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Sample records for delta opiate receptors

  1. In vivo studies of opiate receptors

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

  2. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  3. The distribution of multiple opiate receptors in bovine brain

    International Nuclear Information System (INIS)

    Ninkovic, M.; Hunt, S.P.; Emson, P.C.; Iversen, L.L.

    1981-01-01

    The distribution of μ and delta opiate receptors in bovine brain has been investigated using the selective radioligands [ 3 H]morphine and D-[ 3 H]Ala 2 , D-Leu 5 -enkephalin. Their distributions were found to vary independently through different brain areas with up to a 10-fold difference between the ratio of μ to delta binding sites for the substantia nigra and the dentate gyrus of the hippocampus. (Auth.)

  4. Imaging opiate receptors with positron emission tomography

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5μg/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 μg/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15

  5. Imaging opiate receptors with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wong, D.F.; Links, J.M.; Burns, H.D.; Kuhar, M.J.; Snyder, S.H.; Wagner, H.N. Jr.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.

  6. Production of antibodies which recognize opiate receptors on murine leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

    1988-01-01

    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  7. Morphine analgesia and cerebral opiate receptors: a developmental study

    International Nuclear Information System (INIS)

    Auguy-Valette, A.; Pontonnier, G.; Cros, J.; Gouarderes, C.; Gout, R.

    1978-01-01

    Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. Opiate receptors were detected in the brain of newborn rats; stereospecific binding of [ 3 H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. The number of [ 3 H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity. (author)

  8. Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal.

    Science.gov (United States)

    Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

    2008-11-01

    Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2). To investigate the role for the CRF(2) receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF(2) receptor (CRF(2)-/-). We employed a novel, clinically relevant mouse model of 'spontaneous' opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20-100 mg/kg, i.p.). We found that 8-128 h after the last opiate injection, CRF(2)-/- mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF(2)-/- mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF(2)-/- mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus-pituitary-adrenal axis in the CRF(2) receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF(2) receptor pathway in opiate withdrawal. The CRF(2) receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake.

  9. Change in the properties of the opiate receptors of the brain under conditions of habituation of rats to morphine

    Energy Technology Data Exchange (ETDEWEB)

    Zaitsev, S.V.; Sergeeva, M.G.; Chichenkov, O.N.; Petrov, V.E.; Varfolomeev, S.D.

    1987-02-20

    The influence of prolonged administration of morphine on the properties of the opiate receptors of the rat brain was investigated. For this purpose they conducted an analysis of the isotherms of binding of labeled ..mu..-, sigma-, and chi-ligands: morphine, D-Ala/sup 2/, D-Leu/sup 5/-enkephalin, and ethylketocyclazocin, with membrane preparations of the brains of rats tolerant to morphine, as well as the control animals. For a quantitative determination of the dissociation constants of the ligand-receptor complexes (K) and the concentration of the reagents ((Q)), they used differential method and the method of simulation modeling. It was shown that the values of K and (Q) for individual animals are subjected to substantial dispersion, whereas the ratios (Q)/K undergo minor individual fluctuations, both in the control group and in the group of rats tolerant to morphine. This permits the ratio (Q)/K to be singled out as one of the main parameters for comparing the properties of opiate receptors of various groups of animals. Using this criterion, as well as the method of simulated modeling, it was shown that the development of tolerance is accompanied by a change in the properties of the delta-receptors (the ratio (Q)/K decreases by a factor of more than two). In contrast to the delta-receptors, no significant influence of the tolerance on the properties of the ..mu..- and chi-receptors, as well as the ultrahigh-affinity ligand binding sites, was detected.

  10. Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

    OpenAIRE

    Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

    2008-01-01

    Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. To investigate the role for the CRF2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF2 ...

  11. Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8

    Directory of Open Access Journals (Sweden)

    George Shapovalov

    2013-08-01

    Full Text Available Stimulation of μ-opioid receptors (OPRMs brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment.

  12. Src‐dependent phosphorylation of μ‐opioid receptor at Tyr336 modulates opiate withdrawal

    OpenAIRE

    Zhang, Lei; Kibaly, Cherkaouia; Wang, Yu‐Jun; Xu, Chi; Song, Kyu Young; McGarrah, Patrick W; Loh, Horace H; Liu, Jing‐Gen; Law, Ping‐Yee

    2017-01-01

    Abstract Opiate withdrawal/negative reinforcement has been implicated as one of the mechanisms for the progression from impulsive to compulsive drug use. Increase in the intracellular cAMP level and protein kinase A (PKA) activities within the neurocircuitry of addiction has been a leading hypothesis for opiate addiction. This increase requires the phosphorylation of μ‐opioid receptor (MOR) at Tyr336 by Src after prolonged opiate treatment in vitro. Here, we report that the Src‐mediated MOR p...

  13. Effect of thyrotrophin releasing hormone on opiate receptors of the rat brain

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    Balashov, A.M.; Shchurin, M.R.

    1987-01-01

    It has recently been shown that the hypothalamic thyrotropin releasing hormone (TRH) has the properties of a morphine antagonist, blocking its inhibitory action on respiration and, to a lesser degree, its analgesic action. This suggests that the antagonistic effects of TRH are mediated through its interaction with opiate receptors. The aim of this paper is to study this hypothesis experimentally. Tritium-labelled enkephalins in conjunction with scintillation spectroscopy were used to assess the receptor binding behavior. The results indicate the existence of interconnections between the opiate systems and TRH. Although it is too early to reach definite conclusions on the mechanisms of this mutual influence and its physiological significance it can be tentatively suggested that TRH abolishes the pharmacological effects of morphine by modulating the functional state of opiate reception.

  14. The effect of hyperthyroidism on opiate receptor binding and pain sensitivity

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    Edmondson, E.A. (Baylor College of Medicine, Houston, TX (USA)); Bonnet, K.A.; Friedhoff, A.J. (New York Univ. School of Medicine, NY (USA))

    1990-01-01

    This study was conducted to determine the effect of thyroid hormone on opiate receptor ligand-binding and pain sensitivity. Specific opiate receptor-binding was performed on brain homogenates of Swiss-Webster mice. There was a significant increase in {sup 3}H-naloxone-binding in thyroxine-fed subjects (hyperthyroid). Scatchard analysis revealed that the number of opiate receptors was increased in hyperthyroid mice (Bmax = 0.238 nM for hyperthyroid samples vs. 0.174 nM for controls). Binding affinity was unaffected (Kd = 1.54 nM for hyperthyroid and 1.58 nM for control samples). When mice were subjected to hotplate stimulation, the hyperthyroid mice were noted to be more sensitive as judged by pain aversion response latencies which were half that of control animals. After morphine administration, the hyperthyroid animals demonstrated a shorter duration of analgesia. These findings demonstrate that thyroxine increases opiate receptor number and native pain sensitivity but decreases the duration of analgesia from morphine.

  15. Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit.

    Science.gov (United States)

    Lintas, Alessandra; Chi, Ning; Lauzon, Nicole M; Bishop, Stephanie F; Gholizadeh, Shervin; Sun, Ninglei; Tan, Huibing; Laviolette, Steven R

    2011-08-03

    The basolateral amygdala (BLA), ventral tegmental area (VTA), and nucleus accumbens (NAc) play central roles in the processing of opiate-related associative reward learning and memory. The BLA receives innervation from dopaminergic fibers originating in the VTA, and both dopamine (DA) D1 and D2 receptors are expressed in this region. Using a combination of in vivo single-unit extracellular recording in the NAc combined with behavioral pharmacology studies, we have identified a double dissociation in the functional roles of DA D1 versus D2 receptor transmission in the BLA, which depends on opiate exposure state; thus, in previously opiate-naive rats, blockade of intra-BLA D1, but not D2, receptor transmission blocked the acquisition of associative opiate reward memory, measured in an unbiased conditioned place preference procedure. In direct contrast, in rats made opiate dependent and conditioned in a state of withdrawal, intra-BLA D2, but not D1, receptor blockade blocked opiate reward encoding. This functional switch was dependent on cAMP signaling as comodulation of intra-BLA cAMP levels reversed or replicated the functional effects of intra-BLA D1 or D2 transmission during opiate reward processing. Single-unit in vivo extracellular recordings performed in neurons of the NAc confirmed an opiate-state-dependent role for BLA D1/D2 transmission in NAc neuronal response patterns to morphine. Our results characterize and identify a novel opiate addiction switching mechanism directly in the BLA that can control the processing of opiate reward information as a direct function of opiate exposure state via D1 or D2 receptor signaling substrates.

  16. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

    Science.gov (United States)

    Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  17. Opiate receptor blockade by naltrexone and mood state after acute physical activity.

    OpenAIRE

    Daniel, M; Martin, A D; Carter, J

    1992-01-01

    Acute mood changes occur with various forms of physical activity. Increased levels of endogenous opioids (endorphins) in response to exercise may mediate activity-induced shifts in mood state. Thirteen female and six male aerobics class participants aged 20-46 years received the opiate receptor antagonist naltrexone and a placebo in randomized, double-blind crossover fashion on two separate occasions at the same 75-min high-intensity aerobics class. Mood states were assessed before and after ...

  18. Central but not peripheral opiate receptor blockade prolonged pituitary-adrenal responses to stress.

    Science.gov (United States)

    Odio, M; Brodish, A

    1990-04-01

    Evidence from pharmacological studies suggest that opiate systems may serve either inhibitory or stimulatory functions on stress-induced responses of the hypothalamic-pituitary-adrenocortical (HPA) axis. The objective of these experiments was to determine whether these discrepant findings may result, in part, from differential effects of central or peripheral opiate receptor blockade on HPA axis responses. To this effect, groups of rats received injections of either saline, naltrexone (NHCl) or the quaternary analogue naltrexone methobromide (NMBr). The animals were then exposed to 30 min of a motion stressor and blood samples were obtained from each rat for analysis of ACTH, corticosterone, and prolactin. The data showed that resting and stress-induced levels of prolactin were decreased by NHCl only. Although neither drug affected the magnitude of the stress-induced ACTH and corticosterone responses, treatment with NHCl, but not NMBr, delayed the poststress decline of these responses. Hence, we concluded that central opiate mechanisms may be important for cessation of HPA axis activity, after exposure to stressful situations.

  19. Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS.

    Science.gov (United States)

    Webster, D E; Lu, J; Chen, S-N; Farnsworth, N R; Wang, Z Jim

    2006-06-30

    The dried ripe fruit of Vitex agnus-castus L. (VAC) is widely used for the treatment of premenstrual syndrome (PMS). A previous study reported that extracts of VAC showed affinity to opiate receptors; however, functional activity was not determined. We tested two different VAC extracts in receptor binding and functional assays. Our objectives were: (1) to confirm the opiate affinity; (2) to rule out interference by free fatty acids (FFA); (3) to determine the mode of action of VAC at the mu-opiate receptor. Methanol extracts of VAC were prepared either before (VAC-M1) or after (VAC-M2) extraction with petroleum ether to remove fatty acids. Both extracts showed significant affinities to the mu-opiate receptor, as indicated by the concentration-dependent displacement of [3H]DAMGO binding in Chinese hamster ovary (CHO)-human mu-opiate receptor (hMOR) cells. The IC50 values were estimated to be 159.8 microg/ml (VAC-M1) and 69.5 microg/ml (VAC-M2). Since the defatted extract not only retained, but exhibited a higher affinity (p<0.001), it argued against significant interference by fatty acids. In an assay to determine receptor activation, VAC-M1 and VAC-M2 stimulated [35S]GTPgammaS binding by 41 and 61% (p<0.001), respectively. These results suggested for the first time that VAC acted as an agonist at the mu-opiate receptor, supporting its beneficial action in PMS.

  20. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

    1986-03-01

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

  1. Cholecystokinin-8 suppressed /sup 3/H-etorphine binding to rat brain opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.J.; Fan, S.G.; Ren, M.F.; Han, J.S.

    1989-01-01

    Radioreceptor assay (RRA) was adopted to analyze the influence of CCK-8 on /sup 3/H-etorphine binding to opiate receptors in rat brain synaptosomal membranes (P2). In the competition experiment CCK-8 suppressed the binding of /sup 3/H-etorphine. This effect was completely reversed by proglumide at 1/mu/M. Rosenthal analysis for saturation revealed two populations of /sup 3/H-etorphine binding sites. CCK-8 inhibited /sup 3/H-etorphine binding to the high affinity sites by an increase in Kd and decrease in Bmax without significant changes in the Kd and Bmax of the low affinity sites. This effect of CCK-8 was also completely reversed by proglumide at 1/mu/M. Unsulfated CCK-8 produced only a slight increase in Kd of the high affinity sites without affecting Bmax. The results suggest that CCK-8 might be capable of suppressing the high affinity opioid binding sites via the activation of CCK receptor.

  2. Psychotomimetic opiate receptors labeled and visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

    International Nuclear Information System (INIS)

    Largent, B.L.; Gundlach, A.L.; Snyder, S.H.

    1984-01-01

    3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) has been proposed as a selective dopamine autoreceptor agonist in the central nervous system. This report describes the pharmacology and localization of specific high-affinity binding sites for (+)-[ 3 H]3-PPP in brain. The drug specificity of (+)-[ 3 H]3-PPP binding is identical to that of sigma receptors, which may mediate psychotomimetic effects of some opiates. Haloperidol and the opioid derivatives, pentazocine, cyclazocine, and SKF 10,047 are potent inhibitors of (+)-[ 3 H]3-PPP binding. Stereoselectivity is exhibited for the (+) isomers of cyclazocine and SKF 10.047 at the sigma site, opposite to the stereoselectivity seen at μ, sigma, and k opiate receptors. (+)-[ 3 H]3-PPP does not label dopamine receptors, as potent dopamine agonists and antagonists are weak inhibitors of binding and the localization of specific (+)-[ 3 H]3-PPP binding sites does not parallel that of dopamine neurons. Discrete localizations of (+)-[ 3 H]3-PPP binding sites in many brain areas including limbic, midbrain, brainstem, and cerebellar regions may explain psychotomimetic actions of opiates and behavior effects of 3-PPP. 41 references, 2 figures, 1 table

  3. Change in the properties of the opiate receptors of the brain under conditions of habituation of rats to morphine

    International Nuclear Information System (INIS)

    Zaitsev, S.V.; Sergeeva, M.G.; Chichenkov, O.N.; Petrov, V.E.; Varfolomeev, S.D.

    1987-01-01

    The influence of prolonged administration of morphine on the properties of the opiate receptors of the rat brain was investigated. For this purpose they conducted an analysis of the isotherms of binding of labeled μ-, σ-, and chi-ligands: morphine, D-Ala 2 , D-Leu 5 -enkephalin, and ethylketocyclazocin, with membrane preparations of the brains of rats tolerant to morphine, as well as the control animals. For a quantitative determination of the dissociation constants of the ligand-receptor complexes (K) and the concentration of the reagents ([Q]), they used differential method and the method of simulation modeling. It was shown that the values of K and [Q] for individual animals are subjected to substantial dispersion, whereas the ratios [Q]/K undergo minor individual fluctuations, both in the control group and in the group of rats tolerant to morphine. This permits the ratio [Q]/K to be singled out as one of the main parameters for comparing the properties of opiate receptors of various groups of animals. Using this criterion, as well as the method of simulated modeling, it was shown that the development of tolerance is accompanied by a change in the properties of the δ-receptors (the ratio [Q]/K decreases by a factor of more than two). In contrast to the δ-receptors, no significant influence of the tolerance on the properties of the μ- and chi-receptors, as well as the ultrahigh-affinity ligand binding sites, was detected

  4. Opiate exposure state controls dopamine D3 receptor and cdk5/calcineurin signaling in the basolateral amygdala during reward and withdrawal aversion memory formation.

    Science.gov (United States)

    Rosen, Laura G; Rushlow, Walter J; Laviolette, Steven R

    2017-10-03

    The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms. Using conditioned place preference (CPP) and withdrawal aversion (conditioned place aversion; CPA) procedures in rats, combined with molecular analyses of BLA protein expression, we examined the effects of chronic opiate exposure on the functional role of intra-BLA D3R transmission during the acquisition of opiate reward or withdrawal aversion memories. Remarkably, we report that the state of opiate exposure during behavioural conditioning (opiate-naïve/non-dependent vs. chronically exposed and in withdrawal) controlled the functional role of intra-BLA D3R transmission during the acquisition of both opiate reward memories and withdrawal-aversion associative memories. Thus, whereas intra-BLA D3R blockade had no effect on opiate reward memory formation in the non-dependent state, blockade of intra-BLA D3R transmission prevented the formation of opiate reward and withdrawal aversion memory in the chronically exposed state. This switch in the functional role of D3R transmission corresponded to significant increases in Cdk5 phosphorylation and total expression levels of calcineurin, and a corresponding decrease in intra-BLA D3R expression. Inhibition of either intra-BLA Cdk5 or calcineurin reversed these effects, switching intra-BLA associative memory formation back to a D3R-independent mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation

    DEFF Research Database (Denmark)

    Krogsdam, Anne-M; Nielsen, Curt A F; Neve, Søren

    2002-01-01

    delta-RXR alpha heterodimer bound to an acyl-CoA oxidase (ACO)-type peroxisome-proliferator response element recruited a glutathione S-transferase-NCoR fusion protein in a ligand-independent manner. Contrasting with most other nuclear receptors, PPAR delta was found to interact equally well......The nuclear receptor corepressor (NCoR) was isolated as a peroxisome-proliferator-activated receptor (PPAR) delta interacting protein using the yeast two-hybrid system. NCoR interacted strongly with the ligand-binding domain of PPAR delta, whereas interactions with the ligand-binding domains...

  6. Structure of the [delta]-opioid receptor bound to naltrindole

    Energy Technology Data Exchange (ETDEWEB)

    Granier, Sébastien; Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I.; Kobilka, Brian K. (Stanford-MED)

    2012-07-11

    The opioid receptor family comprises three members, the {mu}-, {delta}- and {kappa}-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The {delta}-opioid receptor ({delta}-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the {mu}-OR and {kappa}-OR have recently been solved. Here we report the crystal structure of the mouse {delta}-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the {mu}-OR and {kappa}-OR, the {delta}-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the {delta}-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

  7. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPAR delta) is involved in regulation of energy homeostasis. Activation of PPAR delta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased

  8. Preparation of (/sup 11/C)buprenorphine - a potential radioligand for the study of the opiate receptor system in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Pike, V.W.; Brady, F.; Horlock, P.L.; Prenant, C.; Crouzel, C.

    1987-01-01

    A method is described for the preparation of (/sup 11/C)buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with ''no carrier added'' (1-/sup 11/C)cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The (1-/sup 11/C)cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced (/sup 11/C)carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from (/sup 11/C)-carbon dioxide). (/sup 11/C)Buprenophine has potential as a radio-ligand for the study of the opiate receptor system in vivo by means of position emission tomography.

  9. Neural substrates of opiate withdrawal.

    Science.gov (United States)

    Koob, G F; Maldonado, R; Stinus, L

    1992-05-01

    Drug withdrawal is an integral part of most types of dependence and, to a large extent, opiate withdrawal has been considered the prototypic, classic measure of opiate dependence. The opiate withdrawal syndrome is characterized by multiple behavioral and physiological signs such as behavioral activation, ptosis, diarrhea, 'wet dog' shakes and motivational dysfunction, which may be represented in the CNS at multiple sites. It seems that the activating effects associated with the opiate withdrawal syndrome may be mediated by the nucleus locus coeruleus. Other signs such as wet dog shakes may involve sites in the hypothalamus important for temperature regulation. Certain other signs such as diarrhea and lacrimation may be dependent on peripheral opiate receptors. The motivational aspects of opiate withdrawal as demonstrated by the aversive stimulus effects or negative reinforcing effects (e.g. disrupted lever-pressing for food and place aversions) may involve those elements of the nucleus accumbens that are known to be important for the acute reinforcing effects of opiates in nondependent rats. Evidence exists at the cellular and molecular level for both 'within-system' and 'between-system' adaptations to dependence. Elucidation of the neural networks, cellular mechanisms and molecular elements involved in opiate withdrawal may provide not only a model for our understanding of the adaptive processes associated with drug dependence but also of those associated with other chronic insults to CNS function.

  10. Multicompartmental analysis of (/sup 11/C)-carfentanil binding to opiate receptors in humans measured by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Douglass, K.H.; Mayberg, H.S.; Dannals, R.F.; Links, J.M.; Wilson, A.A.; Ravert, H.T.; Crozier, W.C.; Wagner, H.N. Jr.

    1989-06-01

    (11C)-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of (11C)-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

  11. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  12. Suppression of alcohol intake by chronic naloxone treatment in P rats: tolerance development and elevation of opiate receptor binding.

    Science.gov (United States)

    Overstreet, D H; Kampov-Polevoy, A B; Rezvani, A H; Braun, C; Bartus, R T; Crews, F T

    1999-11-01

    This study was planned to determine the feasibility of using a slow release naloxone preparation to treat alcoholism, because compliance with medication is a significant problem in alcoholics. Experiments were performed in alcohol-preferring P rats maintained either on continuous access or on limited access (1 hr/day) to alcohol with water and food provided ad libitum. Naloxone (Nx) was administered either by twice daily subcutaneous injections or by slow release (1.1 mg/kg/hr) osmotic minipump. In limited access experiments, Nx was injected immediately before access to alcohol. An initial experiment estimated the dose-effect curve for Nx subcutaneous suppression on alcohol intake. Nx (2.5-20 mg/kg) had a stronger effect during the first 2 hr after injection (ED50 = 2.1 mg/kg); however, the effect was more modest on 24-hr consumption. Similar results were found with chronic Nx treatment. Low doses of Nx (0.5 and 2.0 mg/kg) injected immediately before limited access to alcohol produced almost complete suppression of alcohol intake for at least 14 consecutive days. However, 14 days of treatment with 26 mg/kg/day by minipump or injection produced an initial 50% suppression of 24-hr alcohol intake with the gradual development of tolerance. An acute challenge with Nx immediately after the pumps were scheduled to be empty provided additional evidence of tolerance development in chronically Nx-treated rats. Brain micro-opiate receptors, estimated autoradiographically by using the ligand [3H][D-Ala2,N-Me-Phe4, Gly-ol5][tyrosyl-3,5-3H]-enkephalin, showed that rats chronically exposed to Nx and showing tolerance to Nx suppression of drinking exhibited 17% to 250% increases in [3H][D-Ala2,N-Me-Phe4, Gly-ol5][tyrosyl-3,5-3H]-enkephalin binding. High doses of Nx are required to suppress continuous access alcohol consumption in P rats, and tolerance develops to the ethanol consumption-suppressing effect of Nx that may be related to increases in micro-opiate receptors.

  13. Opiate and opioid withdrawal

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000949.htm Opiate and opioid withdrawal To use the sharing features on this page, ... or withdrawing from opiates. Alternative Names Withdrawal from opioids; Dopesickness; Substance use - opiate withdrawal; Substance abuse - opiate withdrawal; Drug abuse - opiate withdrawal; ...

  14. 11C-labelling of ohmefentanyl: An agonist for μ-opiate receptor

    International Nuclear Information System (INIS)

    Crouzel, C.; Prenant, C.; Comar, D.

    1990-01-01

    Ohmefentanyl: cis-N-[1-(beta-hydroxy-beta-phenylethyl)-3-methyl-4-piperydyl]-N-phenylpropionamide, is a synthetic narcotic analgesic agent with an analgesic activity 28 times more potent than that of fentanyl and 6,300 times more than that of morphine. The authors have developed a method for labelling of this compound with carbon-11 for the purpose of visualizing 'in vivo' the μ receptors by PET

  15. Stimulation of accumbal GABAAreceptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.

    Science.gov (United States)

    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.

  16. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  17. Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence

    Science.gov (United States)

    Lutz, Pierre-Eric; Ayranci, Gulebru; Chu-Sin-Chung, Paul; Matifas, Audrey; Koebel, Pascale; Filliol, Dominique; Befort, Katia; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L

    2014-01-01

    Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. PMID:24874714

  18. Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sadzot, B.; Price, J.C.; Mayberg, H.S.; Douglass, K.H.; Dannals, R.F.; Lever, J.R.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr.; Feldman, M.A. (Johns Hopkins Medical Institutions, Baltimore, MD (USA))

    1991-03-01

    (11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

  19. T-cell receptor gamma delta bearing cells in normal human skin

    NARCIS (Netherlands)

    Bos, J. D.; Teunissen, M. B.; Cairo, I.; Krieg, S. R.; Kapsenberg, M. L.; Das, P. K.; Borst, J.

    1990-01-01

    T-cell antigen receptors (TCR) are divided into common alpha beta and less common gamma delta types. In the murine skin, TCR gamma delta+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR alpha beta+ and TCR gamma delta+

  20. Genomic organization of the human T-cell antigen-receptor alpha/delta locus

    NARCIS (Netherlands)

    Satyanarayana, K.; Hata, S.; Devlin, P.; Roncarolo, M. G.; de Vries, J. E.; Spits, H.; Strominger, J. L.; Krangel, M. S.

    1988-01-01

    Two clusters of overlapping cosmid clones comprising about 100 kilobases (kb) at the human T-cell antigen-receptor alpha/delta locus were isolated from a genomic library. The structure of the germ-line V delta 1 variable gene segment was determined. V delta 1 is located 8.5 kb downstream of the V

  1. Delta opioid receptor on equine sperm cells: subcellular localization and involvement in sperm motility analyzed by computer assisted sperm analyzer (CASA

    Directory of Open Access Journals (Sweden)

    Lacalandra Giovanni M

    2010-06-01

    Full Text Available Abstract Background Opioid receptors and endogenous opioid peptides act not only in the control of nociceptive pathways, indeed several reports demonstrate the effects of opiates on sperm cell motility and morphology suggesting the importance of these receptors in the modulation of reproduction in mammals. In this study we investigated the expression of delta opioid receptors on equine spermatozoa by western blot/indirect immunofluorescence and its relationship with sperm cell physiology. Methods We analyzed viability, motility, capacitation, acrosome reaction and mitochondrial activity in the presence of naltrindole and DPDPE by means of a computer assisted sperm analyzer and a fluorescent confocal microscope. The evaluation of viability, capacitation and acrosome reaction was carried out by the double CTC/Hoechst staining, whereas mitochondrial activity was assessed by means of MitoTracker Orange dye. Results We showed that in equine sperm cells, delta opioid receptor is expressed as a doublet of 65 and 50 kDa molecular mass and is localized in the mid piece of tail; we also demonstrated that naltrindole, a delta opioid receptor antagonist, could be utilized in modulating several physiological parameters of the equine spermatozoon in a dose-dependent way. We also found that low concentrations of the antagonist increase sperm motility whereas high concentrations show the opposite effect. Moreover low concentrations hamper capacitation, acrosome reaction and viability even if the percentage of cells with active mitochondria seems to be increased; the opposite effect is exerted at high concentrations. We have also observed that the delta opioid receptor agonist DPDPE is scarcely involved in affecting the same parameters at the employed concentrations. Conclusions The results described in this paper add new important details in the comprehension of the mammalian sperm physiology and suggest new insights for improving reproduction and for

  2. Proteoglycans act as cellular hepatitis delta virus attachment receptors.

    Directory of Open Access Journals (Sweden)

    Oscar Lamas Longarela

    Full Text Available The hepatitis delta virus (HDV is a small, defective RNA virus that requires the presence of the hepatitis B virus (HBV for its life cycle. Worldwide more than 15 million people are co-infected with HBV and HDV. Although much effort has been made, the early steps of the HBV/HDV entry process, including hepatocyte attachment and receptor interaction are still not fully understood. Numerous possible cellular HBV/HDV binding partners have been described over the last years; however, so far only heparan sulfate proteoglycans have been functionally confirmed as cell-associated HBV attachment factors. Recently, it has been suggested that ionotrophic purinergic receptors (P2XR participate as receptors in HBV/HDV entry. Using the HBV/HDV susceptible HepaRG cell line and primary human hepatocytes (PHH, we here demonstrate that HDV entry into hepatocytes depends on the interaction with the glycosaminoglycan (GAG side chains of cellular heparan sulfate proteoglycans. We furthermore provide evidence that P2XR are not involved in HBV/HDV entry and that effects observed with inhibitors for these receptors are a consequence of their negative charge. HDV infection was abrogated by soluble GAGs and other highly sulfated compounds. Enzymatic removal of defined carbohydrate structures from the cell surface using heparinase III or the obstruction of GAG synthesis by sodium chlorate inhibited HDV infection of HepaRG cells. Highly sulfated P2XR antagonists blocked HBV/HDV infection of HepaRG cells and PHH. In contrast, no effect on HBV/HDV infection was found when uncharged P2XR antagonists or agonists were applied. In summary, HDV infection, comparable to HBV infection, requires binding to the carbohydrate side chains of hepatocyte-associated heparan sulfate proteoglycans as attachment receptors, while P2XR are not actively involved.

  3. Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor

    Science.gov (United States)

    Rhyu, Mee-Ra; Lu, Jian; Webster, Donna E.; Fabricant, Daniel S.; Farnsworth, Norman R.; Wang, Z. Jim

    2008-01-01

    Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Since the opiate system in the brain is intimately associated with mood, temperature and sex hormonal levels, we investigated the activity of black cohosh extracts at the human μ opiate receptor (hMOR) expressed in Chinese hamster ovary cells. The 100% methanol-, 75% ethanol- and 40% 2-propanol- extracts of black cohosh effectively displaced the specific binding of [3H]DAMGO to hMOR. Further studies of the clinically used ethanol extract indicated that black cohosh acted as a mixed competitive ligand, displacing 77 ± 4% [3H]DAMGO to hMOR (Ki = 62.9 μg/ml). Using the [35S]GTPγS assay, the action of black cohosh was found to be consistent with an agonist, with an EC50 of 68.8 ± 7.7 μg/ml. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms. PMID:17177511

  4. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta

    DEFF Research Database (Denmark)

    Yan, Zhen Cheng; Liu, Dao Yan; Zhang, Li Li

    2007-01-01

    Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow...... or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p......Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow...

  5. Photoaffinity labeling of opiate (enkephalin) receptor of rat brain plasma membranes with 125I(D-Ala2, p-N3-Phe4-Met5)-enkephalin

    International Nuclear Information System (INIS)

    Yeung, C.W.T.

    1986-01-01

    A photoreactive (D-Ala 2 , p-N 3 -Phe 4 -Met 5 )enkephalin derivative was prepared, iodinated with carrier free 125 I and then purified by high performance liquid chromatography. The purified radioactive photoprobe was monoiodinated at the amino terminal tyrosine residue. This radioactive photoprobe was used to photoaffinity label plasma membranes prepared from rat brain, spinal cord and cerebellum. The photolabeled plasma membranes were analyzed by sodium dodecyl sulfate gel electrophoresis. A 46,000-daltons band was specifically photolabeled in the plasma membranes of brain and spinal cord but not in the plasma membranes from cerebellum. The photolabeling of this band was inhibited by peptides related to enkephalin by not but substance P or gastrin tetrapeptide. These data demonstrate that the labeled 46,000-daltons band is a protein of the opiate (enkephalin)receptor

  6. Effect of Opiate Receptors Blockade on Microbicidal Potential and Production of IL-1β, TNFα, and IL-10 by Peritoneal Macrophages under Stress Conditions.

    Science.gov (United States)

    Gein, S V; Sharavieva, I L

    2016-07-01

    Rotation stress activated spontaneous and zymosan-induced ROS production. In animals receiving naloxone against the background of rotation stress, ROS production did not increase. Immobilization stress did not change the intensity of spontaneous and zymosan-induced ROS production, but inhibited stimulated ROS production against the background of naloxone treatment. Rotation produced a naloxone-independent inhibitory effect on spontaneous and stimulated IL-1β and TNFα production by macrophages and naloxone-dependent stimulating effect on spontaneous IL-10 production. Rotation stress did not modulate stimulated IL-10 production. In case of immobilization stress, decreased IL-1β and TNFα production was observed in mice exposed to stress under conditions of opiate receptors blockade; IL-10 production was not affected by immobilization stress. Both types of stress significantly increased plasma corticosterone levels, while naloxone had no effect on corticosterone production.

  7. The glutamate receptor delta 2 in relation to cerebellar development and plasticity

    NARCIS (Netherlands)

    Gounko, Natalia V.; Gramsbergen, Albert; van der Want, Johannes J. L.

    2007-01-01

    Understanding what are the mechanisms that strengthen, stabilize and restrict synaptic innervation is a relevant topic in glutamate receptor delta 2 (GluR delta 2)-related research. It also involves targeting and selection of afferent input during formation of the neuronal circuitry in the

  8. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Oude Elferink, Ronald P. J.; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation of PPARdelta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary

  9. Radiosynthesis of an opiate receptor-binding radiotracer for positron emission tomography: [C-11 methyl]-methyl-4-[N-(1-oxopropyl)-N-phenylamino]-4-piperidine carboxylate (C-11 4-carbomethoxyfentanyl)

    International Nuclear Information System (INIS)

    Dannals, R.F.; Ravert, H.T.; Frost, J.J.; Wilson, A.A.; Burns, H.D.; Wagner, H.N. Jr.

    1984-01-01

    The development of high affinity, high specific activity tritium-labeled neurotransmitter receptor ligands has made it possible to determine the spatial distribution and relative regional concentration of several neuroreceptors by means of in vivo receptor labeling techniques in animals. This development made possible the biochemical identification of opiate receptors by autoradiographic visualization in experimental animals. The quantitation and localization of opiate receptors in man using non-invasive methods, such as positron emission tomography, could provide a means of obtaining information about a variety of receptor-linked neuropsychiatric diseases as well as normal brain mechanisms regulating pain and emotions. As part of a continuing program to identify and radiolabel high affinity, highly specific ligands for the opiate receptor, the authors have selected two derivatives of fentanyl, a well-known analgesic, as candidates for radiolabeling: R-31,833 (4-carbomethoxy-fentanyl) and R-34,995 (lofentanil). Carbon-11 labeled R-31,833 was synthesized by the methylation of the appropriate carboxylate with C-11 methyl iodide in dimethylformamide at room temperature and purified by high performance liquid chromatography. The average synthesis time from end-of-bombardment (E.O.B.) was 30 minutes. The average specific activity was determined by ultraviolet spectroscopy to be 890 mCi/μmole end-of-synthesis (approx. 2500 mCi/μmole E.O.B.)

  10. Radiosynthesis of an opiate receptor-binding radiotracer for positron emission tomography: (C-11 methyl)-methyl-4-(N-(1-oxopropyl)-N-phenylamino)-4-piperidine carboxylate (C-11 4-carbomethoxyfentanyl)

    Energy Technology Data Exchange (ETDEWEB)

    Dannals, R.F.; Ravert, H.T.; Frost, J.J.; Wilson, A.A.; Burns, H.D.; Wagner, H.N. Jr.

    1984-01-01

    The development of high affinity, high specific activity tritium-labeled neurotransmitter receptor ligands has made it possible to determine the spatial distribution and relative regional concentration of several neuroreceptors by means of in vivo receptor labeling techniques in animals. This development made possible the biochemical identification of opiate receptors by autoradiographic visualization in experimental animals. The quantitation and localization of opiate receptors in man using non-invasive methods, such as positron emission tomography, could provide a means of obtaining information about a variety of receptor-linked neuropsychiatric diseases as well as normal brain mechanisms regulating pain and emotions. As part of a continuing program to identify and radiolabel high affinity, highly specific ligands for the opiate receptor, the authors have selected two derivatives of fentanyl, a well-known analgesic, as candidates for radiolabeling: R-31,833 (4-carbomethoxy-fentanyl) and R-34,995 (lofentanil). Carbon-11 labeled R-31,833 was synthesized by the methylation of the appropriate carboxylate with C-11 methyl iodide in dimethylformamide at room temperature and purified by high performance liquid chromatography. The average synthesis time from end-of-bombardment (E.O.B.) was 30 minutes. The average specific activity was determined by ultraviolet spectroscopy to be 890 mCi/..mu..mole end-of-synthesis (approx. 2500 mCi/..mu..mole E.O.B.).

  11. Autoradiographic localization of mu and delta opioid receptors in the mesocorticolimbic dopamine system

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P. Jr.

    1989-01-01

    In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDA resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.

  12. Delta/Notch-Like EGF-Related Receptor (DNER Is Not a Notch Ligand.

    Directory of Open Access Journals (Sweden)

    Maxwell Greene

    Full Text Available Delta/Notch-like EGF-related receptor (DNER has been reported to act as a Notch ligand, despite lacking a Delta/Serrate/Lag (DSL binding domain common to all other known ligands. The established Notch ligand Delta-like 1 (DLL1, but not DNER, activated Notch1 in a luciferase assay, prevented the differentiation of myoblasts through Notch signaling, and bound Notch-fc in a cell-based assay. DNER is not a Notch ligand and its true function remains unknown.

  13. gamma delta T lymphocytes and their V gamma 9 and V delta 2 receptor expression in peripheral blood mononuclear cells of active tuberculosis patients before and after treatment.

    Science.gov (United States)

    Saruwatari, N

    2000-01-01

    It has been reported that gamma delta T cells are activated by bacterial infection, and the cells act in an antibacterial manner. We investigated the immunologic role of gamma delta T cells and their receptors in tuberculosis (TB) patients. We examined gamma delta T cells which express receptors composed of V gamma 9 or V delta 2 chains before and after anti-TB chemotherapy, in vitro changes in T cell receptor expression due to stimulation, and the relationship between the proliferative capability of gamma delta T cells and the clinical data before treatment (10 TB patients and 9 healthy volunteers). The ratio of V gamma 9-positive cells to gamma delta T cells decreased significantly in the 10 TB patients before treatment (p delta 9-positive cells had a significantly increased erythrocyte sedimentation rate (p gamma 9- and V delta 2-positive gamma delta T cells (p gamma 9-positive cells together with their growth index might help to further elucidate the disease process in patients with pulmonary TB.

  14. Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats

    Science.gov (United States)

    Henderson, Fraser; May, Walter J.; Gruber, Ryan B.; Discala, Joseph F.; Puscovic, Veljko; Young, Alex P.; Baby, Santhosh M.; Lewis, Stephen J.

    2015-01-01

    This study determined the effects of the peripherally restricted µ-opiate receptor (µ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25 µg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5 mg/kg of NLXmi but was attenuated by a 5.0 mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5 mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5 mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral µ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient. PMID:24284037

  15. Differential regulation of. mu. , delta, kappa opioid receptors by Mn/sup + +/

    Energy Technology Data Exchange (ETDEWEB)

    Szuecs, M.; Oetting, G.M.; Coscia, C.J.

    1986-03-05

    Differential effects of Mn/sup + +/ on three opioid receptor subtypes of rat brain membranes were evaluated. Concentration dependency studies performed with 0.05-20 mM Mn/sup + +/ revealed that only the delta receptors are stimulated at any concentration. The binding of 1 nM /sup 3/H-DAGO was not stimulated by low concentrations (< 1mM) of Mn/sup + +/, and was significantly inhibited at higher concentrations (40% at 20 mM). 1 nM /sup 3/H-EKC (+100nM DAGO and 100nM DADLE) binding was inhibited by Mn/sup + +/ in the entire concentration range. While regulation of ..mu.. receptor binding did not change during postnatal development, delta and kappa binding displayed a pronounced developmental time-dependency. Kappa sites were hardly affected by Mn/sup + +/ at day 5, and adult levels of inhibition were reached only after the third week postnatal. In contrast, 1 nM /sup 3/H-DADLE (+10nM DAGO) binding was most sensitive to Mn/sup + +/ on day 5 after birth (100% stimulation with 5-20 mM). The ED/sub 50/ of Mn/sup + +/ stimulation was unchanged during maturation. These immature delta sites displayed a similar extent of Mn/sup + +/ reversal of Gpp(NH)p inhibition as seen in microsomes, which represent a good model of N/sub i/-uncoupled receptors. These data suggest that ..mu.., delta and kappa receptors are differently coupled to N/sub i/. Moreover, a second divalent cation binding site, in addition to that on N/sub i/ might exist for delta receptors.

  16. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor

    DEFF Research Database (Denmark)

    Geisler, C; Pallesen, G; Platz, P

    1989-01-01

    . Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected...

  17. Ionotropic glutamate receptors (iGluRs) of the delta family (GluD1 ...

    African Journals Online (AJOL)

    ... such as Neurexin1. This review presents current knowledge regarding the expression, structure and function of Glu delta receptors (GluD1, GluD2) in brain, focusing on synapse formation, function and dysfunction. Keywords: iGluRs; GluD1; GluD2; Synaptogenesis; Autism spectrum disorder (ASD); Schizophrenia (SCZ) ...

  18. Ionotropic glutamate receptors (iGluRs) of the delta family (GluD1 ...

    African Journals Online (AJOL)

    Muhammad Zahid Khan

    2016-10-20

    Oct 20, 2016 ... pyramidal neurons.10,34,33 Original studies of delta subunits. mRNA distribution in the .... Figure 2. Signaling pathway of GluD1 receptor in the pyramidal neurons in medial prefrontal cortex (mPFC) and hippocampus. A ... year Plan ''Major Scientific and Technological Special Project for Significant New ...

  19. Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists.

    Science.gov (United States)

    Schaeffer, J I; Haddad, G G

    1985-09-01

    To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40-60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002-2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5-25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

  20. The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine

    DEFF Research Database (Denmark)

    Kristensen, K; Christensen, C B; Christrup, Lona Louring

    1995-01-01

    The binding affinities of racemic methadone and its optical isomers R-methadone and S-methadone were evaluated for the opioid receptors mu1, mu2, delta and kappa, in comparison with that of morphine. The analgesic R-methadone had a 10-fold higher affinity for mu1 receptors than S-methadone (IC50 3.......0 nM and 26.4 nM, respectively). At the mu2 receptor, the IC50 value of R-methadone was 6.9 nM and 88 nM for S-methadone, respectively. As expected, R-methadone had twice the affinity for mu1 and mu2 receptors than the racemate. All of the compounds tested had low affinity for the delta and kappa...... receptors. This result suggests that S-methadone does not essentially contribute to opioid effect of racemic methadone. R-methadone has a receptor binding profile which resembles that of morphine....

  1. Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task.

    Directory of Open Access Journals (Sweden)

    Mary C Olmstead

    Full Text Available Impulsivity is a primary feature of many psychiatric disorders, most notably attention deficit hyperactivity disorder and drug addiction. Impulsivity includes a number of processes such as the inability to delay gratification, the inability to withhold a motor response, or acting before all of the relevant information is available. These processes are mediated by neural systems that include dopamine, serotonin, norepinephrine, glutamate and cannabinoids. We examine, for the first time, the role of opioid systems in impulsivity by testing whether inactivation of the mu- (Oprm1 or delta- (Oprd1 opioid receptor gene alters motor impulsivity in mice. Wild-type and knockout mice were examined on either a pure C57BL6/J (BL6 or a hybrid 50% C57Bl/6J-50% 129Sv/pas (HYB background. Mice were trained to respond for sucrose in a signaled nose poke task that provides independent measures of associative learning (responses to the reward-paired cue and motor impulsivity (premature responses. Oprm1 knockout mice displayed a remarkable decrease in motor impulsivity. This was observed on the two genetic backgrounds and did not result from impaired associative learning, as responses to the cue signaling reward did not differ across genotypes. Furthermore, mutant mice were insensitive to the effects of ethanol, which increased disinhibition and decreased conditioned responding in wild-type mice. In sharp contrast, mice lacking the Oprd1 gene were more impulsive than controls. Again, mutant animals showed no deficit in associative learning. Ethanol completely disrupted performance in these animals. Together, our results suggest that mu-opioid receptors enhance, whereas delta-opioid receptors inhibit, motor impulsivity. This reveals an unanticipated contribution of endogenous opioid receptor activity to disinhibition. In a broader context, these data suggest that alterations in mu- or delta-opioid receptor function may contribute to impulse control disorders.

  2. Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography

    International Nuclear Information System (INIS)

    Tempel, A.; Zukin, R.S.

    1987-01-01

    Highly specific radioligands and quantitative autoradiography reveal strikingly different neuroanatomical patterns for the mu, delta, and kappa opioid receptors of rat brain. The mu receptors are most densely localized in patches in the striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus. In contrast, delta receptors are highly confined, exhibiting selective localization in layers I, II, and VIa of the neocortex, a diffuse pattern in the striatum, and moderate concentration in the pars reticulata of the substantia nigra and in the interpeduncular nucleus. delta receptors are absent in most other brain structures. This distribution is unexpected in that the enkephalins, the putative endogenous ligands of the delta receptor, occur essentially throughout the brain. The kappa receptors of rat brain exhibit a third pattern distinct from that of the mu and delta receptors. kappa receptors occur at low density in patches in the striatum and at particularly high density in the nucleus accumbens, along the pyramidal and molecular layers of the hippocampus, in the granular cell layer of the dentate gyrus, specific midline nuclei of the thalamus, and hindbrain regions. kappa receptors appear to be uniformly distributed across regions in the neocortex with the exception of layer III, which revealed only trace levels of binding. An important conclusion of the present study is that delta receptors occur at high density only in the forebrain and in two midbrain structures, whereas mu and kappa receptors exhibit discrete patterns in most major brain regions

  3. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  4. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  5. Discrete mapping of brain Mu and delta opioid receptors using selective peptides: Quantitative autoradiography, species differences and comparison with kappa receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sharif, N.A.; Hughes, J. (Addenbrookes Hospital Site, Cambridge (England))

    1989-05-01

    The opioid peptides, (3H)DAGO and (3H)DPDPE, bound to rat and guinea pig brain homogenates with a high, nanomolar affinity and to a high density of mu and delta receptors, respectively. (3H)DAGO binding to mu receptors was competitively inhibited by unlabelled opioids with the following rank order of potency: DAGO greater than morphine greater than DADLE greater than naloxone greater than etorphine much greater than U50488 much greater than DPDPE. In contrast, (3H)DPDPE binding to delta receptors was inhibited by compounds with the following rank order of potency: DPDPE greater than DADLE greater than etorphine greater than dynorphin(1-8) greater than naloxone much greater than U50488 much greater than DAGO. These profiles were consistent with specific labelling of the mu and delta opioid receptors, respectively. In vitro autoradiographic techniques coupled with computer-assisted image analyses revealed a discrete but differential anatomical localization of mu and delta receptors in the rat and guinea pig brain. In general, mu and delta receptor density in the rat exceeded that in the guinea pig brain and differed markedly from that of kappa receptors in these species. However, while mu receptors were distributed throughout the brain with hotspots in the fore-, mid- and hindbrain of the two rodents, the delta sites were relatively diffusely distributed, and were mainly concentrated in the forebrain with particularly high levels within the olfactory bulb (OB), n. accumbens and striatum. Notable regions of high density of mu receptors in the rat and guinea pig brain were the accessory olfactory bulb, striatal patches and streaks, amygdaloid nuclei, ventral hippocampal subiculum and dentate gyrus, numerous thalamic nuclei, geniculate bodies, central grey, superior and inferior colliculi, solitary and pontine nuclei and s. nigra.

