages 9 to 18. Conclusions: These declines indicate that the intensity of the homeostatic or restorative processes at the beginning of sleep diminished across adolescence. We propose that this change in sleep regulation is caused by the synaptic pruning that occurs during adolescent brain maturation. Citation: Campbell IG; Darchia N; Higgins LM; Dykan IV; Davis NM; de Bie E; Feinberg I. Adolescent changes in homeostatic regulation of EEG activity in the delta and theta frequency bands during NREM sleep. SLEEP 2011;34(1):83-91. PMID:21203377

Pre-bomb {Delta}{sup 14}C variability and the Suess Effect in Cariaco Basin Surface Waters as Recorded in Hermatypic Corals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guilderson, T; Cole, J; Southon, J

2004-10-28

The {Delta}{sup 14}C content of surface waters in and around the Cariaco Basin were reconstructed from {sup 14}C measurements on sub-annually sampled coral skeletal material. During the late 1930s - early 1940s surface waters within and outside of the Cariaco Basin are similar. Within the Cariaco Basin at Islas Tortugas coral {Delta}{sup 14}C averages -51.9 {+-}3.3 {per_thousand}. Corals collected outside of the basin at Boca de Medio and Los Testigos have {Delta}{sup 14}C values of -53.4 {+-} 3.3 {per_thousand} and -54.3 {+-} 2.6 respectively. Additional {sup 14}C analyses on the Isla Tortugas coral document an {approx} 11 {per_thousand} decrease betweenmore » {approx}1905 (-40.9 {+-}4.5 {per_thousand}) and {approx}1940. The implied Suess Effect trend (-3 {per_thousand}/decade) is nearly as large as that observed in the atmosphere over the same time period. If we assume that there is little to no fossil fuel {sup 14}CO{sub 2} signature in Cariaco surface waters in {approx}1905, the waters have an equivalent reservoir age of {approx}312 years.« less

Drugs of abuse and alcohol consumption among different groups of population on the Greek Island of Lesvos through sewage-based epidemiology.

PubMed

Gatidou, Georgia; Kinyua, Juliet; van Nuijs, Alexander L N; Gracia-Lor, Emma; Castiglioni, Sara; Covaci, Adrian; Stasinakis, Athanasios S

2016-09-01

The occurrence of 22 drugs of abuse, their metabolites, and the alcohol metabolite ethyl sulphate was investigated in raw sewage samples collected during the non-touristic season from three sewage treatment plants (STPs), which serve different sizes and types of population in the Greek island of Lesvos. Using the sewage-based epidemiology approach, the consumption of these substances was estimated. Five target analytes, cocaine (COC), benzoylecgonine (BE), 3,4-methylenedioxymethamphetamine (MDMA), 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) and ethyl sulphate (EtS) were detected at concentrations above their limit of quantification, whereas the rest eighteen target compounds were not detected. THC-COOH was detected in most of the samples with concentrations ranging between <20 and 90ngL(-1), followed by EtS (range <1700-12,243ngL(-1)). COC, BE, and MDMA were present only in the STP that serves Mytilene (the main city of the island), at mean concentrations of 3.9ngL(-1) for COC (95% CI: 1.7-6.1), 9.4ngL(-1) for BE (95% CI: -1.6-23) and 3.2ngL(-1) for MDMA (95% CI: 1.2-5.1). Back-calculations to an amount of used substance indicated more intense use of drugs among city population than rural and University population with average values of 9.5 and 1.2mgday(-1) per 1000 inhabitants for COC (95% CI: -1.43-20.4) and MDMA (95% CI: 0.52-1.85), respectively, and 2.8gday(-1) per 1000 inhabitants for tetrahydrocannabinol (THC) (95% CI: 2.4-3.1), the active ingredient of cannabis. Alcohol consumption was observed to be higher in the city population (5.4mL pure alcohol per day per inhabitant) than in the rural population (3.4mL pure alcohol per day per inhabitant), but the difference was not statistically significant. Consumption of THC differed significantly among the three STPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Selection of solubility parameters for characterization of pharmaceutical excipients.

PubMed

Adamska, Katarzyna; Voelkel, Adam; Héberger, Károly

2007-11-09

The solubility parameter (delta(2)), corrected solubility parameter (delta(T)) and its components (delta(d), delta(p), delta(h)) were determined for series of pharmaceutical excipients by using inverse gas chromatography (IGC). Principal component analysis (PCA) was applied for the selection of the solubility parameters which assure the complete characterization of examined materials. Application of PCA suggests that complete description of examined materials is achieved with four solubility parameters, i.e. delta(2) and Hansen solubility parameters (delta(d), delta(p), delta(h)). Selection of the excipients through PCA of their solubility parameters data can be used for prediction of their behavior in a multi-component system, e.g. for selection of the best materials to form stable pharmaceutical liquid mixtures or stable coating formulation.

Tides Stabilize Deltas until Humans Interfere

NASA Astrophysics Data System (ADS)

Hoitink, T.; Zheng Bing, W.; Vermeulen, B.; Huismans, Y.; Kastner, K.

2017-12-01

Despite global concerns about river delta degradation caused by extraction of natural resources, sediment retention by reservoirs and sea-level rise, human activity in the world's largest deltas intensifies. In this review, we argue that tides tend to stabilize deltas until humans interfere. Under natural circumstances, delta channels subject to tides are more stable than their fluvial-dominated counterparts. The oscillatory tidal flow counteracts the processes responsible for bank erosion, which explains why unprotected tidal channels migrate only slowly. Peak river discharges attenuate the tides, which creates storage space to accommodate the extra river discharge during extreme events and as a consequence, reduce flood risk. With stronger tides, the river discharge is being distributed more evenly over the various branches in a delta, preventing silting up of smaller channels. Human interference in deltas is massive. Storm surge barriers are constructed, new land is being reclaimed and large-scale sand excavation takes place, to collect building material. Evidence from deltas around the globe shows that in human-controlled deltas the tidal motion often plays a destabilizing role. In channels of the Rhine-Meuse Delta, some 100 scour holes are identified, which relates to the altered tidal motion after completion of a storm surge barrier. Sand mining has led to widespread river bank failures in the tidally-influenced Mekong Delta. The catastrophic flood event in the Gauges-Brahmaputra Delta by Cyclone Aila, which caused the inundation of an embanked polder area for over two years, was preceded by river bank erosion at the mouths of formal tidal channels that were blocked by the embankment. Efforts to predict the developments of degrading deltas are few. Existing delta models are capable of reproducing expanding deltas, which is essentially a matter of simulating the transport of sediment from source in a catchment to the sink in a delta. Processes of soil compaction, mixing of sands and clay, and the influence of peat layers complicate the prediction of delta erosion. Considering sea-level rise, sediment depletion and all the direct human modifications in deltas, there is a need for a new generation delta models using quantified erosion resistance from geological records.

Growth laws for delta crevasses in the Mississippi River Delta: observations and modeling

NASA Astrophysics Data System (ADS)

Yocum, T. A.; Georgiou, I. Y.

2016-02-01

River deltas are accumulations of sedimentary deposits delivered by rivers via a network of distributary channels. Worldwide they are threatened by environmental changes, including subsidence, global sea level rise and a suite of other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions, thereby reinitiating the delta cycle. While economically efficient, there are too few analogs of small deltas aside from laboratory studies, numerical modeling studies, theoretical approaches, and limited field driven observations. Anthropogenic crevasses in the modern delta are large enough to overcome limitations of laboratory deltas, and small enough to allow for "rapid" channel and wetland development, providing an ideal setting to investigate delta development mechanics. Crevasse metrics were obtained using a combination of geospatial tools, extracting key parameters (bifurcation length and width, channel order and depth) that were non-dimensionalized and compared to river-dominated delta networks previously studied. Analysis showed that most crevasses in the MRD appear to obey delta growth laws and delta allometry relationships, suggesting that crevasses do exhibit similar planform metrics to larger Deltas; the distance to mouth bar versus bifurcation order demonstrated to be a very reasonable first order estimate of delta-top footprint. However, some crevasses exhibited different growth metrics. To better understand the hydrodynamic and geomorphic controls governing crevasse evolution in the MRD, we assess delta dynamics via a suite of field observations and numerical modeling in both well-established and newly constructed crevasses. Our analysis suggests that delta development is affected by the relative influence of external (upstream and downstream) and internal controls on the hydrodynamic and sediment transport patterns in these systems.

Human common acute lymphoblastic leukemia-derived cell lines are competent to recombine their T-cell receptor delta/alpha regions along a hierarchically ordered pathway.

PubMed

Hansen-Hagge, T E; Yokota, S; Reuter, H J; Schwarz, K; Bartram, C R

1992-11-01

Rearrangements of the T-cell receptor (TCR) delta locus are observed in the majority of human B-cell precursor acute lymphoblastic leukemias (ALL) with a striking predominance of V delta 2(D)D delta 3 recombinations in common ALL (cALL) patients. Recently, we and others showed that almost 20% of cALL cases are characterized by further recombination of V delta 2(D)D delta 3 segments to J alpha elements, thereby deleting the TCR delta locus in analogy to the delta Rec/psi J alpha pathway in differentiating alpha/beta-positive T cells. We report here that two human cALL-derived cell lines, REH and Nalm-6, are competent to recombine the TCR delta/alpha locus under standard tissue culture conditions. Analysis of different REH subclones obtained by limiting dilution of the initial culture showed a biased recombination of V delta 2D delta 3 to distinct J alpha elements. During prolonged tissue culture, a subclone acquired growth advantage and displaced parental cells as well as other subclones. Frequently, the DJ junctions of REH subclones contained extended stretches of palindromic sequences derived from modified D delta 3 coding elements. The other cell line, Nalm-6, started the TCR delta/alpha recombination with an unusual signal joint of a cryptic recombinase signal sequence (RSS) upstream of D delta 3 to the 3' RSS of D delta 3. The RSS dimer was subsequently rearranged in all investigated subclones to an identical J alpha element. Both cell lines might become valuable tools to unravel the complex regulation of TCR delta/alpha recombination pathways in malignant and normal lymphopoiesis.

Water and nitrogen conditions affect the relationships of Delta13C and Delta18O to gas exchange and growth in durum wheat.

PubMed

Cabrera-Bosquet, Llorenç; Molero, Gemma; Nogués, Salvador; Araus, José Luis

2009-01-01

Whereas the effects of water and nitrogen (N) on plant Delta(13)C have been reported previously, these factors have scarcely been studied for Delta(18)O. Here the combined effect of different water and N regimes on Delta(13)C, Delta(18)O, gas exchange, water-use efficiency (WUE), and growth of four genotypes of durum wheat [Triticum turgidum L. ssp. durum (Desf.) Husn.] cultured in pots was studied. Water and N supply significantly increased plant growth. However, a reduction in water supply did not lead to a significant decrease in gas exchange parameters, and consequently Delta(13)C was only slightly modified by water input. Conversely, N fertilizer significantly decreased Delta(13)C. On the other hand, water supply decreased Delta(18)O values, whereas N did not affect this parameter. Delta(18)O variation was mainly determined by the amount of transpired water throughout plant growth (T(cum)), whereas Delta(13)C variation was explained in part by a combination of leaf N and stomatal conductance (g(s)). Even though the four genotypes showed significant differences in cumulative transpiration rates and biomass, this was not translated into significant differences in Delta(18)O(s). However, genotypic differences in Delta(13)C were observed. Moreover, approximately 80% of the variation in biomass across growing conditions and genotypes was explained by a combination of both isotopes, with Delta(18)O alone accounting for approximately 50%. This illustrates the usefulness of combining Delta(18)O and Delta(13)C in order to assess differences in plant growth and total transpiration, and also to provide a time-integrated record of the photosynthetic and evaporative performance of the plant during the course of crop growth.

Carbon and nitrogen isotopic compositions of alkyl porphyrins from the Triassic Serpiano oil shale

NASA Technical Reports Server (NTRS)

Chicarelli, M. I.; Hayes, J. M.; Popp, B. N.; Eckardt, C. B.; Maxwell, J. R.

1993-01-01

The carbon and nitrogen isotopic compositions of seven of the most abundant alkylporphyrins from the Serpiano oil shale (marine, Triassic) were determined. For the C31 and C32 butanoporphyrins, values of delta 13CPDB and delta 15NAIR averaged -24.0% and -3.1%. In contrast, the C31 and C32 methylpropanoporphyrins, DPEP, and a C30 13-nor etioporphyrin had delta 13C and delta 15N values averaging -27.5 and -3.3%, respectively. Carbon and nitrogen isotopic values for kerogen averaged -30.8 and -0.9, whereas those for total extract averaged -31.6, and -4.0%. The butanoporphyrins apparently derive from a biological source different from that giving rise to the other porphyrins, their 13C enrichment not being related to carbon isotopic fractionation accompanying diagenetic reactions. The delta 15N values for all the porphyrins indicate that the depletion of 15N observed in the kerogen is of primary origin. Consistent with the very high abundance of hopanoids and methyl hopanoids in the aliphatic hydrocarbon fraction, it is suggested that cyanobacterial fixation of N2 may have been the main cause of 15N depletion.