  6. Drugs of abuse--opiates.

    OpenAIRE

    Ling, W; Wesson, D R

    1990-01-01

    Treating opiate-dependent patients can be difficult for many physicians because the patients' life-styles, values, and beliefs differ from those of the physicians. Primary care physicians, however, are often involved in the treatment of the medical complications of opiate abuse, and physicians must often manage a patient's opiate dependence until appropriate referral to a drug abuse treatment program can be arranged. Treatment is guided by an understanding of the patient's addictive disease, ...

  7. Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

    Science.gov (United States)

    Bhattacharyya, Sagnik; Egerton, Alice; Kim, Euitae; Rosso, Lula; Riano Barros, Daniela; Hammers, Alexander; Brammer, Michael; Turkheimer, Federico E; Howes, Oliver D; McGuire, Philip

    2017-11-03

    Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [ 11 C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.

  8. Gestational and ovarian sex steroid antinociception: synergy between spinal kappa and delta opioid systems.

    Science.gov (United States)

    Dawson-Basoa, M; Gintzler, A R

    1998-05-25

    Pain thresholds are elevated during gestation and following the simulation of pregnancy blood levels of estrogen and progesterone (hormone simulated pregnancy; HSP). The analgesia associated with both conditions is opioid-mediated and results from the activation of spinal cord kappa and delta (but not mu) opiate receptors. Blockade of spinal kappa or delta opiate receptors, individually, can abolish the antinociception associated with either gestational day 20 or day 19 of HSP. Surprisingly, during either physiological pregnancy or HSP, the magnitude of reduction in the increment in jump thresholds following the combined intrathecal application of suboptimum concentrations of kappa and delta antagonists is indistinguishable from that observed following their individual intrathecal application. These data indicate that gestational and ovarian sex steroid-induced antinociception is not simply the sum of the independent analgesic effects of spinal kappa and delta opioid systems but requires their coincident activation. It is suggested that the synergy that has been reported following the exogenous intrathecal application of kappa and delta opioids also occurs between their endogenous counterparts and underlies the intrinsic analgesia associated with each condition. Utilization of such a mechanism allows for significant physiological effects (analgesia) to be achieved with doses of relevant substrates (dynorphin and enkephalin) which alone would produce minimal receptor activation (and analgesia). This would minimize tolerance and dependence formation. Copyright 1998 Elsevier Science B.V. All rights reserved.

  9. Gold Nanorods Targeted to Delta Opioid Receptor: Plasmon-Resonant Contrast and Photothermal Agents

    Directory of Open Access Journals (Sweden)

    Kvar C. Black

    2008-01-01

    Full Text Available Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (δOR and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for δOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.

  10. Gamma delta T cell receptor analysis supports a role for HSP 70 selection of lymphocytes in multiple sclerosis lesions.

    OpenAIRE

    Battistini, L.; Salvetti, M.; Ristori, G.; Falcone, M.; Raine, C. S.; Brosnan, C. F.

    1995-01-01

    BACKGROUND: Interactions between gamma delta T cells and heat shock proteins (HSP) have been proposed as contributing factors in a number of diseases of possible autoimmune etiology but definitive evidence to support this hypothesis has been lacking. In multiple sclerosis (MS), a chronic inflammatory neurologic disease, HSP and gamma delta T cells are known to colocalize in brain lesions. Analysis of T cell receptor (TCR) gene usage in these lesions has detected evidence of clonality within b...

  11. Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis.

    Science.gov (United States)

    Schmitt, Sarah E; Pargeon, Kimberly; Frechette, Eric S; Hirsch, Lawrence J; Dalmau, Josep; Friedman, Daniel

    2012-09-11

    To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1-123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2-200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named "extreme delta brush" because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

  12. Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on delta-opioid receptor stimulation.

    Science.gov (United States)

    Panneerselvam, Mathivadhani; Tsutsumi, Yasuo M; Bonds, Jacqueline A; Horikawa, Yousuke T; Saldana, Michelle; Dalton, Nancy D; Head, Brian P; Patel, Piyush M; Roth, David M; Patel, Hemal H

    2010-11-01

    Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (δ-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, κ-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and IκBα, while simultaneously decreasing the expression of c-Jun NH(2)-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the δ-opioid receptor to

  13. Glutamate mechanisms underlying opiate memories

    NARCIS (Netherlands)

    Peters, J.; de Vries, T.J.

    2012-01-01

    As the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction

  14. Haplotypes of the porcine peroxisome proliferator-activated receptor delta gene are associated with backfat thickness

    Directory of Open Access Journals (Sweden)

    Blöcker Helmut

    2009-11-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor delta belongs to the nuclear receptor superfamily of ligand-inducible transcription factors. It is a key regulator of lipid metabolism. The peroxisome proliferator-activated receptor delta gene (PPARD has been assigned to a region on porcine chromosome 7, which harbours a quantitative trait locus for backfat. Thus, PPARD is considered a functional and positional candidate gene for backfat thickness. The purpose of this study was to test this candidate gene hypothesis in a cross of breeds that were highly divergent in lipid deposition characteristics. Results Screening for genetic variation in porcine PPARD revealed only silent mutations. Nevertheless, significant associations between PPARD haplotypes and backfat thickness were observed in the F2 generation of the Mangalitsa × Piétrain cross as well as a commercial German Landrace population. Haplotype 5 is associated with increased backfat in F2 Mangalitsa × Piétrain pigs, whereas haplotype 4 is associated with lower backfat thickness in the German Landrace population. Haplotype 4 and 5 carry the same alleles at all but one SNP. Interestingly, the opposite effects of PPARD haplotypes 4 and 5 on backfat thickness are reflected by opposite effects of these two haplotypes on PPAR-δ mRNA levels. Haplotype 4 significantly increases PPAR-δ mRNA levels, whereas haplotype 5 decreases mRNA levels of PPAR-δ. Conclusion This study provides evidence for an association between PPARD and backfat thickness. The association is substantiated by mRNA quantification. Further studies are required to clarify, whether the observed associations are caused by PPARD or are the result of linkage disequilibrium with a causal variant in a neighbouring gene.

  15. Delta-9-tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation.

    Science.gov (United States)

    Wong, H; Hossain, S; Cairns, B E

    2017-11-01

    This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders. Immunohistochemistry was used to explore the peripheral expression of cannabinoid receptors in the masseter muscle while behavioural and electrophysiology experiments were employed to assess the functional effects of intramuscular injection of THC. It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings. Their expression was greater in TRPV1-positive ganglion neurons. Three days after intramuscular injection of NGF, ganglion neuron expression of CB1 and CB2, but not TPRV1, was decreased. In behavioural experiments, intramuscular injection (10 μL) of THC (1 mg/mL) attenuated NGF-induced mechanical sensitization. No change in mechanical threshold was observed in the contralateral masseter muscles and no impairment of motor function was found after intramuscular injections of THC. In anaesthetized rats, the same concentration of THC increased the mechanical thresholds of masseter muscle mechanoreceptors. Co-administration of the CB1 antagonist AM251 blocked the effect of THC on masseter muscle mechanoreceptors while the CB2 antagonist AM630 had no effect. These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF-induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects. Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a

  16. Immunohistochemical observations of methionine-enkephalin and delta opioid receptor in the digestive system of Octopus ocellatus.

    Science.gov (United States)

    Sha, Ailong; Sun, Hushan; Wang, Yiyan

    2013-02-01

    The study was designed to determine whether methionine-enkephalin (met-Enk) or delta opioid receptor was present in the digestive system of Octopus ocellatus. The results showed that they were both in the bulbus oris, esophagus, crop, stomach, gastric cecum, intestine, posterior salivary glands of O. ocellatus, one of them, met-Enk in the rectum, anterior salivary glands, digestive gland. And the distributions were extensive in the digestive system. Strong or general met-Enk immunoreactivity was observed in the inner epithelial cells of the bulbus oris, esophagus, stomach, gastric cecum, intestine, anterior salivary glands and the adventitia of the intestine and rectum, and so was the delta opioid receptor immunoreactivity in the inner epithelial cells of the bulbus oris, esophagus, and crop, however, they were weak in other parts. Combining with delta opioid receptor, met-Enk may be involved in the regulations of food intake, absorption, movement of gastrointestinal smooth muscle and secretion of digestive gland. The different densities of met-Enk and delta opioid receptor may be related to the different functions in the digestive system of O. ocellatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  18. Synthesis and in vivo brain distribution of carbon-11-labeled {delta}-opioid receptor agonists

    Energy Technology Data Exchange (ETDEWEB)

    Pichika, Rama, E-mail: rpichika@ucsd.ed [Department of Radiology, University of California, San Diego, CA (United States); Jewett, Douglas M.; Sherman, Philip S. [Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Traynor, John R. [Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Husbands, Stephen M. [Department of Pharmacy and Pharmacology, University of Bath, Bath (United Kingdom); Woods, James H. [Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Kilbourn, Michael R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States)

    2010-11-15

    Three new radiolabeled compounds, [{sup 11}C]SNC80 ((+)-4-[({alpha}R)-{alpha}-{l_brace}(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl{r_brace}-3-[{sup 11}C] methoxybenzyl-N,N-diethylbenzamide), N,N-diethyl-4-[3-methoxyphenyl-1-[{sup 11}C]methylpiperidin-4-ylidenemethyl) benzamide and N,N-diethyl-4-[(1-[{sup 11}C]methylpiperidin-4-ylidene)phenylmethyl]benzamide, were prepared as potential in vivo radiotracers for the {delta}-opioid receptor. Each compound was synthesized by alkylation of the appropriate desmethyl compounds using [{sup 11}C]methyl triflate. In vivo biodistribution studies in mice showed very low initial brain uptake of all three compounds and no regional specific binding for [{sup 11}C]SNC80. A monkey positron emission tomography study of [{sup 11}C]SNC80 confirmed low brain permeability and uniform regional distribution of this class of opioid agonists in a higher species. Opioid receptor ligands of this structural class are thus unlikely to succeed as in vivo radiotracers, likely due to efficient exclusion from the brain by the P-glycoprotein efflux transporter.

  19. Prenatal development of the porcine TCR Delta repertoire: dominant expression of an invariant T cell receptor V Delta 3-J Delta 3 chain

    Czech Academy of Sciences Publication Activity Database

    Holtmeler, W.; Geisel, W.; Bernert, K.; Butler, J. E.; Šinkora, Marek; Řeháková, Zuzana; Caspary, W. F.

    2004-01-01

    Roč. 34, - (2004), s. 1941-1949 ISSN 0014-2980 R&D Projects: GA ČR GA524/01/0919; GA AV ČR IAA5020303 Grant - others:DFG(DE) HO1521; GA NSF-MCB(XX) 77237 Keywords : gamma delta t cell * junctional diversity * ontogeny Subject RIV: EE - Microbiology, Virology Impact factor: 5.005, year: 2004

  20. The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert; Jensen, Morten Østergaard; Bohr, Henrik

    2003-01-01

    The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analys...

  1. Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors.

    Directory of Open Access Journals (Sweden)

    Roopali Yadav

    Full Text Available The delta family of ionotropic glutamate receptors consists of glutamate δ1 (GluD1 and glutamate δ2 (GluD2 receptors. While the role of GluD2 in the regulation of cerebellar physiology is well understood, the function of GluD1 in the central nervous system remains elusive. We demonstrate for the first time that deletion of GluD1 leads to abnormal emotional and social behaviors. We found that GluD1 knockout mice (GluD1 KO were hyperactive, manifested lower anxiety-like behavior, depression-like behavior in a forced swim test and robust aggression in the resident-intruder test. Chronic lithium rescued the depression-like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social interaction. In the sociability test, GluD1 KO mice spent more time interacting with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS administration was able to rescue social interaction deficits observed in GluD1 KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1 and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of GluD1 leads to aberrant circuitry in prefrontal cortex and amygdala owing to its potential role in presynaptic differentiation and synapse formation. Furthermore, these findings are in agreement with the human genetic studies suggesting a strong association of GRID1 gene with several neuropsychiatric disorders including schizophrenia, bipolar disorder, autism spectrum disorders and major depressive disorder.

  2. The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue.

    Science.gov (United States)

    Sobanski, Piotr; Krajnik, Malgorzata; Shaqura, Mohammed; Bloch-Boguslawska, Elzbieta; Schäfer, Michael; Mousa, Shaaban A

    2014-11-01

    Functional evidence suggests that the stimulation of peripheral and central opioid receptors (ORs) is able to modulate heart function. Moreover, selective stimulation of either cardiac or central ORs evokes preconditioning and, therefore, protects the heart against ischemic injury. However, anatomic evidence for OR subtypes in the human heart is scarce. Human heart tissue obtained during autopsy after sudden death was examined immunohistochemically for mu- (MOR), kappa- (KOR), and delta- (DOR) OR subtypes. MOR and DOR immunoreactivity was found mainly in myocardial cells, as well as on sparse individual nerve fibers. KOR immunoreactivity was identified predominantly in myocardial cells and on intrinsic cardiac adrenergic (ICA) cell-like structures. Double immunofluorescence confocal microscopy revealed that DOR colocalized with the neuronal marker PGP9.5, as well as with the sensory neuron marker calcitonin gene-related peptide (CGRP). CGRP-immunoreactive (IR) fibers were detected either in nerve bundles or as sparse individual fibers containing varicose-like structures. Our findings offer the first hint of an anatomic basis for the existence of OR subtypes in the human heart by demonstrating their presence in CGRP-IR sensory nerve fibers, small cells with an eccentric nucleus resembling ICA cells, and myocardial cells. Taken together, this suggests the role of opioids in both the neural transmission and regulation of myocardial cell function.

  3. Effect of Delta-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans

    NARCIS (Netherlands)

    Beaumont, H.; Jensen, J.; Carlsson, A.; Ruth, M.; Lehmann, A.; Boeckxstaens, G. E.

    2009-01-01

    Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB(1)/CB(2) receptor agonist Delta(9)-tetrahydrocannabinol

  4. Variation in the peroxisome proliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people

    DEFF Research Database (Denmark)

    Grarup, N; Albrechtsen, A; Ek, J

    2007-01-01

    Studies in animals reveal that peroxisome proliferator-activated receptor delta (PPARdelta) regulates glucose metabolism and insulin sensitivity in both the liver and skeletal muscles. Moreover, PPARdelta augments physical endurance and increases oxidative metabolism, thereby averting obesity. Thus...

  5. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    LENUS (Irish Health Repository)

    Fanning, Rebecca A

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  6. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    International Nuclear Information System (INIS)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr.

    1989-01-01

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects

  7. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr. (National Center for Toxicological Research, Jefferson, Arkansas (USA))

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the (35S)TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of (35S)TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects.

  8. The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5 through the CB2 Receptor

    Science.gov (United States)

    Raborn, Erinn S.; Marciano-Cabral, Francine; Buckley, Nancy E.; Martin, Billy R.; Cabral, Guy A.

    2009-01-01

    The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2 receptor-specific antagonist SR144528 but not by the CB1 receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2 knockout mice. Collectively, these results suggest that cannabinoids act through the CB2 receptor to trans-deactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB2 receptor may be a constituent element of a network of G protein-coupled receptor signal transductional systems, inclusive of chemokine receptors, that act coordinately to modulate macrophage migration. PMID:18247131

  9. Separation of cannabinoid receptor affinity and efficacy in delta-8-tetrahydrocannabinol side-chain analogues

    Science.gov (United States)

    Griffin, Graeme; Williams, Stephanie; Aung, Mie Mie; Razdan, Raj K; Martin, Billy R; Abood, Mary E

    2001-01-01

    The activities of a number of side-chain analogues of delta-8-tetrahydrocannabinol (Δ8-THC) in rat cerebellar membrane preparations were tested.The affinities of each compound for the CB1 receptor were compared by their respective abilities to displace [3H]-SR141716A and their efficacies compared by stimulation of [35S]-GTPγS binding.It was found that the affinities varied from 0.19±0.03 nM for 3-norpentyl-3-[6′-cyano,1′,1′-dimethyl]hexyl-Δ8-THC to 395±66.3 nM for 5′-[N-(4-chlorophenyl)]-1′,1′-dimethyl-carboxamido-Δ8-THC.The efficacies of these compounds varied greatly, ranging from the very low efficacy exhibited to acetylenic compounds such as 1′-heptyn-Δ8-THC and 4′-octyn-Δ8-THC to higher efficacy compounds such as 5′-(4-cyanophenoxy)-1′,1′-dimethyl-Δ8-THC and 5′-[N-(4-aminosulphonylphenyl)]-1′,1′ dimethyl-carboxamido Δ8-THC. All agonist activities were antagonized by the CB1-selective antagonist SR141716A.It was found that a ligand's CB1 affinity and efficacy are differentially altered by modifications in the side-chain. Decreasing the flexibility of the side-chain reduced efficacy but largely did not alter affinity. Additionally, the positioning of electrostatic moieties, such as cyano groups, within the side-chain also has contrasting effects on these two properties.In summary, this report details the characterization of a number of novel Δ8-THC analogues in rat cerebellar membranes. It provides the first detailed pharmacological analysis of how the inclusion of electrostatic moieties in the side-chain and also how alteration of the side-chain's flexibility may differentially affect a CB1 cannabinoid receptor ligand's affinity and efficacy. PMID:11159703

  10. Early and persistent ‘extreme delta brush’ in a patient with anti-NMDA receptor encephalitis

    Directory of Open Access Journals (Sweden)

    Stephen VanHaerents

    2014-01-01

    Full Text Available Since its original description in 2007, anti-N-methyl-d-aspartate receptor (anti-NMDAR encephalitis associated with an ovarian teratoma is an increasingly recognized etiology of previously unexplained encephalopathy and encephalitis. Extreme delta brush (EDB is a novel electroencephalogram (EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness, although the specificity of this pattern is unclear. Additionally, the frequency and sensitivity of EDB in anti-NMDAR encephalitis and its implications for outcome have yet to be determined. We report a patient with early evidence of extreme delta brush and persistence of this pattern 17.5 weeks later with little clinical improvement.

  11. Role of delta-opioid receptors in mediating the aversive stimulus effects of morphine withdrawal in the rat.

    Science.gov (United States)

    Funada, M; Schutz, C G; Shippenberg, T S

    1996-04-04

    An unbiased place preference conditioning procedure was used to examine the role of delta-opioid receptors in mediating the aversive effects of opioid withdrawal. Rats were implanted s.c. with two pellets each containing placebo or 75 mg morphine. Single-trial conditioning sessions with saline and the opioid receptor antagonists naloxone (0.001-1.0 mg/kg, s.c.), naltrindole (0.01-3.0 mg/kg, s.c.) or naltriben (0.01-3.0 mg/kg, s.c.) commenced 4 days later. During these conditioning sessions, physical signs of withdrawal were also quantified. Tests of conditioning were conducted on day 5. Naloxone in doses of 0.01-1.0 mg/kg produced significant conditioned place aversions in morphine-implanted animals. A dose of 0.01 mg/kg produced few physical withdrawal signs whereas higher doses resulted in marked wet dog shakes, body weight loss ptosis and diarrhea. No such effects were observed in control (placebo-implanted) animals. Administration of the selective delta-opioid receptor antagonists naltrindole and naltriben produced dose-related place aversions in morphine-implanted animals. The magnitude of these effects did not differ from that observed with naloxone. The minimum effective doses of naltrindole and naltriben were 0.1 mg/kg. Doses of 0.1-1.0 mg/kg produced few, if any, somatic signs of withdrawal whereas higher doses of these antagonists only produced diarrhea and wet-dog shakes. Other withdrawal signs were absent. In contrast to the opioid receptor antagonists tested, the dopamine D1 receptor antagonist SCH23390 failed to produced conditioned place aversions or physical signs of withdrawal in morphine-pelleted animals. These data demonstrate that the selective blockade of either delta- or mu-opioid receptors is sufficient to induce conditioned aversive effects in morphine-dependent animals. They also indicate that physical symptoms associated with precipitated morphine withdrawal differ depending upon the opioid receptor antagonist employed.

  12. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

    NARCIS (Netherlands)

    Ratziu, V.; Harrison, S.A.; Francque, S.; Bedossa, P.; Lehert, P.; Serfaty, L.; Romero-Gomez, M.; Boursier, J.; Abdelmalek, M.; Caldwell, S.; Drenth, J.P.; Anstee, Q.M.; Hum, D.; Hanf, R.; Roudot, A.; Megnien, S.; Staels, B.; Sanyal, A.

    2016-01-01

    BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-delta. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy

  13. Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization

    DEFF Research Database (Denmark)

    Xiang, B; Yu, G H; Guo, J

    2001-01-01

    The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR......) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wild-type DOR, whereas S344G substitution blocked PMA-induced receptor......, and ionomycin resulted in DOR internalization that required phosphorylation of Ser-344. Expression of dominant negative beta-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta-arrestin- and clathrin-dependent mechanism...

  14. Identification of alpha beta and gamma delta T cell receptor-positive cells

    DEFF Research Database (Denmark)

    Geisler, C; Larsen, J K; Plesner, T

    1988-01-01

    distribution and function of these different T cells. In immunofluorescence studies gamma delta TCR+ cells have been identified as CD3+WT-31- or CD3+CD4-CD8- cells. However, this may not be the optimal procedure because gamma delta TCR+ cells are weakly WT-31+, and some are CD8+. The aim of this study...... was to evaluate a panel of monoclonal antibodies (MoAb) directed against different chains of the TCR-T3 complex for a more precise identification of alpha beta+ and gamma delta TCR+ cells in flow cytometric studies. We found that the MoAb anti-Ti-gamma A and delta-TCS-1, recognizing the TCR-gamma and the TCR...

  15. Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors.

    Science.gov (United States)

    Ahonen, Tiina J; Rinne, Maiju; Grutschreiber, Peter; Mätlik, Kert; Airavaara, Mikko; Schaarschmidt, Dieter; Lang, Heinrich; Reiss, David; Xhaard, Henri; Gaveriaux-Ruff, Claire; Yli-Kauhaluoma, Jari; Moreira, Vânia M

    2018-03-26

    Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report that potassium permanganate supported on iron(II) sulfate heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous conversion of Δ 7,8 -opioids to the corresponding 7β-hydroxy-8-ketones. Details of the reaction mechanism are given and the effects of the substituent at position 6 of several opioids on the reaction outcome is discussed. The opioid hydroxy ketones prepared are antagonists at the mu- and delta-opioid receptors. Docking simulations and detailed structure-activity analysis revealed that the presence of the 7β-hydroxy-8-ketone functionality in the prepared compounds can be used to gain activity towards the delta opioid receptor. The 7β-hydroxy-8-ketones prepared with this method can also be regarded as versatile intermediates for the synthesis of other opioids of interest. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production.

    Science.gov (United States)

    Shmist, Yelena A; Goncharov, Igor; Eichler, Maor; Shneyvays, Vladimir; Isaac, Ahuva; Vogel, Zvi; Shainberg, Asher

    2006-02-01

    Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1 - 10 microM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of alpha-sarcomeric actin. The antagonist for the CB2 (10 microM), but not CB1 receptor antagonist (10 microM) abolished the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.

  17. Opioid receptors in human neuroblastoma SH-SY5Y cells: evidence for distinct morphine (. mu. ) and enkephalin (delta) binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Kazmi, S.M.I.; Mishra, R.K.

    1986-06-13

    Human neuroblastoma SH-SY5Y cells exhibited a heterogeneous population of ..mu.. and delta types of opioid binding sites. These specific binding sites displayed the characteristic saturability, stereospecificity and reversibility, expected of a receptor. Scatchard analysis of (/sup 3/H)-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin (DADLE) in the presence of 10/sup -5/M D-Pro/sup 4/-morphiceptin (to block the ..mu.. receptors) and the competitive displacement by various highly selective ligands yielded the binding parameters of delta sites which closely resemble those of the delta receptors in brain and mouse neuroblastoma clones. Similarly, the high affinity binding of (/sup 3/H)-dihydromorphine, together with the higher potency of morphine analogues to displace (/sup 3/H)-naloxone binding established the presence of ..mu.. sites. Guanine nucleotides and NaCl significantly inhibited the association and increased the dissociation of (/sup 3/H)-DADLE binding.

  18. Genomic organization of the mouse peroxisome proliferator-activated receptor beta/delta gene

    DEFF Research Database (Denmark)

    Larsen, Leif K; Amri, Ez-Zoubir; Mandrup, Susanne

    2002-01-01

    containing eight upstream AUG codons. We show that the presence of the 548 nt leader resulted in a low translational efficiency of the corresponding PPARbeta/delta mRNA and propose, based on structural features of the 5'-untranslated region, that translational initiation may be mediated via an internal...

  19. delta-Opioid-induced pharmacologic myocardial hibernation during cardiopulmonary resuscitation.

    Science.gov (United States)

    Fang, Xiangshao; Tang, Wanchun; Sun, Shijie; Weil, Max Harry

    2006-12-01

    Cardiac arrest and cardiopulmonary resuscitation is an event of global myocardial ischemia and reperfusion, which is associated with severe postresuscitation myocardial dysfunction and fatal outcome. Evidence has demonstrated that mammalian hibernation is triggered by cyclic variation of a delta-opiate-like compound in endogenous serum, during which the myocardial metabolism is dramatically reduced and the myocardium tolerates the stress of ischemia and reperfusion without overt ischemic and reperfusion injury. Previous investigations also proved that the delta-opioid agonist elicited the cardioprotection in a model of regional ischemic intact heart or myocyte. Accordingly, we were prompted to search for an alternative intervention of pharmacologically induced myocardial hibernation that would result in rapid reductions of myocardial metabolism and therefore minimize the myocardial ischemic and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation. Prospective, controlled laboratory study. University-affiliated research laboratory. In the series of studies performed in the established rat and pig model of cardiac arrest and cardiopulmonary resuscitation, the delta-opioid receptor agonist, pentazocine, was administered during ventricular fibrillation. : The myocardial metabolism reflected by the concentration of lactate, or myocardial tissue PCO2 and PO2, is dramatically reduced during cardiac arrest and cardiopulmonary resuscitation. These are associated with less severe postresuscitation myocardial dysfunction and longer duration of postresuscitation survival. delta-Opioid-induced pharmacologic myocardial hibernation is an option to minimize the myocardial ischemia and reperfusion injury during cardiac arrest and cardiopulmonary resuscitation.

  20. Frequencies of 32 base pair deletion of the (Delta 32) allele of the CCR5 HIV-1 co-receptor gene in Caucasians: a comparative analysis.

    Science.gov (United States)

    Lucotte, Gérard

    2002-05-01

    The CCR5 gene encodes for the co-receptor for the major macrophage-tropics strains of human immunodeficiency virus (HIV-1), and a mutant allele of this gene (Delta 32) provide to homozygotes a strong resistance against infection by HIV. The frequency of the Delta 32 allele was investigated in 40 populations of 8842 non-infected subjects coming from Europe, the Middle-East and North Africa. A clear north-south decreasing gradient was evident for Delta 32 frequencies, with a significant correlation coefficient (r=0.83). The main frequency value of Delta 32 for Sweden, Norway, Denmark, Finland and Iceland (0.134) is significantly (chi(2)=63.818, PVikings might have been instrumental in disseminating the Delta 32 allele during the eighth to the tenth centuries during historical times. Possibly variola virus has discriminated the Delta 32 carriers in Europe since the eighth century AD, explaining the high frequency of the Delta 32 allele in Europe today.

  1. Plasma membrane cholesterol level and agonist-induced internalization of delta-opioid receptors; colocalization study with intracellular membrane markers of Rab family\

    Czech Academy of Sciences Publication Activity Database

    Brejchová, Jana; Vošahlíková, Miroslava; Roubalová, Lenka; Parenti, M.; Mauri, M.; Chernyavskiy, Oleksandr; Svoboda, Petr

    2016-01-01

    Roč. 48, č. 4 (2016), s. 375-396 ISSN 0145-479X R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional support: RVO:67985823 Keywords : cholesterol * plasma membrane * delta-opioid receptor * internalization * Rab proteins Subject RIV: CE - Biochemistry Impact factor: 2.576, year: 2016

  2. High Efficacy but Low Potency of delta-Opioid Receptor-G Protein Coupling in Brij-58-Treated, Low-Density Plasma Membrane Fragments

    Czech Academy of Sciences Publication Activity Database

    Roubalová, Lenka; Vošahlíková, Miroslava; Brejchová, Jana; Sýkora, Jan; Rudajev, Vladimír; Svoboda, Petr

    2015-01-01

    Roč. 10, č. 8 (2015), e0135664 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : delta - opioid receptor * G protein coupling * detergent * efficacy * potency Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 3.057, year: 2015

  3. Positive modulation of delta-subunit containing GABAA receptors in mouse neurons

    DEFF Research Database (Denmark)

    Vardya, Irina; Hoestgaard-Jensen, Kirsten; Nieto-Gonzalez, Jose Luis

    2012-01-01

    (A) receptors in mouse neurons in vitro and in vivo. Whole-cell patch-clamp recordings were carried out in the dentate gyrus in mouse brain slices. In granule cells, AA29504 (1 μM) caused a 4.2-fold potentiation of a tonic current induced by THIP (1 μM), while interneurons showed a potentiation of 2.6-fold......, and possibly recruits perisynaptic δ-containing receptors to participate in synaptic phasic inhibition in dentate gyrus....

  4. Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

    Science.gov (United States)

    Darmani, N A

    2001-01-01

    We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

  5. {delta}-Opioid receptor-stimulated Akt signaling in neuroblastoma x glioma (NG108-15) hybrid cells involves receptor tyrosine kinase-mediated PI3K activation

    Energy Technology Data Exchange (ETDEWEB)

    Heiss, Anika; Ammer, Hermann [Institute of Pharmacology, Toxicology and Pharmacy Ludwig-Maximilians-University of Munich Koeniginstrasse 16 80539 Muenchen Federal Republic of Germany (Germany); Eisinger, Daniela A., E-mail: eisinger@pharmtox.vetmed.uni-muenchen.de [Institute of Pharmacology, Toxicology and Pharmacy Ludwig-Maximilians-University of Munich Koeniginstrasse 16 80539 Muenchen Federal Republic of Germany (Germany)

    2009-07-15

    {delta}-Opioid receptor (DOR) agonists possess cytoprotective properties, an effect associated with activation of the 'pro-survival' kinase Akt. Here we delineate the signal transduction pathway by which opioids induce Akt activation in neuroblastoma x glioma (NG108-15) hybrid cells. Exposure of the cells to both [D-Pen{sup 2,5}]enkephalin and etorphine resulted in a time- and dose-dependent increase in Akt activity, as measured by means of an activation-specific antibody recognizing phosphoserine-473. DOR-mediated Akt signaling is blocked by the opioid antagonist naloxone and involves inhibitory G{sub i/o} proteins, because pre-treatment with pertussis toxin, but not over-expression of the G{sub q/11} scavengers EBP50 and GRK2-K220R, prevented this effect. Further studies with Wortmannin and LY294002 revealed that phophoinositol-3-kinase (PI3K) plays a central role in opioid-induced Akt activation. Opioids stimulate Akt activity through transactivation of receptor tyrosine kinases (RTK), because pre-treatment of the cells with inhibitors for neurotrophin receptor tyrosine kinases (AG879) and the insulin-like growth factor receptor IGF-1 (AG1024), but not over-expression of the G{beta}{gamma} scavenger phosducin, abolished this effect. Activated Akt translocates to the nuclear membrane, where it promotes GSK3 phosphorylation and prevents caspase-3 cleavage, two key events mediating inhibition of cell apoptosis and enhancement of cell survival. Taken together, these results demonstrate that in NG108-15 hybrid cells DOR agonists possess cytoprotective properties mediated by activation of the RTK/PI3K/Akt signaling pathway.

  6. First report of a healthy Indian heterozygous for delta 32 mutant of HIV-1 co-receptor-CCR5 gene.

    Science.gov (United States)

    Husain, S; Goila, R; Shahi, S; Banerjea, A

    1998-01-30

    The beta-chemokine receptor, CCR5, is a major co-receptor for macrophage tropic non-syncytia-inducing isolates of HIV-1. Recently a 32 bp homozygous deletion in the coding region of CCR5 has been reported in a very small percentage (heritage with varying frequencies (13-20%). However, when a large number of the non-Caucasian population (261 Africans and 423 Asians) were screened for the presence of this deleted allele, not a single case of either homozygous or heterozygous mutant for delta 32 allele of CCR5 was detected. We screened 100 normal individuals and found a single heterozygous case with an identical 32 bp deletion in CCR5 gene reported earlier, the rest possessed wild-type alleles. This deleted gene was inherited in Mendelian fashion among the family members of this individual. Thus, the frequency of this deleted allele in India among unrelated normal individuals is likely to be very low (< 1%). We observed a moderate transdominant effect of this mutant allele in a fusion assay. Finally, we show a significant inhibition of fusion of cell membranes when the 176-bp region of CCR5 was used as an antisense.

  7. Molecular Characterization and Expression Analysis of the Peroxisome Proliferator Activated Receptor Delta ( Gene before and after Exercise in Horse

    Directory of Open Access Journals (Sweden)

    Hyun-Woo Cho

    2015-05-01

    Full Text Available While athletic abilities such as speed, endurance and recovery are important in the horse, genes related to these abilities have not been extensively investigated. Here, we characterized the horse peroxisome proliferator-activated receptor delta (PPARδ gene and analyzed the expression of PPARδ during exercise. PPARδ is a known regulator of β-oxidation, muscle fiber transformation, and running endurance. Through evolutionary analysis using the synonymous and non-synonymous mutation ratio, it was revealed that positive selection occurred in the horse PPARδ gene. Two important domains related to nuclear hormone receptors, C4 zinc finger and ligand binding domain, were also found to be conserved well in horse PPARδ. Horse PPARδ was expressed ubiquitously in many tissues, but the expression level was various depending on the tissues. In the skeletal muscle, PPARδ increased about 2.5 folds after 30 min of exercise. Unlike in muscle, the increase of PPARδ expression was observed at 60 min but not 30 min of exercise in leukocytes. This finding might be useful for testing the endurance of horse using blood samples. Conclusively, the horse PPARδ gene is evolutionarily conserved well and can be used as a biomarker of endurance in horse.

  8. EEG with extreme delta brush in young female with methotrexate neurotoxicity supports NMDA receptor involvement

    DEFF Research Database (Denmark)

    Schmidt, Lisbeth Samsø; Kjær, Troels W; Schmiegelow, Kjeld

    2017-01-01

    Sub-acute neurotoxicity is a well-known complication to high-dose and intrathecal methotrexate (MTX) treatment of children with leukemia. Symptoms can be treated safely by dextromethorphan, a non-competitive antagonist to N-methyl-D-aspartic acid receptor (NMDAR). In a female with subacute MTX...

  9. Excitatory and inhibitory effects of opiates in the rat vas deferens: a dual mechanism of opiate action.

    Science.gov (United States)

    Jacquet, Y F

    1980-10-03

    Both natural (-)-morphine and its unnatural enantiomer (+)-morphine exert an excitatory action on electrically stimulated contractions of rat vas deferens. Preexposure to (-)-morphine results in cross-tolerance to the inhibitory action of beta-endorphin. (-)-Naloxone and its stereoisomer (+)-naloxone also exert an excitatory action, but only (-)-naloxone bocks the inhibtory action of beta-endorphin. Thus morphine exerts a dual action on a peripheral organ: one an inhibitory action mediated by the stereospecific endorphin receptor that is blocked stereospecifically by naloxone, the other an excitatory action mediated by a nonstereospecific receptor that is not blocked by naloxone. The opiate abstinence syndrome is seen as due to the unmasking of the excitatory action of opiates when its concomitant inhibitory influence is removed by selective blockade by naloxone or weakened by selective tolerance. The view that the rat vas deferens is devoid of morphine receptors is now seen as arising from a reverse example of morphine's dual action: the masking of the inhibitory action of morphine by its concomitant and more potent excitatory action.

  10. Buprenorphine in the treatment of opiate dependence.

    Science.gov (United States)

    Wesson, Donald R; Smith, David E

    2010-06-01

    Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (buprenorphine alone) and Suboxone (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment.

  11. Characterization of T cell receptor assembly and expression in a Ti gamma delta-positive cell line

    DEFF Research Database (Denmark)

    Kuhlmann, J; Caspar-Bauguil, S; Geisler, C

    1993-01-01

    - variants of the T cell Lyon were induced and found to produce all of the Ti/CD3 components, with the exception of Ti-delta. Biochemical analysis indicated that: (1) Ti-gamma/CD3 gamma, delta, epsilon complexes were formed in the endoplasmic reticulum in the absence of Ti-delta; (2) the CD3-zeta chain did...

  12. Mu-opioid receptor and delta-opioid receptor differentially regulate microglial inflammatory response to control proopiomelanocortin neuronal apoptosis in the hypothalamus: effects of neonatal alcohol.

    Science.gov (United States)

    Shrivastava, Pallavi; Cabrera, Miguel A; Chastain, Lucy G; Boyadjieva, Nadka I; Jabbar, Shaima; Franklin, Tina; Sarkar, Dipak K

    2017-04-14

    Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus. Neonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6. Some of the alcohol-fed rats additionally received pretreatment of a microglia activation blocker minocycline. Two hours after the last feeding, some of the pups were sacrificed and processed for histochemical detection of microglial cell functions or confocal microscopy for detection of cellular physical interaction or used for gene and protein expression analysis. The rest of the pups were dissected for microglia separation by differential gradient centrifugation and characterization by measuring production of various activation markers and cytokines. In addition, primary cultures of microglial cells were prepared using hypothalamic tissues of neonatal rats and used for determination of cytokine production/secretion and apoptotic activity of neurons. In the hypothalamus, neonatal alcohol feeding elevated cytokine receptor levels, increased the number of microglial cells with amoeboid-type circularity, enhanced POMC and microglial cell physical interaction, and decreased POMC cell numbers. Minocycline reversed these cellular effects of alcohol. Alcohol feeding also increased levels of microglia MOR protein and pro-inflammatory signaling molecules in the hypothalamus, and MOR receptor antagonist naltrexone prevented these effects of alcohol. In primary cultures of hypothalamic microglia, both MOR agonist [D-Ala 2, N-MePhe 4, Gly-ol]-enkephalin (DAMGO) and ethanol increased microglial cellular levels and secretion of pro-inflammatory cell signaling proteins. However

  13. Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation.

    Directory of Open Access Journals (Sweden)

    Nada Charbaji

    Full Text Available Oral mucositis is one of the most common side effects of chemoradiation regimens and manifestation can be dose-limiting for the therapy, can impair the patient's nutritional condition and quality of life due to severe pain. The therapeutic options are limited; often only an alleviation of the symptoms such as pain reduction by using systemic opioids is possible. Stimulating opioid receptors on peripheral neurons and dermal tissue, potent analgesic effects are induced e.g. in skin grafted patients. Advantageous effects on the cell migration and, thus, on the wound healing process are described, too. In this study, we investigated whether opioid receptors are also expressed on oral epithelial cells and if morphine can modulate their cell migration behavior. The expression of the opioid receptors MOR, DOR and KOR on primary human oral epithelial cells was verified. Furthermore, a significantly accelerated cell migration was observed following incubation with morphine. The effect even slightly exceeded the cell migration stimulating effect of TGF-ß: After 14 h of morphine treatment about 86% of the wound area was closed, whereas TGF-ß application resulted in a closed wound area of 80%. With respect to morphine stimulated cell migration we demonstrate that DOR plays a key role and we show the involvement of the MAPK members Erk 1/2 and p38 using Western blot analysis.Further studies in more complex systems in vitro and in vivo are required. Nevertheless, these findings might open up a new therapeutic option for the treatment of oral mucositis.

  14. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development.

    Science.gov (United States)

    Ramadani, Faruk; Bolland, Daniel J; Garcon, Fabien; Emery, Juliet L; Vanhaesebroeck, Bart; Corcoran, Anne E; Okkenhaug, Klaus

    2010-08-10

    B cell development is controlled by a series of checkpoints that ensure that the immunoglobulin (Ig)-encoding genes produce a functional B cell receptor (BCR) and antibodies. As part of this process, recombination-activating gene (Rag) proteins regulate the in-frame assembly of the Ig-encoding genes. The BCR consists of Ig proteins in complex with the immunoreceptor tyrosine-based activation motif (ITAM)-containing Igalpha and Igbeta chains. Whereas the activation of the tyrosine kinases Src and Syk is essential for BCR signaling, the pathways that act downstream of these kinases are incompletely defined. Previous work has revealed a key role for the p110delta isoform of phosphatidylinositol 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell development and mature B cell survival, which depend on agonist-independent or "tonic" BCR signaling, are not substantially affected by a deficiency in p110delta. Here, we show that p110alpha, but not p110beta, compensated in the absence of p110delta to promote early B cell development in the bone marrow and B cell survival in the spleen. In the absence of both p110alpha and p110delta activities, pre-BCR signaling failed to suppress the production of Rag proteins and to promote developmental progression of B cell progenitors. Unlike p110delta, however, p110alpha did not contribute to agonist-induced BCR signaling. These studies indicate that either p110alpha or p110delta can mediate tonic signaling from the BCR, but only p110delta can contribute to antigen-dependent activation of B cells.

  15. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

    Science.gov (United States)

    Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric

    2014-01-01

    Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

  16. Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

    LENUS (Irish Health Repository)

    Meehan, Maria

    2012-02-05

    Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA\\'s primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

  17. Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes.

    OpenAIRE

    Lee, B K; Lee, G S; Stewart, W F; Ahn, K D; Simon, D; Kelsey, K T; Todd, A C; Schwartz, B S

    2001-01-01

    Evidence suggests that lead and selected genes known to modify the toxicokinetics of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD)--may independently influence blood pressure and hypertension risk. We report the relations among ALAD and VDR genotypes, three lead dose measures, and blood pressure and hypertension status in 798 Korean lead workers and 135 controls without occupational exposure to lead. Lead dose was assessed by blood lead,...

  18. Opiates, overeating and obesity: a psychogenetic analysis.

    Science.gov (United States)

    Davis, C; Zai, C; Levitan, R D; Kaplan, A S; Carter, J C; Reid-Westoby, C; Curtis, C; Wight, K; Kennedy, J L

    2011-10-01

    This study provides an original perspective on the associations among endogenous opiates, overeating and obesity. The aim was to assess whether variability in the OPRM1 gene, as assessed by seven single-nucleotide polymorphisms, relates to individual differences in the preference for sweet and fatty foods. We also anticipated that these food preferences would be positively associated with binge eating, hedonic eating and emotionally driven eating-patterns of overeating that would, in turn, predict higher body mass index (BMI). Analysis of variance procedures examined genotype differences in food preferences; bivariate correlation coefficients examined the relationships among food preferences and the overeating variables; and a regression analysis tested the combined influences of the overeating variables on BMI. DNA was extracted from whole blood for the genotyping, and measures of food preferences and eating behaviours were obtained from well-validated self-report questionnaires. Participants were 300 healthy adult men and women recruited from the community. All the predicted associations were supported by statistically significant results. In particular, the G/G genotype group of the functional A118G marker of the OPRM1 gene reported higher preferences for sweet and fatty foods compared with the other two groups. Food preferences were also related to all overeating measures, which in turn accounted for a substantial proportion of the variance in BMI. Our findings suggest that some of the diversity in the preference for highly palatable foods can be explained by genotypic differences in the regulation of mu opioid receptors. The associations reported in this paper are important from a public-health perspective because of the abuse potential of sweet-fat foods and their strong relationship with obesity.

  19. Surface ionization mass spectrometry of opiates

    International Nuclear Information System (INIS)

    Usmanov, D.T.

    2009-07-01

    Key words: surface ionization, adsorption, heterogeneous reactions, surface ionization mass spectrometry, thermodesorption surface ionization spectroscopy, thermoemitter, opiates, extracts of biosamples. Subjects of study. The mass - spectrometric study of thermal - ion emission: surface ionization of opiates by on the surface of oxidized refractory metals. Purpose of work is to establish the regularities of surface ionization (SI) of multi-atomic molecule opiates and their mixtures develop the scientific base of SI methods for high sensitive and selective detection and analysis of these substances in the different objects, including biosamples. Methods of study: surface ionization mass spectrometry, thermodesorption surface ionization spectroscopy. The results obtained and their novelty. For the first time, SI of molecule opiates on the oxidized tungsten surface has been studied and their SI mass-spectra and temperature dependences of ion currents have been obtained, the characteristic heterogeneous reactions of an adsorbed molecules and the channels of monomolecular decays vibrationally-excited ions on their way in mass-spectrometry have been revealed, sublimation energy has been defined, the activation energy of E act , of these decays has been estimated for given period of time. Additivity of the SI mass-spectra of opiate mixtures of has been established under conditions of joint opiate adsorption. High selectivity of SI allows the extracts of biosamples to be analyzed without their preliminary chromatographic separation. The opiates are ionized by SI with high efficiency (from 34 C/mol to 112 C/mol), which provides high sensitivity of opiate detection by SI/MS and APTDSIS methods from - 10 -11 g in the samples under analysis. Practical value. The results of these studies create the scientific base for novel SI methods of high sensitive detection and analysis of the trace amounts of opiates in complicated mixtures, including biosamples without their preliminary

  20. Pharmacoepidemiology of opiate use in the neonatal ICU: Increasing cumulative doses and iatrogenic opiate withdrawal.

    Science.gov (United States)

    Lewis, Tamorah; Erfe, Betty Luan; Ezell, Tarrah; Gauda, Estelle

    2015-01-01

    Neonatal intensive care unit (ICU) care involves use of opiates to treat postoperative, ventilated, or chronically ill infants. Opiates provide necessary analgesia and sedation, but the morbidities include prolonged neonatal abstinence syndrome (NAS) and extended length of stay for dose tapering. Our objective was to quantify trends in opiate exposure in a tertiary care NICU. The authors hypothesize that medical opiate exposure and resultant ICU-acquired NAS would increase over time. Retrospective cross-sectional cohort study. Tertiary care NICU. High-risk inborn infants admitted in fiscal years 2003-2004, 2007-2008, and 2010-2011. Average cumulative morphine exposure (all opiate doses converted to morphine equivalents) per time epoch was compared in cohorts of clinically similar infants. Linear regression was used to assess the primary outcome, assessing changes in opiate exposure over time. Sixty-three infants were included in the final analysis. The primary analysis assessing cumulative opiate exposure per infant showed an increase of 134 mg per time epoch (95% CI-12, 279 mg, p-value 0.071). There was a statistically significant increase in the percent of infants with a diagnosis of iatrogenic NAS, increasing from 9 to 35 to 50 percent (p-value 0.012).

  1. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways

    DEFF Research Database (Denmark)

    He, Hongbo; Yang, Dachun; Ma, Liqun

    2010-01-01

    -gamma expression, whereas neither candesartan nor losartan affected PPAR-delta expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice. Administration...

  2. Poppy Seed Consumption or Opiate Use: The Determination of Thebaine and Opiates of Abuse in Postmortem Fluids and Tissues

    National Research Council Canada - National Science Library

    Johnson, Robert D; Lewis, Russell J; Hattrup, Rachael A

    2005-01-01

    .... Therefore, the interpretation of positive opiate results must be viewed with caution. We have developed a simple method for the simultaneous determination of 8 opiate compounds from one extraction...

  3. Opioid Antagonists May Reverse Endogenous Opiate “Dependence” in the Treatment of Self-Injurious Behavior

    Directory of Open Access Journals (Sweden)

    Curt A. Sandman

    2011-01-01

    Full Text Available Self-injurious behavior (SIB is a primary reason that individuals with neurodevelopmental disabilities (NDD are either retained in restrictive environments or are administered psychotropic medication. There are no known causes and no universally accepted treatments for this complex behavior among individuals with NDD. There is developing evidence, however, that individuals exhibiting SIB have a disturbance of the opiate-mediated pain and pleasure system. One hypothesis is that SIB reflects insensitivity to pain and general sensory depression (hypoalgesia, perhaps related to chronic elevation of endogenous opiates. For instance, many self-injurious individuals do not exhibit the usual signs of pain after their “injurious” behavior. Moreover, for some individuals the addictive properties of elevated endogenous opiates (euphoria may be responsible for maintaining their SIB. In this perspective, SIB may be viewed as an addiction because it supplies the "fix" for tolerant, down-regulated opiate receptors. Reports that levels of endogenous opiates at rest and after SIB episodes predict positive responses to opiate blockers (e.g., naltrexone provide further support for opiate-mediated SIB and form the basis for a rational treatment strategy. Although the long term effects of opiate blockers on SIB are unknown, reduction in SIB following acute treatment provides support that a specific biological system may be dysregulated in a subgroup of patients. It is concluded that naltrexone produces a clinically significant reduction in the serious and life-threatening behavior of self injury for individuals who have not been responsive to any other type of treatment. Several suggestions and cautions are provided for regimens of naltrexone treatment of SIB.

  4. Dynamic Regulation of Delta-Opioid Receptor in Rat Trigeminal Ganglion Neurons by Lipopolysaccharide-induced Acute Pulpitis.

    Science.gov (United States)

    Huang, Jin; Lv, Yiheng; Fu, Yunjie; Ren, Lili; Wang, Pan; Liu, Baozhu; Huang, Keqiang; Bi, Jing

    2015-12-01

    Delta-opioid receptor (DOR) and its endogenous ligands distribute in trigeminal system and play a very important role in modulating peripheral inflammatory pain. DOR activation can trigger p44/42 mitogen-activated protein kinase (ERK1/2) and Akt signaling pathways, which participate in anti-inflammatory and neuroprotective effects. In this study, our purpose was to determine the dynamic changes of DOR in trigeminal ganglion (TG) neurons during the process of acute dental pulp inflammation and elucidate its possible mechanism. Forty rats were used to generate lipopolysaccharide-induced acute pulpitis animal models at 6, 12, and 24 hours and sham-operated groups. Acute pulpitis was confirmed by hematoxylin-eosin staining, and TG neuron activation was determined by anti-c-Fos immunohistochemistry. DOR protein and gene expression in TG was investigated by immunohistochemistry, Western blotting, and real-time polymerase chain reaction, and DOR expression in trigeminal nerves and dental pulp was also determined by immunohistochemistry. To further investigate the mechanism of DOR modulating acute inflammation, the change of pErk1/2 and pAkt in TG was examined by immunohistochemistry. Lipopolysaccharide could successfully induce acute pulpitis and activated TG neurons. Acute pulpitis could dynamically increase DOR protein and gene expression at 6, 12, and 24 hours in TG, and DOR dimerization was significantly increased at 12 and 24 hours. Acute pulpitis also induced the dynamic change of DOR protein in trigeminal nerve and dental pulp. Furthermore, ERK1/2 and Akt signaling pathways were inhibited in TG after acute pulpitis. Increased DOR expression and dimerization may play important roles in peripheral acute inflammatory pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Science.gov (United States)

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress

    Directory of Open Access Journals (Sweden)

    Sanoara Mazid

    2016-12-01

    Full Text Available Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs. Immediately after acute immobilization stress (AIS or one-day after chronic immobilization stress (CIS, the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar

  7. PET imaging of mu- and delta-opioid receptor binding in alcohol dependent and healthy control subjects

    Science.gov (United States)

    Weerts, Elise M.; Wand, Gary S.; Kuwabara, Hiroto; Munro, Cynthia A.; Dannals, Robert F.; Hilton, John; Frost, J. James; McCaul, Mary E.

    2011-01-01

    Background The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain mu opioid receptor (MOR) and delta opioid receptor (DOR) availability in recently abstinent alcohol-dependent and age-matched healthy control men and women with Positron Emission Tomography (PET) imaging. Methods Alcohol dependent subjects completed an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence. Control subjects completed PET imaging following an overnight stay. PET scans with the MOR selective ligand [11C]carfentanil (CFN) were completed in 25 alcohol dependent and 30 control subjects. Most of these same subjects (20 alcohol dependent and 18 controls) also completed PET scans with the DOR selective ligand [11C]methyl-naltrindole (MeNTL). Results Volume of interest and statistical parametric mapping analyses indicated that alcohol dependent subjects had significantly higher [11C]CFN binding potential (BPND) than healthy controls in multiple brain regions including the ventral striatum when adjusting for age, gender and smoking status. There was an inverse relationship between [11C]CFN BPND and craving in several brain regions in alcohol dependent subjects. Groups did not differ in [11C]MeNTL BPND; however, [11C]MeNTL BPND in caudate was positively correlated with recent alcohol drinking in alcohol dependent subjects. Conclusions Our observation of higher [11C]CFN BPND in alcohol dependent subjects can result from up regulation of MOR and/or reduction in endogenous opioid peptides following long-term alcohol consumption, dependence and/or withdrawal. Alternatively, the higher [11C]CFN BPND in alcohol dependent subjects may be an etiological difference that predisposed these individuals to alcohol dependence or may have developed as a result of increased exposure to childhood adversity, stress and other environmental factors known to increase MOR. Although

  8. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  9. Cellular localization and adaptive changes of the cardiac delta opioid receptor system in an experimental model of heart failure in rats.

    Science.gov (United States)

    Treskatsch, Sascha; Feldheiser, Aarne; Shaqura, Mohammed; Dehe, Lukas; Habazettl, Helmut; Röpke, Torsten K; Shakibaei, Mehdi; Schäfer, Michael; Spies, Claudia D; Mousa, Shaaban A

    2016-02-01

    The role of the cardiac opioid system in congestive heart failure (CHF) is not fully understood. Therefore, this project investigated the cellular localization of delta opioid receptors (DOR) in left ventricle (LV) myocardium and adaptive changes in DOR and its endogenous ligand, the precursor peptide proenkephalin (PENK), during CHF. Following IRB approval, DOR localization was determined by radioligand binding using [H(3)]Naltrindole and by double immunofluorescence confocal analysis in the LV of male Wistar rats. Additionally, 28 days following an infrarenal aortocaval fistula (ACF) the extent of CHF and adaptions in left ventricular DOR and PENK expression were examined by hemodynamic measurements, RT-PCR, and Western blot. DOR specific membrane binding sites were identified in LV myocardium. DOR were colocalized with L-type Ca(2+)-channels (Cav1.2) as well as with intracellular ryanodine receptors (RyR) of the sarcoplasmatic reticulum. Following ACF severe congestive heart failure developed in all rats and was accompanied by up-regulation of DOR and PENK on mRNA as well as receptor proteins representing consecutive adaptations. These findings might suggest that the cardiac delta opioid system possesses the ability to play a regulatory role in the cardiomyocyte calcium homeostasis, especially in response to heart failure.

  10. In vitro and in vivo pharmacological profile of UFP-512, a novel selective delta-opioid receptor agonist; correlations between desensitization and tolerance.

    Science.gov (United States)

    Aguila, B; Coulbault, L; Boulouard, M; Léveillé, F; Davis, A; Tóth, G; Borsodi, A; Balboni, G; Salvadori, S; Jauzac, P; Allouche, S

    2007-12-01

    Delta-opioid receptors (DOP receptors) could represent a novel target in the treatment of depressive disorders. To explore this new field of interest, the development of highly selective DOP receptor agonists is essential. UFP-512 [H-Dmt-Tic-NH-CH(CH2-COOH)-Bid], was recently shown to behave in vitro as a selective and potent DOP receptor agonist and to promote antidepressant- and anxiolytic-like effects in vivo (Vergura et al., 2007). Here, we have characterized the pharmacological properties of UFP-512 and established a link between desensitization and tolerance. Studies were performed in the human neuroblastoma SK-N-BE cells to establish i) binding parameters for UFP-512 ii) signalling pathways activated after acute and chronic treatment iii) regulation (phosphorylation and trafficking) of human DOP (hDOP) receptors after sustained activation by UFP-512. In vivo, we studied UFP-512-induced antidepressant-like effects after acute or chronic treatment in the mouse forced swimming test. In vitro, UFP-512 was a high affinity agonist for DOP receptors. While UFP-512 induced marked phosphorylation of DOP receptors on Ser363, we observed a low desensitization of the cAMP pathway, associated with receptor endocytosis and recycling without any reduction on extracellular signal-regulated protein kinase 1/2 activation. In vivo, acute administration of UFP-512 produced an antidepressant-like effect, without any sign of tolerance after chronic administration. There was a correlation between weak desensitization, significant internalization and recycling of the human DOP receptors and lack of tolerance to UFP-512. This suggests that this compound would be a promising drug prototype for exploring innovative treatments for mood disorders.

  11. Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

    Energy Technology Data Exchange (ETDEWEB)

    Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))

    1990-01-01

    The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

  12. The peroxisome proliferator-activated receptor delta +294T > C polymorphism and alcohol consumption on serum lipid levels

    Directory of Open Access Journals (Sweden)

    Wei Xian-Liang

    2011-12-01

    Full Text Available Abstract Background The single nucleotide polymorphism (SNP of peroxisome proliferator-activated receptor delta (PPARD gene affects serum lipid profiles, but to what extent alcohol consumption interferes with this association remains unknown. The present study was undertaken to compare the association of PPARD +294T > C (rs2016520 polymorphism and serum lipid levels in the nondrinkers and drinkers. Methods A total of 685 unrelated nondrinkers and 497 drinkers aged 15-82 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the PPARD +294T > C was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions of the PPARD +294T > C genotypes and alcohol consumption on serum lipid levels were detected by using a factorial regression analysis after controlling for potential confounders. Results The levels of triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, apolipoprotein (Apo A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in nondrinkers (P P > 0.05 for all. The frequencies of TT, TC and CC genotypes were 56.0%, 36.4% and 7.6% in nondrinkers, and 57.2%, 38.0% and 4.8% in drinkers (P > 0.05; respectively. The frequencies of T and C alleles were 74.2% and 25.8% in nondrinkers, and 76.2% and 23.8% in drinkers (P > 0.05; respectively. There was also no significant difference in the genotypic and allelic frequencies between males and females in both groups (P > 0.05 for all. The levels of TC in nondrinkers were different among the three genotypes (P = 0.01, the C allele carriers had higher serum TC levels than the C allele noncarriers. The levels of all seven lipid traits in drinkers were not different among the three genotypes (P > 0.05 for all. The interactions of PPARD +294T > C genotypes and alcohol consumption on serum lipid levels were not detected in the drinkers (P >0.05 for all. Multiple linear regression analysis showed that serum TC, HDL

  13. Effect of tissue-specific acetylcholinesterase inhibitor C-547 on alpha 3 beta 4 and alpha beta epsilon delta acetylcholine receptors in COS cells

    Czech Academy of Sciences Publication Activity Database

    Lindovský, Jiří; Petrov, K.; Krůšek, Jan; Reznik, V.S.; Nikolsky, E. E.; Vyskočil, František

    2012-01-01

    Roč. 688, 1-3 (2012), s. 22-26 ISSN 0014-2999 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA202/09/0806; GA AV ČR(CZ) IAA500110905; GA AV ČR(CZ) IAA100110501; GA AV ČR(CZ) IAA5011411 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : nicotinic ACh receptor * alpha 3 beta 4 * alpha beta epsilon delta * C-547 * anti-cholinesterase Subject RIV: ED - Physiology Impact factor: 2.592, year: 2012

  14. Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

    OpenAIRE

    Schwartz, B S; Lee, B K; Lee, G S; Stewart, W F; Simon, D; Kelsey, K; Todd, A C

    2000-01-01

    A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr ...

  15. Positron-emissionstomografisk kortlaegning af den levende menneskehjernes receptorer

    DEFF Research Database (Denmark)

    Gjedde, A

    2001-01-01

    tracers are used in diseases of the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used in lesions of the cerebral cortex. PET has revealed loss of dopaminergic terminals and dopamine synthetic capacity in Parkinson's disease, MPTP intoxication, and Lesch-Nyhan's syndrome...... receptors in Alzheimer's disease, and benzodiazepine and opiate receptors in stroke, epilepsy, and Huntington's chorea; altered opiate receptors in chronic pain and drug abuse; and release of opiates in analgesia; but changes in serotonin synthesis, transport, and binding in affective or psychotic disorders...

  16. Different amounts of ejaculatory activity, a natural rewarding behavior, induce differential mu and delta opioid receptor internalization in the rat's ventral tegmental area.

    Science.gov (United States)

    Garduño-Gutiérrez, René; León-Olea, Martha; Rodríguez-Manzo, Gabriela

    2013-12-06

    Opioid receptors internalize upon specific agonist stimulation. The in vivo significance of receptor internalization is not well established, partly due to the limited in vivo models used to study this phenomenon. Ejaculation promotes endogenous opioid release which activates opioid receptors at the brain, including the mesolimbic system and medial preoptic area. The objective of the present work was to analyze if there was a correlation between the degree of in vivo mu (MOR) and delta opioid receptor (DOR) internalization in the ventral tegmental area and the execution of different amounts of ejaculatory behavior of male rats. To this aim, we analyzed the brains of rats that ejaculated once or six successive times and of sexually exhausted rats with an established sexual inhibition, using immunofluorescence and confocal microscopy. Results showed that MOR and DOR internalization increased as a consequence of ejaculation. There was a relationship between the amount of sexual activity executed and the degree of internalization for MOR, but not for DOR. MOR internalization was larger in rats that ejaculated repeatedly than in animals ejaculating only once. Significant DOR internalization was found only in animals ejaculating once. Changes in MOR, DOR and beta arrestin2 detection, associated to sexual activity, were also found. It is suggested that copulation to satiety might be useful as a model system to study the biological significance of receptor internalization. © 2013 Published by Elsevier B.V.

  17. Changes in expression of delta FosB and the Fos family proteins following NMDA receptor activation in the rat striatum.

    Science.gov (United States)

    Hollen, K M; Nakabeppu, Y; Davies, S W

    1997-07-01

    Receptor-induced expression of transcription factors of the activator protein-1 (AP-1) family in neurons occurs in a unique temporal pattern which regulates subsequent downstream gene expression. We investigated the expression of the Fos family proteins following injection of the NMDA receptor agonist quinolinic acid (QA) into the rat striatum. The c-Fos protein is rapidly and transiently expressed, followed by the sequential and overlapping expression in the same striatal neurons of FosB, from 4 to 8 h post-lesion and delta FosB from 6 h to beyond 30 h post-lesion. Analysis confirms that mRNA transcripts of both fosB and alternatively spliced delta fosB are expressed in the striatum after QA lesion. The Fos-related antigens Fra-1 and Fra-2 and three previously uncharacterized c-Fos-related proteins were additionally found in the striatum which do not increase following lesion. These proteins are related to the highly conserved DNA-binding domain of c-Fos but are not immunologically related to the FosB protein as has been previously reported for proteins induced following chronic stimulation of the striatum. We additionally demonstrate that the c-Fos and delta FosB proteins expressed following QA lesion bind to the functional AP-1 site in the promoter of the nerve growth factor (NGF) gene, the regulation of which temporally and spatially coincides with the AP-1 protein increases in the QA-lesioned striatum. However, the levels of binding to the NGF AP-1 site do not increase throughout time following lesion despite the induced expression of Fos family proteins, suggesting that the regulation of the NGF gene in this paradigm does not simply involve increased binding to the AP-1 site in the NGF gene promoter.

  18. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

    Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  19. Discontinuation of Opiate Treatment: A Retrospective Review of 49 Patients

    OpenAIRE

    Alen J Salerian

    2015-01-01

    This retrospective study reviews 49 patients- one year with opiate and one year post treatment discontinuation - treated at a private outpatient psychopharmacology center. This retrospective study reviews the health status of 398 patients with two distinct subgroups, 17 local and 32 out-of-town patients. Results revealed significant rise in fatalities after opiate discontinuation. The review results are consistent with increased risk of premature death following opiate discontinuation. It may...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Xavier Viñals

    2015-07-01

    Full Text Available 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.

  2. Patterns of chemokine receptor expression on peripheral blood gamma delta T lymphocytes: strong expression of CCR5 is a selective feature of V delta 2/V gamma 9 gamma delta T cells.

    Science.gov (United States)

    Glatzel, Andrea; Wesch, Daniela; Schiemann, Florian; Brandt, Ernst; Janssen, Ottmar; Kabelitz, Dieter

    2002-05-15

    Gammadelta T lymphocytes play an important role in the immune defense against infection, based on the unique reactivity of human Vdelta2Vgamma9 gammadelta T cells toward bacterial phosphoantigens. Chemokines and their corresponding receptors orchestrate numerous cellular reactions, including leukocyte migration, activation, and degranulation. In this study we investigated the expression of various receptors for inflammatory and homeostatic chemokines on peripheral blood gammadelta T cells and compared their expression patterns with those on alphabeta T cells. Although several of the analyzed receptors (including CCR6, CCR7, CXCR4, and CXCR5) were not differentially expressed on gammadelta vs alphabeta T cells, gammadelta T cells expressed strongly increased levels of the RANTES/macrophage inflammatory protein-1alpha/-1beta receptor CCR5 and also enhanced levels of CCR1-3 and CXCR1-3. CCR5 expression was restricted to Vdelta2 gammadelta T cells, while the minor subset of Vdelta1 gammadelta T cells preferentially expressed CXCR1. Stimulation with heat-killed extracts of Mycobacterium tuberculosis down-modulated cell surface expression of CCR5 on gammadelta T cells in a macrophage-dependent manner, while synthetic phosphoantigen isopentenyl pyrophosphate and CCR5 ligands directly triggered CCR5 down-modulation on gammadelta T cells. The functionality of chemokine receptors CCR5 and CXCR3 on gammadelta T cells was demonstrated by Ca(2+) mobilization and chemotactic response to the respective chemokines. Our results identify high level expression of CCR5 as a characteristic and selective feature of circulating Vdelta2 gammadelta T cells, which is in line with their suspected function as Th1 effector T cells.

  3. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  4. Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    S. Stevens Negus

    2012-01-01

    Full Text Available Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+-4-[(αR-α-((2S,5R-4-allyl-2,5-dimethyl-1-piperazinyl-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine. Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg. SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception.

  5. Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study).

    Science.gov (United States)

    Meliou, E; Kerezoudis, Np; Tosios, Ki; Kiaris, H

    2010-07-27

    Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion.

  6. Opiate addicts in and outside of treatment; Different populations?

    NARCIS (Netherlands)

    M.A. Goossensen (Anne)

    1997-01-01

    textabstractThe core of this study is related to the insight that the population of opiate addicls is quite an invisible group. Some paris of this group can be identified at treatment institutions and in prisons. However, a large pari of the opiate addicls is hard to detect. This is because

  7. NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance

    DEFF Research Database (Denmark)

    Lauritzen, G; Jensen, M B F; Bødtkjer, Ebbe

    2010-01-01

    Altered pH-regulatory ion transport is characteristic of many cancers; however, the mechanisms and consequences are poorly understood. Here, we investigate how a truncated, constitutively active ErbB2 receptor (DeltaNErbB2) common in breast cancer impacts on the Na(+)/H(+)-exchanger NHE1 and the ...

  8. Low nanomolar GABA effects at extrasynaptic a4ß1/ß3delta GABAA receptor subtypes indicate a different binding mode for GABA at these receptors

    DEFF Research Database (Denmark)

    Karim, Nasiara; Wellendorph, Petrine; Absalom, Nathan

    2012-01-01

    Ionotropic GABA(A) receptors are a highly heterogenous population of receptors assembled from a combination of multiple subunits. The aims of this study were to characterize the potency of GABA at human recombinant d-containing extrasynaptic GABA(A) receptors expressed in Xenopus oocytes using...... the two-electrode voltage clamp technique, and to investigate, using site-directed mutagenesis, the molecular determinants for GABA potency at a4ß3d GABA(A) receptors. a4/d-Containing GABA(A) receptors displayed high sensitivity to GABA, with mid-nanomolar concentrations activating a4ß1d (EC(50)=24n......M) and a4ß3d (EC(50)=12nM) receptors. In the majority of oocytes expressing a4ß3d subtypes, GABA produced a biphasic concentration-response curve, and activated the receptor with low and high concentrations (EC(50)(1)=16nM; EC(50)(2)=1.2µM). At a4ß2d, GABA had low micromolar activity (EC(50)=1µ...

  9. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal.

    Science.gov (United States)

    Scavone, J L; Sterling, R C; Van Bockstaele, E J

    2013-09-17

    Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive physical and emotional symptoms. High rates of relapse and limited treatment success rates for opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving abstinence may be further complicated by poly-drug use and co-morbid mental disorders. Research over the past decade has shed light on the influence of endocannabinoids (ECs) on the opioid system. Evidence from both animal and clinical studies point toward an interaction between these two systems, and suggest that targeting the EC system may provide novel interventions for managing opiate dependence and withdrawal. This review will summarize the literature surrounding the molecular effects of cannabinoids and opioids on the locus coeruleus-norepinephrine system, a key circuit implicated in the negative sequelae of opiate addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to abstain from opiates in the clinical setting will also be presented. In summary, the present review details how cannabinoid-opioid interactions may inform novel interventions in the management of opiate dependence and withdrawal. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis

    DEFF Research Database (Denmark)

    Jensen, A W; Hokland, M; Jørgensen, H

    1991-01-01

    to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few...... rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes...

  11. Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors

    NARCIS (Netherlands)

    Yoshida, Y.; Koide, S.; Hirose, N.; Takada, K.; Tomiyama, K; Koshikawa, N.; Cools, A.R.

    1999-01-01

    The effects of the u-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dosedependently increased the levels of dopamine when given intravenously (ug/kg) or via a microdialysis probe placed

  12. Clinical Manifestations of the Opiate Withdrawal Syndrome

    Directory of Open Access Journals (Sweden)

    Faniya Shigakova

    2015-09-01

    Full Text Available Currently, substance abuse is one of the most serious problems facing our society. The aim of this study was to investigate the clinical manifestations of the opiate withdrawal syndrome (OWS. The study included 112 patients (57 women and 55 men aged from 18 to 64 years with opium addiction according to the DSM-IV. To study the clinical manifestation of OWS, the special 25-score scale with four sections to assess severity of sleep disorders, pain syndrome, autonomic disorders, and affective symptoms was used. Given the diversity of the OWS symptoms, attention was focused on three clinical variants, affective, algic and mixed. The OWS affective variant was registered more frequently in women, while the mixed type of OWS was more typical of men.

  13. HIV, opiates, and enteric neuron dysfunction.

    Science.gov (United States)

    Galligan, J J

    2015-04-01

    Human immune deficient virus (HIV) is an immunosuppressive virus that targets CD4(+) T-lymphocytes. HIV infections cause increased susceptibility to opportunistic infections and cancer. HIV infection can also alter central nervous system (CNS) function causing cognitive impairment. HIV does not infect neurons but it does infect astrocytes and microglia in the CNS. HIV can also infect enteric glia initiating an intestinal inflammatory response which causes enteric neural injury and gut dysfunction. Part of the inflammatory response is HIV induced production of proteins including, Transactivator of transcription (Tat) which contribute to neuronal injury after release from HIV infected glial cells. A risk factor for HIV infection is intravenous drug use with contaminated needles and chronic opiate use can exacerbate neural injury in the nervous system. While most research focuses on the actions of Tat and other HIV related proteins and opiates on the brain, recent data indicate that Tat can cause intestinal inflammation and disruption of enteric neuron function, including alteration of Na(+) channel activity and action potential generation. A paper published in this issue of Neurogastroenterology and Motility extends these findings by identifying an interaction between Tat and morphine on enteric neuron Na(+) channels and on intestinal motility in vivo using a Tat expressing transgenic mouse model. These new data show that Tat protein can enhance the inhibitory actions of morphine on action potential generation and propulsive motility. These findings are important to our understanding of how HIV causes diarrhea in infected patients and for the use of opioid drugs to treat HIV-induced diarrhea. © 2015 John Wiley & Sons Ltd.

  14. (D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, R.J.; Sharma, S.D.; Toth, G.; Duong, M.T.; Fang, L.; Bogert, C.L.; Weber, S.J.; Hunt, M.; Davis, T.P.; Wamsley, J.K. (Department of Pharmacology, University of Arizona, College of Medicine, Tucson (United States))

    1991-09-01

    (D-Pen2,4{prime}-125I-Phe4,D-Pen5)enkephalin ((125I)DPDPE) is a highly selective radioligand for the delta opioid receptor with a specific activity (2200 Ci/mmol) that is over 50-fold greater than that of tritium-labeled DPDPE analogs. (125I)DPDPE binds to a single site in rat brain membranes with an equilibrium dissociation constant (Kd) value of 421 {plus minus} 67 pM and a receptor density (Bmax) value of 36.4 {plus minus} 2.7 fmol/mg protein. The high affinity of this site for delta opioid receptor ligands and its low affinity for mu or kappa receptor-selective ligands are consistent with its being a delta opioid receptor. The distribution of these sites in rat brain, observed by receptor autoradiography, is also consistent with that of delta opioid receptors. Association and dissociation binding kinetics of 1.0 nM (125I) DPDPE are monophasic at 25 degrees C. The association rate (k + 1 = 5.80 {plus minus} 0.88 {times} 10(7) M-1 min-1) is about 20- and 7-fold greater than that measured for 1.0 nM (3H) DPDPE and 0.8 nM (3H) (D-Pen2,4{prime}-Cl-Phe4, D-Pen5)enkephalin, respectively. The dissociation rate of (125I)DPDPE (0.917 {plus minus} 0.117 {times} 10(-2) min-1) measured at 1.0 nM is about 3-fold faster than is observed for either of the other DPDPE analogs. The rapid binding kinetics of (125I)DPDPE is advantageous because binding equilibrium is achieved with much shorter incubation times than are required for other cyclic enkephalin analogs. This, in addition to its much higher specific activity, makes (125I)DPDPE a valuable new radioligand for studies of delta opioid receptors.

  15. Delta Dynamics

    DEFF Research Database (Denmark)

    Bendixen, Mette

    A warming climate affects the entire planet, but the Arctic experience a warming that is faster than elsewhere in the world. This influences several processes affecting the evolution of the Arctic coast, and increasing erosion rates are detected throughout large parts of these high-latitude coasts...... to sandy beaches, marshes and deltas. This PhD thesis investigates coastal evolution with a special focus on changes in deltaic environments both during the Holocene and in a modern changing climate. The first part of the thesis (Paper 1 and 2) focus on detailed processes affecting delta evolution...... of a fjord and the second type is a wider fan-shaped open delta. Most deltas are directly coupled to the Greenland Ice Sheet or local icecaps and are highly influenced by the dynamics in the catchments. It is demonstrated how a modern changing climate directly affects delta dynamics, and that Greenlandic...

  16. Distribution of mu, delta, and kappa opioid receptor binding sites in the brain of the one-day-old domestic chick (Gallus domesticus): An in vitro quantitative autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Csillag, A.; Bourne, R.C.; Stewart, M.G. (Open Univ., Milton Keynes (England))

    1990-12-15

    Three highly specific opioid ligands--(D-Ala2,Gly-ol)-enkephalin (DAGO) for mu (mu) receptor sites, (D-Pen2,D-Pen5)-enkephalin (DPDPE) for delta (delta) sites, and U-69593 for kappa (kappa) sites--were used to determine the regional distribution of the three major subtypes of opioid receptor binding sites in the brains of 1-day-old domestic chicks by the technique of quantitative receptor autoradiography. While there was a degree of heterogeneity in the binding levels of each of the ligands, some notable similarities existed in the binding of the mu and kappa ligands in several forebrain regions, and in the optic tectum of the midbrain where mu and delta binding was very high. In the forebrain there was a high level of binding of mu and kappa ligands in the hyperstriatum, and for the mu ligand there was a very distinct lamination of binding sites in hyperstriatum accessorium, intercalatum supremum, dorsale and ventrale. Levels of binding of the mu and kappa ligands were also high in nucleus basalis, and (for mu only) in the neostriatum. The distribution of binding of the delta specific ligand in the forebrain showed marked differences to that of mu and kappa, being particularly low in the hyperstriatum and neostriatum. Very high levels of labelling of delta binding sites were, however, found in the nucleus rotundus. Binding of the three ligands was generally low or absent in the cerebellum and medulla, apart from a distinct labelling of the granule cell layer by the mu-ligand. A kinetic analysis was made of the binding of the three ligands to whole forebrain sections using scintillation counting methods.

  17. Gene number determination and genetic polymorphism of the gamma delta T cell co-receptor WC1 genes

    Directory of Open Access Journals (Sweden)

    Chen Chuang

    2012-10-01

    Full Text Available Abstract Background WC1 co-receptors belong to the scavenger receptor cysteine-rich (SRCR superfamily and are encoded by a multi-gene family. Expression of particular WC1 genes defines functional subpopulations of WC1+ γδ T cells. We have previously identified partial or complete genomic sequences for thirteen different WC1 genes through annotation of the bovine genome Btau_3.1 build. We also identified two WC1 cDNA sequences from other cattle that did not correspond to sequences in the Btau_3.1 build. Their absence in the Btau_3.1 build may have reflected gaps in the genome assembly or polymorphisms among animals. Since the response of γδ T cells to bacterial challenge is determined by WC1 gene expression, it was critical to understand whether individual cattle or breeds differ in the number of WC1 genes or display polymorphisms. Results Real-time quantitative PCR using DNA from the animal whose genome was sequenced (“Dominette” and sixteen other animals representing ten breeds of cattle, showed that the number of genes coding for WC1 co-receptors is thirteen. The complete coding sequences of those thirteen WC1 genes is presented, including the correction of an error in the WC1-2 gene due to mis-assembly in the Btau_3.1 build. All other cDNA sequences were found to agree with the previous annotation of complete or partial WC1 genes. PCR amplification and sequencing of the most variable N-terminal SRCR domain (domain 1 which has the SRCR “a” pattern of each of the thirteen WC1 genes showed that the sequences are highly conserved among individuals and breeds. Of 160 sequences of domain 1 from three breeds of cattle, no additional sequences beyond the thirteen described WC1 genes were found. Analysis of the complete WC1 cDNA sequences indicated that the thirteen WC1 genes code for three distinct WC1 molecular forms. Conclusion The bovine WC1 multi-gene family is composed of thirteen genes coding for three structural forms whose

  18. Character pathology and neuropsychological test performance in remitted opiate dependence

    Directory of Open Access Journals (Sweden)

    Steinfeld Matthew

    2008-11-01

    Full Text Available Abstract Background Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies. Methods The Millon Multiaxial Clinical Inventory (MCMI and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM, 27 subjects in protracted abstinence from methadone maintenance treatment (PA, and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis. Results MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use. Conclusion Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.

  19. Character pathology and neuropsychological test performance in remitted opiate dependence.

    Science.gov (United States)

    Prosser, James M; Eisenberg, Daniel; Davey, Emily E; Steinfeld, Matthew; Cohen, Lisa J; London, Edythe D; Galynker, Igor I

    2008-11-19

    Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies. The Millon Multiaxial Clinical Inventory (MCMI) and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM), 27 subjects in protracted abstinence from methadone maintenance treatment (PA), and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis. MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use. Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.

  20. Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification

    Directory of Open Access Journals (Sweden)

    Jovanović Tatjana

    2012-01-01

    Full Text Available Background/Aim. Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. Methods. The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M and the patients treated with opiate blocker naltrexone (B. In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version. Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. Results. Both groups of patients (M and B had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers

  1. Chronic nicotine-induced changes in gene expression of delta and kappa-opioid receptors and their endogenous ligands in the mesocorticolimbic system of the rat.

    Science.gov (United States)

    Ugur, Muzeyyen; Kaya, Egemen; Gozen, Oguz; Koylu, Ersin O; Kanit, Lutfiye; Keser, Aysegul; Balkan, Burcu

    2017-09-01

    Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. This study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for 6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system. mRNA levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA), amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal cortex were measured by quantitative real-time PCR. Our results showed that nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely, PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4 mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine. Nicotine did not regulate PENK mRNA in any brain region studied. © 2017 Wiley Periodicals, Inc.

  2. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

    Science.gov (United States)

    von Bueren, A O; Schlumpf, M; Lichtensteiger, W

    2008-01-01

    Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

  3. Enhanced bioavailability of opiates after intratracheal administration

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-03-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities (codeine (84%), ethylmorphine (100%), and morphine (87%)) of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability.

  4. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    2010-01-01

    Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

  5. Opiate addiction in Republic of Srpska: Characteristics and etiology

    Directory of Open Access Journals (Sweden)

    Niškanović Jelena

    2013-01-01

    Full Text Available Opiate addiction is a significant social and health problem with a negative impact on individuals' health and their social environment. The aim of this paper is to analyze the characteristics of opiate addicts in order to determine the social and contextual factors underlying the development of addiction. All health care facilities and therapeutic communities which provide care and help addicts are required to fill in the Form of treated addicts. The analysis included people who sought treatment during the period from 25th November 2010 to 21st May 2013 in health care facilities and associations for substance abuse treatment in the Republic of Srpska. The majority of treated addicts belong to opiate addiction (N= 241: 91%. Opiate addicts are mostly males (88.8%, while 11.2% of treated opiate addicts are female. The highest percentage of opiate addicts live in urban areas (86.7%, have secondary education (73.4%, 63.3% are unemployed, while 70.5% live with primary family. Predominant etiologic factor for the development of addiction is peer or partner pressure (29%, pathology of the family as family breakdown or alcoholism (19.3%, while on the third place is low self control (16.8%. For 19.1% of opiate addicts, delinquent behavior started before taking any drugs. The presented data confirms the importance of social environment, like low family control and presence of family pathology. The mentioned factors in combination with negative peer pressure can lead to risky behavior and potential addiction.

  6. Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.

    Science.gov (United States)

    Liu, Zhi-Peng; He, Qing-Hai; Pan, Han-Qing; Xu, Xiao-Bin; Chen, Wen-Bing; He, Ye; Zhou, Jin; Zhang, Wen-Hua; Zhang, Jun-Yu; Ying, Xiao-Ping; Han, Ren-Wen; Li, Bao-Ming; Gao, Tian-Ming; Pan, Bing-Xing

    2017-06-15

    Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABA A R) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABA A R to amygdala inhibition and fear. By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABA A R (GABA A (δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABA A (δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. In sharp contrast to the established role of synaptic GABA A R in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABA A (δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABA A (δ)R. The disinhibition arose from IN-specific expression of GABA A (δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABA A (δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABA A (δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Our findings suggest that GABA A (δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABA A (δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Recidivism with opiate addicted patients on buprenorphine substitution treatment: Case report

    Directory of Open Access Journals (Sweden)

    Crnić Katarina B.

    2017-01-01

    Full Text Available Introduction: Opiate dependence is a serious, chronic and recurrent psychiatric disorder, whose prevalence reach epidemic proportions. This also contributes to a significant increase in mortality, associated with overdose with opiates, as well as the rise in other health and social problems of the society. The methods and availability of treatment do not correspond to increased treatment needs, and treatment success is limited by the characteristics of the disorder, or numerous risk factors, which contribute to a high percentage of recidivism. Good clinical practice guidelines have defined treatment recommendations that include high and low-demanding programs. The personalized and integrative approaches are emphasized. Case report: The patient aged 41 years, intravenous-use opiate addict from his adolescences, with numerous psychological, health and social complications of addiction, is a participant in institutional treatment, following a court order as a measure of obligatory treatment, due to criminal offenses related to addiction. The history of the disease refers to numerous unsuccessful attempts to heal and short-term abstinence in the past, mainly in penal institutions. The patient meets all the criteria defined by the guidelines for inclusion in the buprenorphine maintenance program started in the year 2013. During the four-year treatment, the doses of the drug were adapted as needed; two heroin relapses and many in-risk situations for relapse were registered. The treatment continued with close monitoring of the patient's condition and, with appropriate psychosocial interventions, contribute to keeping the patient in treatment and preventing the development of new complications of addiction, as well an improving the quality of his life. Discussion: Pharmacological treatment of opioid dependence relies on agents belonging to groups of antagonists, agonists and partial agonists of opiate receptors. The earlier programs with abstinence as a

  8. Neurotransmitter Receptor Binding in Bovine Cerebral Microvessels

    Science.gov (United States)

    Peroutka, Stephen J.; Moskowitz, Michael A.; Reinhard, John F.; Synder, Solomon H.

    1980-05-01

    Purified preparations of microvessels from bovine cerebral cortex contain substantial levels of alpha-adrenergic, beta-adrenergic, and histamine 1 receptor binding sites but only negligible serotonin, muscarinic cholinergic, opiate, and benzodiazepine receptor binding. Norepinephrine and histamine may be endogenous regulators of the cerebral microcirculation at the observed receptors.

  9. ( sup 3 H)(D-PEN sup 2 , D-PEN sup 5 ) enkephalin binding to delta opioid receptors on intact neuroblastoma-glioma (NG 108-15) hybrid cells

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, R.J.; Yamamura, H.I. (Univ. of Arizona College of Medicine, Tucson (USA))

    1990-01-01

    ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin binding to intact NG 108-15 cells has been measured under physiological conditions of temperature and medium. The dissociation constant, receptor density, and Hill slope values measured under these conditions are consistent with values obtained by others using membranes prepared from these cells. Kinetic analysis of the radioligand binding to these cells show biphasic association and monophasic dissociation processes suggesting the presence of different receptor affinity states for the agonist. The data show that the binding affinity of ({sup 3}H)(D-Pen{sup 2}, D-Pen{sup 5})enkephalin under physiological conditions is not substantially different to that measured in 50 mM Tris buffer using cell membrane fractions. Unlike DPDPE, the {mu} opioid agonists morphine, normorphine, PL-17, and DAMGO, have much lower affinity for the {delta} receptor measured under these conditions than is observed by studies using 50 mM Tris buffer. The results described here suggest that this assay may serve as a useful model of {delta} opioid receptor binding in vivo.

  10. Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers.

    Science.gov (United States)

    Weaver, Virginia M; Lee, Byung-Kook; Todd, Andrew C; Ahn, Kyu-Dong; Shi, Weiping; Jaar, Bernard G; Kelsey, Karl T; Lustberg, Mark E; Silbergeld, Ellen K; Parsons, Patrick J; Wen, Jiayu; Schwartz, Brian S

    2006-09-01

    Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.

  11. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli

    OpenAIRE

    Nakagawa, Akira; Matsumura, Eitaro; Koyanagi, Takashi; Katayama, Takane; Kawano, Noriaki; Yoshimatsu, Kayo; Yamamoto, Kenji; Kumagai, Hidehiko; Sato, Fumihiko; Minami, Hiromichi

    2016-01-01

    Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four ...

  12. Maintenance medication for opiate addiction: the foundation of recovery.

    Science.gov (United States)

    Bart, Gavin

    2012-01-01

    Illicit use of opiates is the fastest growing substance use problem in the United States, and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to human immunodeficiency virus, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication-assisted detoxification. This article provides a topical review of the three medications approved by the Food and Drug Administration for long-term treatment of opiate dependence: the opioid-agonist methadone, the partial opioid-agonist buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction, but recent studies using extended-release naltrexone injections have shown promise. Although no direct comparisons between extended-release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared with methadone and buprenorphine. Further work is needed to directly compare each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication.

  13. Interaction of trimebutine and Jo-1196 (fedotozine) with opioid receptors in the canine ileum

    Energy Technology Data Exchange (ETDEWEB)

    Allescher, H.D.; Ahmad, S.; Classen, M.; Daniel, E.E. (Technical Univ., Munich, (West Germany))

    1991-05-01

    Receptor binding of the opioid receptor antagonist, ({sup 3}H)diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker ({sup 3}H)saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg) and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu (morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using ({sup 3}H) ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196.

  14. Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides.

    Science.gov (United States)

    Yang, Jun; Liang, Jin-Ying; Li, Peng; Pan, Yan-Juan; Qiu, Pei-Yong; Zhang, Jing; Hao, Fang; Wang, Da-Xin

    2011-06-01

    Periaqueductal gray (PAG) plays a very important role in pain modulation through endogenous opiate peptides including leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep) and dynorphin A(1-13) (DynA(1-13)). Our pervious study has demonstrated that intra-PAG injection of oxytocin (OXT) increases the pain threshold, and local administration of OXT receptor antagonist decreases the pain threshold, in which the antinociceptive role of OXT can be reversed by pre-PAG administration of OXT receptor antagonist. The experiment was designed to investigate the effect of OXT on endogenous opiate peptides in the rat PAG during the pain process. The results showed that (1) the concentrations of OXT, L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased after the pain stimulation; (2) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were decreased by the OXT receptor antagonist; (3) the increased pain threshold induced by the OXT was attenuated by naloxone, an opiate receptor antagonist; and (4) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased by exogenous OXT administration. The data suggested that OXT in the PAG could influence the L-Ek, M-Ek and β-Ep rather than DynA(1-13) to participate in pain modulation, i.e. OXT in the PAG participate in pain modulation by influencing the L-Ek, M-Ek and β-Ep rather than DynA(1-13). Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Spinal Tolerance and Dependence: Some Observations on the Role of Spinal N-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

    Directory of Open Access Journals (Sweden)

    Tony L Yaksh

    2000-01-01

    Full Text Available The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment with N-methyl-D-aspartate (NMDA receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC. This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

  16. Opiate Injection Site Infections--19 years in the UK

    Centers for Disease Control (CDC) Podcasts

    2017-09-06

    Dan Lewer, a public health registrar in England, discusses an increase in infections related to opiate injections in the U.K.  Created: 9/6/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/6/2017.

  17. Lapse and relapse following inpatient treatment of opiate dependence.

    LENUS (Irish Health Repository)

    Smyth, B P

    2010-06-01

    We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.

  18. Involvement of the alpha4beta2 nicotinic receptor subtype in nicotine-induced attenuation of delta9-THC cerebellar ataxia: role of cerebellar nitric oxide.

    Science.gov (United States)

    Smith, Aaron David; Dar, M Saeed

    2007-01-01

    We have recently reported that mediation of intracerebellar nicotine-induced attenuation of cerebellar delta9-THC ataxia was via the alpha4beta2 nAChR. The present study was meant to investigate the role of cerebellar nitric oxide (NO)-guanylyl cyclase (GC) signaling in the alpha4beta2-mediated attenuation in CD-1 male mice. Drugs were given via intracerebellar microinfusion using stereotaxically implanted guide cannulas, with ataxia evaluated by Rotorod. Intracerebellar microinfusion of SNP (sodium nitroprusside, NO donor; 15, 30, 60 pg) and SMT (S-methylisothiourea, inhibitor of inducible NO synthase; 70, 140, 280 fg) significantly enhanced and reduced, respectively, intracerebellar RJR-2403 (selective alpha4beta2 agonist)-induced attenuation of delta9-THC ataxia dose-dependently. Intracerebellar isoliquiritigenin (GC-activator; 1, 2, 4 pg) and ODQ (1H[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, GC inhibitor; 200, 400, 800 fg), significantly enhanced and reduced, respectively, intracerebellar RJR-2403-induced attenuation of delta9-THC ataxia dose-dependently. Further support for the role of NO was evidenced via increases in cerebellar NO(x) (nitrate+nitrite) levels following microinfusion of nicotine or RJR-2403 as compared to control, whereas delta9-THC significantly decreased NO(x) levels. "Nicotine/RJR-2403+delta9-THC" treated mice had cerebellar NO(x) levels significantly increased as compared to mice infused with delta9-THC alone. Results of the present investigation support the role of cerebellar NO-GC signaling in alpha4beta2 nAChR subtype-mediated attenuation of delta9-THC ataxia.