KSC-07pd1511

NASA Image and Video Library

2007-06-15

KENNEDY SPACE CENTER, FLA. -- The second stage of the Delta II launch vehicle for the Dawn spacecraft is lifted alongside the mobile service tower on Launch Pad 17-B at Cape Canaveral Air Force Station. At right can be seen the solid rocket boosters surrounding Delta's first stage. The second stage will be mated with the first stage. The Delta II-Heavy, manufactured by the United Launch Alliance, is scheduled to launch the Dawn spacecraft on its 4-year flight to the asteroid belt. The Delta II-Heavy is the strongest rocket in the Delta II class. It will use three stages and nine solid-fueled booster rockets to propel Dawn on its way. A 9.5-foot payload fairing will protect the spacecraft from the heat and stresses of launch. Dawn's goal is to characterize the conditions and processes of the solar system's earliest epoch by investigating in detail the largest protoplanets that have remained intact since their formations: asteroid Vesta and the dwarf planet Ceres. They reside in the extensive zone between Mars and Jupiter together with many other smaller bodies, called the asteroid belt. Dawn is scheduled to launch July 7. Photo credit: NASA/Jack Pfaller

The second Quito astrolabe catalogue

NASA Astrophysics Data System (ADS)

Kolesnik, Y. B.; Davila, H.

1994-03-01

The paper contains 515 individual corrections {DELTA}α and 235 corrections {DELTA}δ to FK5 and FK5Supp. stars and 50 corrections to their proper motions computed from observations made with the classical Danjon astrolabe OPL-13 at Quito Astronomical Observatory of Ecuador National Polytechnical School during a period from 1964 to 1983. These corrections cover the declination zone from -30deg to +30deg. Mean probable errors of catalogue positions are 0.047" in αcosδ and 0.054" in δ. The systematic trends of the catalogue {DELTA}αalpha_cosδ, {DELTA}αdelta_cosδ, {DELTA}δalpha_, {DELTA}δdelta_ are presented for the observed zone.

Martian deltas: Morphology and distribution

NASA Technical Reports Server (NTRS)

Rice, J. W., Jr.; Scott, D. H.

1993-01-01

Recent detailed mapping has revealed numerous examples of Martian deltas. The location and morphology of these deltas are described. Factors that contribute to delta morphology are river regime, coastal processes, structural stability, and climate. The largest delta systems on Mars are located near the mouths of Maja, Maumee, Vedra, Ma'adim, Kasei, and Brazos Valles. There are also several smaller-scale deltas emplaced near channel mouths situated in Ismenius Lacus, Memnonia, and Arabia. Delta morphology was used to reconstruct type, quantity, and sediment load size transported by the debouching channel systems. Methods initially developed for terrestrial systems were used to gain information on the relationships between Martian delta morphology, river regime, and coastal processes.

Evidence for clonal selection of gamma/delta T cells in response to a human pathogen

PubMed Central

1991-01-01

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens. PMID:1651977

Depositional architecture and evolution of inner shelf to shelf edge delta systems since the Late Oliocene and their respone to the tectonic and sea level change, Pear River Mouth Basin, northern South China Sea

NASA Astrophysics Data System (ADS)

Lin, Changsong; Zhang, Zhongtao; liu, Jingyan; Jiang, Jing

2016-04-01

The Pear River Mouth Basin is located in the northern continent margin of the South China Sea. Since the Late Oligocene, the long-term active fluvial systems (Paleo-Zhujiang) from the western basin margin bebouched into the northern continental margin of the South China Sea and formed widespread deltaic deposits in various depositional geomorphologies and tectonic settings. Based of integral analysys of abundant seismic, well logging and drilling core data, Depositional architecture and evolution of these delta systems and their respone to the tectonic and sea level change are documented in the study. There are two basic types of the delta systems which have been recognized: inner shelf delta deposited in shallow water enviroments and the outer shelf or shelf-edge delta systems occurred in deep water settings. The paleowater depths of these delta systems are around 30 to 80m (inner shelf delta) and 400-1000m (shelf-edge delta) estimated from the thickness (decompaction) of the delta front sequences. The study shows that the inner shelf delta systems are characterized by relatively thin delta forests (20-40m), numereous stacked distributary channel fills, relative coarse river mouth bar deposits and thin distal delta front or distal bar and prodelta deposits. In contrast, the outer shelf or shelf edge delta systems are characteristic of thick (300-800m) and steep (4-60) of deltaic clinoforms, which commonly display in 3D seismic profiles as "S" shape reflection. Large scale soft-sediment deformation structures, slump or debris flow deposits consisting mainly of soft-sediment deformed beds, blocks of sandstones and siltstones or mudstones widely developed in the delta front deposits. The shelf edge delta systems are typically associated with sandy turbidite fan deposits along the prodelta slopes, which may shift basinwards as the progradation of the delta systems. The delta systems underwent several regional cycles of evolution from inner shelf deltas to shelf edge deltas since the Late Oligocene in the study area, and this is consistent with relative sea level changes constrained by interplay of tectonic subsidence or global sea level change and sediment supply. The shelf-edge delta sandy deposits and the associated prodelta turbidite fan systems are the most important oil/gas bearing reservoirs in the continental slope area.

Comparison of Two Methods for Noninvasive Determination of Stroke Volume During Orthostatic Challenge

NASA Technical Reports Server (NTRS)

Doerr, Donald F.; Ratliff, Duane A.; Sithole, Joseph; Convertino, Victor A.

2005-01-01

Background: The real time, beat-by-beat, non-invasive determination of stroke volume (SV) is an important parameter in many aerospace related physiologic protocols. In this study, we compared simultaneous estimates of SV calculated from peripheral pulse waveforms with a more conventional non-invasive technique. Methods: Using a prospective, randomized blinded protocol, ten males and nine females completed 12-mm tilt table protocols. The relative change (%(Delta)) in beat-to-beat SV was estimated non-invasively from changes in pulse waveforms measured by application of infrared finger photoplethysmography (IFP) with a Portapres(Registered TradeMark) blood pressure monitoring device and by thoracic impedance cardiography (TIC). The %(Delta) SV values were calculated from continuous SV measurements in the supine posture and over the first 10 s (T1), second 10 s (T2), and 3.5 minutes (T3) of 80deg head-up tilt (HUT). Results: The average %(Delta) SV measured by IFP at T1 (-11.7 +/- 3.7 %) was statistically less (P <0.02) than the average %(Delta) SV measured by TIC at T1 (-21.7 +/- 3.1 %), while the average %(Delta) SV measured by 1FF at T2 (-16.2 +/- 3.9 %) and T3 (-19.1 +/- 3.8 %) were not statistically distinguishable (P > or = 0.322) than the average %(Delta) SV measured by TIC at T2 (-21.8 +/- 2.5 %), and T3 (-22.6 +/- 2.9 %). Correlation coefficients (r(sup 2)) between IFP and TIC were 0.117 (T1), 0.387 (T2), and 0.7 18 (T3). Conclusion: IFP provides beat-to-beat (real time) assessment of %(Delta) SV after 20 sec of transition to an orthostatic challenge that is comparable to the commonly accepted TIC. Our data support the notion that IFP technology which has flown during space missions can be used to accurately assess physiological status and countermeasure effectiveness for orth static problems that may arise in astronauts after space flight. While the peripherally measured IFP response is slightly delayed, the ease of implementing this monitor in the field is advantageous.

Sediment and water chemistry of the San Juan River and Escalante River deltas of Lake Powell, Utah, 2010-2011

USGS Publications Warehouse

Hornewer, Nancy J.

2014-01-01

Recent studies have documented the presence of trace elements, organic compounds including polycyclic aromatic hydrocarbons, and radionuclides in sediment from the Colorado River delta and from sediment in some side canyons in Lake Powell, Utah and Arizona. The fate of many of these contaminants is of significant concern to the resource managers of the National Park Service Glen Canyon National Recreation Area because of potential health impacts to humans and aquatic and terrestrial species. In 2010, the U.S. Geological Survey began a sediment-core sampling and analysis program in the San Juan River and Escalante River deltas in Lake Powell, Utah, to help the National Park Service further document the presence or absence of contaminants in deltaic sediment. Three sediment cores were collected from the San Juan River delta in August 2010 and three sediment cores and an additional replicate core were collected from the Escalante River delta in September 2011. Sediment from the cores was subsampled and composited for analysis of major and trace elements. Fifty-five major and trace elements were analyzed in 116 subsamples and 7 composited samples for the San Juan River delta cores, and in 75 subsamples and 9 composited samples for the Escalante River delta cores. Six composited sediment samples from the San Juan River delta cores and eight from the Escalante River delta cores also were analyzed for 55 low-level organochlorine pesticides and polychlorinated biphenyls, 61 polycyclic aromatic hydrocarbon compounds, gross alpha and gross beta radionuclides, and sediment-particle size. Additionally, water samples were collected from the sediment-water interface overlying each of the three cores collected from the San Juan River and Escalante River deltas. Each water sample was analyzed for 57 major and trace elements. Most of the major and trace elements analyzed were detected at concentrations greater than reporting levels for the sediment-core subsamples and composited samples. Low-level organochlorine pesticides and polychlorinated biphenyls were not detected in any of the samples. Only one polycyclic aromatic hydrocarbon compound was detected at a concentration greater than the reporting level for one San Juan composited sample. Gross alpha and gross beta radionuclides were detected at concentrations greater than reporting levels for all samples. Most of the major and trace elements analyzed were detected at concentrations greater than reporting levels for water samples.

[Study on the content and carbon isotopic composition of water dissolved inorganic carbon from rivers around Xi'an City].

PubMed

Guo, Wei; Li, Xiang-Zhong; Liu, Wei-Guo

2013-04-01

In this study, the content and isotopic compositions of water dissolved inorganic carbon (DIC) from four typical rivers (Chanhe, Bahe, Laohe and Heihe) around Xi'an City were studied to trace the possible sources of DIC. The results of this study showed that the content of DIC in the four rivers varied from 0.34 to 5.66 mmol x L(-1) with an average value of 1.23 mmol x L(-1). In general, the content of DIC increased from the headstream to the river mouth. The delta13C(DIC) of four rivers ranged from -13.3 per thousand to -7.2 per thousand, with an average value of -10.1 per thousand. The delta13C(DIC) values of river water were all negative (average value of -12.6 per thousand) at the headstream of four rivers, but the delta13C(DIC) values of downstream water were more positive (with an average value of -9.4 per thousand). In addition, delta13C(DIC) of river water showed relatively negative values (the average value of delta13C(DIC) was -10.5 per thousand) near the estuary of the rivers. The variation of the DIC content and its carbon isotope suggested that the DIC sources of the rivers varied from the headstream to the river mouth. The negative delta13C(DIC) value indicated that the DIC may originate from the soil CO2 at the headstream of the rivers. On the other hand, the delta13C(DIC) values of river water at the middle and lower reaches of rivers were more positive, and it showed that soil CO2 produced by respiration of the C4 plants (like corn) and soil carbonates with positive delta13C values may be imported into river water. Meanwhile, the input of pollutants with low delta13C(DIC) values may result in a decrease of delta13C(DIC) values in the rivers. The study indicated that the DIC content and carbon isotope may be used to trace the sources of DIC in rivers around Xi'an City. Our study may provide some basic information for tracing the sources of DIC of rivers in the small watershed area in the Loess Plateau of China.

Affinity and specificity of serine endopeptidase-protein inhibitor interactions. Empirical free energy calculations based on X-ray crystallographic structures.

PubMed

Krystek, S; Stouch, T; Novotny, J

1993-12-05

An empirical function was used to calculate free energy change (delta G) of complex formation between the following inhibitors and enzymes: Kunitz inhibitor (BPTI) with trypsin, trypsinogen and kallikrein; turkey ovomucoid 3rd domain (OMTKY3) with alpha-chymotrypsin and the Streptomyces griseus protease B; the potato chymotrypsin inhibitor with the protease B; and the barely chymotrypsin inhibitor and eglin-c with subtilisin and thermitase. Using X-ray coordinates of the nine complexes, we estimated the contributions that hydrophobic effect, electrostatic interactions and side-chain conformational entropy make towards the stability of the complexes. The calculated delta G values showed good agreement with the experimentally measured ones, the only exception being the kallikrein/BPTI complex whose X-ray structure was solved at an exceptionally low pH. In complexes with different enzymes, the same inhibitor residues contributed identically towards complex formation (delta G(residue) Spearman rank correlation coefficient 0.7 to 1.0). The most productive enzyme-contacting residues in OMTKY3, eglin-c, and the chymotrypsin inhibitors were found in analogous positions on their respective binding loops; thus, our calculations identified a functional (energetic) motif that parallels the well-known structural similarity of the binding loops. The delta G values calculated for BPTI complexed with trypsin (-21.7 kcal) and trypsinogen (-23.4 kcal) were similar and close to the experimental delta G value of the trypsin/BPTI complex (-18.1 kcal), lending support to the suggestion that the 10(7) difference in the observed stabilities (KA) of these two complexes reflects the energetic cost of conformational changes induced in trypsinogen during the pre-equilibrium stages of complex formation. In almost all of the complexes studied, the stabilization free energy contributed by the inhibitors was larger than that donated by the enzymes. In the trypsin-BPTI complex, the calculated delta G contribution of the amino group from the BPTI residue Lys15 (9.7 kcal) was somewhat higher than that arrived at in experiments with semisynthetic inhibitor analogs (7.5 kcal). In OMTKY3, different binding loop residues are known to affect differently the binding (delta delta G) to alpha-chymotrypsin and protease B; a good qualitative agreement was found between the calculated delta G(residue) estimates and the experimental delta delta G data (correlation coefficient 0.7). Large variations were observed in local surface complementarity and related interfacial volume in the two OMTKY3 complexes (by 20 to 60% for some side-chains).(ABSTRACT TRUNCATED AT 400 WORDS)

C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.