  19. Differences in prevalence of prescription opiate misuse among rural and urban probationers.

    Science.gov (United States)

    Havens, Jennifer R; Oser, Carrie B; Leukefeld, Carl G; Webster, J Matthew; Martin, Steven S; O'Connell, Daniel J; Surratt, Hilary L; Inciardi, James A

    2007-01-01

    We compared the prevalence of prescription opiate misuse among 2 cohorts of felony probationers (N = 1525). Multiple logistic regression was utilized to determine the independent correlates of prescription opiate misuse among rural (n = 782) and urban (n = 743) probationers participating in an HIV-intervention study. After adjustment for differences in demographic and drug use characteristics, rural participants were almost five times more likely than their urban counterparts to have misused prescription opiates. The prevalence of prescription opiate misuse was significantly higher among the rural probationers; however, given the paucity of illicit opiates and relatively recent emergence of prescription opiates in rural areas, rural substance abuse treatment may be ill-prepared to treat prescription opiate misuse.

  20. Delta Robot

    OpenAIRE

    Herder, Justus Laurens; van der Wijk, V.

    2010-01-01

    The invention relates to a delta robot comprising a stationary base (2) and a movable platform (3) that is connected to the base with three chains of links (4,5,6), and comprising a balancing system incorporating at least one pantograph (7) for balancing the robot's center of mass, wherein the at least one pantograph has a first free extremity (10) at which it supports a countermass (13) which is arranged to balance the center of mass of the robot.

  1. Tritium labelling of highly selective probes for. delta. -opioid receptors: ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and ( sup 3 H)Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(O-t-Bu)(BUBU)

    Energy Technology Data Exchange (ETDEWEB)

    Fellion, E.; Gacel, G.; Roques, B.P. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France)); Roy, J.; Morgat, J.L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service de Biochimie)

    1990-08-01

    The introduction of bulky residue(s) in linear enkephalin-related hexapeptides represents a new approach in the design of selective probes for {delta}-opioid receptors, displaying the appropriate criteria to investigate biological and pharmacological properties of the assumed binding site ({delta}) of endogenous enkephalins. The selectivities and high affinities of Tyr-D-Ser(O-t-Bu)-Gly-Phe-Leu-Thr(DSTBULET) and especially Tyr-D-Ser(O-t-Bu)Gly-Phe-Leu-Thr(O-t-Bu) (BUBU) associated with a satisfactory resistance to peptidases, make them the most suitable {delta}-probes reported to date. In the present paper, we report the synthesis of DSTBULET and BUBU under tritiated forms with high specific radioactivities. These radio-labelled probes will enable extensive in vitro and in vivo investigations of {delta}-opioid receptors properties to be carried out. (author).

  2. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

    NARCIS (Netherlands)

    Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.

    1988-01-01

    We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

  3. Impact of Spouse's Opiate Dependence on the Partner's

    Directory of Open Access Journals (Sweden)

    Roya Noori

    2008-12-01

    Full Text Available Objective: We aimed to evaluate the influence of drug dependency on sexual function of wives of opium addicts.Materials and methods: In a cross-sectional study, 150 wives of opiate dependent men were assessed for the impact of drug addiction. Sociodemographic factors like age, educational level, job, marital duration and having child were evaluated. Sexual function was measured using relationship and sexuality scale (RSS. Results: Approximately 73% of the participitants were sexually active with having at least one intercourse in the last 2 weeks, and approximately half of the participitants had unsatisfied intercourse. About ninety percent reported negative effect of the addiction on their sexual life. After the spouse addiction, sexual desire, ability to reach orgasm and frequency of sexual intercourse were decreased in 73%, 64% and 67.3%, respectively. Conclusion: The wives of opiate addicts believe that their sexual function has been impaired by the addiction of their husbands.

  4. Comparing the Iowa and Soochow gambling tasks in opiate users

    Directory of Open Access Journals (Sweden)

    Daniel J. Upton

    2012-03-01

    Full Text Available The Iowa Gambling Task (IGT is in many respects the gold-standard for demonstrating decision-making in drug using groups. However, it is not clear how basic task properties such as the frequency and magnitude of rewards and losses affect choice behaviour in drug users and even in healthy players. In this study, we used a variant of the IGT, the Soochow Gambling Task (SGT, to observe choice behaviour in opiate users and healthy decision makers in a task where reward frequency is not confounded with the long-term outcome of each alternative. In both opiate users (n=26 and healthy controls (n=27, we show that reward frequency strongly influences choice behaviour in the IGT and SGT. Neither group showed a consistent preference across tasks for alternatives with good long-term outcomes, but rather, subjects appeared to prefer alternatives that win most frequently. We interpret this as evidence to suggest that healthy players perform better than opiate users on the IGT because they are able to utilize gain-loss frequencies to guide their choice behaviour on the task. This challenges the previous notion that poorer performance on the IGT in drug users is due to an inability to be guided by future consequences.

  5. Genomic and expression analyses of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) loci reveal a similar basic public γδ repertoire in dolphin and human.

    Science.gov (United States)

    Linguiti, Giovanna; Antonacci, Rachele; Tasco, Gianluca; Grande, Francesco; Casadio, Rita; Massari, Serafina; Castelli, Vito; Consiglio, Arianna; Lefranc, Marie-Paule; Ciccarese, Salvatrice

    2016-08-15

    The bottlenose dolphin (Tursiops truncatus) is a mammal that belongs to the Cetartiodactyla and have lived in marine ecosystems for nearly 60 millions years. Despite its popularity, our knowledge about its adaptive immunity and evolution is very limited. Furthermore, nothing is known about the genomics and evolution of dolphin antigen receptor immunity. Here we report a evolutionary and expression study of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) genes. We have identified in silico the TRG and TRA/TRD genes and analyzed the relevant mature transcripts in blood and in skin from four subjects. The dolphin TRG locus is the smallest and simplest of all mammalian loci as yet studied. It shows a genomic organization comprising two variable (V1 and V2), three joining (J1, J2 and J3) and a single constant (C), genes. Despite the fragmented nature of the genome assemblies, we deduced the TRA/TRD locus organization, with the recent TRDV1 subgroup genes duplications, as it is expected in artiodactyls. Expression analysis from blood of a subject allowed us to assign unambiguously eight TRAV genes to those annotated in the genomic sequence and to twelve new genes, belonging to five different subgroups. All transcripts were productive and no relevant biases towards TRAV-J rearrangements are observed. Blood and skin from four unrelated subjects expression data provide evidence for an unusual ratio of productive/unproductive transcripts which arise from the TRG V-J gene rearrangement and for a "public" gamma delta TR repertoire. The productive cDNA sequences, shared both in the same and in different individuals, include biases of the TRGV1 and TRGJ2 genes. The high frequency of TRGV1-J2/TRDV1- D1-J4 productive rearrangements in dolphins may represent an interesting oligo-clonal population comparable to that found in human with the TRGV9- JP/TRDV2-D-J T cells and in primates. Although the features of the TRG and TRA/TRD loci organization reflect

  6. Early Maladaptive Schemas in Opiate and Stimulant Users

    Directory of Open Access Journals (Sweden)

    Zahra Karami

    2015-06-01

    Full Text Available Objectives: Early maladaptive schemas are valid representations of unpleasant childhood experiences that shape a person’s viewpoints of the world, and lead to clinical symptoms such as depression, personality disorders, and substance abuse. Given the importance of this matter, we conducted a research on early maladaptive schemas in substance-abusers, to allow more appropriate preventive measures to be taken with a better understanding of the issue. Methods: For this descriptive-comparative study, 115 patients (91 opiate users and 24 stimulant users visiting drug addiction treatment centers were selected through convenience sampling from persons who were admitted to substance abuse treatment centers (Methadone Maintenance therapy centers, addiction treatment camps and self-help groups and Narcotics Anonymous (NA of Yasuj. Data were collected using a Demographic Information Questionnaire and Young’s Schema Questionnaire-Short Form (SQ-SF. Data analysis was done with ANOVA and t-tests. Results: The results showed a significant difference (P<0.05 between users of opiates and stimulants in terms of vulnerability to harm or illness, enmeshment, subjugation, emotional inhibition, entitlement, insufficient self-control/self-discipline, emotional  deprivation, social isolation, defectiveness, failure/shame, and dependence. The average score of the stimulant-users was higher than that of opiate-users in all the schemas except for the dimensions of abandonment, mistrust, and unrelenting standards. Discussion: Stimulant users have more early maladaptive schemas and are at a greater risk of psychological vulnerability. Early maladaptive schemas can be used by clinicians and researchers as a psychopathology and treatment method for substance dependence disorder.

  7. The Case for Implementing the Levels of Prevention Model: Opiate Abuse on American College Campuses

    Science.gov (United States)

    Daniels-Witt, Quri; Thompson, Amy; Glassman, Tavis; Federman, Sara; Bott, Katie

    2017-01-01

    Opiate abuse in the United States is on the rise among the college student population. This public health crisis requires immediate action from professionals and stakeholders who are committed to addressing the needs of prospective, current, and recovering opiate users using comprehensive prevention methods. Such approaches have been used to…

  8. Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats.

    Science.gov (United States)

    Olmstead, Mary C; Burns, Lindsay H

    2005-09-01

    Ultra-low-dose opioid antagonists enhance opiate analgesia and attenuate tolerance and withdrawal. To determine whether ultra-low-dose naltrexone (NTX) coadministration alters the rewarding effects of opiates or the aversive effects of opiate withdrawal. We used the conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to assess whether ultra-low-dose NTX alters the acute rewarding effects of oxycodone or morphine, or the aversive aspect of withdrawal from either drug. To assess the dose response for ultra-low-dose NTX, a range of NTX doses (0.03-30 ng/kg) was tested in the oxycodone CPP experiment. In order to avoid tolerance or sensitization effects, we used single conditioning sessions and female rats, as females are more sensitive to the conditioning effects of these drugs. Ultra-low-dose NTX (5 ng/kg) blocked the CPP to morphine (5 mg/kg) and the CPA to withdrawal from chronic morphine (5 mg/kg, for 7 days). Coadministration of ultra-low-dose NTX (30 pg/kg) also blocked the CPA to withdrawal from chronic oxycodone administration (3 mg/kg, for 7 days). The effects of NTX on the CPP to oxycodone (3 mg/kg) revealed a biphasic dose response. The two lowest doses (0.03 and 0.3 ng/kg) blocked the CPP, the middle dose (3 ng/kg) was ineffective, and oxycodone combined with the highest dose (30 ng/kg) produced a trend toward a CPP. Ultra-low-dose NTX coadministration blocks the acute rewarding effects of analgesic doses of oxycodone or morphine as well as the anhedonia of withdrawal from chronic administration.

  9. Comparison of the components of mindfulness on Stimulant and opiate addicts

    Directory of Open Access Journals (Sweden)

    Sayeadyounes Mohammadi

    2016-07-01

    Full Text Available Background: Phenomenon of addiction as one of the social problem have the high prevalence, especially among youth. Study and scientific cognition of mental and psychological components of addicts is very important in order to help them to compatibility and reduce their psychological problem. Therefore, the aim of present study was to comparison of mindfulness components on stimulant and opiate addicts. Materials & Methods: In this study 60 addicts (30 opiate addicts and 30 stimulants addicts were studied by using Five Factor Mindfulness Questionnaire (FFMQ. Data were analyzed by using multivariate analysis of variance (MANOVA. Results: findings showed that there was a significant difference between opiate and stimulant addicts in mindfulness components. Conclusion: results illustrated that the opiate addicts gained higher scores than stimulant addicts in mindfulness components. The results also emphasized that mindfulness components are as determinant variable in opiate and stimulant addicts pathology.

  10. Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Dallanoce, Clelia; Magrone, Pietro; Matera, Carlo

    2011-01-01

    A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2...... in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl......-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively....

  11. Peroxisome proliferator-activated receptor (PPAR) alpha and PPAR beta/delta, but not PPAR gamma, modulate the expression of genes involved in cardiac lipid metabolism

    NARCIS (Netherlands)

    Gilde, AJ; van der Lee, KAJM; Willemsen, PHM; Chinetti, G; van der Leij, FR; van der Vusse, GJ; Staels, B; van Bilsen, M

    2003-01-01

    Long-chain fatty acids ( FA) coordinately induce the expression of a panel of genes involved in cellular FA metabolism in cardiac muscle cells, thereby promoting their own metabolism. These effects are likely to be mediated by peroxisome proliferator-activated receptors (PPARs). Whereas the

  12. Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat.

    Science.gov (United States)

    Craft, Rebecca M; Wakley, Alexa A; Tsutsui, Kimberly T; Laggart, Jillian D

    2012-03-01

    The purpose of this study was to determine whether sex differences in cannabinoid (CB)-induced antinociception and motoric effects can be attributed to differential activation of CB(1) or CB(2) receptors. Rats were injected intraperitoneally with vehicle, rimonabant [5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (SR141716A), a putative CB(1) receptor-selective antagonist; 0.1-10 mg/kg] or 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528) (a putative CB(2) receptor-selective antagonist; 1.0-10 mg/kg). Thirty minutes later, Δ(9)-tetrahydrocannabinol (THC; 1.25-40 mg/kg) or 5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol (CP55,940) (0.05-1.6 mg/kg) was injected. Paw pressure and tail withdrawal antinociception, locomotor activity, and catalepsy were measured. Rimonabant dose-dependently antagonized THC and CP55,940 in each test, but was up to 10 times more potent in female than male rats on the nociceptive tests; estimates of rimonabant affinity (apparent pK(B)) for the CB(1) receptor were approximately 0.5 to 1 mol/kg higher in female than male rats. SR144528 partially antagonized THC-induced tail withdrawal antinociception and locomotor activity in females, but this antagonism was not dose-dependent or consistent; no SR144528 antagonism was observed in either sex tested with CP55,940. Neither the time course of rimonabant antagonism nor the plasma levels of rimonabant differed between the sexes. Rimonabant and SR144528 did not antagonize morphine-induced antinociception, and naloxone did not antagonize THC-induced antinociception in either sex. These results suggest that THC produces acute antinociceptive and motoric effects via activation of CB(1), and perhaps under some conditions, CB(2) receptors, in female rats, whereas THC acts primarily at CB(1) receptors in male rats. Higher apparent pK(B) for

  13. Delta Plaza kohvik = Delta Plaza cafe

    Index Scriptorium Estoniae

    2010-01-01

    Tallinnas Pärnu mnt 141 asuva kohviku Delta Plaza sisekujundusest. Sisearhitektid Tiiu Truus ja Marja Viltrop (Stuudio Truus OÜ). Tiiu Truusi tähtsamate tööde loetelu. Büroohoone Delta Plaza arhitektid Marika Lõoke ja Jüri Okas (AB J. Okas & M. Lõoke)

  14. The effect of pain on stroop performance in patients with opiate dependence in sustained remission.

    Science.gov (United States)

    Aniskin, Dmitry B; Fink, Evgeny; Prosser, James; Cohen, Lisa J; Boda, Namratha; Steinfeld, Matthew; Galynker, Igor I

    2011-03-01

    We have demonstrated previously that former opiate-dependent subjects treated and detoxified from methadone maintenance therapy suffer deficits in neuropsychological performance and have abnormal pain thresholds. This study examined the impact of pain on the performance of the Stroop test, a well-known test of neuropsychological performance. Twenty-three former opiate-dependent subjects treated and detoxified from methadone maintenance therapy and 24 comparison (COM) subjects without a history of opiate dependence were tested using the Stroop test under 2 conditions: Stroop under usual conditions and Stroop under painful conditions. The painful condition was induced using a Medoc Thermal Sensory Analyzer to deliver a heat stimulus at and below the subjects' pain threshold. COM subjects performed better than former opiate-dependent subjects, and females performed better than males on the Stroop under usual conditions. These differences were missing when the Stroop under painful conditions was performed. Analysis of these differences revealed that male former opiate-dependent subjects had a larger improvement in Stroop scores under the painful condition than male COM subjects or females of either group. Performance on a neuropsychological test was adversely impacted by previous opiate addiction, and these effects seemed to be greater in males compared with females. Treated patients with opiate dependence showed improvement in Stroop test performance under painful conditions, and this improvement was greater in males than females.

  15. Dorsal and median raphe serotonergic system lesion does not alter the opiate withdrawal syndrome.

    Science.gov (United States)

    Caillé, Stéphanie; Espejo, Emilio F; Koob, George F; Stinus, Luis

    2002-07-01

    Previous pharmacological studies have implicated serotonergic brain systems in opiate withdrawal. To test the hypothesis that serotonin (5-HT) has a critical role in the development of opiate withdrawal, we have employed a near-total brain 5-HT system lesion technique (90% depletion) using 5,7-dihydroxytryptamine combined with induction of opiate dependence by implantation of morphine pellets or by repeated injections of increasing doses of morphine. The effects of serotonergic neuron lesion were examined on spontaneous opiate withdrawal (changes in circadian locomotor activity) and naloxone-precipitated opiate withdrawal syndrome (the somatic aspect). The antiwithdrawal properties of clonidine, an alpha(2)-adrenoceptor agonist currently used for clinical treatment for the somatic signs of opiate withdrawal, were tested also in the lesioned rats. Our findings show that serotonergic lesions in morphine-dependent rats did not alter either the spontaneous or the naloxone-induced withdrawal syndrome (with exception of jumping behavior). Moreover, clonidine alleviated the naloxone-induced withdrawal syndrome in lesioned as well as in sham-operated morphine-dependent rats. These results demonstrate that 5-HT systems are not directly responsible for the development of the somatic opiate withdrawal syndrome in morphine-dependent rats.

  16. Pharmacological Treatment of Neonatal Opiate Withdrawal: Between the Devil and the Deep Blue Sea

    Directory of Open Access Journals (Sweden)

    Anthony Liu

    2011-01-01

    Full Text Available Illicit drug use with opiates in pregnancy is a major global health issue with neonatal withdrawal being a common complication. Morphine is the main pharmacological agent administered for the treatment of neonatal withdrawal. In the past, morphine has been considered by and large inert in terms of its long-term effects on the central nervous system. However, recent animal and clinical studies have demonstrated that opiates exhibit significant effects on the growing brain. This includes direct dose-dependent effects on reduction in brain size and weight, protein, DNA, RNA, and neurotransmitters—possibly as a direct consequence of a number of opiate-mediated systems that influence neural cell differentiation, proliferation, and apoptosis. At this stage, we are stuck between the devil and the deep blue sea. There are no real alternatives to pharmacological treatment with opiates and other drugs for neonatal opiate withdrawal and opiate addiction in pregnant women. However, pending further rigorous studies examining the potential harmful effects of opiate exposure in utero and the perinatal period, prolonged use of these agents in the neonatal period should be used judiciously, with caution, and avoided where possible.

  17. Five-Factor Model Personality Profiles: The Differences between Alcohol and Opiate Addiction among Females.

    Science.gov (United States)

    Raketic, Diana; Barisic, Jasmina V; Svetozarevic, Snezana M; Gazibara, Tatjana; Tepavcevic, Darija Kisic; Milovanovic, Srdjan D

    2017-03-01

    The prevalence of female alcohol and substance abusers has markedly increased. The main objective of this research was to explore personality profiles among females who had alcohol and opiate dependence. The aim of the study is to analyse if there is differences in personality profiles of females addicted to alcohol and opiates. We hypothesized that there might be significant differences in personality profiles among subgroups of women who present with alcohol and opiate use disorders. Of 157 consecutive women with diagnosis of alcohol/opiate addiction, 62 fulfilled following inclusion criteria: age 19-45 years, abstinence from alcohol and opiates for at least 10 days prior to enrollment. Alcohol-dependent group consisted of 30 females, while opiate-dependent group consisted of 32 females. The control group involved 30 age-matched randomly chosen healthy women. The data were collected using the Revised NEO Personality Inventory (NEO-PI-R). The multiple stepwise discriminant analysis was used to determine relations between personality traits and the probability of belonging to one of the study groups. Significant differences in the NEO-PI-R scores were observed between groups for all main personality traits except for Openness to Experience. Compared with controls, substance-dependent women scored significantly higher on Neuroticism and lower on Conscientiousness. Opiate-dependent females scored the highest on Neuroticism and on Extraversion and lowest on Agreeableness and on Conscientiousness. Alcohol-dependent females scored higher on Conscientiousness and lower on Neuroticism compared to opiate-dependent women. The results of our study confirmed significant characteristics in personality profiles among females with alcohol and opiate dependence, as well as the difference between these two groups of substance abusers and their healthy controls. The distinct personality characteristics among different groups of substance addicted women should be taken into account

  18. Delta FosB and AP-1-mediated transcription modulate cannabinoid CB₁ receptor signaling and desensitization in striatal and limbic brain regions.

    Science.gov (United States)

    Lazenka, Matthew F; David, Bethany G; Lichtman, Aron H; Nestler, Eric J; Selley, Dana E; Sim-Selley, Laura J

    2014-10-01

    Repeated Δ(9)-tetrahydrocannabinol (THC) administration produces cannabinoid type 1 receptor (CB₁R) desensitization and downregulation, as well as tolerance to its in vivo pharmacological effects. However, the magnitude of CB₁R desensitization varies by brain region, with CB₁Rs in the striatum and its output nuclei undergoing less desensitization than other regions. A growing body of data indicates that regional differences in CB₁R desensitization are produced, in part, by THC-mediated induction of the stable transcription factor, ΔFosB, and subsequent regulation of CB₁Rs. The purpose of the present study was to determine whether THC-mediated induction of ΔFosB in the striatum inhibits CB₁R desensitization in the striatum and output nuclei. This hypothesis was tested using bitransgenic mice with inducible expression of ΔFosB or ΔcJun, a dominant negative inhibitor of AP-1-mediated transcription, in specific forebrain regions. Mice were treated repeatedly with escalating doses of THC or vehicle for 6.5 days, and CB₁R-mediated G-protein activation was assessed using CP55,940-stimulated [(35)S]GTPγS autoradiography. Overexpression of ΔFosB in striatal dopamine type 1 receptor-containing (D1R) medium spiny neurons (MSNs) attenuated CB₁R desensitization in the substantia nigra, ventral tegmental area (VTA) and amygdala. Expression of ΔcJun in striatal D1R- and dopamine type 2 receptor (D2R)-containing MSNs enhanced CB₁R desensitization in the caudate-putamen and attenuated desensitization in the hippocampus and VTA. THC-mediated in vivo pharmacological effects were then assessed in ΔcJun-expressing mice. Tolerance to THC-mediated hypomotility was enhanced in ΔcJun-expressing mice. These data reveal that ΔFosB and possibly other AP-1 binding proteins regulate CB₁R signaling and adaptation in the striatum and limbic system. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. 77 FR 72752 - Opioid Drugs in Maintenance and Detoxification Treatment of Opiate Addiction; Proposed...

    Science.gov (United States)

    2012-12-06

    ... and Detoxification Treatment of Opiate Addiction; Proposed Modification of Dispensing Restrictions for... of a patient's responsibility and stability to receive opioid addiction treatment medication. Opioid... addiction. The special authorization is required under federal law because these medications can be abused...

  20. Dismantling the Afghan Opiate Economy: A Cultural and Historical Policy Assessment, with Policy Recommendations

    National Research Council Canada - National Science Library

    Byrom, Christopher L

    2005-01-01

    .... Specific lessons are taken from a chapter dedicated to Afghan culture, history, and rural power structures, and applied in chapters analyzing the opiate economy and current counter-narcotics policies...

  1. Opiate addiction and overdose: experiences, attitudes, and appetite for community naloxone provision.

    LENUS (Irish Health Repository)

    Barry, Tomás

    2017-02-28

    More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use.

  2. The bovine T cell receptor alpha/delta locus contains over 400 V genes and encodes V genes without CDR2.

    Science.gov (United States)

    Reinink, Peter; Van Rhijn, Ildiko

    2009-07-01

    Alphabeta T cells and gammadelta T cells perform nonoverlapping immune functions. In mammalian species with a high percentage of very diverse gammadelta T cells, like ruminants and pigs, it is often assumed that alphabeta T cells are less diverse than gammadelta T cells. Based on the bovine genome, we have created a map of the bovine TRA/TRD locus and show that, in cattle, in addition to the anticipated >100 TRDV genes, there are also >300 TRAV or TRAV/DV genes. Among the V genes in the TRA/TRD locus, there are several genes that lack a CDR2 and are functionally rearranged and transcribed and, in some cases, have an extended CDR1. The number of bovine V genes is a multiple of the number in mice and humans and may encode T cell receptors that use a novel way of interacting with antigen.

  3. Multi-criteria ranking and receptor modelling of airborne fine particles at three sites in the Pearl River Delta region of China.

    Science.gov (United States)

    Friend, Adrian J; Ayoko, Godwin A; Guo, Hai

    2011-01-15

    The multi-criteria decision making methods, Preference Ranking Organization METHods for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA), and the two-way Positive Matrix Factorization (PMF) receptor model were applied to airborne fine particle compositional data collected at three sites in Hong Kong during two monitoring campaigns held from November 2000 to October 2001 and November 2004 to October 2005. PROMETHEE/GAIA indicated that the three sites were worse during the later monitoring campaign, and that the order of the air quality at the sites during each campaign was: rural site>urban site>roadside site. The PMF analysis on the other hand, identified 6 common sources at all of the sites (diesel vehicle, fresh sea salt, secondary sulphate, soil, aged sea salt and oil combustion) which accounted for approximately 68.8±8.7% of the fine particle mass at the sites. In addition, road dust, gasoline vehicle, biomass burning, secondary nitrate, and metal processing were identified at some of the sites. Secondary sulphate was found to be the highest contributor to the fine particle mass at the rural and urban sites with vehicle emission as a high contributor to the roadside site. The PMF results are broadly similar to those obtained in a previous analysis by PCA/APCS. However, the PMF analysis resolved more factors at each site than the PCA/APCS. In addition, the study demonstrated that combined results from multi-criteria decision making analysis and receptor modelling can provide more detailed information that can be used to formulate the scientific basis for mitigating air pollution in the region. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(DJ recombinations

    Directory of Open Access Journals (Sweden)

    Jouvin-Marche Evelyne

    2006-04-01

    Full Text Available Abstract Background Adaptative immune repertoire diversity in vertebrate species is generated by recombination of variable (V, diversity (D and joining (J genes in the immunoglobulin (IG loci of B lymphocytes and in the T cell receptor (TR loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level involve recombination signal sequences (RSS. Whereas many data exist, they are scattered in non specialized resources with different nomenclatures (eg. flat files and are difficult to extract. Description IMGT/GeneInfo is an online information system that provides, through a user-friendly interface, exhaustive information resulting from the complex mechanisms of T cell receptor V-J and V-D-J recombinations. T cells comprise two populations which express the αβ and γδ TR, respectively. The first version of the system dealt with the Homo sapiens and Mus musculus TRA and TRB loci whose gene rearrangements allow the synthesis of the αβ TR chains. In this paper, we present the second version of IMGT/GeneInfo where we complete the database for the Homo sapiens and Mus musculus TRG and TRD loci along with the introduction of a quality control procedure for existing and new data. We also include new functionalities to the four loci analysis, giving, to date, a very informative tool which allows to work on V(DJ genes of all TR loci in both human and mouse species. IMGT/GeneInfo provides more than 59,000 rearrangement combinations with a full gene description which is freely available at http://imgt.cines.fr/GeneInfo. Conclusion IMGT/GeneInfo allows all TR information sequences to be in the same spot, and are now available within two computer-mouse clicks. This is useful for biologists and bioinformaticians for the study of T lymphocyte V(DJ gene rearrangements and their applications in immune response analysis.

  5. Pain acceptance and opiate use disorders in addiction treatment patients with comorbid pain.

    Science.gov (United States)

    Lin, Lewei Allison; Bohnert, Amy S B; Price, Amanda M; Jannausch, Mary; Bonar, Erin E; Ilgen, Mark A

    2015-12-01

    Studies from pain treatment settings indicate that poor acceptance of pain may be an important and modifiable risk factor for higher severity of opioid use. However, the degree to which pain acceptance relates to opioid use severity in the addiction treatment population is unknown. In this study of addiction treatment patients with co-morbid pain, we examined correlates of severity of opiate (heroin and prescription opioid) use, with a particular focus on the role of pain acceptance. Patients in residential addiction treatment with comorbid pain (N=501) were stratified into low, moderate and high severity of opiate use. Demographic and clinical characteristics were compared across opiate severity categories. 72% (N=360) of the participants had symptoms that were consistent with an opiate use disorder. Younger age, Caucasian race, female gender, cocaine use and lower pain acceptance were associated with higher severity of opiate use, whereas pain intensity was not. Controlling for demographic and other risk factors, such as substance use and pain intensity, higher pain acceptance was associated with lower odds of severe prescription opioid (AOR 0.50, 95% CI 0.38-0.68 for a one SD increase in pain acceptance) and heroin use (AOR 0.57, 95% CI 0.44-0.75 for a one SD increase in pain acceptance). Problematic opiate use is common in addictions treatment patients with chronic pain. Lower pain acceptance is related to greater opiate use severity, and may be an important modifiable target for interventions to successfully treat both pain and opiate use disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Delta activity independent of its activity as a ligand of Notch

    Directory of Open Access Journals (Sweden)

    Ahimou Francois

    2005-03-01

    Full Text Available Abstract Background Delta, Notch, and Scabrous often function together to make different cell types and refine tissue patterns during Drosophila development. Delta is known as the ligand that triggers Notch receptor activity. Scabrous is known to bind Notch and promote Notch activity in response to Delta. It is not known if Scabrous binds Delta or Delta has activity other than its activity as a ligand of Notch. It is very difficult to clearly determine this binding or activity in vivo as all Notch, Delta, and Scabrous activities are required simultaneously or successively in an inter-dependent manner. Results Using Drosophila cultured cells we show that the full length Delta promotes accumulation of Daughterless protein, fringe RNA, and pangolin RNA in the absence of Scabrous or Notch. Scabrous binds Delta and suppresses this activity even though it increases the level of the Delta intracellular domain. We also show that Scabrous can promote Notch receptor activity, in the absence of Delta. Conclusion Delta has activity that is independent of its activity as a ligand of Notch. Scabrous suppresses this Delta activity. Scabrous also promotes Notch activity that is dependent on Delta's ligand activity. Thus, Notch, Delta, and Scabrous might function in complex combinatorial or mutually exclusive interactions during development. The data reported here will be of significant help in understanding these interactions in vivo.

  7. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  8. Outcomes of coronary artery bypass grafting in patients with a history of opiate use.

    Science.gov (United States)

    Safaei, Nasser

    2008-11-15

    This study aimed at evaluating the outcome of CABG in patients with a history of opiate use. Two hundred male patients, underwent CABG surgery, were evaluated and followed up for 6 months. The patients classified as Group P (with Previous history of opiate use) and Group N (with No history of opiate use). The characteristics and 6-month outcomes were compared between the two groups. Patients in group P further categorized into two subgroups of active and non-active abusers. Two hundred male-patients enrolled in the study, 23 (11.5%) patients had a history of opiate abuse. Nine (4.5%) patients were past users and 14 (7%) cases were current users. There were no significant differences regarding the age, history of hypertension, smoking, ejection fraction before and 6 months after CABG, duration of hospital stay, complications of surgery and function class (pnutritional and activity recommendations after CABG was significantly lower for current opiate users. Also, the need for readmission after CABG due to cardiac complications was independently higher in current opiate users. Carrying out the educational programs to correct the misconception about the beneficial effects of illicit drugs on cardio-vascular disease makes sense.

  9. Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment.

    Science.gov (United States)

    Morse, Siobhan; MacMaster, Samuel

    2015-01-01

    Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18-25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake.

  10. Effect of moderate alcohol consumption on plasma opiate levels in premenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Bhathena, S.J.; Kim, Y.C.; Law, J.S.; Berlin, E.; Judd. J.T.; Reichman, M.E.; Taylor, P.R.; Schatzkin, A. (Dept. of Agriculture, Beltsville, MD (United States) NCI, Bethesda, MD (United States))

    1991-03-15

    Opiate changes have been reported in response to excessive alcohol consumption. Different phases of the menstrual cycle also affect the opiate tone. The authors studied the effect of moderate alcohol consumption and the menstrual cycle per se on plasma opiates. Forty premenopausal women were given alcohol or a soft drink of equal caloric value for 3 menstrual cycles in a cross over study. The subjects were fed a controlled diet containing 35% of energy from fat. Blood was collected in the third menstrual cycle of each period during follicular (F), ovulatory (O) and luteal (L) phases. {beta}-endorphin, met-enkephalin and lwu-enkephalin (LE) were measured by radioimmunoassay. None of the opiates showed significant change after alcohol consumption though LE was consistently higher after alcohol consumption during all three phases of the menstrual cycle. There was a significant decrease in BEN during L phase compared to F phase while both enkephalins were higher during L phase than during F phase. Opiate levels during O phase were intermediate between F and L. Thus, in contrast to previously observed opiate changes following excessive alcohol consumption, they did not observe changes with moderate consumption.

  11. Comparison of temperament and character personality traits in opiate and stimulant addicts

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadeghi Pouya

    2016-11-01

    Full Text Available Background: Phenomenon of addiction as one of the social problems has a high prevalence, especially among youth. The aim of the present study was to compare personality traits based on the temperament and character inventory in opiate and stimulant addicts in Tehran.  Methods: In the present quasi-experimental study, 60 male addicts (30 opiate and 30 stimulant addicts who referred to addiction treatment centers in the suburbs of Tehran were selected through convenience sampling method and were studied using Temperament and Character Inventory (TCI. The participants were sorted according to their age and education.    Results: There was a significant difference between the two groups with regard to harm avoidance, reward dependence, cooperativeness, and self-transcendence traits. Thus, opiate addicts had higher levels of harm avoidance, reward dependence, and cooperativeness, and stimulant addicts had higher levels of self-transcendence. The significance level was set at P<0.01.  Conclusion: The obtained results showed that there was a significant difference between opiate and stimulant addicts. Opiate addicts gained higher scores, compared with stimulant addicts, in Temperament and Character Inventory variables. The obtained results also showed that stimulant addicts were suffering from more severe disorders than opiate addicts. Based on the means of the values of the TCI, personality traits reflecting personality disorders are detectable and predictable in substance abusers. This new understanding is important in the prevention and treatment of addiction.

  12. Regional distribution of opiate alkaloids in experimental animals' brain tissue and blood

    Directory of Open Access Journals (Sweden)

    Đurendić-Brenesel Maja

    2012-01-01

    Full Text Available The aim of this study was to examine the regional distribution of opiate alkaloids from seized heroin in experimental animals' brain regions and blood. Results could be used in the examination of opiate alkaloids' distribution in human biological samples in order to contribute to the solution of the causes of death due to heroin intake. Experimental animals (Wistar rats were treated with seized heroin, and were sacrificed at different time periods: 5, 15, 45 and 120 min after treatment. Opiate alkaloids' (codeine, morphine, acetylcodeine, 6- acetylmorphine and 3,6-diacetylmorphine content was determined in the brain regions (cortex, brainstem, amygdala and basal ganglia and blood of animals using gas chromatography-mass spectrometry (GC-MS method. The highest content of opiate alkaloids in the blood was measured 15 min, and in the brain tissue 45 min after the treatment with heroin. The maximal concentration of opiates was determined in the basal ganglia. The obtained results offer the possibility of selecting this part of the brain tissue as a representative sample for identifying and assessing the content of opiates.

  13. Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis.

    OpenAIRE

    Havlir, D V; Ellner, J J; Chervenak, K A; Boom, W H

    1991-01-01

    Gamma delta (gamma delta) T cell receptor (TCR) expressing T cells comprise 3% of human peripheral blood lymphocytes, yet their role in the immune response remains largely unknown. There is evidence both in humans and in animal models that these cells participate in the immune response to mycobacterial antigens. In mice, exposure to mycobacterial antigens leads to the expansion of gamma delta T cells in draining lymph nodes and lungs. In humans, gamma delta T cell lines with reactivity to myc...

  14. AMP-Activated Protein Kinase Interacts with the Peroxisome Proliferator-Activated Receptor Delta to Induce Genes Affecting Fatty Acid Oxidation in Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Marina Kemmerer

    Full Text Available AMP-activated protein kinase (AMPK maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO. The transcription factor peroxisome proliferator-activated receptor δ (PPARδ also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload.

  15. Delta 2.0

    DEFF Research Database (Denmark)

    Skott, Jeppe; Skott, Charlotte Krog; Jess, Kristine

    DELTA 2.0 er en ny og helt opdateret udgave af Delta, der i ti år været brugt i matematiklærernes grund-, efter- og videreuddannelse. DELTA 2.0 er seriens almene fagdidaktik. Der er også fagdidaktiske overvejelser i de øvrige bøger i serien, men de er knyttet til specifikt matematisk indhold. DEL...

  16. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  17. Evolution of the CD163 family and its relationship to the bovine gamma delta T cell co-receptor WC1

    Directory of Open Access Journals (Sweden)

    Baldwin Cynthia L

    2010-06-01

    Full Text Available Abstract Background The scavenger receptor cysteine rich (SRCR domain is an ancient and conserved protein domain. CD163 and WC1 molecules are classed together as group B SRCR superfamily members, along with Spα, CD5 and CD6, all of which are expressed by immune system cells. There are three known types of CD163 molecules in mammals, CD163A (M130, coded for by CD163, CD163b (M160, coded for by CD163L1 and CD163c-α (CD163L1 or SCART, while their nearest relative, WC1, is encoded by a multigene family so far identified in the artiodactyl species of cattle, sheep, and pigs. Results We annotated the bovine genome and identified genes coding for bovine CD163A and CD163c-α but found no evidence for CD163b. Bovine CD163A is widely expressed in immune cells, whereas CD163c-α transcripts are enriched in the WC1+ γδ T cell population. Phylogenetic analyses of the CD163 family genes and WC1 showed that CD163c-α is most closely related to WC1 and that chicken and platypus have WC1 orthologous genes, previously classified as among their CD163 genes. Conclusion Since it has been shown that WC1 plays an important role in the regulation of γδ T cell responses in cattle, which, like chickens, have a high percentage of γδ T cells in their peripheral blood, CD163c-α may play a similar role, especially in species lacking WC1 genes. Our results suggest that gene duplications resulted in the expansion of CD163c-α-like and WC1-like molecules. This expanded repertoire was retained by species known as "γδ T cell high", but homologous SRCR molecules were maintained by all mammals.

  18. Dynorphin A (2-17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat.

    Science.gov (United States)

    Shippenberg, T S; Funada, M; Schutz, C G

    2000-09-01

    An unbiased place preference conditioning procedure was used to examine the influence of the non-opioid peptide, dynorphin A 2-17 (DYN 2-17), upon the conditioned and unconditioned effects of opiate withdrawal in the rat. Rats were implanted SC with two pellets containing 75 mg morphine or placebo. Single-trial place conditioning sessions with saline and the opioid receptor antagonist naloxone (0.1-1.0 mg/kg; SC) commenced 4 days later. Ten minutes before SC injections, animals received an IV infusion of saline or DYN 2-17 (0.1-5.0 mg/kg). Additional groups of placebo- and morphine-pelleted animals were conditioned with saline and DYN 2-17. During each 30-min conditioning session, somatic signs of withdrawal were quantified. Tests of place conditioning were conducted in pelleted animals 24 h later. Naloxone produced wet-dog shakes, body weight loss, ptosis and diarrhea in morphine-pelleted animals. Morphine-pelleted animals also exhibited significant aversions for an environment previously associated with the administration of naloxone. These effects were not observed in placebo-pelleted animals. DYN 2-17 pretreatment resulted in a dose-related attenuation of somatic withdrawal signs. However, conditioned place aversions were still observed in morphine-pelleted animals that had received DYN 2-17 in combination with naloxone. Furthermore, the magnitude of this effect did not differ from control animals. These data demonstrate that the administration of DYN 2-17 attenuates the somatic, but not the conditioned aversive effects of antagonist-precipitated withdrawal from morphine in the rat. Differential effects of this peptide in modulating the conditioned and unconditioned effects of opiate withdrawal are suggested.

  19. Delta hedging strategies comparison

    DEFF Research Database (Denmark)

    De Giovanni, Domenico; Ortobelli, S.; Rachev, S.T.

    2008-01-01

    In this paper we implement dynamic delta hedging strategies based on several option pricing models. We analyze different subordinated option pricing models and we examine delta hedging costs using ex-post daily prices of S&P 500. Furthermore, we compare the performance of each subordinated model...

  20. The Relationship between Childhood Maltreatment and Opiate Dependency in Adolescence and Middle Age.

    Science.gov (United States)

    Naqavi, Mohammad Reza; Mohammadi, Masood; Salari, Vahid; Nakhaee, Nouzar

    2011-01-01

    Child maltreatment is a global phenomenon with possible serious long-term consequences. The present study aimed to determine the relationship between childhood maltreatment and opiate dependency in older age. In this study, 212 opiate dependent individuals and 216 control subjects were selected consecutively. The data collection instrument was a questionnaire which consisted of background variables, General Health Questionnaire-12 (GHQ-12), and Childhood Trauma Questionnaire (CTQ). The questionnaires were anonymously completed by both groups in a private environment after obtaining informed consents. The mean age in the addicts and non-addicts were 31.4 ± 6.7 and 30.8 ± 7.5, respectively (P = 0.367). Moreover, 84.4% of the opiate abusers and 76.9% percent of the control group were male (P = 0.051). The mean score of CTQ in the study and control groups were 47.2 ± 1.0 and 35.8 ± 0.6, respectively (P emotional abuse (OR = 5.06), physical neglect (OR = 1.96), and sexual abuse (OR = 1.89) were proved to have significant relationships with addiction to opiates. The frequency of all types of childhood maltreatment in the group addicted to opiates was higher than the control group. Emotional abuse, physical neglect, and sexual abuse had significant effects after adjusting other variables.

  1. Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets

    DEFF Research Database (Denmark)

    Adriaenssens, Alice E; Svendsen, Berit; Lam, Brian Y H

    2016-01-01

    expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused...... pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate...

  2. Experimental investigations on hair fibers as diffusion bridges and opiates as solutes in solution.

    Science.gov (United States)

    Skopp, G; Pötsch, L; Aderjan, R

    1996-01-01

    Diffusion experiments were performed using clipped hair fibers as diffusion bridges and aqueous solutions of morphine, codeine and dihydrocodeine. Natural as well as predamaged hair fibers were investigated. The test series were conducted at ambient temperature and at high humidity. After 312 or 372 hours the middle segments of the strands were clipped, washed and analyzed by GC/MS. Only when virgin hair samples were used the solutes passed along the fiber at full length resulting in a positive immunological finding at the end of the diffusion bridge. Most of the washing fluids were positive for opiates. All centerpieces had a high opiate content. The opiate concentration in damaged hair was significantly higher. Radial swelling of the hair fiber with radial diffusion was the first and main process to appear when hair was exposed to water. The diffusion process in hair could not be placed in a simple mathematical treatment.

  3. Stability of opiates in hair fibers after exposure to cosmetic treatment.

    Science.gov (United States)

    Pötsch, L; Skopp, G

    1996-08-15

    The stability of opiates in clipped natural human hair was investigated. Hair fibers were incubated with defined solutions of morphine, codeine and dihydrocodeine (pH 7.4) until saturated. Original opiate-positive hair samples collected from drug addicts also were examined. Commercially available bleaching as well as perming formulas (Poly Blonde Ultra, Poly Lock; Henkel, Düsseldorf, Germany) were applied in vitro to the hair strands of both groups under investigation. After these treatments, the drug concentration had decreased for both bleaching and permanent waving. In the spiked hair, only 2-18% of the starting solution could be found after bleaching. About 20-30% of the drug substances could still be detected after perming. In the authentic hair samples, the drug levels of the formerly opiate positive hair fibers had also been reduced but distinct tendencies could not be observed.

  4. Profiles of quality of life in opiate-dependent individuals after starting methadone treatment : A latent class analysis

    NARCIS (Netherlands)

    de Maeyer, J.; van Nieuwenhuizen, Ch.; Bongers, I.L.; Broekaert, E.; Vanderplasschen, W.

    2013-01-01

    Background This study aimed to identify classes of quality of life (QoL) among opiate-dependent individuals five to ten years after starting methadone treatment in order to tailor services to the needs of this population. Methods A cross-sectional study of 159 opiate-dependent individuals who

  5. Auditory target processing in methadone substituted opiate addicts: The effect of nicotine in controls

    Directory of Open Access Journals (Sweden)

    Zerbin Dieter

    2007-11-01

    Full Text Available Abstract Background The P300 component of the auditory evoked potential is an indicator of attention dependent target processing. Only a few studies have assessed cognitive function in substituted opiate addicts by means of evoked potential recordings. In addition, P300 data suggest that chronic nicotine use reduces P300 amplitudes. While nicotine and opiate effects combine in addicted subjects, here we investigated the P300 component of the auditory event related potential in methadone substituted opiate addicts with and without concomitant non-opioid drug use in comparison to a group of control subjects with and without nicotine consumption. Methods We assessed 47 opiate addicted out-patients under current methadone substitution and 65 control subjects matched for age and gender in an 2-stimulus auditory oddball paradigm. Patients were grouped for those with and without additional non-opioid drug use and controls were grouped for current nicotine use. P300 amplitude and latency data were analyzed at electrodes Fz, Cz and Pz. Results Patients and controls did not differ with regard to P300 amplitudes and latencies when whole groups were compared. Subgroup analyses revealed significantly reduced P300 amplitudes in controls with nicotine use when compared to those without. P300 amplitudes of methadone substituted opiate addicts were in between the two control groups and did not differ with regard to additional non-opioid use. Controls with nicotine had lower P300 amplitudes when compared to patients with concomitant non-opioid drugs. No P300 latency effects were found. Conclusion Attention dependent target processing as indexed by the P300 component amplitudes and latencies is not reduced in methadone substituted opiate addicts when compared to controls. The effect of nicotine on P300 amplitudes in healthy subjects exceeds the effects of long term opioid addiction under methadone substitution.

  6. Hepatitis D (Delta agent)

    Science.gov (United States)

    Complications may include: Chronic active hepatitis Acute liver failure ... Landaverde C, Perrillo R. Hepatitis D. In: Feldman M, Friedman LS, ... 81. Thio CL, Hawkins C. Hepatitis B virus and hepatitis delta ...

  7. Man made deltas

    Science.gov (United States)

    Maselli, Vittorio; Trincardi, Fabio

    2013-01-01

    The review of geochronological and historical data documents that the largest southern European deltas formed almost synchronously during two short intervals of enhanced anthropic pressure on landscapes, respectively during the Roman Empire and the Little Ice Age. These growth phases, that occurred under contrasting climatic regimes, were both followed by generalized delta retreat, driven by two markedly different reasons: after the Romans, the fall of the population and new afforestation let soil erosion in river catchments return to natural background levels; since the industrial revolution, instead, flow regulation through river dams overkill a still increasing sediment production in catchment basins. In this second case, furthermore, the effect of a reduced sediment flux to the coasts is amplified by the sinking of modern deltas, due to land subsidence and sea level rise, that hampers delta outbuilding and increases the vulnerability of coastal zone to marine erosion and flooding. PMID:23722597

  8. Opioid receptors mediate the acquisition, but not the expression of mitragynine-induced conditioned place preference in rats.

    Science.gov (United States)

    Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

    2017-08-14

    Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Man made deltas?

    Science.gov (United States)

    Maselli, V.; Trincardi, F.

    2014-12-01

    During the last few millennia, southern European fluvio-deltaic systems have evolved in response to changes in the hydrological cycle, mostly driven by high-frequency climate oscillations and increasing anthropic pressure on natural landscapes. The review of geochronological and historical data documents that the bulk of the four largest northern Mediterranean and Black Sea deltas (Ebro, Rhone, Po and Danube) formed during two short and synchronous intervals during which anthropogenic land cover change was the main driver for enhanced sediment production. These two major growth phases occurred under contrasting climatic regimes and were both followed by generalized delta retreat, supporting the hypothesis of human-driven delta progradation. Delta retreat, in particular, was the consequence of reduced soil erosion for renewed afforestation after the fall of the Roman Empire, and of river dams construction that overkilled the still increasing sediment production in catchment basins since the Industrial Era. In this second case, in particular, the effect of a reduced sediment flux to the coasts is amplified by the sinking of modern deltas, due to land subsidence and sea level rise, that hampers delta outbuilding and increases the vulnerability of coastal zone to marine erosion and flooding.

  10. Characterization of a 10- to 14-kilodalton protease-sensitive Mycobacterium tuberculosis H37Ra antigen that stimulates human gamma delta T cells.

    OpenAIRE

    Boom, W H; Balaji, K N; Nayak, R; Tsukaguchi, K; Chervenak, K A

    1994-01-01

    gamma delta T-cell receptor-bearing T cells (gamma delta T cells) are readily activated by intracellular bacterial pathogens such as Mycobacterium tuberculosis. The bacterial antigens responsible for gamma delta T-cell activation remain poorly characterized. We have found that heat treatment of live M. tuberculosis bacilli released into the supernatant an antigen which stimulated human gamma delta T cells. gamma delta T-cell activation was measured by determining the increase in percentage of...

  11. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil.

    Science.gov (United States)

    Heinz, Andreas; Reimold, Matthias; Wrase, Jana; Hermann, Derik; Croissant, Bernhard; Mundle, Götz; Dohmen, Bernhard M; Braus, Dieter F; Braus, Dieter H; Schumann, Gunter; Machulla, Hans-Jürgen; Bares, Roland; Mann, Karl

    2005-01-01

    The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all alcoholic individuals. To test the hypothesis that alcohol craving is pronounced among alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). Hospitalized care. Volunteer sample of 25 male alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS. Abstinent alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of alcohol craving. These findings point to a neuronal correlate of alcohol urges.

  12. How to overcome hurdles in opiate substitution treatment? A qualitative study with general practitioners in Belgium.

    Science.gov (United States)

    Fraeyman, Jessica; Symons, Linda; Van Royen, Paul; Van Hal, Guido; Peremans, Lieve

    2016-06-01

    Opiate substitution treatment (OST) is the administration of opioids (methadone or buprenorphine) under medical supervision for opiate addiction. Several studies indicate a large unmet need for OST in general practice in Antwerp, Belgium. Some hurdles remain before GPs engage in OST prescribing. Formulate recommendations to increase engagement of GPs in OST, applicable to Belgium and beyond. In 2009, an exploratory qualitative research was performed using focus group discussions and interviews with GPs. During data collection and analysis, purposive sampling, open and axial coding was applied. The script was composed around the advantages, disadvantages and conditions of engaging in OST in general practice. We conducted six focus groups and two interviews, with GPs experienced in prescribing OST (n = 13), inexperienced GPs (n = 13), and physicians from addiction centres (n = 5). Overall, GPs did not seem very willing to prescribe OST for opiate users. A lack of knowledge about OST and misbehaving patients creates anxiety and makes the GPs reluctant to learn more about OST. The GPs refer to a lack of collaboration with the addiction centres and a need of support (from either addiction centres or experienced GP-colleagues for advice). Important conditions for OST are acceptance of only stable opiate users and more support in emergencies. Increasing GPs' knowledge about OST and improving collaboration with addiction centres are essential to increase the uptake of OST in general practice. Special attention could be paid to the role of more experienced colleagues who can act as advising physicians for inexperienced GPs.

  13. Neurogenetics of acute and chronic opiate/opioid abstinence: treating symptoms and the cause.

    Science.gov (United States)

    Blum, Kenneth; Gold, Mark S; Jacobs, William; McCall, William Vaughn; Febo, Marcelo; Baron, David; Dushaj, Kristina; Demetrovics, Zsolt; Badgaiyan, Rajendra D

    2017-03-01

    This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets. Alterations in functional brain connectivity based on neurobiological mechanisms in heroin dependence and abstinence are also reviewed. A new clinical model an alternative to merely blocking acute withdrawal symptoms as identified in the DSM -5 is proposed. Genetic diagnosis at the onset of detoxification, to determine risk stratification, and identify polymorphic gene targets for pharmaceutical and nutraceutical interventions, followed by the simultaneous initiation of Medication Assisted Therapy (MAT), to enable psychological extinction, and steady pro-dopaminergic therapy with the goal of developing "dopamine homeostasis" is recommended. The objective of these interventions is to prevent future relapse by treating all "Reward Deficiency Syndrome" (RDS) behaviors and eventually make an addiction-free life possible .

  14. Heroin-assisted treatment as a response to the public health problem of opiate dependence

    NARCIS (Netherlands)

    Fischer, Benedikt; Rehm, Jürgen; Kirst, Maritt; Casas, Miguel; Hall, Wayne; Krausz, Michael; Metrebian, Nicky; Reggers, Jean; Uchtenhagen, Ambros; van den Brink, Wim; van Ree, Jan M.

    2002-01-01

    Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased

  15. Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS)

    NARCIS (Netherlands)

    Dijkstra, B.A.G.; Krabbe, P.F.M.; Riezebos, T.G.M.; Staak, C.P.F. van der; Jong, C.A.J. de

    2007-01-01

    AIM: To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. METHODS: The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four

  16. Relationships Between Using Other Substances and Socio-Demographic Characteristics in Opiate Dependents

    Directory of Open Access Journals (Sweden)

    Melike Nebioglu,Hacer Yalniz

    2013-02-01

    Full Text Available Objective: We aimed to determine the variables that can be a risk factor for addiction like age, gender, education level, school cession, first using age, substance use period, frequency and using other addictive substances among people who have a diagnosis of opiate addiction. Methods: This is a descriptive and cross-sectional study in AMBAUM ( Akdeniz University Alcohol and Substance Dependence Research and Practice Center between February 1,2010- April30, 2010. 84 inpatient and outpatient patients (60 men, 24 women between age 14-37, who have a diagnosis of opiate addiction according to DSM IV-TR diagnostic criteria recruited in this study. All participating patients completed a standard questionaire and sociodemographic data form face to face. The results were analyzed with chi-squared test by using SPSS 16 statistics program. Results: In our patients nicotin addiction prevalance is 100%, alcohol using prevalance is 91.7%, cannabis using prevalance 86.9%, ecstasy using prevalance 54.8%, cocain using prevalance 48.8%, polysubstance using prevalance 47.6%, hallucinogen using prevalance 27.4%, addictive medical drug using prevalance 17.9%. Conclusions: This epidemiological study guide us in the monitoring and evalution of the opiate use and prevalance of other substance use with opiate addiction. Keywords: Prevalence, heroin, polysubstance dependence. [TAF Prev Med Bull 2013; 12(1.000: 35-42

  17. Racial Differences in Opiate Administration for Pain Relief at an Academic Emergency Department

    Directory of Open Access Journals (Sweden)

    Dickason, R. Myles

    2015-05-01

    Full Text Available Introduction: The decision to treat pain in the emergency department (ED is a complex, idiosyncratic process. Prior studies have shown that EDs undertreat pain. Several studies demonstrate an association between analgesia administration and race. This is the first Midwest single institution study to address the question of race and analgesia, in addition to examining the effects of both patient and physician characteristics on race-based disparities in analgesia administration. Methods: This was a retrospective chart review of patients presenting to an urban academic ED with an isolated diagnosis of back pain, migraine, or long bone fracture (LBF from January 1, 2007 to December 31, 2011. Demographic and medication administration information was collected from patient charts by trained data collectors blinded to the hypothesis of the study. The primary outcome was the proportion of African-Americans who received analgesia and opiates, as compared to Caucasians, using Pearson’s chi-squared test. We developed a multiple logistic regression model to identify which physician and patient characteristics correlated with increased opiate administration. Results: Of the 2,461 patients meeting inclusion criteria, 57% were African-American and 30% Caucasian (n=2136. There was no statistically significant racial difference in the administration of any analgesia (back pain: 86% vs. 86%, p=0.81; migraine: 83% vs. 73%, p=0.09; LBF: 94% vs. 90%, p=0.17, or in opiate administration for migraine or LBF. African-Americans who presented with back pain were less likely to receive an opiate than Caucasians (50% vs. 72%, p<0.001. Secondary outcomes showed that higher acuity, older age, physician training in emergency medicine, and male physicians were positively associated with opiate administration. Neither race nor gender patient-physician congruency correlated with opiate administration. Conclusion: No race-based disparity in overall analgesia administration was

  18. Acquisition, extinction, and recall of opiate reward memory are signaled by dynamic neuronal activity patterns in the prefrontal cortex.

    Science.gov (United States)

    Sun, Ninglei; Chi, Ning; Lauzon, Nicole; Bishop, Stephanie; Tan, Huibing; Laviolette, Steven R

    2011-12-01

    The medial prefrontal cortex (mPFC) comprises an important component in the neural circuitry underlying drug-related associative learning and memory processing. Neuronal activation within mPFC circuits is correlated with the recall of opiate-related drug-taking experiences in both humans and other animals. Using an unbiased associative place conditioning procedure, we recorded mPFC neuronal populations during the acquisition, recall, and extinction phases of morphine-related associative learning and memory. Our analyses revealed that mPFC neurons show increased activity both in terms of tonic and phasic activity patterns during the acquisition phase of opiate reward-related memory and demonstrate stimulus-locked associative activity changes in real time, during the recall of opiate reward memories. Interestingly, mPFC neuronal populations demonstrated divergent patterns of bursting activity during the acquisition versus recall phases of newly acquired opiate reward memory, versus the extinction of these memories, with strongly increased bursting during the recall of an extinction memory and no associative bursting during the recall of a newly acquired opiate reward memory. Our results demonstrate that neurons within the mPFC are involved in both the acquisition, recall, and extinction of opiate-related reward memories, showing unique patterns of tonic and phasic activity patterns during these separate components of the opiate-related reward learning and memory recall.

  19. Predicting response to opiate antagonists and placebo in the treatment of pathological gambling.

    Science.gov (United States)

    Grant, Jon E; Kim, Suck Won; Hollander, Eric; Potenza, Marc N

    2008-11-01

    Although opiate antagonists have shown promise in the treatment of pathological gambling (PG), individual responses vary. No studies have systematically examined predictors of medication treatment outcome in PG. Understanding clinical variables related to treatment outcome should help generate treatment algorithms for PG. We sought to identify clinical variables associated with treatment outcome in PG subjects receiving opiate antagonists. Two hundred eighty-four subjects [137 (48.2%) women] with DSM-IV PG were treated in one of two double-blind placebo-controlled trials (16 weeks of nalmefene or 18 weeks of naltrexone). Gambling severity was assessed with the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) with positive response defined as > or =35% reduction in PG-YBOCS score for at least 1 month by study endpoint. Depression, anxiety, and psychosocial functioning were included in stepwise logistic regression analyses designed to identify clinical factors independently associated with treatment response. The clinical variable most strongly associated with a positive response to an opiate antagonist was a positive family history of alcoholism (p = 0.006). Among individuals receiving higher doses of opiate antagonists (i.e., nalmefene 50 or 100 mg/day or naltrexone 100 or 150 mg/day), intensity of gambling urges (PG-YBOCS urge subscale) was associated with a positive response on a trend level (p = 0.036). Among individuals receiving placebo, younger age was associated, on a trend level, with positive treatment outcome (p = 0.012). A family history of alcoholism appears to predict response to an opiate antagonist in PG. Future research is needed to identify specific factors (e.g., genetic) mediating favorable responses.

  20. Ganges River Delta

    Science.gov (United States)

    2002-01-01

    The Ganges River forms an extensive delta where it empties into the Bay of Bengal. The delta is largely covered with a swamp forest known as the Sunderbans, which is home to the Royal Bengal Tiger. It is also home to most of Bangladesh, one of the world's most densely populated countries. Roughly 120 million people live on the Ganges Delta under threat of repeated catastrophic floods due to heavy runoff of meltwater from the Himalayas, and due to the intense rainfall during the monsoon season. This image was acquired by Landsat 7's Enhanced Thematic Mapper plus (ETM+) sensor on February 28, 2000. This is a false-color composite image made using green, infrared, and blue wavelengths. Image provided by the USGS EROS Data Center Satellite Systems Branch

  1. /sup 3/H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((/sup 3/H)CTOP), a potent and highly selective peptide for mu opioid receptors in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, K.N.; Knapp, R.J.; Lui, G.K.; Gulya, K.; Kazmierski, W.; Wan, Y.P.; Pelton, J.T.; Hruby, V.J.; Yamamura, H.I.

    1989-01-01

    The cyclic, conformationally restricted octapeptide (3H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((3H)CTOP) was synthesized and its binding to mu opioid receptors was characterized in rat brain membrane preparations. Association rates (k+1) of 1.25 x 10(8) M-1 min-1 and 2.49 x 10(8) M-1 min-1 at 25 and 37 degrees C, respectively, were obtained, whereas dissociation rates (k-1) at the same temperatures were 1.93 x 10(-2) min-1 and 1.03 x 10(-1) min-1 at 25 and 37 degrees C, respectively. Saturation isotherms of (3H)CTOP binding to rat brain membranes gave apparent Kd values of 0.16 and 0.41 nM at 25 and 37 degrees C, respectively. Maximal number of binding sites in rat brain membranes were found to be 94 and 81 fmol/mg of protein at 25 and 37 degrees C, respectively. (3H)CTOP binding over a concentration range of 0.1 to 10 nM was best fit by a one site model consistent with binding to a single site. The general effect of different metal ions and guanyl-5'-yl-imidodiphosphate on (3H)CTOP binding was to reduce its affinity. High concentrations (100 mM) of sodium also produced a reduction of the apparent mu receptor density. Utilizing the delta opioid receptor specific peptide (3H)-(D-Pen2,D-Pen5)enkephalin, CTOP appeared to be about 2000-fold more specific for mu vs. delta opioid receptor than naloxone. Specific (3H)CTOP binding was inhibited by a large number of opioid or opiate ligands.

  2. Visualization of μ1 opiate receptors in rat brain by using a computerized autoradiographic subtraction technique

    International Nuclear Information System (INIS)

    Goodman, R.R.; Pasternak, G.W.

    1985-01-01

    The authors have developed a quantitative computerized subtraction technique to demonstrate in rat brain the regional distribution of μ 1 sites, a common very-high-affinity binding site for both morphine and the enkephalins. Low concentrations of [D-Ala 2 , D-Leu 5 ]enkephalin selectively inhibit the μ 1 binding of [ 3 H]dihydromorphine, leaving μ 2 -sites, while low morphine concentrations eliminate the μ 1 binding of [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin, leaving sigma sites. Thus, quantitative differences between images of sections incubated in the presence and absence of these low concentrations of unlabeled opioid represent μ 1 binding sites. The regional distributions of μ 1 sites labeled with [ 3 H]dihydromorphine were quite similar to those determined by using [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin. High levels of μ 1 binding were observed in the periaqueductal gray, medial thalamus, and median raphe, consistent with the previously described role of μ 1 sites in analgesia. Other regions with high levels of μ 1 binding include the nucleus accumbens, the clusters and subcallosal streak of the striatum, hypothalamus, medial habenula, and the medial septum/diagonal band region. The proportion of total specific binding corresponding to μ 1 sites varied among the regions, ranging from 14% to 75% for [ 3 H][D-Ala 2 , D-Leu 5 ]enkephalin and 20% to 52% for [ 3 H]dihydromorphine

  3. The Niger Delta

    African Journals Online (AJOL)

    AJL

    2009-05-26

    May 26, 2009 ... which Britain won her Nigerian empire--based its activities in the Delta and the Niger valley. British ascendancy in this important trading area justified her claim to supremacy in the Niger territories during the Berlin West African Conference of 1885.” Clearly, petroleum mining is only the latest in a long series ...

  4. Women of Niger Delta

    African Journals Online (AJOL)

    Religion Dept

    Nigeria as a member of the Africa Union (AU),. NEPAD. and ECOWAS, plays a prominent role as a peace keeper in West. African sub-region. Ironically, in the Niger Delta, Nigeria has not been able to maintain peace. The area has not known peace but chaos, abduction, killing, armed robbery, prostitution and kidnapping.

  5. western niger delta, nigeria

    African Journals Online (AJOL)

    HP

    2015-07-21

    Jul 21, 2015 ... Palynomorph species comprising 53 pollen, 7 spores, 2 algae and 6 dinoflagellate cysts were recovered from a section of well 'Y' located in the offshore western Niger Delta and were used for paleoclimatic deductions of the sediments. There was a dominance of the fresh water swamp species over the ...

  6. about the Dirac Delta Function(?)

    Indian Academy of Sciences (India)

    we enter "delta function" in quotes. This produces a less stupendous 58,600 references. As even this is too much, we try Dirac delta function, to get ... this down to 872, while "the delta function of Dirac" yields a comfortable (but not uniformly helpful) 19 ref- erences. Motivated by a desire to include some interesting histor-.

  7. Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life.

    LENUS (Irish Health Repository)

    Ali, M

    2010-03-01

    Perioperative epidural analgesia provides continuous pain control and may have advantages over parenteral opiate administration. This study assessed the impact of epidural analgesia on quality of life (QOL) of patients undergoing major surgery.

  8. Lifetime opiate exposure as an independent and interactive cardiovascular risk factor in males: a cross-sectional clinical study

    Directory of Open Access Journals (Sweden)

    Reece AS

    2013-10-01

    Full Text Available Albert S Reece, Gary K HulseSchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, AustraliaIntroduction: While several studies have identified an increased incidence of cardiovascular disorders in opiate dependence, neither opiates as a cardiovascular risk factor nor their effect on central arterial function has been considered.Methods: Pulse wave analysis (SphygmoCor, AtCorMedical Pty Limited, Sydney, NSW, Australia was undertaken on a cohort of controls and opiate dependent patients and the results compared to their lifetime opiate exposure.Results: Controls (N = 401 were compared with 465 opiate dependent men. The mean (log ages were different and were found to be 28.80 ± 0.49 years versus 35.02 ± 0.39 years (P < 0.0001, respectively. Of the opiate dependent group, 87.7% were treated with buprenorphine, 8.8% with methadone, and 3.4% with naltrexone. Multiple regression analysis was used to adjust for chronologic age (CA. At CA of 60 years, the modeled age in the controls was 66.40 years, and that in the addicted group was 73.11 years, an advancement of 6.71 years, or 10.10%. Exacerbations of age dependent changes in central arterial stiffness, central pressures, pulse rate, ejection duration, diastolic duration, and subendocardial perfusion ratio by opiate dependence were all noted (P < 0.05. Current heroin dose, heroin duration, and the dose duration interaction were all significantly related to the vascular (or “reference” age (RA/CA ratio (all P < 0.006. After multivariate adjustment, the opiate dose duration was independently predictive of RA (P < 0.02. Opiate dose and/or duration were included in a further 25 terms.Conclusion: These data show that opiate use is not benign for the male cardiovascular system, but has a dose response relationship to central arterial stiffness and thus cardiovascular aging, acting independently and interactively with established cardiovascular risk factors

  9. DELTAS: A new Global Delta Sustainability Initiative (Invited)

    Science.gov (United States)

    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

  10. Do anorectic men share personality traits with opiate dependent men? A case-control study.

    Science.gov (United States)

    Abbate-Daga, Giovanni; Amianto, Federico; Rogna, Lorenzo; Fassino, Secondo

    2007-01-01

    Eating disorders (ED) and substance use disorders (SUD) display clinical and psychodynamic analogies. The co-diagnosis of a substance use disorder in male ED patients is frequent. Nevertheless, knowledge about the mutual predisposing factors or personality analogies is currently scarce and hypotheses are controversial. The Temperament and Character Inventory (TCI) was used to assess 21 anorectic men, 79 heroin-dependent men, and 75 control men matched for age and education. Anorectic and opiate-addicted patients displayed higher Harm Avoidance and lower Self-directedness and Cooperativeness. Anorectic men displayed lower Reward Dependence and higher Persistence. Opiate addicts had higher Novelty Seeking and Self-transcendence. Anorectic and heroine-dependent subjects share personality traits related to anxiety, fearfulness and antisocial features. Nevertheless, the personality profile does not completely overlap and this could influence the choice of the "substance" of abuse and the related clinical differences between anorexia and heroin dependence.

  11. One Year Study of Chest X-Ray Changes in Opiate -poisoned Patients in Hamadan

    Directory of Open Access Journals (Sweden)

    Jafari M.R.

    2010-06-01

    Full Text Available Background and Objectives: Intoxication with opiates is one of the most common causes of referring to emergency departments in Iran. Because respiratory signs are one of the most common and important signs in these patients, this study was designed to evaluate the chest x-ray changes of the patients.Methods: The present study was a cross-sectional one. The changes noted in the Chest X-Ray (CXR of the patients having been intoxicated with opiates and referred with respiratory signs of intoxication during the one year period between July 2007 till July 2008 to Farshchian Hospital in Hamadan were studied. The data, then, were gathered and analyzed using T and chi-square statistical tests.Results: Out of 1698 patients having referred due to poisoning with drugs and chemical agents, 318(18.72% patients were admitted due to opiates intoxication. Among them, 214 (67.29% had respiratory signs. 84.1% were male and 15.9% were female. Their average age was 35.6. The most important substance used was opium (57.5%.Most of the cases (84.1% were due to abuse. The most common physical signs were: miosis (83.6%, respiratory distress (74.8%, rales & wheezing (67.3%. The most common radiographic abnormality was pulmonary edema (14.5%. And the most common substance causing pulmonary edema was crack (59.4% revealing a significant statistical difference (p=0.001. Conclusion: As expected, one of the most important complications and common causes of death in opiate-poisoned patients was respiratory problems; we suggest that physicians and staffs working in the emergency department be well-trained in management of such patients.Keywords: Radiography, Thoracic; Analgesics, Opioid; Poisoning; Pulmonary Edema.

  12. Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal.

    Science.gov (United States)

    Stinus, L; Le Moal, M; Koob, G F

    1990-01-01

    Specific brain sites for the opiate abstinence syndrome syndrome have been elusive to delineate, and the classic overt signs of withdrawal such as wet dog shakes, ptosis and teeth chattering appear to be widely represented in the brain. Using a more general motivational test involving a disruption of operant behavior in dependent rats, the brain site most sensitive to the response disruptive effects of intracerebral administration of the opiate antagonist, methylnaloxonium, was the region of the nucleus accumbens, a site also implicated in the acute reinforcing properties of opiates. This disruption of operant responding was hypothesized to reflect the aversive properties of opiate withdrawal. The present study directly tested that hypothesis by exploring whether intercerebral administration of methylnaloxonium produced aversive stimulus effects as measured by the formation of place aversions. Rats implanted intracerebroventricularly or with bilateral cannulae aimed at the medial dorsal thalamus, periaqueductal gray, ventral tegmental area, amygdala or nucleus accumbens were made dependent on morphine by subcutaneous implantation of two 75-mg morphine pellets. The animals were then subjected to place aversion training by pairing of a distinct environment (one of three arms of a three-armed box with distinct texture, markings and smell) with a single injection of methylnaloxonium intracerebroventricularly or intracerebrally. Results showed that at high doses of methylnaloxonium (1000-2000 ng) all sites produced a place aversion. However, lower doses (250-500 ng) produced a significant brain site selectivity with the region of the nucleus accumbens the most sensitive. Observational measurements taken during the postinjection period with the high dose of methylnaloxonium showed that agitation was particularly observed following methylnaloxonium administration into the nucleus accumbens and periaqueductal gray.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Adams Clive E

    2007-01-01

    Full Text Available Abstract Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices, Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065. A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028. People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52 and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49. Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

  14. Positron emission tomography studies of brain receptors

    International Nuclear Information System (INIS)

    Maziere, B.; Maziere, M.

    1991-01-01

    Probing the regional distribution and affinity of receptors in the brain, in vivo, in human and non human primates has become possible with the use of selective ligands labelled with positron emitting radionuclides and positron emission tomography (PET). After describing the techniques used in positron emission tomography to characterize a ligand receptor binding and discussing the choice of the label and the limitations and complexities of the in vivo approach, the results obtained in the PET studies of various neurotransmission systems: dopaminergic, opiate, benzodiazepine, serotonin and cholinergic systems are reviewed

  15. The Effectiveness of Psychodrama in Relapse Prevention and Reducing Depression among Opiate-Dependent Men

    Directory of Open Access Journals (Sweden)

    s dehnavi

    2015-09-01

    Full Text Available Objective: The current study aimed to investigate the effectiveness of psychodrama therapy in relapse prevention (RP and the reduction of depression among opiate-dependent male patients. Method: A quasi-experimental research design along with pre-post tests and follow-up and control group was employed for this study. Using convenience sampling method, the number of 20 opiate-dependent men who had referred to addiction treatment clinics in Kermanshah (Iran and successfully passed detoxification program was randomly selected as the participants of the study. The experimental group participated in a twelve-session therapy plan during six weeks. Beck Depression Inventory (BDI was used for data collection purposes. Results: The results of ANCOVA revealed the existence of a significant difference between the two groups in the post-test and follow-up scores. Conclusion: According to the findings, it can be argued that psychodrama intervention can be used as an effective program in the reduction of depression and relapse prevention among opiate-dependent men.

  16. The Effectiveness of Psychodrama in Improving Quality of Life among Opiate-dependent Male Patients

    Directory of Open Access Journals (Sweden)

    Saeed Dehnavi

    2016-05-01

    Full Text Available The current paper aimed to investigate the effectiveness of psychodrama therapy in the improvement of the quality of life(QOL for opiate-dependent male patients. It was aquasi-experimental research study, using pre-and posttesting plan with a control group. A total of 30 individuals were selected among male clients with opiate dependence, who were referred to addiction treatment clinics in Kermanshah (Iran and successfully passed the detoxification programs, by a convenience sampling technique. The subjects were randomly placed into two experimental and control groups. The experimental group participated in a twelve-session psychodrama therapy plan for 6 weeks, while the control group received no intervention. In order to collect data, the SF-36 questionnaire was applied. Data analysis was performed by analysis of covariance (ANCOVA. The ANCOVA results revealed that there is a significant difference between two groups in the post-test stage. As seen from the findings, the psychodrama intervention can be used as an effective modality to enhance the quality of life among male patients with opiate dependence.

  17. Initiation of opiate addiction in a Canadian prison: a case report

    Directory of Open Access Journals (Sweden)

    Lim Ronald

    2006-03-01

    Full Text Available Abstract Background In North America, the harms of illicit drug use have been responded to primarily through law enforcement interventions. This strategy has resulted in record populations of addicted individuals being incarcerated in both Canada and the United States. The incarceration of non-violent drug offenders has become increasingly controversial as studies demonstrate the harms, including elevated HIV risk behavior, of incarcerating injection drug users. Other harms, such as the initiation of illicit drug use by prison inmates who previously did not use drugs, have been less commonly described. Case Presentation We report on the case of an individual who initiated non-injection opiate use in a Canadian prison and developed an addiction to the drug. Upon release into the community, the individual continued using opiates and sought treatment at a clinic. The patient feared that he might initiate injection use of opiates if his cravings could not be controlled. The patient was placed on methadone maintenance therapy. Conclusion While anecdotal reports indicate that initiation in prison of the use of addictive illicit substances is frequent, documentation through clinical experience is rare, and the public health implications of this behavior have not been given sufficient attention in the literature. Strategies of incarcerating non-violent drug offenders and attempting to keep illicit drugs out of prisons have not reduced the harms and costs of illicit drug use. Effective, practical alternatives are urgently needed; expanded community diversion programs for non-violent drug offenders deserve particular attention.

  18. Women and addiction (alcohol and opiates): comparative analysis of psychosocial aspects.

    Science.gov (United States)

    Raketić, Diana; Stamatović Gajić, Branka; Gajić, Tomislav; Jovanović, Mirjana

    2013-01-01

    Nowadays women constitute one third of all addicts. In the last decade, there has been a remarkable growth in scientific interest in biochemical and psychosocial aspects of women's addiction. Many researches point out the specific character of women's addiction. The aim of the study was to assess and compare psychosocial aspects, including the sociodemographic characteristics as well as the specific aspects of functioning of family and interpersonal relationships of the subjects addicted to opiates and alcohol. There were two substance addict groups (32 and 30 subjects addicted to drugs and alcohol, respectively) and the control group, consisting of 30 subjects (no substance addiction). A socio-demographic data questionnaire and semi-structured Addiction Severity Index (ASI) interview were used. The results of the research indicated that there were statistically significant differences between the compared groups in respect to the age of the subjects, family history of addiction disorders, education, parenthood, employment work status, and marital status. The subjects addicted to opiates differed significantly in respect to manifestation of aggressive, delinquent behaviour, infectious diseases, presence of addicts-partnerships, but there were no significant differences in relation to physical abuse, sexual abuse and self-assessment of depression. The results of this research suggest that subjects addicted to opiates differed largely from the subjects addicted to alcohol in terms of the age of the subjects, education level, family relationships, partnerships and social relationships, which all have to be taken into consideration when designing a therapy protocol and planning activities for prevention.

  19. Personality Traits and Psychopathology in Nicotine and Opiate Dependents Using the Gateway Drug Theory

    Directory of Open Access Journals (Sweden)

    Bahareh Amirabadi

    2015-03-01

    Full Text Available Objectives: According to the gateway drug theory, tobacco use is a predisposing factor for future substance abuse. This study was conducted to compare nicotine and opiate dependents to identify the differences between their personality traits and psychopathology that makes them turn to other substances after cigarette smoking. Methods: A causal-comparative study was conducted. Three groups were randomly selected: nicotine dependents, opiate dependents and ordinary individuals (non-dependent population. Cloninger’s Temperament and Character Inventory-Revised, the Fagerstrom Test for Nicotine Dependence, Maudsley Addiction Profile, the Beck Depression Inventory, and Beck Anxiety Inventory were used to collect data. Analysis of variance was used to analyze data. Results: Opiate dependents had higher ‘novelty seeking’ and lower ‘cooperativeness’ scores as compared to the other two groups. They also had higher anxiety and depression scores than the other two groups. Discussion: Higher ‘novelty seeking’ and lower ‘cooperativeness’ scores are important personality traits predicting

  20. Up-regulation of µ-opioid receptors in the spinal cord of morphine ...

    Indian Academy of Sciences (India)

    Unknown

    brain: a quantitative autoradiographic study; Brain Res. 477. 382–386. Diaz A, Pazos A, Florez J and Hurle M A 2000 Autoradiogra- phic mapping of µ-opioid receptors during opiate tolerance and supersensitivity in the rat central nervous system; Naunyn. Schmiedebergs Arch. Pharmacol. 362 101–109. Dum J, Meyer G, ...

  1. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  2. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  3. Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice.

    Science.gov (United States)

    Balerio, Graciela N; Aso, Ester; Berrendero, Fernando; Murtra, Patricia; Maldonado, Rafael

    2004-11-01

    The possible interactions between Delta9-tetrahydrocannabinol (Delta9-THC) and nicotine remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to explore the interactions between these two drugs of abuse by evaluating the consequences of Delta9-THC administration on the somatic manifestations and the aversive motivational state associated with nicotine withdrawal in mice. Acute Delta9-THC administration significantly decreased the incidence of several nicotine withdrawal signs precipitated by mecamylamine or naloxone, such as wet-dog-shakes, paw tremor and scratches. In both experimental conditions, the global withdrawal score was also significantly attenuated by acute Delta9-THC administration. This effect of Delta9-THC was not due to possible adaptive changes induced by chronic nicotine on CB1 cannabinoid receptors, as the density and functional activity of these receptors were not modified by chronic nicotine administration in the different brain structures investigated. We also evaluated the consequences of Delta9-THC administration on c-Fos expression in several brain structures after chronic nicotine administration and withdrawal. c-Fos was decreased in the caudate putamen and the dentate gyrus after mecamylamine precipitated nicotine withdrawal. However, acute Delta9-THC administration did not modify c-Fos expression under these experimental conditions. Finally, Delta9-THC also reversed conditioned place aversion associated to naloxone precipitated nicotine withdrawal. Taken together, these results indicate that Delta9-THC administration attenuated somatic signs of nicotine withdrawal and this effect was not associated with compensatory changes on CB1 cannabinoid receptors during chronic nicotine administration. In addition, Delta9-THC also ameliorated the aversive motivational consequences of nicotine withdrawal.

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

    Science.gov (United States)

    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.

  5. Efficacy of Cognitive Behavioral Therapy on Opiate Use and Retention in Methadone Maintenance Treatment in China: A Randomised Trial.

    Directory of Open Access Journals (Sweden)

    Shujun Pan

    Full Text Available Methadone maintenance treatment (MMT is widely available in China; but, high rates of illicit opiate use and dropout are problematic. The aim of this study was to test whether cognitive behavioral therapy (CBT in conjunction with MMT can improve treatment retention and reduce opiate use.A total of 240 opiate-dependent patients in community-based MMT clinics were randomly assigned to either weekly CBT plus standard MMT (CBT group, n=120 or standard MMT (control group, n=120 for 26 weeks. The primary outcomes were treatment retention and opiate-negative urine test results at 12 weeks and 26 weeks. The secondary outcomes were composite scores on the Addiction Severity Index (ASI and total scores on the Perceived Stress Scale (PSS at 12 weeks and 26 weeks.Compared to the control group in standard MMT, the CBT group had higher proportion of opiate-negative urine tests at both 12 weeks (59% vs. 69%, p<0.05 and 26 weeks (63% vs. 73%, p<0.05; however, the retention rates at 12 weeks (73.3% vs. 74.2%, p=0.88 and 26 weeks were not different (55.8% vs. 64.2%, p=0.19 between the two groups. At both 12 and 26 weeks, all of the ASI component scores and PSS total scores in the CBT group and control group decreased from baseline; but the CBT group exhibited more decreases in ASI employment scores at week 26 and more decrease in the PSS total score at week 12 and week 26.CBT counselling is effective in reducing opiate use and improving employment function and in decreasing stress level for opiate-dependent patients in MMT in China.ClinicalTrials.gov NCT01144390.

  6. Sexual transmissibility of HIV among opiates users with concurrent sexual partnerships: An egocentric network study in Yunnan, China

    Science.gov (United States)

    Li, Jian; Liu, Hongjie; Li, Jianhua; Luo, Jian; Koram, Nana; Detels, Roger

    2011-01-01

    Aims To investigate the patterns of concurrent sexual partnerships among young opiate users and sexual transmissibility of HIV in concurrent sexual partnerships in drug-use and sexual networks. Design Cross-sectional design. Participants 426 young opiate users in Yunnan, China. Measurement Respondent-driven sampling (RDS) was used to recruit participants. Multiple logistic regressions were performed to analyze the relationships of concurrent sexual partnerships with egocentric social network components, risky sexual behavior for HIV, and drug-use practices. Findings The RDS-adjusted prevalence of concurrent sexual partners was 42.9% among opiate users. Opiate users with concurrent sexual partnerships were more likely to engage in risky HIV-related sexual behavior, compared to those without. Specifically, they were more likely to report having had four or more sexual partners (26.3% vs. 2.0%), having had a spouse or boy/girl friends who also had concurrent sexual partnerships (28.1% vs. 8.2%), having exchanged drug for sex (12.4% vs. 3.8%), having had sexual partners who were non-injection drug users (22.6% vs. 10.1%), having had sexual partners who were injection drug users (25.3% vs. 13.5%), and having used club drugs (26.3% vs. 13.5%). There were no significant differences in consistent condom use between opiate users with sexual concurrency and those without. The same proportion (25.8%) of opiate users in the two groups reported having consistently used condoms when having sex with regular partners, and 46.3% of opiate users with sexual concurrency and 36.4% of those without such concurrency consistently used condoms with non-regular partners. Conclusion The expansion of the HIV epidemic from high risk populations to the general population in China may be driven by concurrent sexual partnerships. Behavioral interventions targeting safer sex should be integrated into harm reduction programmes. PMID:21457169

  7. Thermostatted delta f

    International Nuclear Information System (INIS)

    Krommes, J.A.

    2000-01-01

    The delta f simulation method is revisited. Statistical coarse-graining is used to rigorously derive the equation for the fluctuation delta f in the particle distribution. It is argued that completely collisionless simulation is incompatible with the achievement of true statistically steady states with nonzero turbulent fluxes because the variance of the particle weights w grows with time. To ensure such steady states, it is shown that for dynamically collisionless situations a generalized thermostat or W-stat may be used in lieu of a full collision operator to absorb the flow of entropy to unresolved fine scales in velocity space. The simplest W-stat can be implemented as a self-consistently determined, time-dependent damping applied to w. A precise kinematic analogy to thermostatted nonequilibrium molecular dynamics (NEMD) is pointed out, and the justification of W-stats for simulations of turbulence is discussed. An extrapolation procedure is proposed such that the long-time, steady-state, collisionless flux can be deduced from several short W-statted runs with large effective collisionality, and a numerical demonstration is given

  8. Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

    Science.gov (United States)

    Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Silverman, Kenneth

    2014-01-01

    We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users. © Society for the Experimental Analysis of Behavior.

  9. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  10. Women and addiction (alcohol and opiates: Comparative analysis of psychosocial aspects

    Directory of Open Access Journals (Sweden)

    Raketić Diana

    2013-01-01

    Full Text Available Introduction. Nowadays women constitute one third of all addicts. In the last decade, there has been a remarkable growth in scientific interest in biochemical and psychosocial aspects of women’s addiction. Many researches point out the specific character of women’s addiction. Objective. The aim of the study was to assess and compare psychosocial aspects, including the socio-demographic characteristics as well as the specific aspects of functioning of family and interpersonal relationships of the subjects addicted to opiates and alcohol. Methods. There were two substance addict groups (32 and 30 subjects addicted to drugs and alcohol, respectively and the control group, consisting of 30 subjects (no substance addiction. A socio-demo- graphic data questionnaire and semi-structured Addiction Severity Index (ASI interview were used. Results. The results of the research indicated that there were statistically significant differences between the compared groups in respect to the age of the subjects, family history of addiction disorders, education, parenthood, employment work status, and marital status. The subjects addicted to opiates differed significantly in respect to manifestation of aggressive, delinquent behaviour, infectious diseases, presence of addicts-partnerships, but there were no significant differences in relation to physical abuse, sexual abuse and self-assessment of depression. Conclusion. The results of this research suggest that subjects addicted to opiates differed largely from the subjects addicted to alcohol in terms of the age of the subjects, education level, family relationships, partnerships and social relationships, which all have to be taken into consideration when designing a therapy protocol and planning activities for prevention.

  11. Opiate System Mediate the Antinociceptive Effects of Coriandrum sativum in Mice

    Science.gov (United States)

    Taherian, Abbas Ali; Vafaei, Abbas Ali; Ameri, Javad

    2012-01-01

    Our previous study showed that Coriandrum sativum (CS) has antinociceptive effects, but the mechanisms that mediate this effect are not clear. The present study was designed to test the role of opiate system in the antinociceptive effects of CS on acute and chronic pain in mice using Hot Plate (HP), Tail Flick (TF) and Formalin (FT) tests and also to compare its effect with dexamethasone (DEX) and stress (ST). Young adult male albino mice (25-30 g) in 33 groups (n = 8 in each group) were used in this study. CS (125 250, 500 and 1000 mg/Kg IP), DEX (0.5, 1 and 2 mg/Kg IP), vehicle (VEH) or swim stress were used 30 min before the pain evaluation tests. Acute and chronic pain was assessed by HP, TF and FT models. In addition, Naloxone (NAL, 2 mg/Kg, IP) was injected 15 min before the CS extract administration in order to assess the role of opiate system in the antinociception of CS. Results indicated that CS, DEX and ST have analgesic effects (p < 0.01) in comparison with the control group and higher dose of CS was more effective (p < 0.001). Besides, pretreatment of NAL modulates the antinociceptive effects of CS in all models (p < 0.001). The above findings showed that CS, DEX and ST have modulator effects on pain. These findings further indicate that the CS extract has more analgesic effects than DEX and ST and also provides the evidence for the existence of an interaction between antinociceptive effects of CS and opiate system. PMID:24250493

  12. Auditory sensitivity in opiate addicts with and without a history of noise exposure

    Directory of Open Access Journals (Sweden)

    Vishakha Rawool

    2011-01-01

    Full Text Available Several case reports suggest that some individuals are susceptible to hearing loss from opioids. A combination of noise and opium exposure is possible in either occupational setting such as military service or recreational settings. According to the Drug Enforcement Agency of the U.S. Department of Justice, prescriptions for opiate-based drugs have skyrocketed in the past decade. Since both opium and noise independently can cause hearing loss, it is important to know the prevalence of hearing loss among individuals who are exposed to opium or both opium and noise. The purpose of this research was to evaluate auditory sensitivity in individuals with a history of opium abuse and/or occupational or nonoccupational noise exposure. Twenty-three men who reported opiate abuse served as participants in the study. Four of the individuals reported no history of noise exposure, 12 reported hobby-related noise exposure, 7 reported occupational noise exposure including 2 who also reported hobby-related noise exposure. Fifty percent (2/4 of the individuals without any noise exposure had a hearing loss confirming previous reports that some of the population is vulnerable to the ototoxic effects of opioids. The percentage of population with hearing loss increased with hobby-related (58% and occupational noise exposure (100%. Mixed MANOVA revealed a significant ear, frequency, and noise exposure interaction. Health professionals need to be aware of the possible ototoxic effects of opioids, since early detection of hearing loss from opium abuse may lead to cessation of abuse and further progression of hearing loss. The possibility that opium abuse may interact with noise exposure in determining auditory thresholds needs to be considered in noise exposed individuals who are addicted to opiates. Possible mechanisms of cochlear damage from opium abuse, possible reasons for individual susceptibility, and recommendations for future studies are presented in the article.

  13. Lifetime ATS use and increased HIV risk among not-in-treatment opiate injectors in Malaysia.

    Science.gov (United States)

    Chawarski, Marek C; Vicknasingam, Balasingam; Mazlan, Mahmud; Schottenfeld, Richard S

    2012-07-01

    Malaysia has been experiencing significant drug abuse problems since the 1970s, and drug abuse is the major driver of HIV transmission in Malaysia. We investigated risk factors for HIV associated with use of amphetamine type stimulants (ATS) among not-in-treatment opiate injectors in Malaysia. Between October of 2006 and May of 2008, we conducted a series of surveys in three major urban areas of Malaysia. A total of 732 opiate IDUs (679 males and 53 females) were enrolled in the three surveys. The survey instruments consisted of a structured interview on demographic characteristics, drug use history (including year of first use, and past month history of use of illicit drugs; lifetime and past month history of IDU or needle or equipment sharing), and HIV status. There were 194/704 (27.6%) HIV positive participants in the sample. Two factors were significantly associated with HIV infection in this sample: lifetime history of ATS use (OR [95%CI]: 2.3 [1.5-3.6]) and lifetime history of sharing of injection equipment (OR [95% CI]: 4.2 [1.8-9.8]). Both HIV-positive and HIV-negative participants reported high levels of current needle/equipment sharing practices: 82% vs. 75%, respectively. ATS use spread rapidly in the study sample after 1997 and is associated with an increased risk of HIV infection in this population already at high risk because of opiate IDU. Out-of-treatment IDUs in Malaysia engage in high risk behaviors regardless of their HIV status. Increased education and public health prevention measures are needed to reduce HIV transmission risks in this population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Mida pakub Delta? / Teele Kurm

    Index Scriptorium Estoniae

    Kurm, Teele

    2011-01-01

    Politsei- ja Piirivalveamet võtab kasutusele ühise Siseministeeriumi infotehnoloogia- ja arenduskeskuse ning Webmedia AS koostööna loodud dokumendihaldussüsteemi Delta. Kust sai Delta oma nime? Projekti "Dokumendihaldussüsteemi juurutamine Siseministeeriumi haldusalas" eesmärgid

  15. Challenges from the Niger Delta

    African Journals Online (AJOL)

    User

    2012-01-24

    Jan 24, 2012 ... diverse ethnic groups under what came to be known as Nigeria. The ethnic communities that ... Bolade and Adelemo. National Security and Sustainable Development in Nigeria: Challenges from the Niger Delta ... recommended the creation of the Niger Delta Development Board. Azaiki. (2003:48) states ...

  16. Different role for mouse and human CD3delta/epsilon heterodimer in preT cell receptor (preTCR) function: human CD3delta/epsilon heterodimer restores the defective preTCR function in CD3gamma- and CD3gammadelta-deficient mice

    Czech Academy of Sciences Publication Activity Database

    Pan, Q.; Brodeur, J.F.; Drbal, Karel; Vibhuti, P.D.