PubMed

Robertson, Danielle M; Ho, Su-Inn; Cavanagh, H Dwight

2010-08-01

In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.

Stable Isotope Composition of Dissolved Sulphate and Carbonate in Selected Natural Systems.

NASA Astrophysics Data System (ADS)

Staniaszek, Piotr

In this thesis, isotope and concentration data are used to discuss the origin of sulphate in different systems; lakes and groundwaters in the Crowsnest Pass and Kikomun Creek Park, hot and cold springs in the Rocky Mountains, and vegetation under the influence of anthropogenic SO _2 and/or biogenic H_2 S emissions. Since sulphur cycling is intertwined with carbon cycling, carbon isotope data were also obtained for dissolved carbonate in some systems. It was concluded that very little of the oxygen in sulphate in lakes and hot springs of western Canada was derived from the associated water. In lakes and groundwater in the Crowsnest Pass, two major sources of sulphur were identified: sulphate from evaporites (delta^{34} S = +26perthous, delta^{18}O positive) on the northern side of the pass, and sulphur from oxidation of sulphides on the southern side (delta ^{34}S and delta ^{18}O both negative). Although hundreds of kilometers apart, some springs were found to have isotopically similar SO_4 ^{2-}. This suggests a common source, e.g. anhydrite associated with Mississippian limestones and cherts. However, data for chemical parameters indicate that such a source is not homogeneous or other sources are involved for some ions. Each spring possesses individual composition traits. The delta^{13} C value of total dissolved carbon at spring orifices was found to vary linearly with temperature according to the relationship: delta^{13} C = 0.11 times t - 9.67perthous (r = 0.948). It is difficult to attribute such a relationship to biogenic processes which are expected to yield more variable delta^{13}C values. From a number of possible mechanisms, it would seem that a physical property such as the temperature dependent of CO _2 solubility might be the underlying cause. Sulphate in plant tissues is derived from the soil, atmospheric gaseous compounds, and perhaps mechanically trapped aerosols. Data for delta^ {18}O values of sulphate in plants have not been reported previously. For plants growing in the vicinity of industrial SO_2 emissions it was found that the delta^{18 }O values in sulphate are influenced by the delta^{18}O values of local precipitation (comparison of data from Alberta, Canada, and California, USA). Thistles with very high sulphur concentrations (12,000 ppm) growing near the sour gas processing plant at Crossfield, Alberta were examined. It was concluded from the isotope data that they derived their sulphur from deeper soil. In contrast, grass with shallower roots contained much higher proportions of industrially emitted sulphur. In the vicinity of springs emitting H _2S, a linear correlation was found between delta^{34}S and delta^{18}O values in plant sulphate and that in springs. Mosses did not follow this trend. Their delta^{18 }O values were higher than for other adjacent plants.

The Microstructure of Active and Quiet Sleep as Cortical Delta Activity Emerges in Infant Rats

PubMed Central

Seelke, Adele M. H.; Blumberg, Mark S.

2008-01-01

Study objectives: Previous investigators have suggested that quiet sleep (QS) in rats develops rapidly upon the emergence of cortical delta activity around postnatal day (P)11 and that the presence of “half-activated” active sleep (AS) suggests that infant sleep is initially disorganized. To address these issues, we examined the temporal organization of sleep states during the second postnatal week in rats as delta activity emerges. Design: Subjects were P9, P11, and P13 Sprague-Dawley rats. Electroencephalogram and nuchal electromyogram electrodes were implanted, and data were recorded at thermoneutrality for 2 hours. Results: At all ages, using electromyogram and behavioral criteria, QS (defined as nuchal atonia and behavioral quiescence) dominated the first third of each sleep period, whereas AS (defined as nuchal atonia accompanied by myoclonic twitching) dominated the last third. When delta activity, which was first detected at P11, could be added to the definition of QS, gross assessments of sleep-state organization were not altered, although it was now possible to identify brief periods of QS interposed between periods of AS. No evidence of “half-activated” AS was found. Finally, “slow activity transients” were detected and were primarily associated with QS; their rate of occurrence declined as delta activity emerged. Conclusions: When delta activity emerges at P11, it integrates smoothly with periods of QS, as defined using electromyogram and behavioral criteria alone. Delta activity helps to refine estimates of QS duration but does not reflect a significant alteration of sleep-state organization. Rather, this organization is expressed much earlier in ontogeny as fluctuations in muscle tone and associated phasic motor activity. Citation: Seelke AMH; Blumberg MS. The microstructure of active and quiet sleep as cortical delta activity emerges in infant rats. SLEEP 2008;31(5):691–699. PMID:18517038

Quantitative near-infrared spectroscopy on patients with peripheral vascular disease

NASA Astrophysics Data System (ADS)

Franceschini, Maria-Angela; Fantini, Sergio; Palumbo, Renato; Pasqualini, Leonella; Vaudo, Gaetano; Franceschini, Edoardo; Gratton, Enrico; Palumbo, Barbara; Innocente, Salvatore; Mannarino, Elmo

1998-01-01

We have used near-infrared spectroscopy to measure the hemoglobin saturation at rest and during exercise on patients affected by peripheral vascular disease (PVD). The instrument used in our study is a frequency-domain tissue oximeter which employs intensity modulated (110 MHz) laser diodes. We examined 9 subjects, 3 of which were controls and 6 were patients affected by stage II PVD. The optical probe was located on the calf muscle of the subjects. The measurement protocol consisted of: (1) baseline (approximately 5 min); (2) stationary bicycle exercise (approximately 5 min); (3) recovery (approximately 15 min). The change in hemoglobin saturation during exercise ((Delta) Y) and the recovery time after exercise (trec) were significantly greater in the PVD patients ((Delta) Y equals -21 +/- 3%, trec equals 5.9 +/- 3.8 min) than in the control subjects ((Delta) Y equals 2 +/- 3%, trec equals 0.6 +/- 0.1 min).

GTARG - The TOPEX/Poseidon ground track maintenance maneuver targeting program

NASA Technical Reports Server (NTRS)

Shapiro, Bruce E.; Bhat, Ramachandra S.

1993-01-01

GTARG is a computer program used to design orbit maintenance maneuvers for the TOPEX/Poseidon satellite. These maneuvers ensure that the ground track is kept within +/-1 km with of an = 9.9 day exact repeat pattern. Maneuver parameters are determined using either of two targeting strategies: longitude targeting, which maximizes the time between maneuvers, and time targeting, in which maneuvers are targeted to occur at specific intervals. The GTARG algorithm propagates nonsingular mean elements, taking into account anticipated error sigma's in orbit determination, Delta v execution, drag prediction and Delta v quantization. A satellite unique drag model is used which incorporates an approximate mean orbital Jacchia-Roberts atmosphere and a variable mean area model. Maneuver Delta v magnitudes are targeted to precisely maintain either the unbiased ground track itself, or a comfortable (3 sigma) error envelope about the unbiased ground track.

Chemotypes of Pistacia atlantica leaf essential oils from Algeria.

PubMed

Gourine, Nadhir; Bombarda, Isabelle; Yousfi, Mohamed; Gaydou, Emile M

2010-01-01

The essential oils obtained by hydrodistillation of Pistacia atlantica Desf. leaves collected from different regions of Algeria were analyzed by GC and GC-MS. The essential oil was rich in monoterpenes and oxygenated sesquiterpenes. The major components were alpha-pinene (0.0-67%), delta-3-carene (0.0-56%), spathulenol (0.5-22%), camphene (0.0-21%), terpinen-4-ol (0.0-16%) and beta-pinene (0.0-13%). Among the various components identified, twenty were used for statistical analyses. The result of principal component analysis (PCA) showed the occurrence of three chemotypes: a delta-3-carene chemotype (16.4-56.2%), a terpinen-4-ol chemotype (10.8-16.0%) and an alpha-pinene/camphene chemotype (10.9-66.6%/3.8-20.9%). It was found that the essential oil from female plants (delta-3-carene chemotype) could be easily differentiated from the two other chemotypes corresponding to male trees.

Watershed-Scale Modeling of Land-Use and Altered Environment Impacts on Aquatic Weed Growth in the Delta

NASA Technical Reports Server (NTRS)

Bubenheim, David; Potter, Christopher; Zhang, Minghua

2016-01-01

The California Sacramento-San Joaquin River Delta is the hub for California's water supply, conveying water from Northern to Southern California agriculture and communities while supporting important ecosystem services, agriculture, and communities in the Delta. Changes in climate, long-term drought, and water quality have all been suspected as playing role in the dramatic expansion of invasive aquatic plants and their impact on ecosystems of the San Francisco Bay / California Delta complex. NASA Ames Research Center, USDA-Agricultural Research Service, the State of California, UC Davis, and local governments have partnered under a USDA sponsored project (DRAAWP) to develop science-based, adaptive-management strategies for invasive aquatic plants in Sacramento-San Joaquin Delta. Critical to developing management strategies is to understand how the Delta is affected by both the magnitude of fluctuations in land-use and climate / drought induced altered environments and how the plants respond to these altered environments. We utilize the Soil Water Assessment Tool (SWAT), a watershed-scale model developed to quantify the impact of land management practices in large and complex watersheds on water quality, as the backbone for a customized Delta model - Delta-SWAT. The model uses land-use, soils, elevation, and hydrologic routing to characterize pesticide and nutrient transport from the Sacramento and San Joaquin rivers watersheds and loading into the Delta. Land-use within the Delta, as well as water extraction to supply those functions, and the resulting return of water to Delta waterways are included in Delta-SWAT. Hydrologic transport within the Delta has required significant attention to address the lack of elevation driven transport processes. Delta-SWAT water quality trend estimates are compared with water quality monitoring conducted throughout the Delta. Aquatic plant response to water quality and other environmental factors is carried out using a customized model component. Plant response to the range of water quality factors, response times, and altered temperature and light regimes of the Delta have required gap-filling studies to provide model parameters. Delta-SWAT provides a tool for evaluating temporal and spatial effects of land-use and altered environments in the Delta and contributing watersheds on aquatic weed growth. Using Delta-SWAT for simulation modeling allows evaluation of historic and current conditions as well as consideration potential climate change and management practice outcomes. Delta-SWAT adds to the scientific understanding of dynamics in the Delta and enhances development of science-informed, management strategies and practices.

Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts.

PubMed

Zhou, X; Ideker, R E; Blitchington, T F; Smith, W M; Knisley, S B

1995-09-01

To study the optical transmembrane potential change (delta F) induced during shocks, optical recordings were obtained in 15 isolated perfused rabbit hearts treated with the potentiometric dye di-4-ANEPPS and diacetyl monoxime. Shock electrodes were sutured on the right and left ventricles. A laser beam 30 microns in diameter was used to optically excite di-4-ANEPPS. Fluorescence from a region 150 microns in diameter was recorded during a shock. In the macroscopic study (six animals), there were nine recording spots that were 3 mm apart between the two shock electrodes. In the microscopic study, there were three recording regions that were 3 mm away from either shock electrode and midway between them, with nine recording spots that were 30 microns (three animals), 100 microns (three animals), and 300 microns (three animals) apart in each region. After 20 S1 stimuli, a 10-ms truncated exponential S2 shock of defibrillation-threshold strength was given during the plateau of the last S1 action potential. In the microscopic study, shocks were also given during diastole, with delta F recordings at the three recording regions. Shocks of both polarities were tested. delta F during the shock was expressed as a percentage of the fluorescence change during the S1 upstroke action potential amplitude (the S1 Fapa), ie, delta F/Fapa%. In the macroscopic study, the magnitudes of delta F/Fapa% from recording spots 1 to 9, numbered from the left to the right ventricular electrodes, were 77 +/- 41%, 46 +/- 32%, 32 +/- 27%, 28 +/- 20%, 37 +/- 25%, 24 +/- 20%, 33 +/- 22%, 37 +/- 25%, and 59 +/- 29%, respectively (P < .05 among the nine spots). Depolarization or hyperpolarization could occur near either shock electrode with both shock polarities, but the magnitude of hyperpolarization was 1.8 +/- 0.9 times that of depolarization at the same recording spot when the shock polarity was reversed (P < .01). In the microscopic study, the change in delta F/Fapa% varied significantly over the microscopic regions examined. The maximum values of delta F/Fapa% for hyperpolarizing shocks during diastole reached only 7 +/- 10% of those for shocks during the plateau (P < .01). During diastole, the time until a new action potential occurred after the beginning of the shock was shorter when the membrane was depolarized (1.1 +/- 0.5 ms) than when it was hyperpolarized (12.8 +/- 9.1 ms, P < .01). Conclusions are as follows: (1) A shock can induce either hyperpolarization or depolarization. (2) Hyperpolarization or depolarization during a shock can occur near either the anodal or cathodal shock electrode. (3) Variation of delta F/Fapa% exists within a microscopic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal steroids in post-menopausal women: relation to obesity and to bone mineral content.

PubMed

Brody, S; Carlström, K; Lagrelius, A; Lunell, N O; Möllerström, G

1987-04-01

Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Broca's index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Effect of thermal decarbonation on the stable isotope composition of carbonates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Durakiewicz, T.; Sharp, Z. D.; Papike, J. J.