    2006-01-01

    Roč. 43, č. 11 (2006), s. 1741-1750 ISSN 0161-5890 Institutional research plan: CEZ:AV0Z50520514 Keywords : CD3 * preTCR * receptor signaling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.768, year: 2006

  17. Death matters: understanding heroin/opiate overdose risk and testing potential to prevent deaths.

    Science.gov (United States)

    Strang, John

    2015-07-01

    To describe work undertaken over a 20-year period, investigating overdose characteristics among survivors, effects of acute heroin administration, clustering of risk of overdose fatality and potential interventions to reduce this fatal outcome. Privileged-access interviewers obtained data from non-treatment as well as treatment samples; experimental study of drop in oxygen saturation following heroin/opiate injection; investigation of clusterings of death following prison release and treatment termination; and study of target populations as intervention work-force, including family as well as peers, and action research built into pilot implementation. Overdose has been experienced by about half of heroin/opiate misusers, with even higher proportions having witnessed an overdose, and with high levels of willingness to intervene. Heroin/opiates are associated with the majority of drug-related deaths, despite relative scarcity of use. Heroin injection causes a rapid drop in oxygen saturation, recovering only slowly over the next half hour. Deaths from drug overdose are greatly more likely on prison release and post-discharge from detoxification and other in-patient or residential settings. High levels of declared willingness to intervene are matched by active interventions. Both drug-using peers and family members show ability to improve knowledge and gain confidence from training. Audit study of take-home schemes finds approximately 10% of dispensed naloxone is used in real-life emergency situations. Overdose is experienced by most users, with heroin/opiates contributing disproportionately to drug overdose deaths. High-risk times (e.g. after prison release) are now clearly identified. Peers and family are a willing potential intervention work-force, but are rarely trained or given pre-supply of naloxone. Large-scale naloxone provision (e.g. national across Scotland and Wales) is now being delivered, while large-scale randomized trials (e.g. N-ALIVE prison

  18. Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review.

    Science.gov (United States)

    Angarita, Gustavo A; Emadi, Nazli; Hodges, Sarah; Morgan, Peter T

    2016-04-26

    Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders.

  19. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial

    DEFF Research Database (Denmark)

    Rafiq, Sulman; Steinbrüchel, Daniel Andreas; Wanscher, Michael Jaeger

    2014-01-01

    significantly lower average pain scores from the day of surgery throughout the third postoperative day. Extensive nausea and vomiting, was found in no patient in the multimodal group but in 13 patients in the morphine group, p levels demonstrated a non....... 1, p = 0.31). 30-day mortality was 1 vs. 2, p = 0.54. CONCLUSIONS: In patients undergoing cardiac surgery, a multimodal regimen offered significantly better analgesia than a traditional opiate regimen. Nausea and vomiting complaints were significantly reduced. No safety issues were observed...

  20. Estimating high-risk cannabis and opiate use in Ankara, Istanbul and Izmir.

    Science.gov (United States)

    Kraus, Ludwig; Hay, Gordon; Richardson, Clive; Yargic, Ilhan; Ilhan, Mustafa Necmi; Ay, Pinar; Karasahin, Füsun; Pinarci, Mustafa; Tuncoglu, Tolga; Piontek, Daniela; Schulte, Bernd

    2017-09-01

    Information on high-risk drug use in Turkey, particularly at the regional level, is lacking. The present analysis aims at estimating high-risk cannabis use (HRCU) and high-risk opiate use (HROU) in the cities of Ankara, Istanbul and Izmir. Capture-recapture and multiplier methods were applied based on treatment and police data stratified by age and gender in the years 2009 and 2010. Case definitions refer to ICD-10 cannabis (F.12) and opiate (F.11) disorder diagnoses from outpatient and inpatient treatment records and illegal possession of these drugs as recorded by the police. High-risk cannabis use was estimated at 28 500 (8.5 per 1000; 95% confidence interval 7.3-10.3) and 33 400 (11.9 per 1000; 95% confidence interval 10.7-13.5) in Ankara and Izmir, respectively. Using multipliers based on capture-recapture estimates for Izmir, HRCU in Istanbul was estimated up to 166 000 (18.0 per 1000; range: 2.8-18.0). Capture-recapture estimates of HROU resulted in 4800 (1.4 per 1000; 95% confidence interval 0.9-1.9) in Ankara and multipliers based on these gave estimates up to 20 000 (2.2 per 1000; range: 0.9-2.2) in Istanbul. HROU in Izmir was not estimated due to the low absolute numbers of opiate users. While HRCU prevalence in both Ankara and Izmir was considerably lower in comparison to an estimate for Berlin, the rate for Istanbul was only slightly lower. Compared with the majority of European cities, HROU in these three Turkish cities may be considered rather low. [Kraus L, Hay G, Richardson C, Yargic I, Ilhan N M, Ay P, Karasahin F, Pinarci M, Tuncoglu T, Piontek D, Schulte B Estimating high-risk cannabis and opiate use in Ankara, Istanbul and Izmir Drug Alcohol Rev 2016;00:000-000]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

  1. Parallel increases in sister chromatid exchanges at base level and with UV treatment in human opiate users

    International Nuclear Information System (INIS)

    Shafer, D.A.; Falek, A.; Madden, J.J.; Tadayon, F.; Pline, M.; Kuehnle, J.C.; Mendelson, J.

    1983-01-01

    The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G 1 and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corrobate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism. (orig.)

  2. DELTA beam position monitor

    International Nuclear Information System (INIS)

    Brinker, S.; Heisterhagen, R.; Wille, K.

    1991-01-01

    For the electron storage ring DELTA (Dortmund ELectron Test Accelerator) a beam-position-monitor system based on button pickups has been designed. Two different concepts for the monitor electronics have been developed obtaining a long-term stability better than ± 150 μm and a short-term resolution below ± 10 μm. There are no hybrids integrated in the electronic circuits as all four button signals should be amplified and digitized to provide redundancy. First, a concept using four separated electronic branches, one for each button, was tested. Then a concept with a multiplexer in front followed by only one amplifier was designed. This concept, the electronic circuits and the measurements are presented

  3. DELTA 3D PRINTER

    Directory of Open Access Journals (Sweden)

    ȘOVĂILĂ Florin

    2016-07-01

    Full Text Available 3D printing is a very used process in industry, the generic name being “rapid prototyping”. The essential advantage of a 3D printer is that it allows the designers to produce a prototype in a very short time, which is tested and quickly remodeled, considerably reducing the required time to get from the prototype phase to the final product. At the same time, through this technique we can achieve components with very precise forms, complex pieces that, through classical methods, could have been accomplished only in a large amount of time. In this paper, there are presented the stages of a 3D model execution, also the physical achievement after of a Delta 3D printer after the model.

  4. Sexual transmissibility of HIV among opiate users with concurrent sexual partnerships: an egocentric network study in Yunnan, China.

    Science.gov (United States)

    Li, Jian; Liu, Hongjie; Li, Jianhua; Luo, Jian; Koram, Nana; Detels, Roger

    2011-10-01

    To investigate the patterns of concurrent sexual partnerships among young opiate users and sexual transmissibility of human immunodeficiency virus (HIV) in concurrent sexual partnerships in drug-use and sexual networks. Cross-sectional design. A total of 426 young opiate users in Yunnan, China. Young opiate users recruited from their network ties. Respondent-driven sampling (RDS) was used to recruit participants. Multiple logistic regressions were performed to analyze the relationships of concurrent sexual partnerships with egocentric social network components, risky sexual behavior for HIV and drug-use practices. The RDS-adjusted prevalence of concurrent sexual partners was 42.9% among opiate users. Opiate users with concurrent sexual partnerships were more likely to engage in risky HIV-related sexual behavior, compared to those without. Specifically, they were more likely to report having had four or more sexual partners (26.3% versus 2.0%), having had a spouse or boy/girlfriends who also had concurrent sexual partnerships (28.1% versus 8.2%), having exchanged drug for sex (12.4% versus 3.8%), having had sexual partners who were non-injection drug users (22.6% versus 10.1%), having had sexual partners who were injection drug users (25.3% versus 13.5%) and having used club drugs (26.3% versus 13.5%). There were no significant differences in consistent condom use between opiate users with sexual concurrency and those without. The same proportion (25.8%) of opiate users in the two groups reported having consistently used condoms when having sex with regular partners, and 46.3% of opiate users with sexual concurrency and 36.4% of those without such concurrency consistently used condoms with non-regular partners. The expansion of the human immunodeficiency virus epidemic from high-risk populations to the general population in China may be driven by concurrent sexual partnerships. Behavioral interventions targeting safer sex should be integrated into harm reduction

  5. Clinical applications of gamma delta T cells with multivalent immunity

    Directory of Open Access Journals (Sweden)

    Drew C Deniger

    2014-12-01

    Full Text Available Gamma delta T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1-5% of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the Vgamma9Vdelta2 subset of gamma delta T cells and have been used in clinical trials of cancer where objective responses were detected. The Vgamma9Vdelta2 TCR heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of gamma delta T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-Vgamma9Vdelta2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs, tumor-derived artificial antigen presenting cells (aAPC, or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized MHC Class-I chain-related A was a stimulus for gamma delta T cells expressing TCRdelta1 isotypes, and plate-bound activating antibodies have expanded Vdelta1 and Vdelta2 cells ex vivo. Clinically-sufficient quantities of TCRdelta1, TCRdelta2, and TCRdelta1negTCRdelta2neg have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of alpha beta TCRs, chimeric antigen receptors (CARs, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal gamma delta T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of Vgamma9Vdelta2 T cells.

  6. Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice

    International Nuclear Information System (INIS)

    Fioramonti, J.; Fargeas, M.J.; Bueno, L.

    1988-01-01

    The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with 51 Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK

  7. Simultaneous quantification of cocaine, amphetamines, opiates and cannabinoids in vitreous humor.

    Science.gov (United States)

    Peres, Mariana Dadalto; Pelição, Fabrício Souza; Caleffi, Bruno; De Martinis, Bruno Spinosa

    2014-01-01

    A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was samples taken from individuals whose blood had screened positive for drugs of abuse. All the individuals screened positive for COC in the blood (seven samples) also had positive results in VH; COC concentration ranged from 30.81 to 283.97 ng/mL (mean 186.98 ng/mL) and benzoylecgonine concentration ranged from 11.47 to 460.98 ng/mL (mean 133.91 ng/mL). It was also noticed that, in five cases, cocaethylene was detected. AEME was also quantified in one case. The use of AMP detected by blood analysis was confirmed in the VH of one individual (24.31 ng/mL). However, samples taken from three individuals whose blood tested positive for carboxy-tetrahydrocannabinol presented negative results. The results demonstrated that VH is a suitable alternative biological sample to determine COC, AMPs, opiates and their metabolites.

  8. A national study of the retention of Irish opiate users in methadone substitution treatment

    LENUS (Irish Health Repository)

    Mullen, Louise

    2012-07-02

    Background: Retention in treatment is a key indicator of methadone treatment success. The study aims to identify factors that are associated with retention. Objectives: To determine retention in treatment at 12 months for Irish opiate users in methadone substitution treatment and to indicate factors that increase the likelihood of retention. Methods: National cohort study of randomly selected opiate users commencing methadone treatment in 1999, 2001, and 2003 (n = 1269). Results: Sixty-one percent of patients attending methadone treatment remained in continuous treatment for more than 1 year. Retention in treatment at 12 months was associated with age, gender, facility type, and methadone dose. Age and gender were no longer significant when adjusted for other variables in the model. Those who attended a specialist site were twice as likely to leave methadone treatment within 12 months compared with those who attended a primary care physician. The most important predictor of retention in treatment was methadone dose. Those who received <60 mg of methadone were three times more likely to leave treatment. Conclusion: Retention in methadone treatment is high in Ireland in a variety of settings. The main factors influencing retention in methadone treatment was an adequate methadone dose and access to a range of treatment settings including from primary care physicians. Scientific Significance: Providing an adequate dose of methadone during treatment will increase the likelihood of treatment retention. Methadone treatment by the primary care physician is a successful method of retaining opioid users in treatment.

  9. [High-dose buprenorphine substitution during incarceration. Management of opiate addicts].

    Science.gov (United States)

    Revnaud-Maurupt, Catherine; Caer, Yves; Escaffre, Noëlle; Gagneau, Murielle; Galinier, Anne; Marzo, Jean-Noël; Meroueh, Fadi

    2005-04-09

    To describe the social and medical profiles of incarcerated (in detention or after sentencing) opiate addicts, whether or not they had already begun substitution treatment at arrival, and assess the impact of high-dose buprenorphine substitution therapy on the health of prisoners and the course of their incarceration. A prospective survey was conducted on opiate addicts on admission to prison and after 2 months of incarceration, from December 2001 to February 2003, in 6 prison centres in the South East of France. During incarceration, no significant difference (other than in medical follow-up) appeared between the prisoners receiving substitution treatment and those who went through withdrawal on arrival. The first group differed from the second in several respects: their occupational history before incarceration was less stable, their history of drug addiction and incarceration was more serious (injection, psychotropic use, number of prior incarcerations, early age at first incarceration). The buprenorphine patients also differed in their more intense use of medical follow-up before incarceration. The impact of buprenorphine substitution therapy during incarceration could not be demonstrated, but prisoners receiving this treatment had a substantially different profile than those who were not receiving treatment when they arrived in prison.

  10. Determination of mu-, delta- and kappa-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Hloušková, Martina; Cechová, Kristina; Stolařová, Kateřina; Roubalová, Lenka; Svoboda, Petr

    2017-01-01

    Roč. 12, č. 10 (2017), č. článku e0186797. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA17-05903S; GA ČR(CZ) GA17-07070S Institutional support: RVO:67985823 Keywords : morphine * rat brain cortex * opioid receptors * drug withdrawal * cholesterol Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.806, year: 2016

  11. A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice

    OpenAIRE

    1992-01-01

    We have previously reported that T cells bearing T cell receptors (TCRs) of gamma/delta type appear at a relatively early stage of primary infection with Listeria monocytogenes in mice. To characterize the early-appearing gamma/delta T cells during listeriosis, we analyzed the specificity and cytokine production of the gamma/delta T cells in the peritoneal cavity in mice inoculated intraperitoneally with a sublethal dose of L. monocytogenes. The early-appearing gamma/delta T cells, most of wh...

  12. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...... time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral...... phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors....

  13. in the Niger-Delta

    African Journals Online (AJOL)

    Nekky Umera

    Disciplinary Journal, Ethiopia. Vol. ... Asagba, R. B. - Department of Psychology, University of Ibadan, Nigeria. Abstract. The Niger Delta Region of Nigeria has ..... Journal of Abnormal Psychology, 101, 234-. 245. Arnold, A; Cooper,C and Robertson, ...

  14. The primary response of human gamma/delta + T cells to Mycobacterium tuberculosis is restricted to V gamma 9-bearing cells

    OpenAIRE

    1991-01-01

    We have previously reported that peripheral blood gamma/delta + T cells proliferate in high frequency (1 in 2-20) in response to heat-killed Mycobacterium tuberculosis (M.tb.). In the present study, the T cell receptor phenotype of mycobacteria-responsive human gamma/delta + T cells was analyzed in primary cultures with a set of monoclonal antibodies (mAbs) directed against V gamma 9, V delta 1, and V delta 2. When unseparated T cells were stimulated with M.tb., all proliferating gamma/delta ...

  15. Research on Adaptive Delta Modulators

    Science.gov (United States)

    1979-10-01

    practical, and instead, other techni- ques are employed such as Transform Coding, Delta PCM ( DPCM ) or Adaptive Deltamodulation (ADM). One transform coding... DPCM system proposed for use on the space shuttle is contained in the IEEE Transactions on Communica- tions, Nov., 1978, p.1671. It is seen that the...delta modu- lator achieves comparable quality at a much lower cost, size, power consumption and at a much improved error sensi- tivity. 65) A DPCM system

  16. Endogenous Opioid-Induced Neuroplasticity of Dopaminergic Neurons in the Ventral Tegmental Area Influences Natural and Opiate Reward

    NARCIS (Netherlands)

    Pitchers, Kyle K.; Coppens, Caroline M.; Beloate, Lauren N.; Fuller, Jonathan; Van, Sandy; Frohmader, Karla S.; Laviolette, Steven R.; Lehman, Michael N.; Coolen, Lique M.

    2014-01-01

    Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance.

  17. Evaluation of short-term psychological functions in opiate addicts after ablating the nucleus accumbens via stereotactic surgery.

    Science.gov (United States)

    He, Fei; Guan, Hao; Zhao, Zhijing; Miao, Xinfang; Zhou, Qin; Li, Lihong; Huang, Dongmei; Liu, Anheng; Miao, Danmin

    2008-01-01

    To investigate the short-term psychological function of opiate addicts who have undergone ablative stereotactic surgery targeting the nucleus accumbens (NAc) for alleviating opiate drug psychological dependence. The psychological functional status of 14 opiate addicts was assessed by standardized psychological tests both before and approximately 3 months after stereotactic surgery. Standardized tests included the Wechsler Adult Intelligence Scale-Revised Chinese (WAIS-RC), the Clinical Memory Scale of Chinese (CMS), the Eysenck Personality Questionnaire (EPQ) and the Symptom Checklist 90 (SCL-90). The evaluation of psychological dimensions included intelligence, memory, personality characteristics and mental health symptoms. Compared with the preoperative state, there was no statistically significant difference in full-scale intelligence quotient (IQ) postoperatively, but without Bonferroni correction a significant decline by 13.55% (p memory quotient (MQ) of CMS demonstrated a significant decline of 10.65% (p memory and attention appeared to decline postoperatively. In addition, there was a trend towards change in some personality characteristics postoperatively. The postoperative mental health levels of the patients increased, indicating a trend towards improvement. Stereotactic ablation of the NAc in opiate addicts may be associated with short-term negative psychological functions. Advisement regarding the safety of the new surgical modality and recommendations for further investigation are necessary. Copyright 2008 S. Karger AG, Basel.

  18. Investigating the Relationship between Sexual and Chemical Addictions by Comparing Executive Function in Pedophiles, Opiate Addicts and Healthy Controls

    Science.gov (United States)

    Cohen, Lisa J.; Nesci, Cristina; Steinfeld, Matthew; Haeri, Sophia; Galynker, Igor

    2011-01-01

    Disorders of driven sexual behavior have been conceptualized as sexual addictions. In the following study, we compared 51 subjects with pedophilia, 53 subjects with opiate addiction, and 84 healthy control subjects on neuropsychological tests that tap executive functions. The test battery included the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, the Matching Familiar Figures Test (MFFT), Porteus Mazes, Controlled Word Association (COWA), and Trailmaking Test. The groups differed on tests of cognitive flexibility and set switching (WCST), sustained attention (Stroop), and impulsivity (MFFT and Porteus Mazes). There were no differences on verbal fluency (COWA). The subjects with pedophilia differed significantly from those with opiate addiction on several tests, with longer latency to response on MFFT and fewer completed mazes but also fewer errors on Porteus Mazes. Thus, while both subjects with pedophilia and those with opiate addiction show executive dysfunction, the nature of that dysfunction may differ between the two groups; specifically, opiate addicted subjects may be more prone to cognitive impulsivity. PMID:21107145

  19. Buprenorphine Initiation and Linkage to Outpatient Buprenorphine do not Reduce Frequency of Injection Opiate Use Following Hospitalization.

    Science.gov (United States)

    Cushman, Phoebe A; Liebschutz, Jane M; Anderson, Bradley J; Moreau, Merredith R; Stein, Michael D

    2016-09-01

    Buprenorphine has established effectiveness for outpatient treatment of opioid use disorder. Our previously published STOP (Suboxone Transition to Opiate Program) trial showed that buprenorphine induction, stabilization, and linkage to outpatient treatment in opioid-dependent inpatients (injection and non-injection drug users) decreased illicit opioid use over 6months. The present study was a planned subgroup analysis of injection opiate users from STOP. To determine if inpatient buprenorphine initiation and linkage to outpatient buprenorphine reduce injection opiate users' frequency of injection opiate use (IOU). Inpatient injection opiate users at a safety-net hospital were randomized to buprenorphine linkage (induction, stabilization, bridge prescription, and facilitated referral to outpatient treatment) or detoxification (5-day inpatient buprenorphine taper). Conditional fixed-effects Poisson regression was used to estimate the effects of intervention on 30-day (self-report) at 1, 3, and 6months, measured using 30-day timeline follow-back. The secondary outcome was linkage effectiveness, measured as % presenting to initial outpatient buprenorphine visits after hospital discharge. Analysis was limited to persons (n=62 randomized to detoxification and n=51 to linkage) with baseline IOU. There were no significant differences in age, ethnicity, or baseline IOU frequency. At follow-up, linkage patients (70.6%) were significantly more likely (pbuprenorphine visits than detoxification patients (9.7%). However, there was no significant between group difference in the rate of IOU at 1- (IRR=0.73, p=0.32), 3- (IRR=1.20, p=0.54), or 6-month (IRR=0.73, p=0.23) follow-ups. Using person-day analysis, participants self-reported IOU on 5.8% of follow-up days in which they used prescription buprenorphine and 37.5% of non-buprenorphine days. Using a generalized estimating equation, the estimated odds of IOU was 4.57 times higher (pbuprenorphine days. Despite STOP's success in

  20. Integration of Complementary and Alternative Medicine Therapies into Primary-Care Pain Management for Opiate Reduction in a Rural Setting.

    Science.gov (United States)

    Mehl-Madrona, Lewis; Mainguy, Barbara; Plummer, Julie

    2016-08-01

    Opiates are no longer considered the best strategy for the long-term management of chronic pain. Yet, physicians have made many patients dependent on them, and these patients still request treatment. Complementary and alternative medicine (CAM) therapies have been shown to be effective, but are not widely available and are not often covered by insurance or available to the medically underserved. Group medical visits (GMVs) provided education about non-pharmacological methods for pain management and taught mindfulness techniques, movement, guided imagery, relaxation training, yoga, qigong, and t'ai chi. Forty-two patients attending GMVs for at least six months were matched prospectively with patients receiving conventional care. No one increased their dose of opiates. Seventeen people reduced their dose, and seven people stopped opiates. On a 10-point scale of pain intensity, reductions in pain ratings achieved statistical significance (p = 0.001). The average reduction was 0.19 (95% confidence interval [CI] 0.12-0.60; p = 0.01). The primary symptom improved on average by -0.42 (95% CI -0.31 to -0.93; p = 0.02) on the My Medical Outcome Profile, 2nd version. Improvement in the quality-of-life rating was statistically significant (p = 0.007) with a change of -1.42 (95% CI = -0.59 to -1.62). In conventional care, no patients reduced their opiate use, and 48.5% increased their dose over the two years of the project. GMVs that incorporated CAM therapies helped patients reduce opiate use. While some patients found other physicians to give them the opiates they desired, those who persisted in an environment of respect and acceptance significantly reduced opiate consumption compared with patients in conventional care. While resistant to CAM therapies initially, the majority of patients came to accept and to appreciate their usefulness. GMVs were useful for incorporating non-reimbursed CAM therapies into primary medical care.

  1. Light microscopic autoradiographic localization of mu and delta opioid binding sites in the mouse central nervous system

    International Nuclear Information System (INIS)

    Moskowitz, A.S.; Goodman, R.R.

    1984-01-01

    Much work has been done on opioid systems in the rat CNS. Although the mouse is widely used in pharmacological studies of opioid action, little has been done to characterize opioid systems in this species. In the present study the distribution of mu and delta opioid binding sites in the mouse CNS was examined using a quantitative in vitro autoradiography procedure. Tritiated dihydromorphine was used to visualize mu sites and [3H-d-Ala2-d-Leu5]enkephalin with a low concentration of morphine was used to visualize delta sites. Mu and delta site localizations in the mouse are very similar to those previously described in the rat (Goodman, R.R., S.H. Snyder, M.J. Kuhar, and W.S. Young, 3d (1980) Proc. Natl. Acad. Sci. U.S.A. 77:6239-6243), with certain exceptions and additions. Mu and delta sites were observed in sensory processing areas, limbic system, extrapyramidal motor system, and cranial parasympathetic system. Differential distributions of mu and delta sites were noted in many areas. Mu sites were prominent in laminae I, IV, and VI of the neocortex, in patches in the striatum, and in the ventral pallidum, nucleus accumbens, medial and midline thalamic nuclei, medial habenular nucleus, interpeduncular nucleus, and laminae I and II of the spinal cord. In contrast, delta sites were prominent in all laminae of the neocortex, olfactory tubercle, diffusely throughout the striatum, and in the basal, lateral, and cortical nuclei of the amygdala. The determination of the differential distributions of opioid binding sites should prove useful in suggesting anatomical substrates for the actions of opiates and opioids

  2. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the "Meconium Project".

    Science.gov (United States)

    Pichini, Simona; Puig, Carme; Zuccaro, Piergiorgio; Marchei, Emilia; Pellegrini, Manuela; Murillo, Janeth; Vall, Oriol; Pacifici, Roberta; García-Algar, Oscar

    2005-10-04

    For the first time in Europe, the "Meconium Project" aimed to estimate the prevalence of drug use by pregnant women and the effects of exposure to illicit drugs during pregnancy on the fetus and infant. Between October 2002 and February 2004, 1151 (79%) dyads among the 1439 mother-infant dyads from the Hospital del Mar, Barcelona, Spain, met eligibility criteria and agreed to participate in the study. We present preliminary results on the first 830 meconium samples and 549 mother-infant dyads, for which statistical analysis of socio-economic and demographic characteristics and newborn somatometry was completed. The meconium analysis showed an overall 7.9% positivity for drugs of abuse, with 6-monoacetylmorphine and cocaine being the analytes, most frequently found in samples positive for opiates and cocaine. Structured interview disclosed 1.3, 1.8 and 1.3% of mothers exposed to opiates, cocaine and both drugs, while only one mother declared ecstasy consumption. Meconium analysis showed that prevalence of opiates, cocaine and combined drugs exposure was 8.7, 4.4 and 2.2%, respectively, and confirmed the case of ecstasy use. Arecoline, the main areca nut alkaloid, was found in meconium specimens from four Asiatic newborns, whose mothers declared beetle nut consumption during pregnancy. Parental ethnicity was not associated with drug use, nor was the social class, although a higher tendency toward drug consumption was observed in professional and partly skilled mothers. Drug consuming mothers showed a higher number of previous pregnancies and abortions (pconsumer mothers (meconium negative test), probably due to a lack of family planning. Consumption of opiates and cocaine during pregnancy was associated with active tobacco smoking, a higher number of smoked cigarettes and cannabis use. Exposure status and smoking behavior correlated with significantly lower birth weight in newborns from mothers exposed only to cocaine and to opiates and cocaine simultaneously. Of the

  3. Molecular and Neuronal Plasticity Mechanisms in the Amygdala-Prefrontal Cortical Circuit: Implications for Opiate Addiction Memory Formation

    Directory of Open Access Journals (Sweden)

    Laura G Rosen

    2015-11-01

    Full Text Available The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related ‘trigger’ memories that may persist for lengthy periods of time, even during abstinence, in both humans and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC and basolateral nucleus of the amygdala (BLA share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway’s ventral tegmental area (VTA and nucleus accumbens (NAc and can modulate dopamine (DA transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modelling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK and the Ca2+/calmodulin

  4. Selegiline prevents long-term changes in dopamine efflux and stress immobility during the second and third weeks of abstinence following opiate withdrawal.

    Science.gov (United States)

    Grasing, K; Ghosh, S

    1998-08-01

    Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline on in vitro measures of dopamine efflux following opiate withdrawal. Treatment with 2.0 mg/kg/day of selegiline did not modify the severity of opiate withdrawal, as assessed by weight loss over the first 3 days of abstinence. Opiate withdrawal increased immobility in response to a forced warm water swim test performed during the second and third weeks of abstinence following the onset of withdrawal. Brain slices obtained from the nucleus accumbens of opiate-withdrawn animals immediately following swim stress testing displayed diminished efflux of tritiated dopamine after two in vitro exposures to cocaine or amphetamine. Cocaine increases neurotransmitter efflux through blockade of dopamine reuptake, while amphetamine augments efflux by stimulating release of dopamine from intracellular storage vesicles. Although slices from opiate withdrawal subjects showed decreases in efflux after in vitro treatment with these agents, no differences were observed after exposure to 4-aminopyridine, which increases neurotransmitter release by prolonging action potential duration. These findings indicate mechanisms of action that are specific for catecholamine neurotransmitter systems are important for demonstrating long-term changes in dopaminergic function following opiate withdrawal. Selegiline prevented decreases in the efflux of tritiated dopamine in slices obtained from opiate-withdrawn subjects. In addition, selegiline decreased withdrawal-induced immobility during warm water swim testing. In conclusion, treatment with selegiline can prevent long-term changes in stress-induced immobility and deficits in presynaptic dopaminergic function that occur following the

  5. Salinity Impacts on Agriculture and Groundwater in Delta Regions

    Science.gov (United States)

    Clarke, D.; Salehin, M.; Jairuddin, M.; Saleh, A. F. M.; Rahman, M. M.; Parks, K. E.; Haque, M. A.; Lázár, A. N.; Payo, A.

    2015-12-01

    Delta regions are attractive for high intensity agriculture due to the availability of rich sedimentary soils and of fresh water. Many of the world's tropical deltas support high population densities which are reliant on irrigated agriculture. However environmental changes such as sea level rise, tidal inundation and reduced river flows have reduced the quantity and quality of water available for successful agriculture. Additionally, anthropogenic influences such as the over abstraction of ground water and the increased use of low quality water from river inlets has resulted in the accumulation of salts in the soils which diminishes crop productivity. Communities based in these regions are usually reliant on the same water for drinking and cooking because surface water is frequently contaminated by commercial and urban pollution. The expansion of shallow tube well systems for drinking water and agricultural use over the last few decades has resulted in mobilisation of salinity in the coastal and estuarine fringes. Sustainable development in delta regions is becoming constrained by water salinity. However salinity is often studied as an independent issue by specialists working in the fields of agriculture, community water supply and groundwater. The lack of interaction between these disciplines often results in corrective actions being applied to one sector without fully assessing the effects of these actions on other sectors. This paper describes a framework for indentifying the causes and impacts of salinity in delta regions based on the source-pathway-receptor framework. It uses examples and scenarios from the Ganges-Brahmaputra-Meghna delta in Bangladesh together with field measurements and observations made in vulnerable coastal communities. The paper demonstrates the importance of creating an holistic understanding of the development and management of water resources to reduce the impact of salinity in fresh water in delta regions.

  6. Hair analysis for opiates: hydromorphone and hydrocodone as indicators of heroin use.

    Science.gov (United States)

    Madry, Milena M; Bosshard, Mona M; Kraemer, Thomas; Baumgartner, Markus R

    2016-05-01

    Identification of external contamination is a challenge in hair analysis. This study investigates metabolite ratios of hydromorphone to morphine and hydrocodone to codeine as indicators to distinguish contamination from heroin use provided that hydromorphone/hydrocodone intake is excluded. Hair samples after external contamination with street heroin proved to be negative for hydromorphone/hydrocodone. Hair samples from individuals with suspected street heroin use/contamination or opiate medication were analyzed for 6-monoacetylmorphine, morphine, acetylcodeine, codeine, hydromorphone and hydrocodone, and metabolite ratios of hydromorphone to morphine and hydrocodone to codeine were assessed. Hair samples from individuals with medicinal heroin/morphine/codeine use displayed significantly higher metabolite ratios than those with suspected street heroin use/contamination. Hydromorphone/hydrocodone are solely formed during body passage. Thus, metabolite ratios can be used to distinguish morphine/heroin use from external contamination.

  7. ECOTOURISM IN THE DANUBE DELTA

    Directory of Open Access Journals (Sweden)

    Corina-Florina TĂTAR

    2017-06-01

    Full Text Available The Danube delta is a wetland of primordial importance for wildlife and humans alike. The former resources trigger a specific form of leisure for the latter, namely ecotourism whose manifestation is featured in the current research paper through an analysis of the foreign and domestic arrivals as well as a succinct presentation of its fauna resources. This primitive location, its seclusion and its unique resources invite the tourist to authenticity, immersion and self discovery, in other words a responsible type of tourism. The total tourist arrivals for the Danube delta amounted to 88000 in 2012, thus indicating its remoteness from mass tourism.

  8. A proto-Okavango Delta?

    Science.gov (United States)

    Podgorski, J. E.; Kgotlhang, L.; Ngwisanyi, T.; Ploug, C.; Auken, E.; Kinzelbach, W. K.; Green, A. G.

    2010-12-01

    The Okavango Delta within the Kalahari Desert of northwestern Botswana is one of the world's largest inland deltas and the largest wetland in southern Africa. An annual flood originating from the Okavango River in the northwest passes through the upper panhandle region of the delta before inundating the 150 km x 150 km fan where most water is lost to evapotranspiration. The fan occupies an active graben at the southwestern end of the East Africa rift zone. The focus of faulting is along the fan’s southeastern end where the Kunyere-Thamalakane faults show 200-300 m of dip-slip offset, forming a backstop to the movement of water and sediments. An airborne TEM survey was flown over the entire delta in 2007 with 2 km line spacing. A preliminary inversion of the entire data set has been undertaken using a quasi-2D inversion scheme that includes resistivity, layer thickness, and transmitter height as parameters. Tests with a many-layer model indicate that a four-layer model explains the data. Inversion results are corroborated by limited borehole data. The TEM model includes significant lateral and vertical variations in electrical resistivity. In the central region of the fan, a near-surface high resistivity layer is underlain sequentially by a more conductive layer (about 100 m depth) and a more resistive half-space (about 160 m depth), the latter of which could be a fresh water aquifer. This resistive feature has a fan-like form. A plausible evolutionary scenario that explains the TEM data includes a proto-Okavango Delta (highly resistive half-space ) and a lake (intermediate-depth conductive layer). During a climatic episode similar to today’s, a proto-Okavango Delta sequence would have been deposited against a fault, much as the Kunyere-Thamalakane faults today delineate the southeastern margin of the present Okavango Delta. This region would have then been flooded by a Pleistocene lake system that inundated much of northern Botswana and was the source of

  9. Plasticity of gamma delta T cells: impact on the anti-tumor response

    Directory of Open Access Journals (Sweden)

    Virginie eLafont

    2014-12-01

    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  10. Delta Vegetation and Land Use [ds292

    Data.gov (United States)

    California Department of Resources — Vegetation and land use are mapped for the approximately 725,000 acres constituting the Legal Delta portion of the Sacramento and San Joaquin River Delta area....

  11. Delta Vegetation and Land Use [ds292

    Data.gov (United States)

    California Natural Resource Agency — Vegetation and land use are mapped for the approximately 725,000 acres constituting the Legal Delta portion of the Sacramento and San Joaquin River Delta area....

  12. Recognition of nonpeptide antigens by human V gamma 9V delta 2 T cells requires contact with cells of human origin.

    Science.gov (United States)

    Green, A E; Lissina, A; Hutchinson, S L; Hewitt, R E; Temple, B; James, D; Boulter, J M; Price, D A; Sewell, A K

    2004-06-01

    SUMMARY It is becoming apparent that gamma delta T cells form an important part of the adaptive immune response. However, the ligands recognized by gamma delta T cell receptors (TCRs) and the exact biological function of the cells that express this receptor remain unclear. Numerous studies have shown that the dominant human peripheral blood subset of gamma delta T cells, which express a V gamma 9V delta 2 TCR, can activate in response to low molecular weight nonpeptidic molecules. Some of these components have been purified from bacteria or parasites. We examined the activation of polyclonal gamma delta T cell lines, clones with V gamma 9V delta 2 and V gamma 9V delta 1 TCRs, and gamma delta T cells directly ex vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP) antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). V gamma 9V delta 2 T cells were able to respond to multiple small organic molecules of highly variable structure whereas cells expressing a similar V gamma 9 chain paired with a V delta 1 chain failed to recognize these antigens. Thus, the TCR delta chain appears to make an important contribution to the recognition of these antigens. The kinetics of responses to alkylphosphate and alkylamine antigens differ from those of responses to the nBP pamidronate. These different classes of antigen are believed to have differed mechanisms of action. Such differences explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still retain their ability to activate gamma delta T cells while alkylphosphate and alkylamine antigens cannot. We also demonstrate that a substantial proportion of the cells that produce IFN gamma directly ex vivo in response to PPD are gamma delta T cells and that gamma delta T cell activation requires contact with cells of human origin.

  13. Delta Scuti variables. Lecture 6

    International Nuclear Information System (INIS)

    Cox, A.N.

    1983-01-01

    The class of variables near or on the upper main sequence, the delta Scuti variables, are not only the usual ones about the masses, radii, and luminosities, but also the age, rotation, element diffusion to change the surface layer composition, the occurance of convection and the presence of radial and nonradial pulsation modes

  14. about the Dirac Delta Function(?)

    Indian Academy of Sciences (India)

    Mouse Games. As any child of ten will tell you, to write an article on the Dirac delta function (or on anything else, for that matter), one must first log into 'Google' or 'Yahoo' or a similar search engine. A judicious combination of click- ing, cutting and pasting - and voila, an article of any desired length is ready in an ...

  15. Variation in leaf water delta D and delta 18O values during the evapotranspiration process

    International Nuclear Information System (INIS)

    Leopoldo, P.R.; Foloni, L.L.

    1984-01-01

    A theoretical model was developed to evaluate leaf water delta D and delta 18 O variation in relation to: leaf temperature, relative humidity converted to leaf temperature and delta D and delta 18 O values of atmospheric water vapour and soil water. (M.A.C.) [pt

  16. Hospice, opiates, and acute care service use among the elderly before death from heart failure or cancer.

    Science.gov (United States)

    Setoguchi, Soko; Glynn, Robert J; Stedman, Margaret; Flavell, Carol M; Levin, Raisa; Stevenson, Lynne Warner

    2010-07-01

    Advances in heart failure (HF) treatments have prolonged survival, but more patients die of HF than of any type of cancer. Little is known about the current practice in end-of-life (EOL) care in HF. Two EOL cohorts (HF and cancer) were identified using Medicare data linked with pharmacy and cancer registry data. We assessed use of hospice, opiates, and acute care services (hospitalizations, emergency department [ED] visits, intensive care unit [ICU] admissions, and death in acute care). Time trends and predictors of use were assessed using multivariate regression including demographics and cardiovascular and noncardiovasuclar comorbidities. Among 5,836 HF patients with median age of 85, 77% female and 4% black, 20% were referred to hospice compared to 51% of 7,565 cancer patients. A modest rise in hospice use over time was parallel in the 2 groups. Twenty-two percent of HF patients filled opiate prescriptions during 60 days before death compared to 46% of cancer patients. Use of acute care services in the 30 days before death was higher for HF (64% vs 39% for ED visits, 60% vs 45% for hospitalizations, and 19% vs 7% for ICU admission). More HF patients died during acute hospitalizations than cancer patients (39% vs 21%). Patients dying of HF were less likely to be supported by hospice and opiates but more likely to die in hospitals than patients with cancer. Our study suggests that opportunities may exist to improve hospice and opiate use in HF patients. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  17. Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

    Directory of Open Access Journals (Sweden)

    Nicole L. Johnson

    2011-06-01

    Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

  18. Niger Delta Development Commission and Sustainable ...

    African Journals Online (AJOL)

    The study is on Niger Delta Development Commission and sustainable development of Niger Delta region of Nigeria, the case of Rivers State. The main objective of the study is to examine the impact of the activities of Niger Delta Development Commission on sustainable development of Rivers State in particular, and Niger ...

  19. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  20. Influence of Psychiatric and Personality Disorders on Smoking Cessation Among Individuals in Opiate Dependence Treatment.

    Science.gov (United States)

    Cooperman, Nina A; Lu, Shou-En; Richter, Kimber P; Bernstein, Steven L; Williams, Jill M

    2016-01-01

    We aimed to evaluate how psychiatric and personality disorders influence smoking cessation goals and attempts among people with opiate dependence who smoke. This information could aid the development of more effective cessation interventions for these individuals. Participants (N = 116) were recruited from two methadone clinics, completed the Millon Clinical Multiaxial Inventory-III, and were asked about their smoking behavior and quitting goals. We used the Least Absolute Shrinkage and Selection Operator (LASSO) method, a technique commonly used for studies with small sample sizes and large number of predictors, to develop models predicting having a smoking cessation goal, among those currently smoking daily, and ever making a quit attempt, among those who ever smoked. Almost all participants reported ever smoking (n = 115, 99%); 70% (n = 80) had made a serious quit attempt in the past; 89% (n = 103) reported current daily smoking; and 59% (n = 61) had a goal of quitting smoking and staying off cigarettes. Almost all (n = 112, 97%) had clinically significant characteristics of a psychiatric or personality disorder. White race, anxiety, and a negativistic personality facet (expressively resentful) were negative predictors of having a cessation goal. Overall, narcissistic personality pattern and a dependent personality facet (interpersonally submissive) were positive predictors of having a cessation goal. Somatoform disorder, overall borderline personality pattern, and a depressive personality facet (cognitively fatalistic) were negative predictors of ever making a quit attempt. Individual histrionic (gregarious self-image), antisocial (acting out mechanism), paranoid (expressively defensive), and sadistic (pernicious representations) personality disorder facets were positive predictors of ever making a quit attempt. Each model provided good discrimination for having a smoking cessation goal or not (C-statistic of .76, 95% CI [0.66, 0.85]) and ever making a quit

  1. Influence of Psychiatric and Personality Disorders on Smoking Cessation among Individuals in Opiate Dependence Treatment

    Science.gov (United States)

    Cooperman, Nina A.; Lu, Shou-En; Richter, Kimber P.; Bernstein, Steven L.; Williams, Jill M.

    2016-01-01

    Objective We aimed to evaluate how psychiatric and personality disorders influence smoking cessation goals and attempts among people with opiate dependence who smoke. This information could aid the development of more effective cessation interventions for these individuals. Methods Participants (N=116) were recruited from two methadone clinics, completed the Millon Clinical Multiaxial Inventory–III, and were asked about their smoking behavior and quitting goals. We used the Least Absolute Shrinkage and Selection Operator (LASSO) method, a technique commonly used for studies with small sample sizes and large number of predictors, to develop models predicting having a smoking cessation goal, among those currently smoking daily, and ever making a quit attempt, among those who ever smoked. Results Almost all participants reported ever smoking (n = 115, 99%); 70% (n = 80) had made a serious quit attempt in the past; 89% (n = 103) reported current daily smoking; and, 59% (n = 61) had a goal of quitting smoking and staying off cigarettes. Almost all (n = 112, 97%) had clinically significant characteristics of a psychiatric or personality disorder. White race, anxiety, and a negativistic personality facet (expressively resentful) were negative predictors of having a cessation goal. Overall narcissistic personality pattern and a dependent personality facet (interpersonally submissive) were positive predictors of having a cessation goal. Somatoform disorder, overall borderline personality pattern, and a depressive personality facet (cognitively fatalistic) were negative predictors of ever making a quit attempt. Individual histrionic (gregarious self-image), antisocial (acting out mechanism), paranoid (expressively defensive), and sadistic (pernicious representations) personality disorder facets were positive predictors of ever making a quit attempt. Each model provided good discrimination for having a smoking cessation goal or not (C-statistic of .76, 95% CI[0.66, 0

  2. Effectiveness of Cognitive-Behavioral Group Therapy on Improving Quality of Life in Opiate Addicts under Methadone Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Fereshteh Momeni

    2013-04-01

    Full Text Available Objective: This study was aimed to assess the effectiveness of cognitive- behavioral group therapy on improvement of quality of life in opiate patients under methadone maintenance treatment. Method: This was a semi experimental study using control group also pre-test, post-test and follow-up. Thirty six patients on MMT were selected between the entire opiate addicts referred to Iranian national center for addiction studies within judgmental sampling and were randomly assigned into experimental and control groups. They were all administered the WHOQOL-BREF. In experimental group, cognitive behavior group therapy was performed in 8 sessions and the control group was registered in the waiting list for the CBGT. Findings: Data analysis revealed that the mean WHOQOL-BREF score in the experimental group had significant higher increase when compared with that of the control group. But it wasn’t significant in follow up. Conclusion: Results demonstrated the effectiveness of cognitive–behavior group therapy On improvement of quality of life of opiate addicts on MMT in short term but didn’t seem to be effective in long term.

  3. Do consumers substitute opium for hashish? An economic analysis of simultaneous cannabinoid and opiate consumption in a legal regime.

    Science.gov (United States)

    Chandra, Siddharth; Chandra, Madhur

    2015-11-01

    To analyze interrelationships in the consumption of opiates and cannabinoids in a legal regime and, specifically, whether consumers of opiates and cannabinoids treat them as substitutes for each other. Econometric dynamic panel data models for opium consumption are estimated using the generalized method of moments (GMM). A unique dataset containing information about opiate (opium) consumption from the Punjab province of British India for the years 1907-1918 is analyzed (n=252) as a function of its own price, the prices of two forms of cannabis (the leaf (bhang), and the resin (charas, or hashish)), and wage income. Cross-price elasticities are examined to reveal substitution or complementarity between opium and cannabis. Opium is a substitute for charas (or hashish), with a cross price elasticity (βˆ3) of 0.14 (p0.10). Opium consumption (βˆ1=0.47 to 0.49, popium is slightly responsive (inelastic) to changes in its own price (βˆ2=-0.34 to -0.35, pOpium and hashish, a form of cannabis, are substitutes. In addition, opium consumption displays properties of habit persistence and slight price and wage income responsiveness (inelasticity) consistent with an addictive substance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Do Consumers Substitute Opium for Hashish? An Economic Analysis of Simultaneous Cannabinoid and Opiate Consumption in a Legal Regime

    Science.gov (United States)

    Chandra, Madhur

    2015-01-01

    Aim To analyze interrelationships in the consumption of opiates and cannabinoids in a legal regime and, specifically, whether consumers of opiates and cannabinoids treat them as substitutes for each other. Method Econometric dynamic panel data models for opium consumption are estimated using the generalized method of moments (GMM). A unique dataset containing information about opiate (opium) consumption from the Punjab province of British India for the years 1907–1918 is analyzed (n=272) as a function of its own price, the prices of two forms of cannabis (the leaf (bhang), and the resin (charas, or hashish)), and wage income. Cross-price elasticities are examined to reveal substitution or complementarity between opium and cannabis. Results Opium is a substitute for charas (or hashish), with a cross price elasticity (β3) of 0.14 (p 0.10). Opium consumption (β1 = 0.47 to 0.49, p opium is slightly responsive (inelastic) to changes in its own price (β2 = −0.34 to −0.35, p Opium and hashish, a form of cannabis, are substitutes. In addition, opium consumption displays properties of habit persistence and slight price and wage income responsiveness (inelasticity) consistent with an addictive substance. PMID:26455552

  5. Involvement of μ- and κ-, but not δ-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine

    OpenAIRE

    Shahbazian, Anaid; Heinemann, Akos; Schmidhammer, Helmut; Beubler, Eckhard; Holzer-Petsche, Ulrike; Holzer, Peter

    2002-01-01

    Opiates inhibit gastrointestinal propulsion, but it is not clear which opioid receptor types are involved in this action. For this reason, the effect of opioid receptor – selective agonists and antagonists on intestinal peristalsis was studied.Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves.μ-Opioid receptor agonists (DAMGO, morphine)...

  6. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino-cy...

  7. Human semen inhibits T rosette formation through an opiate mediated mechanism.

    Science.gov (United States)

    Fabbri, A; Gnessi, L; Perricone, R; De Sanctis, G; Moretti, C; De Carolis, C; Fontana, L; Isidori, A; Fraioli, F

    1985-04-01

    Seminal plasma contains high levels of opioid peptides and both seminal plasma and endogenous opioids can influence the immune system. In order to investigate whether these two findings can be related, semen was collected from 7 normal subjects, and assayed for beta-endorphin content and for its in vitro ability to inhibit the total T rosette formation of human lymphocytes in the presence or in the absence of 10(-6) M naloxone, an universal opiate antagonist. The results were as follows: 1) immunoreactive beta-endorphin content in seminal plasma was 4 to 12 times higher than the peripheral plasma levels detected in the same subjects (76.1 +/- 42.1 SD vs 10.5 +/- 2.0 SD pg/ml); 2) increasing concentrations of seminal plasma (1%, 5%, and 10%) in RPMI 1640 significantly depressed the T rosette formation ability of lymphocytes; and 3) the simultaneous addition to the incubation mixture of 10(-6) M naloxone prevented the phenomenon, while naloxone per se was ineffective. The possibility that endogenous opioids may play a role in the immunomodulatory action of human semen is suggested.

  8. Degradation of Opioids and Opiates During Acid Hydrolysis Leads to Reduced Recovery Compared to Enzymatic Hydrolysis.

    Science.gov (United States)

    Sitasuwan, Pongkwan; Melendez, Cathleen; Marinova, Margarita; Mastrianni, Kaylee R; Darragh, Alicia; Ryan, Emily; Lee, L Andrew

    2016-10-01

    Drug monitoring laboratories utilize a hydrolysis process to liberate the opiates from their glucuronide conjugates to facilitate their detection by tandem mass spectrometry (MS). Both acid and enzyme hydrolysis have been reported as viable methods, with the former as a more effective process for recovering codeine-6-glucuronide and morphine-6-glucuronide. Here, we report concerns with acid-catalyzed hydrolysis of opioids, including a significant loss of analytes and conversions of oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine. The acid-catalyzed reaction was monitored in neat water and patient urine samples by liquid chromatography-time-of-flight and tandem MS. These side reactions with acid hydrolysis may limit accurate quantitation due to loss of analytes, possibly lead to false positives, and poorly correlate with pharmacogenetic profiles, as cytochrome P450 enzyme (CYP2D6) is often involved with oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine conversions. Enzymatic hydrolysis process using the purified, genetically engineered β-glucuronidase (IMCSzyme ® ) addresses many of these concerns and demonstrates accurate quantitation and high recoveries for oxycodone, hydrocodone, oxymorphone and hydromorphone. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Violent criminal behavior and perspectives on treatment of criminality in opiate treatment.

    Science.gov (United States)

    Mays, Darren M; Gordon, Adam J; Kelly, Mary E; Forman, Steven D

    2005-06-01

    This study describes and compares the characteristics of patients within a VA Opiate Substitution Therapy Program (OSTP) who report arrests for non-violent and violent crimes and describes patients' attitudes and preferences of criminal treatment within an OSTP. An anonymous survey was distributed to all veterans at one VA-OSTP. Analyses were conducted to describe the sample characteristics and their associations with prior violent and non-violent criminal behavior. A majority of participants were Caucasian, male, middle-aged, unemployed, and had a history of injection drug use. Participants reported arrests for violent (44%), non-violent (47%), and unspecified crimes (16%). There were few significant differences on demographic and drug use characteristics between participants who reported arrests for any violent and only non-violent crimes, and no arrests. Slightly fewer than half the subjects were satisfied with their ability to access treatment for past criminal behavior within or outside of the VA treatment settings. More veterans reporting violent arrests were satisfied with services addressing criminal behavior within the VA-OSTP than were veterans reporting only nonviolent arrests. Nearly equal proportions of veterans reporting violent (45%) and non-violent (44%) arrests reported dissatisfaction with such services received outside of the VA-OSTP. Prior violent criminal behavior is common among participants of a VA-OSTP. Many individuals with criminal histories seek treatment for criminality within VA-OSTP.

  10. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    LENUS (Irish Health Repository)

    Smyth, Bobby P

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants\\' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

  11. Opiate withdrawal syndrome in buprenorphine abusers admitted to a rehabilitation center in Tunisia.

    Science.gov (United States)

    Derbel, Ines; Ghorbel, Asma; Akrout, Férièle Messadi; Zahaf, Abdelmajid

    2016-12-01

    Illicit use of high dosage buprenorphine has been well documented in several countries, including Tunisia. The aim of this survey is to assess the buprenorphine withdrawal syndrome time course, and how it may be affected by the population characteristics among subjects admitted to a rehabilitation center in Tunisia. A prospective research has permitted study of the socio-demographic characteristics and assessment of buprenorphine withdrawal syndrome among 32 subjects admitted for buprenorphine dependence by using the clinical opiate withdrawal scale. An ANOVA was conducted to examine the effect of different factors on the withdrawal scores. 32 subjects were included. Among them 30 were males, 27 had been injecting buprenorphine, 16 were poly-drug abusers and 2 had a history of mental disorders. Buprenorphine withdrawal syndrome was of a mild intensity and had a delayed onset. Withdrawal mean scores varied between 0 and 9, and maximum values were reached at day 21. These scores varied significantly over time (pbuprenorphine had significant effects on the withdrawal scores (phistory of mental disorders did not have any significant effect on the withdrawal scores. This study has permitted description of buprenorphine withdrawal syndrome among patients going through a detoxification treatment at a rehabilitation center. Understanding this syndrome would help elaborate effective and suitable buprenorphine dependence management plans.

  12. Proliferative activation of quiescent Rat-1A cells by delta FosB.

    Science.gov (United States)

    Nakabeppu, Y; Oda, S; Sekiguchi, M

    1993-07-01

    Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that delta FosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although delta FosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of delta FosB transforms Rat-1A cells as does expression of FosB. The transforming ability of delta FosB suggests that delta FosB may lead to proliferative activation of quiescent cells without activating AP-1-responsive genes. To address this question, FosB or delta FosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-delta FosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-delta FosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N-terminal region and the DNA binding domain of FosB or delta FosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

  13. Astrometric Observation of Delta Cepheus

    Science.gov (United States)

    Warren, Naomi; Wilson, Betsie; Estrada, Chris; Crisafi, Kim; King, Jackie; Jones, Stephany; Salam, Akash; Warren, Glenn; Collins, S. Jananne; Genet, Russell

    2012-04-01

    Members of a Cuesta College astronomy research seminar used a manually-controlled 10-inch Newtonian Reflector telescope to determine the separation and position angle of the binary star Delta Cepheus. It was observed on the night of Saturday, October 29, 2011, at Star Hill in Santa Margarita, California. Their values of 40.2 arc seconds and 192.4 degrees were similar to those reported in the WDS (1910).

  14. Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

    Science.gov (United States)

    2012-01-01

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

  15. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    Science.gov (United States)

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  16. Tides Stabilize Deltas until Humans Interfere

    Science.gov (United States)

    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

  17. Migration in Deltas: An Integrated Analysis

    Science.gov (United States)

    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

  18. Future Deltas Utrecht University research focus area: towards sustainable management of sinking deltas

    Science.gov (United States)

    Stouthamer, E.; van Asselen, S.

    2015-11-01

    Deltas are increasingly under pressure from human impact and climate change. To deal with these pressures that threat future delta functioning, we need to understand interactions between physical, biological, chemical and social processes in deltas. This requires an integrated approach, in which knowledge on natural system functioning is combined with knowledge on spatial planning, land and water governance and legislative frameworks. In the research focus area Future Deltas of Utrecht University an interdisciplinary team from different research groups therefore works together. This allows developing integrated sustainable and resilient delta management strategies, which is urgently needed to prevent loss of vital delta services.

  19. Different Levels in Orexin Concentrations and Risk Factors Associated with Higher Orexin Levels: Comparison between Detoxified Opiate and Methamphetamine Addicts in 5 Chinese Cities

    Directory of Open Access Journals (Sweden)

    Haoran Zhang

    2013-01-01

    Full Text Available This study sought to explore the degree of orexin levels in Chinese opiate and methamphetamine addicts and the differences between them. The cross-sectional study was conducted among detoxified drug addicts from Mandatory Detoxification Center (MDC in five Chinese cities. Orexin levels were assayed with radioimmunoassay (RIA. Mann-Whitney U test and Kruskal-Wallis test were used to detect differences across groups, and logistic regression was used to explore the association between orexin levels and characteristics of demographic and drug abuse. Between November 2009 and January 2011, 285 opiates addicts, 112 methamphetamine addicts, and 79 healthy controls were enrolled. At drug withdrawal period, both opiate and methamphetamine addicts had lower median orexin levels than controls, and median orexin levels in opiate addicts were higher than those in methamphetamine addicts (all above P<0.05. Adjusted odds of the above median concentration of orexin were higher for injection than “chasing the dragon” (AOR = 3.1, 95% CI = 1.2–7.9. No significant factors associated with orexin levels of methamphetamine addicts were found. Development of intervention method on orexin system by different administration routes especially for injected opiate addicts at detoxification phase may be significant and was welcome.

  20. Physicians' knowledge of and willingness to prescribe naloxone to reverse accidental opiate overdose: challenges and opportunities.

    Science.gov (United States)

    Beletsky, Leo; Ruthazer, Robin; Macalino, Grace E; Rich, Josiah D; Tan, Litjen; Burris, Scott

    2007-01-01

    Naloxone, the standard treatment for heroin overdose, is a safe and effective prescription drug commonly administered by emergency room physicians or first responders acting under standing orders of physicians. High rates of overdose deaths and widely accepted evidence that witnesses of heroin overdose are often unwilling or unable to call 9-1-1 has led to interventions in several US cities and abroad in which drug users are instructed in overdose rescue techniques and provided a "take-home" dose of naloxone. Under current Food and Drug Administration (FDA) regulations, such interventions require physician involvement. As part of a larger study to evaluate the knowledge and attitudes of doctors towards providing drug treatment and harm reduction services to injection drug users (IDUs), we investigated physician knowledge and willingness to prescribe naloxone. Less than one in four of the respondents in our sample reported having heard of naloxone prescription as an intervention to prevent opiate overdose, and the majority reported that they would never consider prescribing the agent and explaining its application to a patient. Factors predicting a favorable attitude towards prescribing naloxone included fewer negative perceptions of IDUs, assigning less importance to peer and community pressure not to treat IDUs, and increased confidence in ability to provide meaningful treatment to IDUs. Our data suggest that steps to promote naloxone distribution programs should include physician education about evidence-based harm minimization schemes, broader support for such initiatives by professional organizations, and policy reform to alleviate medicolegal concerns associated with naloxone prescription. FDA re-classification of naloxone for over-the-counter sales and promotion of nasal-delivery mechanism for this agent should be explored.

  1. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  2. Evolving deltas: Conceptualising coevolution with engineered interventions

    Science.gov (United States)

    Welch, Amy; Nicholls, Robert; Lazar, Attila

    2017-04-01

    Mid to low latitude deltas have been populated for thousands of years due to their fertile soil and coastal location. This has led to an alteration in the land cover of deltas to primary agriculture and dense rural settlements and more recently, major cities and megacities have developed on or adjacent to many deltas. Deltas may be prosperous in terms of their outputs and services; however, they are also susceptible to many hazards due to their location and low-lying nature. Hazards include storm surges, fluvial flooding and erosion of both coastal and riverine areas, as well as subsidence, relative sea-level rise and pollution. This can have severe impacts on the delta, its population and its services. Therefore engineered interventions have been used for some time to protect the population and the valuable land from the consequences of hazards. Coevolution can be described as a feedback loop between nature and humans: each has an effect on how the other behaves and hence this inter-dependence interaction continues. Therefore the natural evolution of the delta interacts with engineered interventions, such as promoting accelerated subsidence over time, necessitating further adaptation. The deltaic landscape and associated livelihoods are thus the result of this co-evolution process between natural delta processes and engineered interventions. This presentation will identify and discuss various drivers and consequences of large scale engineered interventions, comparing and contrasting the management approaches taken in five populated deltas (Ganges-Brahmaputra-Meghna, Yangtze, Rhine-Meuse-Scheldt, Mekong and Nile). The type of engineered intervention and management approaches had a direct effect on the coevolution of deltas, with each of the deltas being at different stages in terms of extent of coevolution. A qualitative timeline of the typical steps of coevolution between the human system and the delta system of the studied deltas was produced. The major

  3. Inhibition of NMDARs in the nucleus reticularis of the thalamus produces delta frequency bursting

    Directory of Open Access Journals (Sweden)

    Yuchun Zhang

    2009-11-01

    Full Text Available Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV on cells of the nucleus reticularis (nRT in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta frequency. The APV-induced delta frequency bursting is abolished by dopamine D2 receptor antagonist, indicating that dopamine and NMDAR antagonist work synergistically to stimulate delta frequency bursting. Our results have significant implications concerning the electrophysiological basis of schizophrenia and bring together the NMDAR hypofunction, dopamine, and GABA theories of the disease. Our results suggest that NMDAR hypofunction and dopamine work synergistically on the GABAergic cells of the nRT to generate the delta frequency EEG oscillations, a thalamocortical dysrhythmia (TCD in the awake state that is an established abnormality in schizophrenia.

  4. Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

    Science.gov (United States)

    Fischedick, Justin; Van Der Kooy, Frank; Verpoorte, Robert

    2010-02-01

    Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.

  5. Delta FosB regulates wheel running.

    Science.gov (United States)

    Werme, Martin; Messer, Chad; Olson, Lars; Gilden, Lauren; Thorén, Peter; Nestler, Eric J; Brené, Stefan

    2002-09-15

    DeltaFosB is a transcription factor that accumulates in a region-specific manner in the brain after chronic perturbations. For example, repeated administration of drugs of abuse increases levels of DeltaFosB in the striatum. In the present study, we analyzed the effect of spontaneous wheel running, as a model for a natural rewarding behavior, on levels of DeltaFosB in striatal regions. Moreover, mice that inducibly overexpress DeltaFosB in specific subpopulations of striatal neurons were used to study the possible role of DeltaFosB on running behavior. Lewis rats given ad libitum access to running wheels for 30 d covered what would correspond to approximately 10 km/d and showed increased levels of DeltaFosB in the nucleus accumbens compared with rats exposed to locked running wheels. Mice that overexpress DeltaFosB selectively in striatal dynorphin-containing neurons increased their daily running compared with control littermates, whereas mice that overexpress DeltaFosB predominantly in striatal enkephalin-containing neurons ran considerably less than controls. Data from the present study demonstrate that like drugs of abuse, voluntary running increases levels of DeltaFosB in brain reward pathways. Furthermore, overexpression of DeltaFosB in a distinct striatal output neuronal population increases running behavior. Because previous work has shown that DeltaFosB overexpression within this same neuronal population increases the rewarding properties of drugs of abuse, results of the present study suggest that DeltaFosB may play a key role in controlling both natural and drug-induced reward.

  6. THE IMPACT OF OPIATE PAIN MEDICATIONS AND PSYCHOACTIVE DRUGS ON THE QUALITY OF COLON PREPARATION IN OUTPATIENT COLONOSCOPY

    Science.gov (United States)

    Kushnir, Vladimir M.; Bhat, Pavan; Chokshi, Reena V.; Lee, Alexander; Borg, Brian B.; Gyawali, C. Prakash; Sayuk, Gregory S.

    2014-01-01

    Background Suboptimal colon preparation is a significant barrier to quality colonoscopy. The impact of pharmacologic agents associated with gastrointestinal dysmotility on quality of colon preparation has not been well characterized. Aims Evaluate impact of opiate pain medication and psychoactive medications on colon preparation quality in outpatient undergoing colonoscopy. Methods Outpatients undergoing colonoscopy at a single medical center during a 6-month period were retrospectively identified. Demographics, clinical characteristics and pharmacy records were extracted from electronic medical records. Colon preparation adequacy was evaluated using a validated composite colon preparation score. Results 2600 patients (57.3±12.9 years, 57% female) met the inclusion and exclusion criteria. 223 (8.6%) patients were regularly using opioids, 92 antipsychotics, 83 tricyclic antidepressants and 421 non-tricyclic antidepressants. Opioid use was associated with inadequate colon preparation both with low dose (OR=1.4, 95%CI 1.0-2.1, p=0.05) and high dose opioid users (OR=1.7, 95%CI 1.1-2.9, p=0.039) in a dose dependent manner. Other significant predictors of inadequate colon preparation included use of tricyclics (OR=1.9, 95%CI 1.1-3.0, p=0.012), non-tricyclic antidepressants (OR=1.5, 95%CI 1.1-2.0, p=0.013), and antipsychotic medications (OR=2.2, 95%CI 1.4-3.4, p=0.001). Conclusions Opiate pain medication use independently predict inadequate quality colon preparation in a dose dependent fashion; furthermore psychoactive medications have even more prominent effects and further potentate the negative impact of opiates with concurrent use. PMID:24012559

  7. Benzodiazepine maintenance in opiate substitution treatment: Good or bad? A retrospective primary care case-note review.

    Science.gov (United States)

    Bakker, Adam; Streel, Emmanuel

    2017-01-01

    Co-prescribing benzodiazepines to patients in opiate substitution treatment is controversial and often alleged to increase mortality. In an inner-London general practice, patients with problematic benzodiazepine co-dependence were allowed benzodiazepine maintenance treatment (BMT) since 1994, providing an opportunity for analysis. 1) Case-note review of all 278 opiate substitution treatment patients, accruing 1289 patient treatment years; 46% had concurrent BMT. 2) National Health Service database search for patients who died after leaving accrued a further 883 years of information; only patients who left the UK were unaccounted for (4%). Three groups were studied: 1) never obtained benzodiazepine prescription (NOB): n=80); 2) briefly/occasionally prescribed benzodiazepines (BOP): n=71; 3) BMT: n=127. Treatment retention (months); deaths/100 patient treatment years; deaths after leaving the service/100 years of information. Treatment retention: NOB: 34 months; BOP: 51 months; BMT: 72 months. In-treatment mortality: NOB: 1.79/100 patient treatment years; BOP: 0.33/100 patient treatment years; BMT: 1.31/100 patient treatment years. Deaths after leaving service: NOB: 2.24/100 years of information, BOP: 0.63/100 years of information. However, mortality for previously BMT-patients increased by 450% to 5.90/100 years of information. BMT patients had longer treatment retention than NOB or BOP and lower mortality than NOB patients. It is unlikely that patients had access to prescribed benzodiazepines on leaving the service because of restrictions in the national guidelines but co-dependent patients are a high-risk group who may stand to gain most benefit from opiate substitution treatment if combined with benzodiazepine-maintenance.

  8. Methadone, Cocaine, Opiates and Metabolite Disposition in Umbilical Cord and Correlations to Maternal Methadone Dose and Neonatal Outcomes

    Science.gov (United States)

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2011-01-01

    Objectives To explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure. Methods Subjects, 19 opioid-dependent pregnant women from two clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment, and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared to those in placenta and meconium, and urine specimens collected throughout gestation. Results Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the 3rd trimester and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine and opiate positive specimens than umbilical cord. Conclusion Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion. PMID:21743375

  9. The Niger Delta Amnesty Program

    Directory of Open Access Journals (Sweden)

    Benjamin A. Okonofua

    2016-06-01

    Full Text Available The armed conflict between militias and government forces in Nigeria’s Niger Delta region has spanned for more than two decades, defying all solutions. A disarmament, demobilization, and reintegration (DDR program was established in August 2015 in effort to end the violence and has remained in place. It is a radically different approach from past approaches that displayed zero tolerance to all political challenges to oil production or the allocation of oil profits. The approach appeared to be immediately successful in that it forced a ceasefire, engaged militants in planned programs to rehabilitate and reintegrate them into civilian society, and opened up the oil wells (many of which had been shut due to the crisis with the effect of increasing government revenue, which depends 85% on oil exports. Yet, few studies have attempted to understand the dynamics within the country that are responsible for the design and implementation of this broad policy shift or to understand whether and how the current initiative is able to end the conflict and institute peace beyond the short term. This study, therefore, is important because it provides a critical perspective that anticipates and explains emerging issues with the Niger Delta Amnesty Program, which have implications for DDR adaptation and implementation all over the world. Ultimately, the research demonstrates how the DDR program both transforms the Niger Delta conflict and becomes embroiled in intense contestations not only about the mechanism for transforming the targeted population but also whether and how the program incorporates women who are being deprioritized by the program.

  10. Ecogeomorphic Feedbacks that Grow Deltas

    Science.gov (United States)

    Ma, H.; Larsen, L.; Wagner, W.

    2017-12-01

    Coastal river deltas are complex and dynamic ecosystems where vegetation plays an essential role in influencing (as well as being influenced by) physical processes, creating a strong potential for ecogeomorphic feedbacks. However, understanding of the relative strenghts of feedback between vegetation species and topography along different portions of the marsh elevation/zonation gradient is poorly developed, particularly for freshwater, deltaic marshes. In part, this knowledge gap is due to difficulties associated with adequate sampling within heterogeneous vegetation communities to delineate bi-directional feedback applicable at the delta scale.. Emerging technology (high resolution remote sensing and high resolution LiDAR) and data analysis techniques like transfer entropy have made it possible to overcome these difficulties. Here, results of the transfer entropy analysis were consistent with widespread understanding of marsh zonation, yet produced additional insight into which vegetation communities specifically had a dominant impact on topographic change. Ecogeomorphic feedback that has a substantial short-term impact on evolving topography was resolvable only within native vegetation communities (Nelumbo lutea and Polygonum spp.) that occur over low to moderate elevations within the Wax Lake Delta tidal prism. In contrast, nonnative vegetation communities (Colocasia esculenta and Eichhonia crasspies) are not as functional at accreting sediment as native communities. The transfer entropy analysis suggests that different vegetation communities play functionally different roles in landscape evolution that should be differentiated in a model. Within such a model, it would be most critical to resolve detailed flow characteristics at low to low-middle island elevations, where submerged aquatic vegetation and Nelumbo are abundant, as these communities exert the strongest influence on topographic change. Furthermore, within elevation zones, it is likely important to

  11. Autoradiographic localization of benzomorphan binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Crain, B.J.; Kwenjen Chang; McNamara, J.O.; Valdes, F.

    1985-07-17

    The benzomorphan subpopulation of opiate binding sites was labeled by (TH)diprenorphine in the presence of unlabeled ligands selected to quench and delta opiate binding sites. The distribution of benzomorphan binding sites was then localized autoradiographically. The distribution differs from the distributions of , delta and kappa opiate binding and is quite similar to the distribution of US -endorphin immunoreactivity. These observations support the hypothesis, based on biochemical studies in brain membranes, that benzomorphan binding sites may represent the ligand recognition sites of putative epsilon receptors. (Auth.). 34 refs.; 3 figs.

  12. Climate Change and the Delta

    Directory of Open Access Journals (Sweden)

    Michael Dettinger

    2016-10-01

    Full Text Available doi: http://dx.doi.org/10.15447/sfews.2016v14iss3art5Anthropogenic climate change amounts to a rapidly approaching, “new” stressor in the Sacramento–San Joaquin Delta system. In response to California’s extreme natural hydroclimatic variability, complex water-management systems have been developed, even as the Delta’s natural ecosystems have been largely devastated. Climate change is projected to challenge these management and ecological systems in different ways that are characterized by different levels of uncertainty. For example, there is high certainty that climate will warm by about 2°C more (than late-20th-century averages by mid-century and about 4°C by end of century, if greenhouse-gas emissions continue their current rates of acceleration. Future precipitation changes are much less certain, with as many climate models projecting wetter conditions as drier. However, the same projections agree that precipitation will be more intense when storms do arrive, even as more dry days will separate storms. Warmer temperatures will likely enhance evaporative demands and raise water temperatures. Consequently, climate change is projected to yield both more extreme flood risks and greater drought risks. Sea level rise (SLR during the 20th century was about 22 cm, and is projected to increase by at least 3-fold this century. SLR together with land subsidence threatens the Delta with greater vulnerabilities to inundation and salinity intrusion. Effects on the Delta ecosystem that are traceable to warming include SLR, reduced snowpack, earlier snowmelt and larger storm-driven streamflows, warmer and longer summers, warmer summer water temperatures, and water-quality changes. These changes and their uncertainties will challenge the operations of water projects and uses throughout the Delta’s watershed and delivery areas. Although the effects of of climate change on Delta ecosystems may be profound, the end results are difficult to predict

  13. Climate change and the Delta

    Science.gov (United States)

    Dettinger, Michael; Anderson, Jamie; Anderson, Michael L.; Brown, Larry R.; Cayan, Daniel; Maurer, Edwin P.

    2016-01-01

    Anthropogenic climate change amounts to a rapidly approaching, “new” stressor in the Sacramento–San Joaquin Delta system. In response to California’s extreme natural hydroclimatic variability, complex water-management systems have been developed, even as the Delta’s natural ecosystems have been largely devastated. Climate change is projected to challenge these management and ecological systems in different ways that are characterized by different levels of uncertainty. For example, there is high certainty that climate will warm by about 2°C more (than late-20th-century averages) by mid-century and about 4°C by end of century, if greenhouse-gas emissions continue their current rates of acceleration. Future precipitation changes are much less certain, with as many climate models projecting wetter conditions as drier. However, the same projections agree that precipitation will be more intense when storms do arrive, even as more dry days will separate storms. Warmer temperatures will likely enhance evaporative demands and raise water temperatures. Consequently, climate change is projected to yield both more extreme flood risks and greater drought risks. Sea level rise (SLR) during the 20th century was about 22cm, and is projected to increase by at least 3-fold this century. SLR together with land subsidence threatens the Delta with greater vulnerabilities to inundation and salinity intrusion. Effects on the Delta ecosystem that are traceable to warming include SLR, reduced snowpack, earlier snowmelt and larger storm-driven streamflows, warmer and longer summers, warmer summer water temperatures, and water-quality changes. These changes and their uncertainties will challenge the operations of water projects and uses throughout the Delta’s watershed and delivery areas. Although the effects of climate change on Delta ecosystems may be profound, the end results are difficult to predict, except that native species will fare worse than invaders. Successful

  14. Deformed nucleon and double-delta coupling

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Afsar (Institute of Physics, Bhubaneswar (India))

    1991-11-01

    Although the coupling constant (f{sub {pi}{Delta}{Delta}} /f{sub {pi}NN}) {sup 2} is of much importance in the context of current research in the role of the double-delta in hadron physics, so far the naive quark model value has been used, which is shown to be poor. Here we obtain a better value for this coupling constant in a deformed nucleon model which would help us to rectify this defect and enable us to conduct a proper study of the exotic double-delta channel. (author).

  15. delta 9-THC metabolites in meconium: identification of 11-OH-delta 9-THC, 8 beta,11-diOH-delta 9-THC, and 11-nor-delta 9-THC-9-COOH as major metabolites of delta 9-THC.

    Science.gov (United States)

    ElSohly, M A; Feng, S

    1998-01-01

    Gas chromatography-mass spectrometry (GC-MS) analysis of meconium specimens screening positive for cannabinoids by the EMIT 20 Assay showed a low confirmation rate for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). A study was designed to investigate the possible contribution of other delta 9-tetrahydrocannabinol (THC) metabolites, including glucuronides, to the overall response of the EIA. delta 9-THC-glucuronide was synthesized in order to develop the most efficient procedure for hydrolysis of glucuronides in meconium. Procedures were developed for the extraction and GC-MS analysis of delta 9-THC, 11-OH-delta 9-THC, 8 alpha- and 8 beta-OH-delta 9-THC, 8 beta,11-diOH-delta 9-THC, and THCCOOH, after enzymatic hydrolysis of meconium extracts. It is concluded that enzymatic hydrolysis of meconium extracts is necessary for efficient recovery of delta 9-THC metabolites; delta 9-THC and its 8-OH metabolite(s) are basically absent in meconium specimens; and 11-OH-delta 9-THC and 8 beta,11-diOH-delta 9-THC contribute significantly to the immunoassay response of meconium extracts. Analysis of several meconium specimens that screened positive for cannabinoids but failed to confirm for THCCOOH showed significant amounts of 11-OH-delta 9-THC and 8 beta,11-diOH-delta 9-THC. Therefore, GC-MS confirmation of cannabinoids in meconium should include analysis for these two metabolites in addition to THCCOOH.

  16. Has the sun set on kappa3-opioid receptors?

    Science.gov (United States)

    Connor, Mark; Kitchen, Ian

    2006-02-01

    Mu-opioid receptor agonists are a mainstay of clinical analgesia, despite the significant unwanted effects and dependence liability associated with drugs like morphine. The quest for opioids that produce analgesia with fewer undesirable effects has lead to the putative identification of multiple opioid receptor subtypes, despite the identification of only four opioid-related receptor genes. One such putative receptor subtype is the kappa3 receptor, activation of which supposedly produces analgesia in animals. In the present issue of this Journal, Olianas and co-workers have demonstrated that the prototypic kappa3 agonist naloxone benzoylhydrazone is actually a partial agonist at the cloned mu, delta, and kappa opioid receptors and an antagonist at opioid-like NOP receptors. Together with a recent study that showed that high-affinity naloxone benzoylhydrazone binding is abolished in triple mu/delta/kappa receptor knockout mice, the present study provides strong evidence that in vivo effects attributed to kappa3 receptor activation probably just reflect the combined actions of a particularly nonselective opioid drug. Indeed, molecular identification of any of the proposed subtypes of mu, delta, and kappa opioid receptors has proven elusive, suggesting that it is perhaps time to retire the notion of opioid receptor subtypes until definitive evidence for their existence is provided.

  17. Heterologous expression of a deuterated membrane-integrated receptor and partial deuteration in methylotrophic yeasts

    International Nuclear Information System (INIS)

    Massou, S.; Puech, V.; Talmont, F.; Demange, P.; Lindley, N.D.; Tropis, M.; Milon, A.

    1999-01-01

    Methylotrophic yeast has previously been shown to be an excellent system for the cost-effective production of perdeuterated biomass and for the heterologous expression of membrane receptors. A protocol for the expression of 85% deuterated, functional human μ-opiate receptor was established. For partially deuterated biomass, deuteration level and distribution were determined for fatty acids, amino acids and carbohydrates. It was shown that prior to biosynthesis of lipids and amino acids (and of carbohydrates, to a lower extent), exchange occurs between water and methanol hydrogen atoms, so that 80%-90% randomly deuterated biomass and over-expressed proteins may be obtained using only deuterated water

  18. Psychosocial interventions in opiate substitution treatment services: does the evidence provide a case for optimism or nihilism?

    Science.gov (United States)

    Day, Ed; Mitcheson, Luke

    2017-08-01

    Clinical guidelines from around the world recommend the delivery of psychosocial interventions as part of routine care in opiate substitution treatment (OST) programmes. However, although individual studies demonstrate benefit for structured psychosocial interventions, meta-analytical reviews find no benefit for manual-based treatments beyond 'routine counselling'. We consider the question of whether OST medication alone is sufficient to produce the required outcomes, or whether greater efforts should be made to provide high-quality psychosocial treatment alongside medication. In so doing, we consider the nuances and limitations of the evidence and the organizational barriers to transferring it into routine practice. The evidence base for psychosocial interventions in opiate substitution treatment (OST) services can be interpreted both positively and negatively. Steering a path between overly optimistic or nihilistic interpretations of the value of psychosocial treatment in OST programmes is the most pragmatic approach. Greater attention should be paid to elements common to all psychological treatments (such as therapeutic alliance), but also to the sequencing and packaging of psychosocial elements and their linkage to peer-led interventions. © 2017 Society for the Study of Addiction.

  19. Incidence of hepatitis C in drug injectors: the role of homelessness, opiate substitution treatment, equipment sharing, and community size.

    Science.gov (United States)

    Craine, N; Hickman, M; Parry, J V; Smith, J; Walker, A M; Russell, D; Nix, B; May, M; McDonald, T; Lyons, M

    2009-09-01

    A prospective cohort study estimated the incidence of hepatitis C virus (HCV) in drug injectors in South Wales (UK). In total, 286/481 eligible seronegative individuals were followed up after approximately 12 months. Dried blood spot samples were collected and tested for anti-HCV antibody and behavioural data were collected at baseline and follow-up. HCV incidence was 5.9/100 person-years [95% confidence interval (CI) 3.4-9.5]. HCV incidence was predicted by community size [incident rate ratio (IRR) 6.6, 95% CI 2.11-20.51, P = 0.001], homelessness (IRR 2.9, 95% CI 1.02-8.28, P = 0.047) and sharing injecting equipment (IRR 12.7, 95% CI 1.62-99.6, P = 0.015). HCV incidence was reduced in individuals in opiate substitution treatment (IRR 0.34, 95% CI 0.12-0.99, P = 0.047). In order to reduce follow-up bias we used multiple imputation of missing data using switching regression; after imputation estimated HCV incidence was 8.5/100 person-years (95% CI 5.4-12.7). HCV incidence varies with community size, equipment sharing and homelessness are associated with increased HCV incidence and opiate substitution treatment may be protective against HCV.

  20. Effectiveness of Cognitive-Behavioral Group Therapy on Craving, Depression & Anxiety among the Opiate Abusers Under MMT

    Directory of Open Access Journals (Sweden)

    Fereshte Momeni

    2010-04-01

    Full Text Available Objectives: This study aimed at evaluating the effectiveness of cognitive-behavioral group therapy on craving, symptoms of depression and anxiety among the patients under MMT. Methods: In this experimental study, 36 opiate addicts under MMT were selected out of all the patients referring to Iranian National Center of Addiction Studies on a judgmental sampling method and were randomly allocated to two experimental and control groups. In experimental group, a total sum of 8 sessions (one session per week of cognitive behavioral group therapy were delivered. The main theme of these sessions were efficient management of craving, negative mood and anxiety. Data were gathered with different questionnaires including the questionnaire of demographic data, RPS for craving assessment, BDI-II for depression and BAI for anxiety. Different methods of statistical analysis were implemented. Results: The results indicated that post test and follow-up scores of craving index were decreased significantly (P<0.05. Depression and Anxiety scores showed significant decrease as well. Discussion: Considering the above mentioned findings, we concluded that cognitive-behavioral group therapy was effective in significantly decreasing craving and symptoms of anxiety and depression in opiate addicts under MMT.

  1. Molecular modeling of interactions of the non-peptide antagonist YM087 with the human vasopressin V1a, V2 receptors and with oxytocin receptors.

    Science.gov (United States)

    Giełdoń, Artur; Kaźmierkiewicz, Rajmund; Ślusarz, Rafał; Ciarkowski, Jerzy

    2001-12-01

    The nonapeptide hormones arginine vasopressin (CYFQNCPRG-NH2, AVP) and oxytocin (CYIQNCPLG-NH2, OT), control many essential functions in mammals. Their main activities include the urine concentration (via stimulation of AVP V2 receptors, V2R, in the kidneys), blood pressure regulation (via stimulation of vascular V1a AVP receptors, V1aR), ACTH control (via stimulation of V1b receptors, V1bR, in the pituitary) and labor and lactation control (via stimulation of OT receptors, OTR, in the uterus and nipples, respectively). All four receptor subtypes belong to the GTP-binding (G) protein-coupled receptor (GPCR) family. This work consists of docking of YM087, a potent non-peptide V1aR and V2R - but not OTR - antagonist, into the receptor models based on relatively new theoretical templates of rhodopsin (RD) and opiate receptors, proposed by Mosberg et al. (Univ. of Michigan, Ann Arbor, USA). It is simultaneously demonstrated that this RD template satisfactorily compares with the first historical GPCR structure of bovine rhodopsin (Palczewski et al., 2000) and that homology-modeling of V2R, V1aR and OTR using opiate receptors as templates is rational, based on relatively high (20-60%) sequence homology among the set of 4 neurophyseal and 4 opiate receptors. YM087 was computer-docked to V1aR, V2R and OTR using the AutoDock (Olson et al., Scripps Research Institute, La Jolla, USA) and subsequently relaxed using restrained simulated annealing and molecular dynamics, as implemented in AMBER program (Kollman et al., University of California, San Francisco, USA). From about 80 diverse configurations, sampled for each of the three ligand/receptor systems, 3 best energy-relaxed complexes were selected for mutual comparisons. Similar docking modes were found for the YM087/V1aR and YM087/V2R complexes, diverse from those of the YM087/OTR complexes, in agreement with the molecular affinity data.

  2. Entropy and optimality in river deltas

    Science.gov (United States)

    Tejedor, Alejandro; Longjas, Anthony; Edmonds, Douglas A.; Zaliapin, Ilya; Georgiou, Tryphon T.; Rinaldo, Andrea; Foufoula-Georgiou, Efi

    2017-10-01

    The form and function of river deltas is intricately linked to the evolving structure of their channel networks, which controls how effectively deltas are nourished with sediments and nutrients. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. To date, however, a unified theory explaining how deltas self-organize to distribute water and sediment up to the shoreline remains elusive. Here, we provide evidence for an optimality principle underlying the self-organized partition of fluxes in delta channel networks. By introducing a suitable nonlocal entropy rate (nER) and by analyzing field and simulated deltas, we suggest that delta networks achieve configurations that maximize the diversity of water and sediment flux delivery to the shoreline. We thus suggest that prograding deltas attain dynamically accessible optima of flux distributions on their channel network topologies, thus effectively decoupling evolutionary time scales of geomorphology and hydrology. When interpreted in terms of delta resilience, high nER configurations reflect an increased ability to withstand perturbations. However, the distributive mechanism responsible for both diversifying flux delivery to the shoreline and dampening possible perturbations might lead to catastrophic events when those perturbations exceed certain intensity thresholds.

  3. Morphodynamics of ebb-tidal deltas

    NARCIS (Netherlands)

    Ridderinkhof, W.

    2016-01-01

    Ebb-tidal deltas are bodies of sand that are located seaward of tidal inlets. The latter connect the open sea with a back-barrier basin and separate barrier islands. The morphology (e.g., sand volume, geometry, shoal formation) of ebb-tidal deltas evolves continuously, both due to natural processes

  4. Floating City IJmeer : Accelerator for Delta Technology

    NARCIS (Netherlands)

    De Graaf, R.; Fremouw, M.; Van Bueren, B.; Czapiewska, K.; Kuijper, M.

    2006-01-01

    Climate change, sea level rise, population growth and ongoing urbanization result in higher vulnerability of the Rhine delta because it will result in increased flooding frequency, increasing investments and increased use of water, energy and other resources. The Rhine Delta also faces strong

  5. Electromagnetic excitation of the Delta(1232) resonance

    Energy Technology Data Exchange (ETDEWEB)

    V. Pascalutsa; M. Vanderhaeghen; Shin Nan Yang

    2006-09-05

    We review the description of the lowest-energy nucleon excitation--the Delta(1232)-resonance. Much of the recent effort has been focused on the precision measurements of the nucleon to Delta transition by means of electromagnetic probes. We review the results of those measurements and confront them with the state-of-the-art calculations based on chiral effective-field theories (EFT), lattice QCD, and QCD-inspired models. Some of the theoretical approaches are reviewed in detail. In particular, we describe the chiral EFT of QCD in the energy domain of the Delta-resonance, and its applications to the electromagnetic nucleon-to-Delta transition (gamma N Delta). We also describe the recent dynamical and unitary-isobar models of pion electroproduction which are extensively used in the extraction of the gamma* N Delta form factors from experiment. Furthermore, we discuss the link of the gamma* N Delta form factors to generalized parton distributions (GPDs), as well as the predictions of perturbative QCD for these transition form factors. The present status of understanding the Delta-resonance properties and the nature of its excitation is summarized.

  6. Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.

    Science.gov (United States)

    Szeto, H H; Soong, Y; Wu, D; Olariu, N; Kett, A; Kim, H; Clapp, J F

    1999-01-01

    We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.

  7. [Establishment of delta block matching technique].

    Science.gov (United States)

    Lü, Qin-Feng; Zhang, Wei; Zhu, Fa-Ming; Yan, Li-Xing

    2006-04-01

    To establish delta block HLA-matching technique, DNA was extracted from whole blood by salting-out method, delta block was amplified by polymerase chain reaction (PCR), and PCR product was detected by GeneScan. The results showed that delta block had polymorphism in 104 samples without sibship of the Han people from Zhejiang province. The range of DNA fragment length was 81-393 bp and could be divided into 4 groups: 81-118 bp, 140-175 bp, 217-301 bp, 340-393 bp. The numbers of DNA fragments were 6-32. It is concluded that the method of delta block matching is reliable and can be applied to select donors for the patients to be transplanted. It is the first time to get delta block data of the Han people in China.

  8. Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.

    Science.gov (United States)

    Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M

    2007-11-30

    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a

  9. Sympathoadrenal, cardiovascular and blood gas responses to highly selective mu and delta opioid peptides.

    Science.gov (United States)

    Kiritsy-Roy, J A; Marson, L; Van Loon, G R

    1989-12-01

    The relative importance of mu and delta opioid receptors in brain regulation of sympathoadrenal, cardiovascular and respiratory function was investigated using highly selective mu and delta opioid peptide analogs. Groups of conscious rats received i.c.v. injections of either the mu-selective agonist, [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) or the delta-selective agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE). Blood pressure and heart rate were recorded continuously via a chronic catheter in the carotid artery, and arterial blood samples were taken at intervals through the same catheter for determination of blood pH, pCO2, pO2 and plasma catecholamine concentrations. Both DAMGO and DPDPE increased plasma catecholamine levels and blood pressure in a dose-related manner. The slopes of the dose-response lines were parallel, but the delta compound was about 250 times less potent than DAMGO. Only the highest dose of 5 nmol of DAMGO caused a significant bradycardia, mediated by parasympathetic (vagal) activation. DAMGO and DPDPE also induced dose-dependent acidosis, with DAMGO again being much more potent than DPDPE. The effects of both DAMGO and DPDPE on plasma catecholamines, blood pressure and blood gases were antagonized by a mu-selective dose of naloxone (0.4 mg/kg i.a.). Intracerebroventricular administration of the delta-selective antagonist, ICI 174,864, only partially attenuated sympathoadrenal and blood gas responses to DAMGO or DPDPE. The pressor responses to DAMGO or DPDPE were resistant to antagonism by ICI 174,864. These results indicate that brain opioid receptors regulating autonomic outflow, cardiovascular and respiratory function are mainly of the mu type, although a delta opioid system may contribute to sympathoadrenal and respiratory effects of opioids.

  10. Delta connected resonant snubber circuit

    Science.gov (United States)

    Lai, J.S.; Peng, F.Z.; Young, R.W. Sr.; Ott, G.W. Jr.

    1998-01-20

    A delta connected, resonant snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the dc supply voltage through the main inverter switches and the auxiliary switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter. 36 figs.

  11. Delta connected resonant snubber circuit

    Science.gov (United States)

    Lai, Jih-Sheng; Peng, Fang Zheng; Young, Sr., Robert W.; Ott, Jr., George W.

    1998-01-01

    A delta connected, resonant snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the dc supply voltage through the main inverter switches and the auxiliary switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter.

  12. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  13. Differentiation of Boc-protected alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptide positional isomers by electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Raju, G; Ramesh, V; Srinivas, R; Sharma, G V M; Shoban Babu, B

    2010-06-01

    Two new series of Boc-N-alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptides containing repeats of L-Ala-delta(5)-Caa/delta(5)-Caa-L-Ala and beta(3)-Caa-delta(5)-Caa/delta(5)-Caa-beta(3)-Caa (L-Ala = L-alanine, Caa = C-linked carbo amino acid derived from D-xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion trap tandem mass spectrometry (MS/MS). MS(n) spectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Boc-group, and the side chain. The dipeptide positional isomers are differentiated by the collision-induced dissociation (CID) of the protonated peptides. The loss of 2-methylprop-1-ene is more pronounced for Boc-NH-L-Ala-delta-Caa-OCH(3) (1), whereas it is totally absent for its positional isomer Boc-NH-delta-Caa-L-Ala-OCH(3) (7), instead it shows significant loss of t-butanol. On the other hand, second isomeric pair shows significant loss of t-butanol and loss of acetone for Boc-NH-delta-Caa-beta-Caa-OCH(3) (18), whereas these are insignificant for its positional isomer Boc-NH-beta-Caa-delta-Caa-OCH(3) (13). The tetra- and hexapeptide positional isomers also show significant differences in MS(2) and MS(3) CID spectra. It is observed that 'b' ions are abundant when oxazolone structures are formed through five-membered cyclic transition state and cyclization process for larger 'b' ions led to its insignificant abundance. However, b(1)(+) ion is formed in case of delta,alpha-dipeptide that may have a six-membered substituted piperidone ion structure. Furthermore, ESI negative ion MS/MS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MS/MS of pairs of di-, tetra-, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers. Copyright 2010 John Wiley & Sons, Ltd.

  14. Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

    DEFF Research Database (Denmark)

    Glintborg, B.; Olsen, L.; Poulsen, H.

    2008-01-01

    Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

  15. Investigating the relationship between sexual and chemical addictions by comparing executive function in subjects with pedophilia or opiate addiction and healthy controls.