2001-01-01

The unusual texture and stable isotope variability of carbonates in AH84001 have been used as evidence for early life on Mars (Romanek et al., 1994; McKay et al., 1996). Oxygen and carbon isotope variability is most commonly attributed to low-temperature processes, including Rayleigh-like fractionation associated with biological activity. Another possible explanation for the isotopic variability in meteoritic samples is thermal decarbonation. In this report, different carbonates were heated in a He-stream until decomposition temperatures were reached. The oxygen and carbon isotope ratios ({delta}{sup 18}O and {delta}{sup 13}C values) of the resulting gas were measured on a continuous flow isotope ratiomore » mass spectrometer. The aim of this work is to evaluate the possibility that large isotopic variations can be generated on a small scale abiogenically, by the process of thermal decarbonation. Oxygen isotope fractionations of >4{per_thousand} have been measured during decarbonation of calcite at high temperatures (McCrea, 1950), and in excess of 6{per_thousand} for dolomite decarbonated between 500 and 600 C (Sharma and Clayton, 1965). Isotopic fractionations of this magnitude, coupled with Rayleigh-like distillation behavior could result in very large isotopic variations on a small scale. To test the idea, calcite, dolomite and siderite were heated in a quartz tube in a He-stream in excess of 1 atmosphere. Simultaneous determinations of {delta}{sup 13}C and {Delta}{sup 18}O values were obtained on 250 {micro}l aliquots of the CO{sub 2}-bearing He gas using an automated 6-way switching valve system (Finnigan MAT GasBench II) and a Finnigan MAT Delta Plus mass spectrometer. It was found that decarbonation of calcite in a He atmosphere begins at 720 C, but the rate significantly increases at temperatures of 820 C. After an initial light {delta}{sup 18}O value of -14.1{per_thousand} at 720 C associated with very early decarbonation, {delta}{sup 18}0 values increase to a constant -11.8{per_thousand}, close to the accepted value of -12.09{per_thousand} (PDB). After 10 minutes at 820 C, the {delta}{sup 18}O values and signal strength both begin to decrease linearly to a {delta}{sup 18}O value of -14.75 and very low amounts of CO{sub 2} (Fig. 1). In contrast, the {delta}{sup 13}C values are extremely constant (0.12 {+-} 0.25{per_thousand}) for all measurements, in very good agreement with accepted values of 0.33{per_thousand} (PDB). There is much less isotopic variability during dolomite decarbonation. CO{sub 2} is first detected at 600 C. The signal strength increases by an order of magnitude between 670 and 700 C and again at 760 C. Both {delta}{sup 13}C and {delta}{sup 18}O values are nearly constant over the entire temperature range and sample size. For oxygen, the measured {delta}{sup 18}O values averaged -20.9 {+-} 0.7{per_thousand} (n = 30). Including only samples over 700 C, the average is -21.2 {+-} 0.2{per_thousand} compared to the accepted value of -21{per_thousand}. Carbon is similarly constant. The average {delta}{sup 13}C value is -2.50{per_thousand} compared to the accepted value of -2.62{per_thousand}. Far more variability is seen during the decomposition of siderite. Two samples were analyzed. In both samples, the initial {delta}{sup 18}O values were far lower than expected.« less

Lava delta deformation as a proxy for submarine slope instability

NASA Astrophysics Data System (ADS)

Di Traglia, Federico; Nolesini, Teresa; Solari, Lorenzo; Ciampalini, Andrea; Frodella, William; Steri, Damiano; Allotta, Benedetto; Rindi, Andrea; Marini, Lorenzo; Monni, Niccolò; Galardi, Emanuele; Casagli, Nicola

2018-04-01

The instability of lava deltas is a recurrent phenomenon affecting volcanic islands, which can potentially cause secondary events such as littoral explosions (due to interactions between hot lava and seawater) and tsunamis. It has been shown that Interferometric Synthetic Aperture Radar (InSAR) is a powerful technique to forecast the collapse of newly emplaced lava deltas. This work goes further, demonstrating that the monitoring of lava deltas is a successful strategy by which to observe the long-term deformation of subaerial-submarine landslide systems on unstable volcanic flanks. In this paper, displacement measurements derived from Synthetic Aperture Radar (SAR) imagery were used to detect lava delta instability at Stromboli volcano (Italy). Recent flank eruptions (2002-2003, 2007 and 2014) affected the Sciara del Fuoco (SdF) depression, created a "stacked" lava delta, which overlies a pre-existing scar produced by a submarine-subaerial tsunamigenic landslide that occurred on 30 December 2002. Space-borne X-band COSMO-SkyMED (CSK) and C-band SENTINEL-1A (SNT) SAR data collected between February 2010 and October 2016 were processed using the SqueeSAR algorithm. The obtained ground displacement maps revealed the differential ground motion of the lava delta in both CSK and SNT datasets, identifying a stable area (characterized by less than 2 mm/y in both datasets) within the northern sector of the SdF and an unstable area (characterized by velocity fields on the order of 30 mm/y and 160 mm/y in the CSK and SNT datasets, respectively) in the central sector of the SdF. The slope stability of the offshore part of the SdF, as reconstructed based on a recently performed multibeam bathymetric survey, was evaluated using a 3D Limit Equilibrium Method (LEM). In all the simulations, Factor of Safety (F) values between 0.9 and 1.1 always characterized the submarine slope between the coastline and -250 m a.s.l. The critical surfaces for all the search volumes corresponded to the 30 December 2002 landslide, which involved the lava delta and its surrounding areas. InSAR data provided the post-effusive deformation field after the 2007 and 2014 flank eruptions, whereas LEM results highlighted that the accumulation of lava flows on the prone-to-failure SdF submarine slope is the main cause of the detected lava delta deformation. Lava delta instability, measured also at Pico Island (Azores) and Kilauea volcano (Hawaii), is evidence of the broader spectrum of instability phenomena that take place in the coastal or submarine area of the flanks of the volcanoes. At Kilauea, past lava deltas have moved faster than the surrounding slope and the recorded movements relate only to the collapses of the deltas themselves, producing rapid mass wasting near the coasts. In contrast, at Stromboli and Pico, lava deltas move at the same velocity as the surrounding slope. In these cases, the displacement at lava deltas can be considered as a proxy for the deformation of submarine slides. There are very few studies dealing with lava delta deformation, thus, the analysis presented in this work will benefit the monitoring of submarine slopes in other prone-to-failure coastal or island volcanic systems which have the potential to generate tsunamis.

Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep.

PubMed

Haney, Margaret; Gunderson, Erik W; Rabkin, Judith; Hart, Carl L; Vosburg, Suzanne K; Comer, Sandra D; Foltin, Richard W

2007-08-15

Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons; yet, no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers. This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors: eating topography, mood, cognitive performance, physiologic measures, and sleep. HIV-positive marijuana smokers (n = 10) completed 2 16-day inpatient phases. Each dronabinol (5 and 10 mg) and marijuana (2.0% and 3.9% Delta9-tetrahydrocannabinol [THC]) dose was administered 4 times daily for 4 days, but only 1 drug was active per day, thereby maintaining double-blind dosing. Four days of placebo washout separated each active cannabinoid condition. As compared with placebo, marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers. All cannabinoid conditions produced significant intoxication, except for low-dose dronabinol (5 mg); the intoxication was rated positively (eg, "good drug effect") with little evidence of discomfort and no impairment of cognitive performance. Effects of marijuana and dronabinol were comparable, except that only marijuana (3.9% THC) improved ratings of sleep. These data suggest that for HIV-positive marijuana smokers, both dronabinol (at doses 8 times current recommendations) and marijuana were well tolerated and produced substantial and comparable increases in food intake.

Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

PubMed

Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

2017-10-04

Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

Hair analysis in order to evaluate drug abuse in driver's license regranting procedures.

PubMed

Tassoni, G; Mirtella, D; Zampi, M; Ferrante, L; Cippitelli, M; Cognigni, E; Froldi, R; Cingolani, M

2014-11-01

In Italy, driving under the influence of drugs determines the suspension of the offender's driver's license. To regain the license the person must be drug free during an observation period. People whose license has been revoked or suspended can obtain, or re-obtain their driver's license subject to the judgment of a medical commission. The exclusion of illicit drug use is determined by means of toxicological analysis, mainly on urine or hair matrices. We reported the results of several years of experience of the forensic toxicology laboratory of the University of Macerata in the use of hair analysis for the assessment of past exposure to drugs in people suspected of driving under the influence of drugs. From 2004 to 2013, 8612 hair samples, were analyzed for opiates, cocaine and delta-9-tetrahydrocannabinol (Δ(9)-THC) using gas chromatography/mass spectrometry (GC/MS) method. We used a cutoff (SoHT or national guidelines) to determine the positive data, regardless of the hair sample concentrations. 1213 samples resulted positive, 71.7% were positive for cocaine and metabolites, 19.8% for morphine and metabolites, 8.5% for Δ(9)-THC. We also studied the timeframe of the abuse, as well as gender and age distribution of positive subjects. Moreover, we analyzed the possible deterrent effect of the hair analysis on driving under the influence of psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Concentration Dependence of the (Delta)s Term in the Gibbs Free Energy Function: Application to Reversible Reactions in Biochemistry

ERIC Educational Resources Information Center

Gary, Ronald K.

2004-01-01

The concentration dependence of (delta)S term in the Gibbs free energy function is described in relation to its application to reversible reactions in biochemistry. An intuitive and non-mathematical argument for the concentration dependence of the (delta)S term in the Gibbs free energy equation is derived and the applicability of the equation to…

78 FR 21491 - DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... SMALL BUSINESS ADMINISTRATION [License No. 02/02-0662, 02/02-0661] DeltaPoint Capital IV, L.P., DeltaPoint Capital IV (New York), L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P. and DeltaPoint...

Sediment transport dynamics linked to morphological evolution of the Selenga River delta, Lake Baikal, Russia

NASA Astrophysics Data System (ADS)

Dong, T. Y.; Nittrouer, J.; McElroy, B. J.; Czapiga, M. J.; Il'icheva, E.; Pavolv, M.; Parker, G.

2014-12-01

The Selenga River delta, Lake Baikal, Russia, is approximately 700 km2 in size and contains three active lobes that receive varying amounts of water and sediment discharge. This delta represents a unique end-member in so far that the system is positioned along the deep-water (~1500 m) margin of Lake Baikal and therefore exists as a shelf-edge delta. In order to evaluate the morphological dynamics of the Selenga delta, field expeditions were undertaken during July 2013 and 2014, to investigate the morphologic, sedimentologic, and hydraulic nature of this delta system. Single-beam bathymetry data, sidescan sonar data, sediment samples, and aerial survey data were collected and analyzed to constrain: 1) channel geometries within the delta, 2) bedform sizes and spatial distributions, 3) grain size composition of channel bed sediment as well as bank sediment, collected from both major and minor distributary channels, and 4) elevation range of the subaerial portion of the delta. Our data indicate that the delta possesses downstream sediment fining, ranging from predominantly gravel and sand near the delta apex to silt and sand at the delta-lake interface. Field surveys also indicate that the Selenga delta has both eroding and aggrading banks, and that the delta is actively incising into some banks that consist of terraces, which are defined as regions that are not inundated by typical 2- to 4-year flood discharge events. Therefore the terraces are distinct from the actively accreting regions of the delta that receive sedimentation via water inundation during regular river floods. We spatially constrain the regions of the Selenga delta that are inundated during floods versus terraced using a 1-D water-surface hydrodynamic model that produces estimates of stage for flood water discharges, whereby local water surface elevations produced with the model are compared to the measured terrestrial elevations. Our analyses show that terrace elevations steadily decrease downstream for all lobes, and that the delta is undergoing an active phase of erosion, characterized by channel incision and extensive lateral erosion of terraces; this process of delta 'self-cannibalization' contributes to the downstream sediment flux and morphological evolution of the delta.

Decoupling Shoreline Behavior Over Variable Time and Space Scales

NASA Astrophysics Data System (ADS)

Hapke, C. J.; Plant, N. G.; Henderson, R.; Schwab, W. C.; Nelson, T. R.

2016-12-01

Despite global concerns about river delta degradation caused by extraction of natural resources, sediment retention by reservoirs and sea-level rise, human activity in the world's largest deltas intensifies. In this review, we argue that tides tend to stabilize deltas until humans interfere. Under natural circumstances, delta channels subject to tides are more stable than their fluvial-dominated counterparts. The oscillatory tidal flow counteracts the processes responsible for bank erosion, which explains why unprotected tidal channels migrate only slowly. Peak river discharges attenuate the tides, which creates storage space to accommodate the extra river discharge during extreme events and as a consequence, reduce flood risk. With stronger tides, the river discharge is being distributed more evenly over the various branches in a delta, preventing silting up of smaller channels. Human interference in deltas is massive. Storm surge barriers are constructed, new land is being reclaimed and large-scale sand excavation takes place, to collect building material. Evidence from deltas around the globe shows that in human-controlled deltas the tidal motion often plays a destabilizing role. In channels of the Rhine-Meuse Delta, some 100 scour holes are identified, which relates to the altered tidal motion after completion of a storm surge barrier. Sand mining has led to widespread river bank failures in the tidally-influenced Mekong Delta. The catastrophic flood event in the Gauges-Brahmaputra Delta by Cyclone Aila, which caused the inundation of an embanked polder area for over two years, was preceded by river bank erosion at the mouths of formal tidal channels that were blocked by the embankment. Efforts to predict the developments of degrading deltas are few. Existing delta models are capable of reproducing expanding deltas, which is essentially a matter of simulating the transport of sediment from source in a catchment to the sink in a delta. Processes of soil compaction, mixing of sands and clay, and the influence of peat layers complicate the prediction of delta erosion. Considering sea-level rise, sediment depletion and all the direct human modifications in deltas, there is a need for a new generation delta models using quantified erosion resistance from geological records.

The diversity of (13)C isotope discrimination in a Quercus robur full-sib family is associated with differences in intrinsic water use efficiency, transpiration efficiency, and stomatal conductance.

PubMed

Roussel, Magali; Dreyer, Erwin; Montpied, Pierre; Le-Provost, Grégoire; Guehl, Jean-Marc; Brendel, Oliver

2009-01-01

(13)C discrimination in organic matter with respect to atmospheric CO(2) (Delta(13)C) is under tight genetic control in many plant species, including the pedunculate oak (Quercus robur L.) full-sib progeny used in this study. Delta(13)C is expected to reflect intrinsic water use efficiency, but this assumption requires confirmation due to potential interferences with mesophyll conductance to CO(2), or post-photosynthetic discrimination. In order to dissect the observed Delta(13)C variability in this progeny, six genotypes that have previously been found to display extreme phenotypic values of Delta(13)C [either very high ('high Delta') or low ('low Delta') phenotype] were selected, and transpiration efficiency (TE; accumulated biomass/transpired water), net CO(2) assimilation rate (A), stomatal conductance for water vapour (g(s)), and intrinsic water use efficiency (W(i)=A/g(s)) were compared with Delta(13)C in bulk leaf matter, wood, and cellulose in wood. As expected, 'high Delta' displayed higher values of Delta(13)C not only in bulk leaf matter, but also in wood and cellulose. This confirmed the stability of the genotypic differences in Delta(13)C recorded earlier. 'High Delta' also displayed lower TE, lower W(i), and higher g(s). A small difference was detected in photosynthetic capacity but none in mesophyll conductance to CO(2). 'High Delta' and 'low Delta' displayed very similar leaf anatomy, except for higher stomatal density in 'high Delta'. Finally, diurnal courses of leaf gas exchange revealed a higher g(s) in 'high Delta' in the morning than in the afternoon when the difference decreased. The gene ERECTA, involved in the control of water use efficiency, leaf differentiation, and stomatal density, displayed higher expression levels in 'low Delta'. In this progeny, the variability of Delta(13)C correlated closely with that of W(i) and TE. Genetic differences of Delta(13)C and W(i) can be ascribed to differences in stomatal conductance and stomatal density but not in photosynthetic capacity.

Paleolimnological investigations of anthropogenic environmental change in Lake Tanganyika: I. An introduction to the project

USGS Publications Warehouse

Cohen, A.S.; Palacios-Fest, M. R.; McGill, J.; Swarzenski, P.W.; Verschuren, D.; Sinyinza, R.; Songori, T.; Kakagozo, B.; Syampila, M.; O'Reilly, C. M.; Alin, S.R.

2005-01-01

We investigated paleolimnological records from a series of river deltas around the northeastern rim of Lake Tanganyika, East Africa (Tanzania and Burundi) in order to understand the history of anthropogenic activity in the lake's catchment over the last several centuries, and to determine the impact of these activities on the biodiversity of littoral and sublittoral lake communities. Sediment pollution caused by increased rates of soil erosion in deforested watersheds has caused significant changes in aquatic communities along much of the lake's shoreline. We analyzed the effects of sediment discharge on biodiversity around six deltas or delta complexes on the east coast of Lake Tanganyika: the Lubulungu River delta, Kabesi River delta, Nyasanga/Kahama River deltas, and Mwamgongo River delta in Tanzania; and the Nyamuseni River delta and Karonge/Kirasa River deltas in Burundi. Collectively, these deltas and their associated rivers were chosen to represent a spectrum of drainage-basin sizes and disturbance levels. By comparing deltas that are similar in watershed attributes (other than disturbance levels), our goal was to explore a series of historical "experiments" at the watershed scale, with which we could more clearly evaluate hypotheses of land use or other effects on nearshore ecosystems. Here we discuss these deltas, their geologic and physiographic characteristics, and the field procedures used for coring and sampling the deltas, and various indicators of anthropogenic impact. ?? Springer 2005.

Delta Vision, Delta Voices: The Mississippi Delta Beyond 2000

DOT National Transportation Integrated Search

2000-05-10

This Report has taken its guidance from a single overriding goal: To recognize the enormous natural, capital, and cultural resources of the Delta, and to enable all of the Delta's citizens to participate as full and successful partners in America's s...

Approaches to defining deltaic sustainability in the 21st century

NASA Astrophysics Data System (ADS)

Day, John W.; Agboola, Julius; Chen, Zhongyuan; D'Elia, Christopher; Forbes, Donald L.; Giosan, Liviu; Kemp, Paul; Kuenzer, Claudia; Lane, Robert R.; Ramachandran, Ramesh; Syvitski, James; Yañez-Arancibia, Alejandro

2016-12-01

Deltas are among the most productive and economically important of global ecosystems but unfortunately they are also among the most threatened by human activities. Here we discuss deltas and human impact, several approaches to defining deltaic sustainability and present a ranking of sustainability. Delta sustainability must be considered within the context of global biophysical and socioeconomic constraints that include thermodynamic limitations, scale and embeddedness, and constraints at the level of the biosphere/geosphere. The development, functioning, and sustainability of deltas are the result of external and internal inputs of energy and materials, such as sediments and nutrients, that include delta lobe development, channel switching, crevasse formation, river floods, storms and associated waves and storm surges, and tides and other ocean currents. Modern deltas developed over the past several thousand years with relatively stable global mean sea level, predictable material inputs from drainage basins and the sea, and as extremely open systems. Human activity has changed these conditions to make deltas less sustainable, in that they are unable to persist through time structurally or functionally. Deltaic sustainability can be considered from geomorphic, ecological, and economic perspectives, with functional processes at these three levels being highly interactive. Changes in this functioning can lead to either enhanced or diminished sustainability, but most changes have been detrimental. There is a growing understanding that the trajectories of global environmental change and cost of energy will make achieving delta sustainability more challenging and limit options for management. Several delta types are identified in terms of sustainability including those in arid regions, those with high and low energy-intensive management systems, deltas below sea level, tropical deltas, and Arctic deltas. Representative deltas are ranked on a sustainability range. Success in sustainable delta management will depend on utilizing natural delta functioning and an ecological engineering approach.

Identification of a new 6-bromo-5,9-eicosadienoic acid from the anemone Condylactis gigantea and the zoanthid Palythoa caribaeorum.

PubMed

Carballeira, N M; Reyes, M

1995-11-01

A new brominated fatty acid, 6-bromo-5,9-eicosadienoic acid [1] was identified in the phospholipids (mainly phosphatidylethanolamine) of the anemone Condylactis gigantea and the zoanthid Palythoa caribaeorum. The delta 5,9 fatty acids, 5,9-octadecadienoic acid, 5,9-eicosadienoic acid, 5,9-docosadienoic acid, and 5,9-tetracosadienoic acid, were also identified in both organisms. Structural elucidation was accomplished by spectroscopic and chemical means. Our results further corroborate that delta 5,9 phospholipid fatty acids are not unique to sponges, as recognized previously, but can be found in other marine invertebrates such as anemones and zoanthids. An improved procedure for the synthesis of picolinyl esters is also described.

Migration in Deltas: An Integrated Analysis

NASA Astrophysics Data System (ADS)

Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

2017-04-01

Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of consistent scenarios from global to delta scales, developed in consultation with major stakeholders. Initial results suggest that migration decision-making strongly interacts with diverse measures for adaptation of land, water and agricultural management. A key normative challenge is to identify the parameters of successful migration and adaptation across delta regions, to inform policy analysis and formulation. Key words: Deltas, sea-level rise, migration and adaptation Acknowledgement: DECCMA (Deltas, Vulnerability & Climate Change: Migration & Adaptation) project is part of the Collaborative ADAPTATION Research Initiative in Africa and Asia (CARIAA), with financial support from the UK Government's Department for International Development (DFID) and the International Development Research Centre (IDRC), Canada.

Micro-CT evaluation of apical delta morphologies in human teeth.

PubMed

Gao, Xianhua; Tay, Franklin R; Gutmann, James L; Fan, Wei; Xu, Ting; Fan, Bing

2016-11-07

The apical delta is an intricate system within the root canal and incompletely debridement may affect the long-term prognosis of root canal therapy. The aim of the present study is to investigate the morphologic features of apical deltas in human teeth with micro-computed tomography (micro-CT) using a centreline-fitting algorithm. One hundred and thirty-six apical deltas were detected in 1400 teeth. Molars had more apical deltas (15.8%) than anterior teeth (6.3%). In maxillary molars, the mesiobuccal root had a significantly higher prevalence of apical delta than the palatal root or the distobuccal root. The median vertical distance of the apical delta was 1.87 mm with 13% more than 3 mm. The median diameter and length of the apical delta branches were 132.3 and 934.5 μm. Apical delta branches were not straight with cross-sectional shapes being non-circular. These morphological features of apical delta may complicate debridement of the infected root canal system.

Modified method for estimating petroleum source-rock potential using wireline logs, with application to the Kingak Shale, Alaska North Slope

USGS Publications Warehouse

Rouse, William A.; Houseknecht, David W.

2016-02-11

In 2012, the U.S. Geological Survey completed an assessment of undiscovered, technically recoverable oil and gas resources in three source rocks of the Alaska North Slope, including the lower part of the Jurassic to Lower Cretaceous Kingak Shale. In order to identify organic shale potential in the absence of a robust geochemical dataset from the lower Kingak Shale, we introduce two quantitative parameters, $\\Delta DT_\\bar{x}$ and $\\Delta DT_z$, estimated from wireline logs from exploration wells and based in part on the commonly used delta-log resistivity ($\\Delta \\text{ }log\\text{ }R$) technique. Calculation of $\\Delta DT_\\bar{x}$ and $\\Delta DT_z$ is intended to produce objective parameters that may be proportional to the quality and volume, respectively, of potential source rocks penetrated by a well and can be used as mapping parameters to convey the spatial distribution of source-rock potential. Both the $\\Delta DT_\\bar{x}$ and $\\Delta DT_z$ mapping parameters show increased source-rock potential from north to south across the North Slope, with the largest values at the toe of clinoforms in the lower Kingak Shale. Because thermal maturity is not considered in the calculation of $\\Delta DT_\\bar{x}$ or $\\Delta DT_z$, total organic carbon values for individual wells cannot be calculated on the basis of $\\Delta DT_\\bar{x}$ or $\\Delta DT_z$ alone. Therefore, the $\\Delta DT_\\bar{x}$ and $\\Delta DT_z$ mapping parameters should be viewed as first-step reconnaissance tools for identifying source-rock potential.

Sedimentation and lithofacies relations in the Holocene Pahang Delta Complex, East Coast Malay Peninsula, Malaysia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farshori, M.Z.; Jantan, A.

1994-07-01

A detailed study of the Pahang River Delta was undertaken in order to understand the development, architecture, geometrical characteristics, and structural sequential organization of the sand bodies on the east coast of the Malay Peninsula. The present delta indicates that although marine wave regimes are dominant, as exhibited by the cuspate-shaped delta, fluvial and tidal influences are substantial, as evident from the bedforms and sand bars morphology. The Pahang Delta system provides a unique case study for a tropical fluvio-marine windwave-dominated delta, which was profoundly influenced by seasonal storms. The deltaic sand is coarse and moderately sorted, and contains abundantmore » clay clasts. The southern coastline of the Pahang Delta is continuously modified by the erosive attack of the storm waves. The delta is subjected to extremely high-energy storm waves and fluvially formed sand bodies, such as channel mouth bars, dominant in other types of deltas that have been replaced by strand plains, sand bars and sand flats. The combination of high wave energy and strong littoral drift along the east coast of the Malay Peninsula results in changing the orientation of the sand bodies in the Pahang Delta. No modern wind-dominated delta is comparable to the Pahang Delta system. However, some modern deltas show many similarities in general morphology and sand distribution. The authors have developed a comprehensive sedimentological model of fluvio-marine sand-body variability in tropical wind-dominated deltas. The results of the studies will enlarge the applicability of geometrical studies to subsurface exploration of hydrocarbons.« less

Atmospheric Propagation Analysis Program

DTIC Science & Technology

1993-01-01

1 0 9060’ Ors MI ot9 SWt We1M’ LSol ISo I 97 Delta T Temp Deg Fahrenheit Delta T Temp Deg Fahrenheit Date System Time Large 4-Bar Tank Grad Targ Grad...SS firt 0 SIX 1299 IC Ie IOO are Lce’tItor i"W ELVE ~99L’s P969 wz-s U&I _ _ _ _ _ _ _ _ _ _ _ _ _ _ 131__ _ _ _ _ _ _ _ _ _ L t Wi ISO IM M’s0 Vev...2. 4.6 1008. 02/ 27002 :54 0.0 58.9 2. 10.1 1008. 02/2621:30 0.9 60.9 1. 9.2 1008. 02/2703:00 0.0 57.3 1. 12 1002. 0222:5 .6. . . 00.0/20:4 0159.2 3. 91

[Tetrahydrocannabinol pharmacokinetics; new synthetic cannabinoids; road safety and cannabis].

PubMed

Goullé, Jean-Perre; Guerbet, Michel

2014-03-01

Delta-9-tetrahydrocannabinol (THC) is the main psychoactive ingredient of cannabis, a drug which is commonly smoked This paper focuses on the pharmacokinetics of THC. The average THC content in cannabis plant material has risen by a factor offour over the past 20 years, from 4% to 16%. This increase has important implications not only for the pharmacokinetics but also for the pharmacology of THC The mean bioavailability of THC in smoked cannabis is about 25%. In a cigarette containing 3.55% of THC, a peak plasma level of about 160 ng/mL occurs approximately 10 min after inhalation. THC is quickly cleared from plasma in a multiphasic manner and is widely distributed to tissues, leading to its pharmacologic effects. Body fat is a long-term storage site. This particular pharmacokinetic behavior explains the lack of correlation between the THC blood level and clinical effects, contrary to ethanol. The main THC metabolites are 11-OH-THC (the only active metabolite) and THC-COOH, which is eliminated in feces and urine over several weeks. Therefore, abstinence can be established by analyzing THC-COOH in urine, while blood THC analysis is used to confirm recent exposure. Cannabis is the main illicit drug found among vehicle drivers. Various traffic safety studies indicate that recent use of this drug at least doubles the risk of causing an accident, and that simultaneous alcohol consumption multiplies this risk by afactor of 14. Since 2009, synthetic cannabinoids have emerged on the illicit drug market. These substances act on the same CB1 receptors as THC, but with higher afinity. Their pharmacokinetics differs from that of THC, as they are metabolized into multiple derivatives, most of which are more active than THC itself.

Understanding marijuana's effects on functional connectivity of the default mode network in patients with schizophrenia and co-occurring cannabis use disorder: A pilot investigation.

PubMed

Whitfield-Gabrieli, Susan; Fischer, Adina S; Henricks, Angela M; Khokhar, Jibran Y; Roth, Robert M; Brunette, Mary F; Green, Alan I

2018-04-01

Nearly half of patients with schizophrenia (SCZ) have co-occurring cannabis use disorder (CUD), which has been associated with decreased treatment efficacy, increased risk of psychotic relapse, and poor global functioning. While reports on the effects of cannabis on cognitive performance in patients with SCZ have been mixed, study of brain networks related to executive function may clarify the relationship between cannabis use and cognition in these dual-diagnosis patients. In the present pilot study, patients with SCZ and CUD (n=12) and healthy controls (n=12) completed two functional magnetic resonance imaging (fMRI) resting scans. Prior to the second scan, patients smoked a 3.6% tetrahydrocannabinol (THC) cannabis cigarette or ingested a 15mg delta-9-tetrahydrocannabinol (THC) pill. We used resting-state functional connectivity to examine the default mode network (DMN) during both scans, as connectivity/activity within this network is negatively correlated with connectivity of the network involved in executive control and shows reduced activity during task performance in normal individuals. At baseline, relative to controls, patients exhibited DMN hyperconnectivity that correlated with positive symptom severity, and reduced anticorrelation between the DMN and the executive control network (ECN). Cannabinoid administration reduced DMN hyperconnectivity and increased DMN-ECN anticorrelation. Moreover, the magnitude of anticorrelation in the controls, and in the patients after cannabinoid administration, positively correlated with WM performance. The finding that DMN brain connectivity is plastic may have implications for future pharmacotherapeutic development, as treatment efficacy could be assessed through the ability of therapies to normalize underlying circuit-level dysfunction. Copyright © 2017. Published by Elsevier B.V.

Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.

PubMed

Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi

2017-11-15

The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

HER2 isoforms co-expression differently tunes mammary tumor phenotypes affecting onset, vasculature and therapeutic response

PubMed Central

Balboni, Tania; Ianzano, Marianna L.; Laranga, Roberta; Landuzzi, Lorena; Giusti, Veronica; Ceccarelli, Claudio; Santini, Donatella; Taffurelli, Mario; Di Oto, Enrico; Asioli, Sofia; Amici, Augusto; Pupa, Serenella M.; De Giovanni, Carla; Tagliabue, Elda; Iezzi, Manuela; Nanni, Patrizia; Lollini, Pier-Luigi

2017-01-01

Full-length HER2 oncoprotein and splice variant Delta16 are co-expressed in human breast cancer. We studied their interaction in hybrid transgenic mice bearing human full-length HER2 and Delta16 (F1 HER2/Delta16) in comparison to parental HER2 and Delta16 transgenic mice. Mammary carcinomas onset was faster in F1 HER2/Delta16 and Delta16 than in HER2 mice, however tumor growth was slower, and metastatic spread was comparable in all transgenic mice. Full-length HER2 tumors contained few large vessels or vascular lacunae, whereas Delta16 tumors presented a more regular vascularization with numerous endothelium-lined small vessels. Delta16-expressing tumors showed a higher accumulation of i.v. injected doxorubicin than tumors expressing full-length HER2. F1 HER2/Delta16 tumors with high full-length HER2 expression made few large vessels, whereas tumors with low full-length HER2 and high Delta16 contained numerous small vessels and expressed higher levels of VEGF and VEGFR2. Trastuzumab strongly inhibited tumor onset in F1 HER2/Delta16 and Delta16 mice, but not in full-length HER2 mice. Addiction of F1 tumors to Delta16 was also shown by long-term stability of Delta16 levels during serial transplants, in contrast full-length HER2 levels underwent wide fluctuations. In conclusion, full-length HER2 leads to a faster tumor growth and to an irregular vascularization, whereas Delta16 leads to a faster tumor onset, with more regular vessels, which in turn could better transport cytotoxic drugs within the tumor, and to a higher sensitivity to targeted therapeutic agents. F1 HER2/Delta16 mice are a new immunocompetent mouse model, complementary to patient-derived xenografts, for studies of mammary carcinoma onset, prevention and therapy. PMID:28903354

Prediction of protein mutant stability using classification and regression tool.

PubMed

Huang, Liang-Tsung; Saraboji, K; Ho, Shinn-Ying; Hwang, Shiow-Fen; Ponnuswamy, M N; Gromiha, M Michael

2007-02-01

Prediction of protein stability upon amino acid substitutions is an important problem in molecular biology and the solving of which would help for designing stable mutants. In this work, we have analyzed the stability of protein mutants using two different datasets of 1396 and 2204 mutants obtained from ProTherm database, respectively for free energy change due to thermal (DeltaDeltaG) and denaturant denaturations (DeltaDeltaG(H(2)O)). We have used a set of 48 physical, chemical energetic and conformational properties of amino acid residues and computed the difference of amino acid properties for each mutant in both sets of data. These differences in amino acid properties have been related to protein stability (DeltaDeltaG and DeltaDeltaG(H(2)O)) and are used to train with classification and regression tool for predicting the stability of protein mutants. Further, we have tested the method with 4 fold, 5 fold and 10 fold cross validation procedures. We found that the physical properties, shape and flexibility are important determinants of protein stability. The classification of mutants based on secondary structure (helix, strand, turn and coil) and solvent accessibility (buried, partially buried, partially exposed and exposed) distinguished the stabilizing/destabilizing mutants at an average accuracy of 81% and 80%, respectively for DeltaDeltaG and DeltaDeltaG(H(2)O). The correlation between the experimental and predicted stability change is 0.61 for DeltaDeltaG and 0.44 for DeltaDeltaG(H(2)O). Further, the free energy change due to the replacement of amino acid residue has been predicted within an average error of 1.08 kcal/mol and 1.37 kcal/mol for thermal and chemical denaturation, respectively. The relative importance of secondary structure and solvent accessibility, and the influence of the dataset on prediction of protein mutant stability have been discussed.

Effects of the nitric oxide synthase inhibitor L-NMMA on cerebrovascular and cardiovascular responses to hypoxia and hypercapnia in humans.

PubMed

Ide, Kojiro; Worthley, Matthew; Anderson, Todd; Poulin, Marc J

2007-10-01

Cerebral blood flow is highly sensitive to alterations in the partial pressures of O(2) and CO(2) (P(O(2)) and P(CO(2)), respectively) in the arterial blood. In humans, the extent to which nitric oxide (NO) is involved in this regulation is unclear. We hypothesized that the NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA), attenuates the sensitivity of middle cerebral artery blood velocity (V(p)) to isocapnic hypoxia (end-tidal P(O(2)) = 50 Torr) and euoxic hypercapnia (end-tidal P(CO(2)) = +9 Torr above resting values) in 10 volunteers (age, 28.7 +/- 1.3 years; height, 179.2 +/- 2.4 cm; weight, 78.0 +/- 3.7 kg; mean +/- s.e.m.). The techniques of transcranial Doppler ultrasound and dynamic end-tidal forcing were used to measure(V(p)), and control end-tidal P(O(2)) and end-tidal P(CO(2)), respectively. At baseline (isocapnic euoxia), following intravenous administration of l-NMMA, mean arterial blood pressure (MAP) increased (76.3 +/- 7.3 to 86.2 +/- 9.4 mmHg) and heart rate (HR) decreased (59.5 +/- 9.0 to 55.2 +/- 9.5 beats min(-1)) but (V(p)) was unchanged. Hypoxia-induced increases in MAP, HR and were similar with and without l-NMMA (5.0 +/- 0.7 versus 7.1 +/- 1.0 mmHg, 11.5 +/- 1.4 versus 12.4 +/- 1.5 beats min(-1), 6.5 +/- 0.8 versus 6.6 +/- 0.8 cm s(-1) for DeltaMAP, DeltaHR and Delta , respectively). Hypercapnia-induced increases in MAP, HR and (V(p)) were similar with and without l-NMMA (7.4 +/- 3.1 versus 8.1 +/- 2.2 mmHg, 10.4 +/- 4.6 versus 10.0 +/- 4.2 beats min(-1), 16.5 +/- 1.5 versus 17.6 +/- 1.5 cm s(-1) for DeltaMAP, DeltaHR and Delta(V(p)) , respectively) but the sensitivity of the(V(p)) response at the removal of hypercapnia was attenuated with l-NMMA. In young healthy humans, pharmacological blockade of nitric oxide synthesis does not affect the increases in cerebral blood flow with hypoxia and hypercapnia, suggesting that nitric oxide is not required for the cerbrovascular responses to hypoxia and hypercapnia.

Adaptive Delta Management: cultural aspects of dealing with uncertainty

NASA Astrophysics Data System (ADS)

Timmermans, Jos; Haasnoot, Marjolijn; Hermans, Leon; Kwakkel, Jan

2016-04-01

Deltas are generally recognized as vulnerable to climate change and therefore a salient topic in adaptation science. Deltas are also highly dynamic systems viewed from physical (erosion, sedimentation, subsidence), social (demographic), economic (trade), infrastructures (transport, energy, metropolization) and cultural (multi-ethnic) perspectives. This multi-faceted dynamic character of delta areas warrants the emergence of a branch of applied adaptation science, Adaptive Delta Management, which explicitly focuses on climate adaptation of such highly dynamic and deeply uncertain systems. The application of Adaptive Delta Management in the Dutch Delta Program and its active international dissemination by Dutch professionals results in the rapid dissemination of Adaptive Delta Management to deltas worldwide. This global dissemination raises concerns among professionals in delta management on its applicability in deltas with cultural conditions and historical developments quite different from those found in the Netherlands and the United Kingdom where the practices now labelled as Adaptive Delta Management first emerged. This research develops an approach and gives a first analysis of the interaction between the characteristics of different approaches in Adaptive Delta Management and their alignment with the cultural conditions encountered in various delta's globally. In this analysis, first different management theories underlying approaches to Adaptive Delta Management as encountered in both scientific and professional publications are identified and characterized on three dimensions: The characteristics dimensions used are: orientation on today, orientation on the future, and decision making (Timmermans, 2015). The different underlying management theories encountered are policy analysis, strategic management, transition management, and adaptive management. These four management theories underlying different approaches in Adaptive Delta Management are connected to Hofstede's (1983) cultural dimensions, of which uncertainty avoidance and long-term orientation are of particular relevance for our analysis. Our conclusions comment on the suitability of approaches in Adaptive Delta Management rooted in different management theories are more suitable for specific delta countries than others. The most striking conclusion is the unsuitability of rational policy analytic approaches for The Netherlands. Although surprising this conclusion finds some support in the process dominated approach taken in the Dutch Delta Program. In addition, the divergence between Vietnam, Bangladesh and Myanmar, all located in South East Asia, is striking. References Hofstede, G. (1983). The cultural relativity of organizational practices and theories. Journal of international business studies, 75-89. Jos Timmermans, Marjolijn Haasnoot, Leon Hermans, Jan Kwakkel, Martine Rutten and Wil Thissen (2015). Adaptive Delta Management: Roots and Branches, IAHR The Hague 2015.

Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping.

PubMed

Mealey, Katrina L; Meurs, Kathryn M

2008-09-15

To evaluate the breed distribution of the ABCB1-1Delta polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified. Cross-sectional study. 5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping. From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function. The ABCB1-1Delta allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Delta allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously). The ABCB1-1Delta polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Delta polymorphism to make appropriate pharmacologic choices for these patients.

Evaluation of Sources of Nitrate Beneath Food Processing Wastewater-Application Sites near Umatilla, Oregon

USGS Publications Warehouse

Frans, Lonna; Paulson, Anthony; Richerson, Phil; Striz, Elise; Black, Curt

2009-01-01

Water samples from wells were collected beneath and downgradient of two food-processing wastewater-application sites near Umatilla, Oregon. These samples were analyzed for nitrate stable isotopes, nutrients, major ions, and age-dating constituents to determine if nitrate-stable isotopes can be used to differentiate food-processing waste from other potential sources of nitrate. Major-ion data from each site were used to determine which samples were associated with the recharge of the food-processing wastewater. End-member mixing analysis was used to determine the relative amounts of each identified end member within the samples collected from the Terrace Farm site. The delta nitrogen-15 (delta 15N) of nitrate generally ranged between +2 and +9 parts per thousand and the delta oxygen-18 (delta 18O) of nitrate generally ranged between -2 and -7 parts per thousand. None of the samples that were determined to be associated with the wastewater were different from the samples that were not affected by the wastewater. The nitrate isotope values measured in this study are also characteristic of ammonium fertilizer, animal and human waste, and soil nitrate; therefore, it was not possible to differentiate between food-processing wastewater and the other nitrate sources. Values of delta 15N and delta 18O of nitrate provided no more information about the sources of nitrate in the Umatilla River basin than did a hydrologic and geochemical understanding of the ground-water system derived from interpreting water-level and major-ion chemistry data.

Leaf and wood carbon isotope ratios, specific leaf areas and wood growth of Eucalyptus species across a rainfall gradient in Australia.

PubMed

Schulze, Ernst-Detlef; Turner, Neil C; Nicolle, Dean; Schumacher, Jens

2006-04-01

Leaves and samples of recent wood of Eucalyptus species were collected along a rainfall gradient parallel to the coast of Western Australia between Perth in the north and Walpole in the south and along a southwest to northeast transect from Walpole in southwestern Australia, to near Mount Olga in central Australia. The collection included 65 species of Eucalyptus sampled at 73 sites and many of the species were collected at several sites along the rainfall gradient. Specific leaf area (SLA) and isotopic ratio of 13C to 12C (delta 13C) of leaves that grew in 2002, and tree ring growth and delta 13C of individual cell layers of the wood were measured. Rainfall data were obtained from the Australian Bureau of Meteorology for 29 locations that represented one or a few closely located collection sites. Site-averaged data and species-specific values of delta 13C decreased with decreasing annual rainfall between 1200 and 300 mm at a rate of 1.63 per thousand per 1000 mm decrease in rainfall. Responses became variable in the low rainfall region (< 300 mm), with some species showing decreasing delta 13C with rainfall, whereas delta 13C increased or remained constant in other species. The range of delta 13C values in the low rainfall region was as large as the range observed at sites receiving > 300 mm of annual rainfall. Specific leaf area varied between 2 and 6 m2 kg(-1) and tended to increase with decreasing annual rainfall in some species, but not all, whereas delta 13C decreased with SLA. The relationship between delta 13C and SLA was highly species and soil-type specific. Leaf-area-based nitrogen (N) content varied between 2 and almost 6 g m(-2) and decreased with rainfall. Thus, thicker leaves were associated with higher N content and this compensated for the effect of drought on delta 13C. Nitrogen content was also related to soil type and species identity. Based on a linear mixed model, statistical analysis of the whole data set showed that 27% of the variation in delta 13C was associated with changes in SLA, 16% with soil type and only 1% with rainfall. Additionally, 21% was associated with species identity. For a subset of sites with > 300 mm rainfall, 43% of the variation was explained by SLA, 13% by soil type and only 3% by rainfall. The species effect decreased to 9% because there were fewer species in the subset of sites. The small effect of rainfall on delta 13C was further supported by a path analysis that yielded a standardized path coefficient of 0.38 for the effect of rainfall on SLA and -0.50 for the effect of SLA on delta 13C, but an insignificantly low standardized path coefficient of -0.05 for the direct effect of rainfall on delta 13C. Thus, in contrast to our hypothesis that delta 13C decreases with rainfall independent of soil type and species, we detected no statistically significant relationship between rainfall and delta 13C in leaves of trees growing at sites receiving < 300 mm of rainfall annually. Rainfall affected delta 13C indirectly through soil type (a surrogate for water-holding capacity) across the rainfall gradient. Annual tree rings are not clearly visible in evergreen Eucalyptus species, even in the seasonally cool climate of SW Australia. Generally, visible density transitions in the wood are related not to a strict annual cycle but to periods of growth associated mainly with rainfall. The relationship between delta 13C of leaves and the width of these stem increments was not statistically significant. Analysis of stem growth periods showed that delta 13C in wood responded to rainfall events, but carbohydrate storage and reallocation also affected the isotopic signature. Although delta 13C in wood of any one species varied over a range of 2 to 4 per thousand, there was a general relationship between delta 13C of the leaves and the annual range of delta 13C in wood. We conclude that species-specific traits are important in understanding the response of Eucalyptus to rainfall and that the diversity of the genus may reflect its response to the large climatic gradient in Australia and to the large annual and interannual variations in rainfall at any one location.

Effect of mouthwash and accelerated aging on the color stability of esthetic restorative materials.

PubMed

Lee, Y K; El Zawahry, M; Noaman, K M; Powers, J M

2000-06-01

To evaluate the color stability of esthetic restorative materials after immersion in mouthwashes and accelerated aging. Compomers and resin-based composites (RBC) were measured at baseline and repeatedly after immersion in three kinds of mouthwash (Listerine, Peridex, Rembrandt Age Defying) for 24 hrs and 7 days, and after aging for 150 kJ/m2. Color was measured according to CIE L*a*b* color scale on a reflection spectrophotometer. After immersion for 7 days, the mouthwash groups did not produce significantly higher color changes than the distilled water group, except with some mouthwashes used with Tetric-Ceram. After immersion for 7 days and aging for 150 kJ/m2, the mouthwash groups did not produce significantly higher color changes than the distilled water group. Aging in weathering chamber produced color change (deltaE*) of 1.1-3.9, which was mainly influenced by the material. With some exceptions, the color changes from immersion of the RBCs and compomers in mouthwashes were not perceptible (deltaE*<3.3).

Spectroscopic, and thermal studies of some new binuclear transition metal(II) complexes with hydrazone ligands containing acetoacetanilide and isoxazole.

PubMed

Chen, Zhimin; Wu, Yiqun; Gu, Donghong; Gan, Fuxi

2007-11-01

A new chelating ligand, 2-(2-(5-tert-butylisoxazol-3-yl)hydrazono)-N-(2,4-dimethylphenyl)-3-oxobutanamide (HL), and its four binuclear transition metal complexes, M(2)(L)(2) (micro-OCH(3))(2) [M=Ni(II), Co(II), Cu(II), Zn(II)], were synthesized using the procedure of diazotization, coupling and metallization. Their structures were postulated based on elemental analysis, (1)H NMR, MALDI-MS, FT-IR spectra and UV-vis electronic absorption spectra. Smooth films of these complexes on K9 glass substrates were prepared using the spin-coating method and their absorption properties were evaluated. The thermal properties of the metal(II) complexes were investigated by thermogravimetry (TG) and differential scanning calorimetry (DSC). Different thermodynamic and kinetic parameters namely activation energy (E*), enthalpy of activation (DeltaH*), entropy of activation (DeltaS*) and free energy change of activation (DeltaG*) are calculated using Coats-Redfern (CR) equation.

Electromagnetic scattering calculations on the Intel Touchstone Delta

NASA Technical Reports Server (NTRS)

Cwik, Tom; Patterson, Jean; Scott, David

1992-01-01

During the first year's operation of the Intel Touchstone Delta system, software which solves the electric field integral equations for fields scattered from arbitrarily shaped objects has been transferred to the Delta. To fully realize the Delta's resources, an out-of-core dense matrix solution algorithm that utilizes some or all of the 90 Gbyte of concurrent file system (CFS) has been used. The largest calculation completed to date computes the fields scattered from a perfectly conducting sphere modeled by 48,672 unknown functions, resulting in a complex valued dense matrix needing 37.9 Gbyte of storage. The out-of-core LU matrix factorization algorithm was executed in 8.25 h at a rate of 10.35 Gflops. Total time to complete the calculation was 19.7 h-the additional time was used to compute the 48,672 x 48,672 matrix entries, solve the system for a given excitation, and compute observable quantities. The calculation was performed in 64-b precision.

KSC-07pd1509

NASA Image and Video Library

2007-06-15

KENNEDY SPACE CENTER, FLA. -- The second stage of the Delta II launch vehicle for the Dawn spacecraft arrives on Launch Pad 17-B at Cape Canaveral Air Force Station where it will be mated with the first stage. The Delta II-Heavy, manufactured by the United Launch Alliance, is scheduled to launch the Dawn spacecraft on its 4-year flight to the asteroid belt. The Delta II-Heavy is the strongest rocket in the Delta II class. It will use three stages and nine solid-fueled booster rockets to propel Dawn on its way. A 9.5-foot payload fairing will protect the spacecraft from the heat and stresses of launch. Dawn's goal is to characterize the conditions and processes of the solar system's earliest epoch by investigating in detail the largest protoplanets that have remained intact since their formations: asteroid Vesta and the dwarf planet Ceres. They reside in the extensive zone between Mars and Jupiter together with many other smaller bodies, called the asteroid belt. Dawn is scheduled to launch July 7. Photo credit: NASA/Jack Pfaller

KSC-07pd1515

NASA Image and Video Library

2007-06-15

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 17-B at Cape Canaveral Air Force Station, workers maneuver the second stage of the Delta II launch vehicle onto the first stage for mating. The Delta II-Heavy, manufactured by the United Launch Alliance, is scheduled to launch the Dawn spacecraft on its 4-year flight to the asteroid belt. The Delta II-Heavy is the strongest rocket in the Delta II class. It will use three stages and nine solid-fueled booster rockets to propel Dawn on its way. A 9.5-foot payload fairing will protect the spacecraft from the heat and stresses of launch. Dawn's goal is to characterize the conditions and processes of the solar system's earliest epoch by investigating in detail the largest protoplanets that have remained intact since their formations: asteroid Vesta and the dwarf planet Ceres. They reside in the extensive zone between Mars and Jupiter together with many other smaller bodies, called the asteroid belt. Dawn is scheduled to launch July 7. Photo credit: NASA/Jack Pfaller

Notch ligands Delta1 and Jagged1 transmit distinct signals to T-cell precursors

PubMed Central

Lehar, Sophie M.; Dooley, James; Farr, Andrew G.; Bevan, Michael J.

2009-01-01

Signaling through the Notch pathway plays an essential role in inducing T-lineage commitment and promoting the maturation of immature thymocytes. Using an in vitro culture system, we show that 2 different classes of Notch ligands, Jagged1 or Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells expressing either Jagged1 or Delta1 inhibit the differentiation of DN1 thymocytes into the B-cell lineage, but only the Delta1-expressing stromal cells promote the proliferation and maturation of T-cell progenitors through the early double-negative (DN) stages of thymocyte development. Whereas the majority of bone marrow-derived stem cells do not respond to Jagged1 signals, T-cell progenitors respond to Jagged1 signals during a brief window of their development between the DN1 and DN3 stages of thymic development. During these stages, Jagged1 signals can influence the differentiation of immature thymocytes along the natural killer (NK) and γδ T-cell lineages. PMID:15486060

Mississippi River delta as seen from the Gemini 9-A spacecraft

NASA Technical Reports Server (NTRS)

1966-01-01

The Mississippi River delta, and Gulf coasts of Louisiana, Mississippi, Alabama and Florida as seen from the Gemini 9-A spacecraft during its first revolution of the earth. Florida peninsula is seen at upper right corner of picture. lake Pontchartrain is at lower left. new orleans is located between the lake and the U-shaped bend in the river. Large bay at top left center is Mobile Bay. Apalachicola, Florida, is the point of land at top center of picture. Note alluvial deposit at mouths of Mississippi.

What's on the Surface? Physics and Chemistry of Delta-Doped Surfaces

NASA Technical Reports Server (NTRS)

Hoenk, Michael

2011-01-01

Outline of presentation: 1. Detector surfaces and the problem of stability 2. Delta-doped detectors 3. Physics of Delta-doped Silicon 4. Chemistry of the Si-SiO2 Interface 5. Physics and Chemistry of Delta-doped Surfaces a. Compensation b. Inversion c. Quantum exclusion. Conclusions: 1. Quantum confinement of electrons and holes dominates the behavior of delta-doped surfaces. 2. Stability of delta-doped detectors: Delta-layer creates an approx 1 eV tunnel barrier between bulk and surface. 3. At high surface charge densities, Tamm-Shockley states form at the surface. 4. Surface passivation by quantum exclusion: Near-surface delta-layer suppresses T-S trapping of minority carriers. 5. The Si-SiO2 interface compensates the surface 6. For delta-layers at intermediate depth, surface inversion layer forms 7. Density of Si-SiO2 interface charge can be extremely high (>10(exp 14)/sq cm)

Circuits and methods for impedance determination using active measurement cancelation

DOEpatents

Jamison, David K.

2016-12-13

A delta signal and opposite delta signal are generated such that a sum of the two signals is substantially zero. The delta signal is applied across a first set of electrochemical cells. The opposite delta signal is applied across a second set of electrochemical cells series connected to the first set. A first held voltage is established as the voltage across the first set. A second held voltage is established as the voltage across the second set. A first delta signal is added to the first held voltage and applied to the first set. A second delta signal is added to the second held voltage and applied to the second set. The current responses due to the added delta voltages travel only into the set associated with its delta voltage. The delta voltages and the current responses are used to calculate the impedances of their associated cells.

Pheromones and pheromone receptors are required for proper sexual development in the homothallic ascomycete Sordaria macrospora.

PubMed

Mayrhofer, Severine; Weber, Jan M; Pöggeler, Stefanie

2006-03-01

The homothallic, filamentous ascomycete Sordaria macrospora is self-fertile and produces sexual fruiting bodies (perithecia) without a mating partner. Even so, S. macrospora transcriptionally expresses two pheromone-precursor genes (ppg1 and ppg2) and two pheromone-receptor genes (pre1 and pre2). The proteins encoded by these genes are similar to alpha-factor-like and a-factor-like pheromones and to G-protein-coupled pheromone receptors of the yeast Saccharomyces cerevisiae. It has been suggested that in S. macrospora, PPG1/PRE2 and PPG2/PRE1 form two cognate pheromone-receptor pairs. To investigate their function, we deleted (delta) pheromone-precursor genes (delta ppg1, delta ppg2) and receptor genes (delta pre1, delta pre2) and generated single- as well as double-knockout strains. No effect on vegetative growth, fruiting-body, and ascospore development was seen in the single pheromone-mutant and receptor-mutant strains, respectively. However, double-knockout strains lacking any compatible pheromone-receptor pair (delta pre2/delta ppg2, delta pre1/delta ppg1) and the double-pheromone mutant (delta ppg1/delta ppg2) displayed a drastically reduced number of perithecia and sexual spores, whereas deletion of both receptor genes (delta pre1/delta pre2) completely eliminated fruiting-body and ascospore formation. The results suggest that pheromones and pheromone receptors are required for optimal sexual reproduction of the homothallic S. macrospora.

Growth laws for sub-delta crevasses in the Mississippi River Delta

NASA Astrophysics Data System (ADS)

Yocum, T. A.; Georgiou, I. Y.; Straub, K. M.

2017-12-01

River deltas are threatened by environmental change, including subsidence, global sea level rise, reduced sediment inputs and other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions to reinitiate the delta cycle. Deltas were studied extensively using numerical models, theoretical and conceptual frameworks, empirical scaling relationships, laboratory models and field observations. But predicting the future of deltas relies on field observations where for most deltas data are still lacking. Moreover, empirical and theoretical scaling laws may be influenced by the data used to develop them, while laboratory deltas may be influenced by scaling issues. Anthropogenic crevasses in the MRD are large enough to overcome limitations of laboratory deltas, and small enough to allow for rapid channel and wetland development, providing an ideal setting to investigate delta development mechanics. Here we assessed growth laws of sub-delta crevasses (SDC) in the MRD, in two experimental laboratory deltas (LD - weakly and strongly cohesive) and compared them to river dominated deltas worldwide. Channel and delta geometry metrics for each system were obtained using geospatial tools, bathymetric datasets, sediment size, and hydrodynamic observations. Results show that SDC follow growth laws similar to large river dominated deltas, with the exception of some that exhibit anomalous behavior with respect to the frequency and distance to a bifurcation and the fraction of wetted delta shoreline (allometry metrics). Most SDC exhibit a systematic decrease of non-dimensional channel geometries with increased bifurcation order, indicating that channels are adjusting to decreased flow after bifurcations occur, and exhibit linear trends for land allometry and width-depth ratio, although geometries decrease more rapidly per bifurcation order. Measured distance to bifurcations in SDC and LD appear longer compared to those predicted by power law metrics. With less channel splitting in some crevasses, channel extension creates wetted perimeter faster than or at the same rate as wetted area, which explains why some SDC displayed fractal growth of the wetted allometry.

Effect of environmental change on the morphology of tidally influenced deltas over multi-decadal timescale

NASA Astrophysics Data System (ADS)

Angamuthu, Balaji; Darby, Stephen; Nicholls, Robert

2017-04-01

An understanding of the geomorphological processes affecting deltas is essential to improve our understanding of the risks that deltas face, especially as human impacts are likely to intensify in the future. Unfortunately, there is limited reliable data on river deltas, meaning that the task of demonstrating the links between morphodynamic and environmental change is challenging. This presentation aims to answer the questions of how delta morphology evolves over multi-decadal timescales under multiple drivers, focussing on tidally-influenced deltas, as some of these, such as the Ganges-Brahmaputra-Meghna (GBM) delta are heavily populated. A series of idealised model simulations over 102 years were used to explore the influence of three key drivers on delta morphodynamics, both individually and together: (i) varying combinations of water and sediment discharges from the upstream catchment, (ii) varying rates of relative sea-level rise (RSLR), and (iii) selected human interventions within the delta, such as polders, cross-dams and changing land cover. Model simulations revealed that delta progradation rates are more sensitive to variations in water discharge than variations in fluvial sediment supply. Unlike mere aggradation during RSLR, the delta front experienced aggradational progradation due to tides. As expected, the area of the simulated sub-aerial delta increases with increasing sediment discharge, but decreases with increasing water discharge. But, human modifications are important. For example, the sub-aerial delta shrinks with increasing RSLR, but it does not when the sub-aerial delta is polderised, provided the polders are restricted from erosion. However, the polders are vulnerable to flooding as they lose relative elevation and can make the delta building process unsustainable. Cross-dams built to steer zones of land accretion within the delta accomplish their local goal, but may not result in net land gain at the scale of the delta. Applying these results to the contemporary GBM delta implies that cross-dams and polders have been a key control on the morphodynamic evolution of the GBM delta over the last 60 years. However, with increased fluvial water discharge and rates of RSLR likely under greenhouse gas (GHG) -driven warming, the continuing use of sediment starved polders will only increase the vulnerability of poldered areas from regular flooding, and eventually may lead to catastrophic, permanent, inundation of the land. Hence, the future trend of morphological evolution of the GBM delta depends on local human intervention, including measures to raise the elevation of the land to cope with the continuing trend of RSLR and varying fluvial discharges. The model findings provide a basis to establish guidelines for planned future management interventions to prevent the delta from destruction.

Natural disturbance shapes benthic intertidal macroinvertebrate communities of high latitude river deltas

USGS Publications Warehouse

Churchwell, Roy T.; Kendall, Steve J.; Blanchard, Amy L.; Dunton, Kenneth H.; Powell, Abby N.

2016-01-01

Unlike lower latitude coastlines, the estuarine nearshore zones of the Alaskan Beaufort Sea are icebound and frozen up to 9 months annually. This annual freezing event represents a dramatic physical disturbance to fauna living within intertidal sediments. The main objectives of this study were to describe the benthic communities of Beaufort Sea deltas, including temporal changes and trophic structure. Understanding benthic invertebrate communities provided a baseline for concurrent research on shorebird foraging ecology at these sites. We found that despite continuous year-to-year episodes of annual freezing, these estuarine deltas are populated by a range of invertebrates that represent both marine and freshwater assemblages. Freshwater organisms like Diptera and Oligochaeta not only survive this extreme event, but a marine invasion of infaunal organisms such as Amphipoda and Polychaeta rapidly recolonizes the delta mudflats following ice ablation. These delta sediments of sand, silt, and clay are fine in structure compared to sediments of other Beaufort Sea coastal intertidal habitats. The relatively depauperate invertebrate community that ultimately develops is composed of marine and freshwater benthic invertebrates. The composition of the infauna also reflects two strategies that make life on Beaufort Sea deltas possible: a migration of marine organisms from deeper lagoons to the intertidal and freshwater biota that survive the 9-month ice-covered period in frozen sediments. Stable isotopic analyses reveal that both infaunal assemblages assimilate marine and terrestrial sources of organic carbon. These results provide some of the first quantitative information on the infaunal food resources of shallow arctic estuarine systems and the long-term persistence of these invertebrate assemblages. Our data help explain the presence of large numbers of shorebirds in these habitats during the brief summer open-water period and their trophic importance to migrating waterfowl and nearshore populations of estuarine fishes that are the basis of subsistence lifestyles by native inhabitants of the Beaufort Sea coast.

The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Domb, Abraham J; Hoffman, Amnon

2017-11-15

The lipophilic phytocannabinoids cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized compounds that currently cannot be administered orally. Copyright © 2017. Published by Elsevier B.V.

Sudden onset unexplained encephalopathy in infants: think of cannabis intoxication.

PubMed

Lavi, Eran; Rekhtman, David; Berkun, Yackov; Wexler, Isaiah

2016-03-01

The use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations. During the initial interview of caregivers, no history of exposure to neurotoxic agents was obtained. All three patients were subsequently diagnosed with cannabis intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC). The infants recovered with supportive care that included fluids and monitoring. The non-specific symptomatology of cannabis intoxication in infants together with the wide differential for unexplained acute onset encephalopathy may delay diagnosis and lead to inappropriate procedures and interventions such as antimicrobial treatments and imaging studies. Healthcare personnel of emergency rooms, urgent care centers, and general clinics should be aware of the potential risk of cannabis ingestion in young infants. A thorough medical history and toxic screen are warranted in all infants with unexplained decreased sensorium.

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

PubMed

Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

2010-01-01

For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.

Quantification of Cannabinoid Content in Cannabis

NASA Astrophysics Data System (ADS)

Tian, Y.; Zhang, F.; Jia, K.; Wen, M.; Yuan, Ch.

2015-09-01

Cannabis is an economically important plant that is used in many fields, in addition to being the most commonly consumed illicit drug worldwide. Monitoring the spatial distribution of cannabis cultivation and judging whether it is drug- or fiber-type cannabis is critical for governments and international communities to understand the scale of the illegal drug trade. The aim of this study was to investigate whether the cannabinoids content in cannabis could be spectrally quantified using a spectrometer and to identify the optimal wavebands for quantifying the cannabinoid content. Spectral reflectance data of dried cannabis leaf samples and the cannabis canopy were measured in the laboratory and in the field, respectively. Correlation analysis and the stepwise multivariate regression method were used to select the optimal wavebands for cannabinoid content quantification based on the laboratory-measured spectral data. The results indicated that the delta-9-tetrahydrocannabinol (THC) content in cannabis leaves could be quantified using laboratory-measured spectral reflectance data and that the 695 nm band is the optimal band for THC content quantification. This study provides prerequisite information for designing spectral equipment to enable immediate quantification of THC content in cannabis and to discriminate drug- from fiber-type cannabis based on THC content quantification in the field.

Cannabis, a complex plant: different compounds and different effects on individuals

PubMed Central

2012-01-01

Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions. There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way. What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics. In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals. PMID:23983983

Effectiveness of a Marijuana Expectancy Manipulation: Piloting the Balanced-Placebo Design for Marijuana

PubMed Central

Metrik, Jane; Rohsenow, Damaris J.; Monti, Peter M.; McGeary, John; Cook, Travis A. R.; de Wit, Harriet; Haney, Margaret; Kahler, Christopher W.

2009-01-01

Although alcohol and nicotine administration studies have demonstrated that manipulating subjects’ expectancies regarding drug content affects drug response, research with marijuana has not adequately studied drug expectancy effects. The present pilot study was the first to evaluate the credibility and effect of expectancy manipulation on subjective measures and smoking patterns using a marijuana administration balanced-placebo design (BPD). In a 2 × 2 instructional set (told delta-9-tetrahydrocannabinol [THC] vs. told no THC) by drug (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, the authors examined the effect of marijuana expectancy manipulation and the pharmacologic effect on affective and physiologic measures, cigarette ratings, and smoking behavior with 20 marijuana smokers (mean age = 20 years; 25% female). Large main effects of expectancy were found on ratings of cigarette potency, strength, taste, smell, and satisfaction, and observed smoking behavior. Pharmacologic effects were particularly evident for self-reported physical reactions to marijuana and cigarette potency and satisfaction ratings. This study demonstrated the feasibility of the BPD research with marijuana and yielded promising results for future studies examining the independent and combined effects of marijuana pharmacology and expectancies. PMID:19653787

Neurological Disorders in Medical Use of Cannabis: An Update.

PubMed

Solimini, Renata; Rotolo, Maria Concetta; Pichini, Simona; Pacifici, Roberta

2017-01-01

Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Phytocannabinoids modulate emotional memory processing through interactions with the ventral hippocampus and mesolimbic dopamine system: implications for neuropsychiatric pathology.

PubMed

Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-02-01

Growing clinical and preclinical evidence suggests a potential role for the phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is associated with acute and neurodevelopmental propsychotic side effects through its interaction with central cannabinoid type 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus (VHipp) potentiates affective memory formation through inputs to the mesolimbic dopamine (DA) system, thereby altering emotional salience attribution. These changes in DA activity and salience attribution, evoked by dysfunctional VHipp regulatory actions and THC exposure, could predispose susceptible individuals to psychotic symptoms. Although THC can accelerate the onset of schizophrenia, CBD displays antipsychotic properties, can prevent the acquisition of emotionally irrelevant memories, and reverses amphetamine-induced neuronal sensitization through selective phosphorylation of the mechanistic target of rapamycin (mTOR) molecular signaling pathway. This review summarizes clinical and preclinical evidence demonstrating that distinct phytocannabinoids act within the VHipp and associated corticolimbic structures to modulate emotional memory processing through changes in mesolimbic DA activity states, salience attribution, and signal transduction pathways associated with schizophrenia-related pathology.

Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments.

PubMed

Renard, Justine; Norris, Christopher; Rushlow, Walter; Laviolette, Steven R

2017-04-01

Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders. In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties. However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties. Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties. This review summarizes clinical and pre-clinical evidence demonstrating CBD's modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT 1A receptor system, and their downstream molecular signaling effects. Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.