    Science.gov (United States)

    Cohen, Lisa J; Nesci, Cristina; Steinfeld, Matthew; Haeri, Sophia; Galynker, Igor

    2010-11-01

    Disorders of driven sexual behavior have been conceptualized as sexual addictions. In the following study, we compared 51 subjects with pedophilia, 53 subjects with opiate addiction, and 84 healthy control subjects on neuropsychological tests that tap executive functions. The test battery included the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, the Matching Familiar Figures Test (MFFT), Porteus Mazes, Controlled Word Association (COWA), and Trailmaking Test. The groups differed on tests of cognitive flexibility and set switching (WCST), sustained attention (Stroop), and impulsivity (MFFT and Porteus Mazes). There were no differences on verbal fluency (COWA). The subjects with pedophilia differed significantly from those with opiate addiction on several tests, with longer latency to response on MFFT and fewer completed mazes but also fewer errors on Porteus Mazes. Thus, while both subjects with pedophilia and those with opiate addiction show executive dysfunction, the nature of that dysfunction may differ between the two groups; specifically, opiate addicted subjects may be more prone to cognitive impulsivity.

  16. Rise and Fall of one of World's largest deltas; the Mekong delta in Vietnam

    Science.gov (United States)

    Minderhoud, P. S. J.; Eslami Arab, S.; Pham, H. V.; Erkens, G.; van der Vegt, M.; Oude Essink, G.; Stouthamer, E.; Hoekstra, P.

    2017-12-01

    The Mekong delta is the third's largest delta in the world. It is home to almost 20 million people and an important region for the food security in South East Asia. As most deltas, the Mekong delta is the dynamic result of a balance of sediment supply, sea level rise and subsidence, hosting a system of fresh and salt water dynamics. Ongoing urbanization, industrialization and intensification of agricultural practices in the delta, during the past decades, resulted in growing domestic, agricultural and industrial demands, and have led to a dramatic increase of fresh water use. Since the year 2000, the amount of fresh groundwater extracted from the subsurface increased by 500%. This accelerated delta subsidence as the groundwater system compacts, with current sinking rates exceeding global sea level rise up to an order of magnitude. These high sinking rates have greatly altered the sediment budget of the delta and, with over 50% of the Mekong delta surface elevated less than 1 meter above sea level, greatly increase vulnerability to flooding and storm surges and ultimately, permanent inundation. Furthermore, as the increasingly larger extractions rapidly reduce the fresh groundwater reserves, groundwater salinization subsequently increases. On top of that, dry season low-flows by the Mekong river cause record salt water intrusion in the delta's estuarine system, creating major problems for rice irrigation. We present the work of three years research by the Dutch-Vietnamese `Rise and Fall' project on land subsidence and salinization in both groundwater and surface water in the Vietnamese Mekong delta.

  17. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino......-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic...... acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate...

  18. Tidal controls on river delta morphology

    Science.gov (United States)

    Hoitink, A. J. F.; Wang, Z. B.; Vermeulen, B.; Huismans, Y.; Kästner, K.

    2017-09-01

    River delta degradation has been caused by extraction of natural resources, sediment retention by reservoirs, and sea-level rise. Despite global concerns about these issues, human activity in the world’s largest deltas intensifies. Harbour development, construction of flood defences, sand mining and land reclamation emerge as key contemporary factors that exert an impact on delta morphology. Tides interacting with river discharge can play a crucial role in the morphodynamic development of deltas under pressure. Emerging insights into tidal controls on river delta morphology suggest that--despite the active morphodynamics in tidal channels and mouth bar regions--tidal motion acts to stabilize delta morphology at the landscape scale under the condition that sediment import during low flows largely balances sediment export during high flows. Distributary channels subject to tides show lower migration rates and are less easily flooded by the river because of opposing non-linear interactions between river discharge and the tide. These interactions lead to flow changes within channels, and a more uniform distribution of discharge across channels. Sediment depletion and rigorous human interventions in deltas, including storm surge defence works, disrupt the dynamic morphological equilibrium and can lead to erosion and severe scour at the channel bed, even decades after an intervention.

  19. Morphine potentiates neurodegenerative effects of HIV-1 Tat through actions at μ-opioid receptor-expressing glia.

    Science.gov (United States)

    Zou, Shiping; Fitting, Sylvia; Hahn, Yun-Kyung; Welch, Sandra P; El-Hage, Nazira; Hauser, Kurt F; Knapp, Pamela E

    2011-12-01

    Individuals infected with human immunodeficiency virus-1 who abuse opiates can have a higher incidence of virus-associated neuropathology. Human immunodeficiency virus does not infect neurons, but viral proteins such as transactivator of transcription and glycoprotein 120, originating from infected glia, are neurotoxic. Moreover, functional changes in glial cells that enhance inflammation and reduce trophic support are increasingly implicated in human immunodeficiency virus neuropathology. In previous studies, co-exposure with morphine enhanced transactivator of transcription neurotoxicity towards cultured striatal neurons. Since those cultures contained µ-opioid receptor-expressing astroglia and microglia, and since glia are the principal site of infection in the central nervous system, we hypothesized that morphine synergy might be glially mediated. A 60 hour, repeated measures paradigm and multiple co-culture models were used to investigate the cellular basis for opiate-enhanced human immunodeficiency virus neurotoxicity. Morphine co-exposure significantly enhanced transactivator of transcription-induced neuron death when glia were present. Synergistic effects of morphine on transactivator of transcription neurotoxicity were greatest with neuron-glia contact, but also occurred to a lesser extent with glial conditioned medium. Importantly, synergy was lost if glia, but not neurons, lacked µ-opioid receptors, indicating that opiate interactions with human immunodeficiency virus converge at the level of µ-opioid receptor-expressing glia. Morphine enhanced transactivator of transcription-induced inflammatory effectors released by glia, elevating reactive oxygen species, increasing 3-nitrotyrosine production by microglia, and reducing the ability of glia to buffer glutamate. But neuron survival was reduced even more with glial contact than with exposure to conditioned medium, suggesting that noxious elements associated with cell contact augment the toxicity due to

  20. Reduced complexity modeling of Arctic delta dynamics

    Science.gov (United States)

    Piliouras, A.; Lauzon, R.; Rowland, J. C.

    2017-12-01

    How water and sediment are routed through deltas has important implications for our understanding of nutrient and sediment fluxes to the coastal ocean. These fluxes may be especially important in Arctic environments, because the Arctic ocean receives a disproportionately large amount of river discharge and high latitude regions are expected to be particularly vulnerable to climate change. The Arctic has some of the world's largest but least studied deltas. This lack of data is due to remote and hazardous conditions, sparse human populations, and limited remote sensing resources. In the absence of data, complex models may be of limited scientific utility in understanding Arctic delta dynamics. To overcome this challenge, we adapt the reduced complexity delta-building model DeltaRCM for Arctic environments to explore the influence of sea ice and permafrost on delta morphology and dynamics. We represent permafrost by increasing the threshold for sediment erosion, as permafrost has been found to increase cohesion and reduce channel migration rates. The presence of permafrost in the model results in the creation of more elongate channels, fewer active channels, and a rougher shoreline. We consider several effects of sea ice, including introducing friction which increases flow resistance, constriction of flow by landfast ice, and changes in effective water surface elevation. Flow constriction and increased friction from ice results in a rougher shoreline, more frequent channel switching, decreased channel migration rates, and enhanced deposition offshore of channel mouths. The reduced complexity nature of the model is ideal for generating a basic understanding of which processes unique to Arctic environments may have important effects on delta evolution, and it allows us to explore a variety of rules for incorporating those processes into the model to inform future Arctic delta modelling efforts. Finally, we plan to use the modeling results to determine how the presence

  1. The opiate sufentanil alters the inflammatory, endocrine, and metabolic responses to endotoxin in dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Endert, E.; Ackermans, M. T.; van Lanschot, J. J.; Sauerwein, H. P.; Romijn, J. A.

    1998-01-01

    Sufentanil is a synthetic mu-opioid receptor agonist frequently used in anesthesia and critically ill patients. To evaluate the effects of sufentanil on the inflammatory, neuroendocrine, and metabolic responses to endotoxin, we studied six dogs during saline infusion (control), during sufentanil

  2. Endogenous Opiates in the Nucleus Tractus Solitarius Mediate Electroacupuncture-Induced Sleep Activities in Rats

    Directory of Open Access Journals (Sweden)

    Chiung-Hsiang Cheng

    2011-01-01

    Full Text Available Electroacupuncture (EA possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17 acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhances non-rapid eye movement (NREM sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS. In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the μ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of δ-receptor antagonist, natrindole, and the κ-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the μ-opioid receptors.

  3. Cannabinoid receptor localization in brain

    Energy Technology Data Exchange (ETDEWEB)

    Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. (National Institute of Mental Health, Bethesda, MD (USA))

    1990-03-01

    (3H)CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of (3H)CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.

  4. Comparison of childhood sexual histories in subjects with pedophilia or opiate addiction and healthy controls: is childhood sexual abuse a risk factor for addictions?

    Science.gov (United States)

    Cohen, Lisa J; Forman, Howard; Steinfeld, Matthew; Fradkin, Yuli; Frenda, Steven; Galynker, Igor

    2010-11-01

    Given the recent interest in the concept of sexual addictions, it is instructive to study subjects with pedophilia alongside chemically addicted individuals and non-addicted controls in order to help identify which factors may determine the objects of people's respective addictions, as well as any factors that may predispose people to developing an addictive disorder. In this study, we considered whether childhood sexual abuse (CSA) is a specific risk factor for pedophilia as opposed to other types of addictive disorders by comparing the childhood sexual histories of 48 pedophilic sex offenders, 25 subjects with opiate addiction in remission, and 61 healthy controls. CSA was assessed with The Sexual History Questionnaire and the Child Trauma Questionnaire (CTQ). Compared with both opiate addicted subjects and healthy controls, subjects with pedophilia were more likely to report experiencing adult sexual advances when they were children and a first sexual contact by age 13 with a partner at least 5 years older. Although both subjects with pedophilia and those with opiate addiction first had sex at a younger age than healthy controls, opiate addicted subjects, compared with healthy controls, reported neither increased reception of sexual advances as children nor increased rates of first sexual contact before age 13 with a partner at least 5 years older. Further, subjects with pedophilia but not those with opiate addiction scored significantly higher than healthy controls on the CTQ. Sexual abuse in childhood may be a specific risk factor for sexual addictions such as pedophilia but may not be a specific risk factor for chemical addictions.

  5. Delta Relaxation Enhanced Magnetic Resonance

    Science.gov (United States)

    Alford, Jamu K.

    Generally speaking, targeted molecular imaging has always been difficult to perform with magnetic resonance. The difficulty does not arise with the magnetic resonance imaging (MRI) technique or equipment itself, but rather with the targeted contrast agents, which the method requires. Also referred to as activatable contrast agents, or MRI probes, targeted contrast agents are pharmaceuticals that will selectively bind to a particular biological (target) molecule. They are used to highlight a certain tissue or the difference between healthy and diseased tissue. Unfortunately, nearly all MRI probes are non-specific, causing localized increases in MR image intensity in both the unbound and target-bound states. Therefore, brightening in a conventional MRI image, following probe injection, does not positively indicate the presence of the target molecule. Herein, a novel method known as delta relaxation enhanced magnetic resonance (dreMR, pronounced "dreamer") is presented that utilizes variable magnetic field technology to produce image contrast related to the dependence of the sample's longitudinal relaxation rates upon the strength of the main magnetic field of the MRI scanner. Since only bound contrast agent shows significant magnetic field dependence, it is an indicator of the bound probe, which is in turn a marker for the target molecule. This work details the development of the dreMR method, focusing on the specialized hardware necessary to provide a clinical, static-field MRI the ability to modulate its main magnetic field throughout an MRI sequence. All modifications were performed in such a manner that the host MRI system was not degraded or permanently modified in any way. The three parts of this technology are: the insertable electromagnet, the power supply system and the control system. The insertable electromagnet modifies the magnetic field, the power system drives the electromagnet, and the control system generates the magnetic field waveform envelope and

  6. Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells.

    Science.gov (United States)

    Vila, L M; Haftel, H M; Park, H S; Lin, M S; Romzek, N C; Hanash, S M; Holoshitz, J

    1995-04-01

    Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.

  7. Affinity crosslinking of /sup 125/I-human beta-endorphin to cell lines possessing either mu or delta type opioid binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Keren, O.; Gioannini, T.L.; Hiller, J.M.; Simon, E.J.

    1986-01-01

    Affinity crosslinking of human /sup 125/I-beta-Endorphin to cell lines possessing either mu or delta binding sites was carried out. Autoradiography of SDS-PAGE gels from these crosslinked cell lines revealed that these two sites contain major peptide subunits that differ in molecular size. This confirms our earlier finding in mammalian brain which demonstrated separate and distinct subunits for mu and delta opioid receptors.

  8. PPAR{delta} is a fatty acid sensor, which enhances mitochondrial oxidation in insulin

    DEFF Research Database (Denmark)

    Ravnskjaer, Kim; Frigerio, Francesca; Boergesen, Michael

    2010-01-01

    The peroxisome proliferator-activated receptor delta (PPARdelta) is implicated in regulation of mitochondrial processes in a number of tissues, and PPARdelta activation is associated with decreased susceptibility to ectopic lipid deposition and metabolic disease. Here we show that PPARdelta...... against adverse effects on GSIS associated with prolonged fatty acid exposure. The presented results indicate that the nuclear receptor PPARdelta is a fatty acid sensor that adapts beta-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial...

  9. The opiate antagonist, naltrexone, in the treatment of trichotillomania: results of a double-blind, placebo-controlled study.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Schreiber, Liana R N; Kim, Suck Won

    2014-02-01

    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly improved with naltrexone (P = 0.026). Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant. Future studies will have to examine whether pharmacological modulation of the opiate system may provide promise in controlling pulling behavior in a subgroup of individuals with TTM.

  10. Delta Electroproduction in 12-C

    Energy Technology Data Exchange (ETDEWEB)

    McLauchlan, Steven [Univ. of Glasgow, Scotland (United Kingdom)

    2003-01-01

    The Δ-nucleus potential is a crucial element in the understanding of the nuclear system. Previous electroexcitation measurements in the delta region reported a Q2 dependence of the Δ mass indicating that this potential is dependent on the momentum of the Δ. Such a dependence is not observed for protons and neutrons in the nuclear medium. This thesis presents the experimental study of the electroexcitation of the Δ resonance in 12C, performed using the high energy electron beam at the Thomas Jefferson National Accelerator Facility, and the near 4π acceptance detector CLAS that enables the detection of the full reaction final state. Inclusive, semi inclusive, and exclusive cross sections were measured with an incident electron beam energy of 1.162GeV over the Q2 range 0.175-0.475 (GeV/c)2. A Q2 dependence of the Δ mass was only observed in the exclusive measurements indicating that the Δ-nucleus potential is affected by the momentum of the Δ.

  11. On the origin of delta spots

    International Nuclear Information System (INIS)

    Tang, F.

    1983-01-01

    Mount Wilson sunspot drawings from 1966 through 1980 were used in conjunction with Hα filtergrams from Big Bear Solar Observatory to examine the origin of delta spots, spots with bipolar umbrae within one penumbra. Of the six cases we studied, five were formed by the union of non-paired spots. They are either shoved into one another by two neighboring growing bipoles or by a new spot born piggy-back style on an existing spot of opposite polarity. Proper motions of the growing spots take on curvilinear paths around one another to avoid a collision. This is the shear motion observed in delta spots (Tanaka, 1979). In the remaining case, the delta spot was formed by spots that emerged as a pair. Our findings indicate no intrinsic differences in the formation or the behavior between delta spots of normal magnetic configuration. (orig.)

  12. Astrobee Periodic Technical Review (PTR) Delta 3

    Science.gov (United States)

    Provencher, Christopher; Smith, Marion F.; Smith, Ernest Everett; Bualat, Maria Gabriele; Barlow, Jonathan Spencer

    2017-01-01

    Astrobee is a free flying robot for the inside of the International Space Station (ISS). The Periodic Technical Review (PTR) delta 3 is the final design review of the system presented to stakeholders.

  13. Damped Oscillator with Delta-Kicked Frequency

    Science.gov (United States)

    Manko, O. V.

    1996-01-01

    Exact solutions of the Schrodinger equation for quantum damped oscillator subject to frequency delta-kick describing squeezed states are obtained. The cases of strong, intermediate, and weak damping are investigated.

  14. Delta-nucleus dynamics: proceedings of symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P. (eds.)

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta ..delta..(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe ..delta..-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  15. Propagator for the double delta potential

    International Nuclear Information System (INIS)

    Cacciari, Ilaria; Moretti, Paolo

    2006-01-01

    The propagator for the double delta potential is calculated starting from the integral form of the Schroedinger equation. A compact expression of its Laplace transform is found, that can be explicitly inverted in some limiting cases

  16. California Black Rail - Central Delta [ds17

    Data.gov (United States)

    California Department of Resources — Results of taped-call black rail surveys of in-stream habitat within certain waterways in the central Sacramento / San Joaquin Delta during 1992 and 1993. TIME...

  17. Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program

    Directory of Open Access Journals (Sweden)

    Reece AS

    2007-11-01

    Full Text Available Abstract Background There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. Methods A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. Results There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. Conclusion Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction.

  18. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

    Directory of Open Access Journals (Sweden)

    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  19. Development and validation of a gas chromatography-mass spectrometry assay for opiates and cocaine in human teeth.

    Science.gov (United States)

    Pellegrini, Manuela; Casá, Adriana; Marchei, Emilia; Pacifici, Roberta; Mayné, Ruth; Barbero, Vanessa; Garcia-Algar, Oscar; Pichini, Simona

    2006-02-24

    A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of opiates (6-monoacetylmorphine, morphine and codeine) and cocaine and metabolites (cocaine, benzoylecgonine and cocaethylene) in human teeth. After addition of nalorphine as internal standard, pulverized samples were incubated in HCl at 37 degrees C for 18 h. Then, after pH adjustment to 6, and the analytes were extracted with two volumes of 3 ml of chloroform/isopropanol (9:1). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 7.5 (6.0 in case of codeine) to 500 ng/g with mean absolute recoveries ranged between 74.1 and 92.1% for the different analytes and precision and accuracy always better than 15%. The method was applied to the analysis of teeth from drug-addicts to assess past chronic consumption and verify self-reported declarations. In case of opiates, concentration range was 36.5-570.0 ng/g for 6-monoacetylmorphine, 8.7-154.8 ng/g for morphine and 7.9-127.9 ng/g for codeine. Cocaine concentration ranged between 5.6 and 57.2 ng/g with its principal metabolite benzoylecgonine varying from 12.6 to 81.7 ng/g and cocaethylene present in only one sample at 10 ng/g value. Teeth can be a promising non-invasive biological matrix in biomedical analysis for both clinical and forensic purposes.

  20. Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification.

    Science.gov (United States)

    Vernon, Margaret K; Reinders, Stefan; Mannix, Sally; Gullo, Kristen; Gorodetzky, Charles W; Clinch, Thomas

    2016-09-01

    The Short Opiate Withdrawal Scale (SOWS)-Gossop is a 10-item questionnaire developed to evaluate opioid withdrawal symptom severity. The scale was derived from the original 32-item Opiate Withdrawal Scale in order to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The objective of this study was to examine the psychometric properties and provide score interpretation guidelines for the SOWS-Gossop 10-item version. Blinded, pooled data from two trials assessing the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid detoxification were used to evaluate the quantitative psychometric properties and score interpretation of the SOWS-Gossop. Five hundred fifty-five (N=555) observations were available at baseline with numbers decreasing to n=213 at day 7. Mean (standard deviation) SOWS-Gossop scores were 10.4 (6.86) at baseline, 8.7 (6.49) on day 1, 10.5 (7.21) on day 2, and 3.1 (3.95) on day 7. Confirmatory factor analysis indicated that the SOWS-Gossop items loaded on a single factor consistent with a single total score. Intra-class correlations (95% confidence interval) were 0.78 (0.70-0.85) between baseline and day 1, 0.84 (0.79-0.89) between days 4 and 5, and 0.88 (0.83-0.91) between days 6 and 7, demonstrating good test-retest reliability. Mean SOWS-Gossop scores varied significantly (popioid withdrawal and has excellent psychometric properties. The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Stellar delta matter with delta-meson coupling constants constrained by QCD sum rule

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Antonio Ferreira da [Secretaria de Educacao, Cultura e Desportos do Estado de Roraima (SECD/RR), Boa Vista, RR (Brazil); Oliveira, Jose Carlos Teixeira de [Universidade Federal de Roraima (UFRR), Boa Vista, RR (Brazil); Rodrigues, Hilario [Centro Federal de Educacao Tecnologica (CEFET-RJ), Rio de Janeiro, RJ (Brazil); Duarte, Sergio Barbosa [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Chiapparini, Marcelo [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil)

    2010-07-01

    The considerable presence of delta-resonances (30% of baryonic population) in the dense phase of relativistic heavy ion collisions leads to a great interest in the study of the delta matter formation in the deep interior of compact stars. In the present work we determine the equation of state and the population of baryons and leptons and discuss the effects of the baryon-meson coupling constants to the formation of delta matter in the stellar medium. We use the non-linear Walecka model consisting of the octet of baryons of spin 1=2 (n, p, {Lambda}{sup 0}, {Sigma}{sup -}, {Sigma}{sup 0}, {Sigma}{sup +}, {Xi}{sup -}, {Xi}{sup 0}) and baryonic resonances of spin 3=2, represented by the delta resonances ({Delta}{sup -}, ({Delta}{sup 0}, ({Delta}{sup +}, ({Delta}{sup ++}) and {Omega}{sup -}, in the baryonic sector. In the leptonic sector we consider the electrons and muons. The coupling constants between the hyperons {Lambda}, {Sigma}, and {Xi} and the mesons {omega} and {rho} are fixed by using SU(6) symmetry, while the hyperons-{sigma} coupling constants are constrained by the consistence of the hypernuclear potential in the nuclear matter with hypernuclear data. In addition, we use the finite density QCD sum rule to determine the possible values of delta-meson coupling constants. (author)

  2. More about the Viking hypothesis of origin of the delta32 mutation in the CCR5 gene conferring resistance to HIV-1 infection.

    Science.gov (United States)

    Lucotte, Gérard; Dieterlen, Florent

    2003-11-01

    The chemokine receptor CCR5 constitutes the major coreceptor for the HIV-1, because a mutant allele of the CCR5 gene named delta32 was shown to provide to homozygotes a strong resistance against infection. In the present study the frequency of the delta32 allele was collected in 36 European populations and in Cyprus, and the highest allele frequencies were found in Nordic countries. We constructed an allele map of delta32 frequencies in Europe; the map is in accordance to the Vikings hypothesis of the origin of the mutation and his dissemination during the eighth to the tenth centuries.

  3. Angiopoietin-like 4 mediates PPAR delta effect on lipoprotein lipase-dependent fatty acid uptake but not on beta-oxidation in myotubes.

    Directory of Open Access Journals (Sweden)

    Marius R Robciuc

    Full Text Available Peroxisome proliferator-activated receptor (PPAR delta is an important regulator of fatty acid (FA metabolism. Angiopoietin-like 4 (Angptl4, a multifunctional protein, is one of the major targets of PPAR delta in skeletal muscle cells. Here we investigated the regulation of Angptl4 and its role in mediating PPAR delta functions using human, rat and mouse myotubes. Expression of Angptl4 was upregulated during myotubes differentiation and by oleic acid, insulin and PPAR delta agonist GW501516. Treatment with GW501516 or Angptl4 overexpression inhibited both lipoprotein lipase (LPL activity and LPL-dependent uptake of FAs whereas uptake of BSA-bound FAs was not affected by either treatment. Activation of retinoic X receptor (RXR, PPAR delta functional partner, using bexarotene upregulated Angptl4 expression and inhibited LPL activity in a PPAR delta dependent fashion. Silencing of Angptl4 blocked the effect of GW501516 and bexarotene on LPL activity. Treatment with GW501516 but not Angptl4 overexpression significantly increased palmitate oxidation. Furthermore, Angptl4 overexpression did not affect the capacity of GW501516 to increase palmitate oxidation. Basal and insulin stimulated glucose uptake, glycogen synthesis and glucose oxidation were not significantly modulated by Angptl4 overexpression. Our findings suggest that FAs-PPARdelta/RXR-Angptl4 axis controls the LPL-dependent uptake of FAs in myotubes, whereas the effect of PPAR delta activation on beta-oxidation is independent of Angptl4.

  4. Beteigeuze (Alpha Orionis) und Mintaka (Delta Orionis)

    Science.gov (United States)

    Vollmann, Wolfgang

    2013-02-01

    Magnitude measures transformed to Johnson V of Alpha Orionis (Betelgeuse) and Delta Orionis with a wide-angle lens and DSLR are presented and discussed. Alpha Orionis light changes are shown clearly. The primary and secondary eclipses of Delta Orionis with amplitudes of 0.12 and 0.05 mag respectively are clearly recorded. They occur near phase 0.00 and 0.50 respectively of current elements from VSX (2).

  5. Tracking Nile Delta Vulnerability to Holocene Change

    OpenAIRE

    Marriner, Nick; Flaux, Cl?ment; Morhange, Christophe; Stanley, Jean-Daniel

    2013-01-01

    Understanding deltaic resilience in the face of Holocene climate change and human impacts is an important challenge for the earth sciences in characterizing the full range of present and future wetland responses to global warming. Here, we report an 8000-year mass balance record from the Nile Delta to reconstruct when and how this sedimentary basin has responded to past hydrological shifts. In a global Holocene context, the long-term decrease in Nile Delta accretion rates is consistent with i...

  6. Migration in Vulnerable Deltas: A Research Strategy

    Science.gov (United States)

    Hutton, C.; Nicholls, R. J.; Allan, A.

    2015-12-01

    C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata. soton.ac.ukAbstractGlobally, deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

  7. The Okavango delta: The value of tourism

    OpenAIRE

    G Mopelwa; J Blignaut

    2014-01-01

    In Botswana, tourism is the second most important economic activity after diamond mining and trading. The Okavango Delta in northern Botswana is the largest single tourist centre in the country. This study estimates the total economic value of tourism in the Okavango Delta and compares this value to that of other sectors in the economy of Botswana. The results are compared to results of similar studies for tourist destinations elsewhere in the world, and the policy implications of the finding...

  8. Purification and characterization of mu-specific opioid receptor from rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, J.; Cho, T.M.; Ge, B.L.; Loh, H.H.

    1986-03-05

    A mu-specific opioid receptor was purified to apparent homogeneity from rat brain membranes by 6-succinylmorphine affinity chromatography, Ultrogel filtration, wheat germ agglutinin affinity chromatography, and isoelectric focusing. The purified receptor had a molecular weight of 58,000 as determined by polyacrylamide gel electrophoresis, and was judged to be homogeneous by the following criteria: (1) a single band on the SDS gel; and (2) a specific opioid binding activity of 17,720 pmole/mg protein, close to the theoretical value. In addition, the 58,000 molecular weight value agrees closely with that determined by covalently labelling purified receptor with bromoacetyl-/sup 3/H-dihydromorphine or with /sup 125/I-beta-endorphin and dimethyl suberimidate. To their knowledge, this is the first complete purification of an opioid receptor that retains its ability to bind opiates.

  9. Growth laws for sub-delta crevasses in the Mississippi River Delta

    Science.gov (United States)

    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

  10. The Okavango: Whose Delta is it?

    Science.gov (United States)

    Magole, Lapologang; Magole, Lefatshe Innocent

    The Okavango Delta is amongst the largest Ramsar sites ( http://www.ramsar.org/sitelist.pdf) in the world and an important wetland for community livelihoods, conservation and tourism in Botswana. Over the years, the utilization of the delta has shifted from communal use to state control, with an increased use for conservation and tourism. This increased use for conservation and tourism has manifested in the physical expansion of the conservation area - Moremi Game Reserve and the formation of Wildlife Management Areas (WMAs) around the reserve, whose primary land use is wildlife utilization. The expansion of the conservation area has translated into several practical matters, including expansion of the area for non-hunting activities or photographic areas. The livelihoods of local communities of the Okavango delta who depended on fishing, hunter-gathering, livestock rearing, rain-fed agriculture and flood recession farming have been negatively affected by the expansion of conservation and tourism in the delta. The livelihoods alternatives in the form of Community Based Natural Resource Management (CBNRM) and tourism have not provided substitutes for the people as the communities are still reliant on the same old livelihood sources as in the past, albeit within smaller and restricted areas. This paper explores the ownership of the natural resources within the Okavango Delta. It asks and attempts to answer the following questions: Who owns and controls the use of the land? Who has access to other resources there in? Who makes the decisions on how the delta resources should be managed and used? Who benefits from the delta resources? We argue firstly that ownership of the delta as defined by legal parameters and demonstrated in natural resource management practice is vested on government. Secondly, government, after assuming ownership of the delta continues to sell its stake to the international community, at the expense of local ownership and access to resources. We

  11. Repeated exposure to morphine alters surface expression of AMPA receptors in the rat medial prefrontal cortex.

    Science.gov (United States)

    Mickiewicz, Amanda L; Napier, T Celeste

    2011-01-01

    Behavioral sensitization describes the intensification of motor activity that results from repeated exposure to drugs of misuse, and the underlying neuronal adaptations are hypothesized to model aspects of the brain changes that occur in humans misusing such drugs. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor is an ionotropic glutamate receptor involved in the neuroplasticity that accompanies acute and repeated drug administration. Changing surface expression is one means to regulate AMPA receptor function, and the present study tested the hypothesis that behavioral sensitization to the μ-opioid receptor agonist morphine is accompanied by changes in the subcellular distribution of AMPA receptors in limbic brain regions. To test this hypothesis, we used a protein cross-linking assay to assess cell surface and intracellular levels of GluA1 and GluA2 subunits in the nucleus accumbens, medial prefrontal cortex and ventral pallidum. Repeated morphine treatment decreased surface expression of GluA1 in the medial prefrontal cortex without affecting levels of GluA2. In contrast, surface levels of GluA1 or GluA2 were unchanged in the nucleus accumbens and ventral pallidum, demonstrating that although AMPA receptors in accumbal and pallidal regions are critical mediators of behaviors induced by repeated opiate exposure, these effects are not accompanied by changes in surface expression. The findings reveal that the involvement of AMPA receptor trafficking in opiate-induced behavioral sensitization is relegated to selective regions and that AMPA receptors in the medial prefrontal cortex may be particularly sensitive to these actions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

    Science.gov (United States)

    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.

  13. RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents.

    Science.gov (United States)

    Elhabazi, Khadija; Humbert, Jean-Paul; Bertin, Isabelle; Quillet, Raphaelle; Utard, Valérie; Schneider, Séverine; Schmitt, Martine; Bourguignon, Jean-Jacques; Laboureyras, Emilie; Ben Boujema, Meric; Simonnet, Guy; Ancel, Caroline; Simonneaux, Valérie; Beltramo, Massimiliano; Bucher, Bernard; Sorg, Tania; Meziane, Hamid; Schneider, Elodie; Petit-Demoulière, Benoit; Ilien, Brigitte; Bihel, Frédéric; Simonin, Frédéric

    2017-05-15

    Although opiates represent the most effective analgesics, their use in chronic treatments is associated with numerous side effects including the development of pain hypersensitivity and analgesic tolerance. We recently identified a novel orally active neuropeptide FF (NPFF) receptor antagonist, RF313, which efficiently prevents the development of fentanyl-induced hyperalgesia in rats. In this study, we investigated the properties of this compound into more details. We show that RF313 exhibited a pronounced selectivity for NPFF receptors, antagonist activity at NPFF1 receptor (NPFF1R) subtype both in vitro and in vivo and no major side effects when administered in mice up to 30 mg/kg. When co-administered with opiates in rats and mice, it improved their analgesic efficacy and prevented the development of long lasting opioid-induced hyperalgesia. Moreover, and in marked contrast with the dipeptidic NPFF receptor antagonist RF9, RF313 displayed negligible affinity and no agonist activity (up to 100 μM) toward the kisspeptin receptor. Finally, in male hamster, RF313 had no effect when administered alone but fully blocked the increase in LH induced by RFRP-3, while RF9 per se induced a significant increase in LH levels which is consistent with its ability to activate kisspeptin receptors. Altogether, our data indicate that RF313 represents an interesting compound for the development of therapeutic tools aiming at improving analgesic action of opiates and reducing adverse side effects associated with their chronic administration. Moreover, its lack of agonist activity at the kisspeptin receptor indicates that RF313 might be considered a better pharmacological tool, when compared to RF9, to examine the regulatory roles of RF-amide-related peptides and NPFF1R in reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Opioid research in amphibians: an alternative pain model yielding insights on the evolution of opioid receptors

    Science.gov (United States)

    Stevens, Craig W.

    2011-01-01

    This review summarizes the work from our laboratory investigating mechanisms of opioid analgesia using the Northern grass frog, Rana pipiens. Over the last dozen years, we have accumulated data on the characterization of behavioral effects after opioid administration on radioligand binding by using opioid agonist and antagonist ligands in amphibian brain and spinal cord homogenates, and by cloning and sequencing opioid-like receptor cDNA from amphibian central nervous system (CNS) tissues. The relative analgesic potency of mu, delta, and kappa opioids is highly correlated between frogs and other mammals, including humans. Radioligand binding studies using selective opioid agonists show a similar selectivity profile in amphibians and mammals. In contrast, opioid antagonists that are highly selective for mammalian mu, delta, and kappa opioid receptors were not selective in behavioral and binding studies in amphibians. Three opioid-like receptor cDNAs were cloned and sequenced from amphibian brain tissues and are orthologs to mammalian mu, delta, and kappa opioid receptors. Bioinformatics analysis of the three types of opioid receptor cDNAs from all vertebrate species with full datasets gave a pattern of the molecular evolution of opioid receptors marked by the divergence of mu, delta, and kappa opioid receptor sequences during vertebrate evolution. This divergence in receptor amino acid sequence in later-evolved vertebrates underlies the hypothesis that opioid receptors are more type-selective in mammals than in nonmammalian vertebrates. The apparent order of receptor type evolution is kappa, then delta, and, most recently, the mu opioid receptor. Finally, novel bioinformatics analyses suggest that conserved extracellular receptor domains determine the type selectivity of vertebrate opioid receptors. PMID:15464208

  15. Interdisciplinary and Distance Education in the Delta: The Delta Health Education Partnership.

    Science.gov (United States)

    Skorga, Phyllis

    2002-01-01

    Describes the Delta Health Education Partnership, an interdisciplinary distance education program intended to recruit, educate, and retain interdisciplinary groups of primary care health practitioners to increase access to health care in medically underserved and health professional shortage areas of the lower Mississippi Delta. It spans six…

  16. Houtman Abrolhos Isotope (delta 18O, delta 13C) Data for 1795 to 1994

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DESCRIPTION: VARIABLES AND UNITS: Column #1: core depth in mm Column #2: delta C-13 vs V-PDB Column #3: delta O-18 vs V-PDB Column #4: assigned date in years A.D....

  17. The Enabling Delta Life Initiative - Global Programme of Action on Deltas - Programme description

    NARCIS (Netherlands)

    Driel, van W.F.; Skyllerstedt, S.; Wosten, J.H.M.

    2014-01-01

    Being ‘hotspots’ of human activity with generally high population densities, deltas are vulnerable to changes induced by a range of driving forces, both natural and anthropogenic. In addition to already existing challenges, uncertainty of the possible impacts of climate change, low lying deltas

  18. Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))

    1991-01-01

    The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

  19. Holocene evolution of a wave-dominated fan-delta: Godavari delta, India

    Science.gov (United States)

    Saito, Y.; Nageswara Rao, K.; Nagakumar, K.; Demudu, G.; Rajawat, A.; Kubo, S.; Li, Z.

    2013-12-01

    The Godavari delta is one of the world's largest wave-dominated deltas. The Godavari River arises in the Western Ghats near the west coast of India and drains an area of about 3.1x10^5 km^2, flowing about 1465 km southeast across the Indian peninsula to the Bay of Bengal. The Godavari delta consists of a gentle seaward slope from its apex (12 m elevation) at Rajahmundry and a coastal beach-ridge plain over a distance of about 75 km and covers ~5200 km^2 as a delta plain. The river splits into two major distributary channels, the Gautami and the Vasishta, at a barrage constructed in the mid-1800s. The coastal environment of the deltaic coast is microtidal (~1 m mean tidal range) and wave-dominated (~1.5 m mean wave height in the June-September SW monsoon season, ~0.8 m in the NE monsoon season). Models of the Holocene evolution of the Godavari delta have changed from a zonal progradation model (e.g. Nageswara Rao & Sadakata, 1993) to a truncated cuspate delta model (Nageswara Rao et al., 2005, 2012). Twelve borehole cores (340 m total length), taken in the coastal delta plain during 2010-2013, yielded more than 100 C-14 dates. Sediment facies and C-14 dates from these and previous cores and remote-sensing data support a new delta evolution model. The Holocene coastal delta plain is divided into two parts by a set of linear beach ridges 12-14 km landward from the present shoreline in the central part of the delta. The location of the main depocenter (lobe) has shifted during the Holocene from 1) the center to 2) the west, 3) east, 4) center, 5) west, and 6) east. The linear beach ridges separate the first three from the last three stages. These lobe shifts are controlled by river channel shifts near the apex. Just as the current linear shoreline of the central part of the delta and the concave-up nearshore topography are the result of coastal erosion of a cuspate delta, the linear beach ridges indicate a former eroded shoreline. An unconformity within the deltaic

  20. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors

    OpenAIRE

    Bocarsly, Miriam E.; Berner, Laura A.; Hoebel, Bartley G.; Avena, Nicole M.

    2011-01-01

    Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets...

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

    Science.gov (United States)

    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.

  2. Tracking Nile Delta vulnerability to Holocene change.

    Science.gov (United States)

    Marriner, Nick; Flaux, Clément; Morhange, Christophe; Stanley, Jean-Daniel

    2013-01-01

    Understanding deltaic resilience in the face of Holocene climate change and human impacts is an important challenge for the earth sciences in characterizing the full range of present and future wetland responses to global warming. Here, we report an 8000-year mass balance record from the Nile Delta to reconstruct when and how this sedimentary basin has responded to past hydrological shifts. In a global Holocene context, the long-term decrease in Nile Delta accretion rates is consistent with insolation-driven changes in the 'monsoon pacemaker', attested throughout the mid-latitude tropics. Following the early to mid-Holocene growth of the Nile's deltaic plain, sediment losses and pronounced erosion are first recorded after ~4000 years ago, the corollaries of falling sediment supply and an intensification of anthropogenic impacts from the Pharaonic period onwards. Against the backcloth of the Saharan 'depeopling', reduced river flow underpinned by a weakening of monsoonal precipitation appears to have been particularly conducive to the expansion of human activities on the delta by exposing productive floodplain lands for occupation and irrigation agriculture. The reconstruction suggests that the Nile Delta has a particularly long history of vulnerability to extreme events (e.g. floods and storms) and sea-level rise, although the present sediment-starved system does not have a direct Holocene analogue. This study highlights the importance of the world's deltas as sensitive archives to investigate Holocene geosystem responses to climate change, risks and hazards, and societal interaction.

  3. Tracking Nile Delta vulnerability to Holocene change.

    Directory of Open Access Journals (Sweden)

    Nick Marriner

    Full Text Available Understanding deltaic resilience in the face of Holocene climate change and human impacts is an important challenge for the earth sciences in characterizing the full range of present and future wetland responses to global warming. Here, we report an 8000-year mass balance record from the Nile Delta to reconstruct when and how this sedimentary basin has responded to past hydrological shifts. In a global Holocene context, the long-term decrease in Nile Delta accretion rates is consistent with insolation-driven changes in the 'monsoon pacemaker', attested throughout the mid-latitude tropics. Following the early to mid-Holocene growth of the Nile's deltaic plain, sediment losses and pronounced erosion are first recorded after ~4000 years ago, the corollaries of falling sediment supply and an intensification of anthropogenic impacts from the Pharaonic period onwards. Against the backcloth of the Saharan 'depeopling', reduced river flow underpinned by a weakening of monsoonal precipitation appears to have been particularly conducive to the expansion of human activities on the delta by exposing productive floodplain lands for occupation and irrigation agriculture. The reconstruction suggests that the Nile Delta has a particularly long history of vulnerability to extreme events (e.g. floods and storms and sea-level rise, although the present sediment-starved system does not have a direct Holocene analogue. This study highlights the importance of the world's deltas as sensitive archives to investigate Holocene geosystem responses to climate change, risks and hazards, and societal interaction.

  4. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  5. [The development and application of an immunoenzyme assay kit for the detection of compounds of the opiate family in human biological liquids].

    Science.gov (United States)

    Nikolaeva, T L; Belkina, E V; Bogatyreva, E A; Gribkova, S E; Proskurina, N V; Smirnova, V K; Lapenkov, M I

    2008-01-01

    Monoclonal antimorphine antibodies both free and conjugated with horse- radish peroxidase have been raised and used to develop an assay kit for the detection of narcotic opiate-based drugs by an immuno-enzyme assay (IEA). The kit contains all ingredients necessary for the enzymatic reaction. A total of 215 urine and blood samples were analysed using the new kit. The results were compared with the data obtained by thin layer chromatography and high-performance liquid chromatography. False negative results were absent while false positive (inconclusive) results were recorded in three cases, probably due to the fact that sensitivity of IEA is higher than that of control methods. It is concluded that the kit may be used in laboratory screening studies for detecting opiates in biological fluids.

  6. Comparison of prescriber evaluations and patient-directed self-reports in office-based practice for buprenorphine treatment of opiate-dependent individuals in France, 2002

    OpenAIRE

    Lavie, Estelle; Fats?as, M?lina; Daulou?de, Jean-Pierre; Denis, C?cile; Dubernet, Jacques; Cattan, Laurent; Auriacombe, Marc

    2008-01-01

    The objective of this cross-sectional evaluation study was to compare data generated through prescriber assessments, and data generated from independent direct contact with opiate-dependent patients in office-based practice to evaluate buprenorphine treatment for modality of buprenorphine absorption, benzodiazepine use, and depressive symptoms. A group of buprenorphine office-based practice prescribers was selected to participate in this study. They were asked to screen for inclusion all thei...

  7. The Okavango delta: The value of tourism

    Directory of Open Access Journals (Sweden)

    G Mopelwa

    2014-07-01

    Full Text Available In Botswana, tourism is the second most important economic activity after diamond mining and trading. The Okavango Delta in northern Botswana is the largest single tourist centre in the country. This study estimates the total economic value of tourism in the Okavango Delta and compares this value to that of other sectors in the economy of Botswana. The results are compared to results of similar studies for tourist destinations elsewhere in the world, and the policy implications of the findings are highlighted. The study uses secondary data to estimate the direct consumptive and non-consumptive use value, and a survey among tourists to determine the existence value of the Okavango Delta.

  8. El plan del delta - Holanda

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1963-09-01

    Full Text Available Holland is very poor in land resources. Hence its development has been directed towards intensive industrialization and maximum agricultural exploitation. The western part of the country is below sea level and is occupied by 65 percent of the population. Originally the coast consisted of a number of islands, estuaries and slight elevations. Man has transformed this coastline, first making a number of artificial lakes, or polders, and then converting these into fertile districts. These projects protect the soil by means of dykes, which require careful conservation, but even so violent floods are not infrequent. One of the difficult problems involved in this vast enterprise is the complex system of water supply, lines of communication and flow of the rivers into the sea along the estuary zone. This zone is on the south west, and to protect it a National Commission has been set up. After careful study, it was decided that the best defense against the violence of the sea would consist in closing off the inroads of the sea into the continental coastline. The set of hydraulic projects which constitutes this plan for the improvement of the sea defences will take 25 years to fulfil. The general project is highly ambitious and includes both maritime, road and structural works, in which there is a variety of stonework constructions. This paper describes, in brief outline, the main contents of the 11 headings into which the general construction project has been subdivided. In addition, this is supplemented with information on the projects which are already initiated and on the constructional procedure that is being adopted. Of these latter projects, the Nabla bridge is of particular interest. It is situated on the delta. It is made in prestressed concrete, and consists of 17 spans, of 60 length each. This enormous structure, in addition to its great length, and supporting a 22.8 ms wide roadway, is subjected to the tremendous forces 11» of the sea on one

  9. Liquefaction potential of Nile delta, Egypt

    Science.gov (United States)

    Fergany, Elsayed; Omar, Khaled

    2017-06-01

    Understanding how sedimentary basins respond to seismic-wave energy generated by earthquake events is a significant concern for seismic-hazard estimation and risk analysis. The main goal of this study is assessing the vulnerability index, Kg, as an indicator for liquefaction potential sites in the Nile delta basin based on the microtremor measurements. Horizontal to Vertical spectral ratio analyses (HVSR) of ambient noise data, which was conducted in 2006 at 120 sites covering the Nile delta from south to north were reprocessed using Geopsy software. HVSR factors of amplification, A, and fundamental frequency, F, were calculated and Kg was estimated for each measurement. The Kg value varies widely from south toward north delta and the potential liquefaction places were estimated. The higher vulnerability indices are associated with sites located in southern part of the Nile delta and close to the branches of Nile River. The HVSR factors were correlated with geologic setting of the Nile delta and show good correlations with the sediment thickness and subsurface stratigraphic boundaries. However, we note that sites located in areas that have greatest percentage of sand also yielded relatively high Kg values with respect to sites in areas where clay is abundant. We concluded that any earthquake with ground acceleration more than 50 gal at hard rock can cause a perceived deformation of sandy sediments and liquefaction can take place in the weak zones of Kg ≥ 20. The worst potential liquefaction zones (Kg > 30) are frequently joined to the Damietta and Rosetta Nile River branches and south Delta where relatively coarser sand exists. The HVSR technique is a very sensitive tool for lithological stratigraphy variations in two dimensions and varying liquefaction susceptibility.

  10. The Comparison of Early Maladaptive Schema’s Domains Between Successful And Non-Successful Opiate Addicts and Non-Clinical Persons

    Directory of Open Access Journals (Sweden)

    Bahram Sahand

    2009-10-01

    Full Text Available Introduction: The current research was done in order to compare the early maladaptive schema’s domains between successful and non-successful opiate addicts and non-clinical persons in Tehran. Method: The research design was causal effect method. In this purpose 90 men (include successful and non-successful opiate addicts, and non-clinical persons (30 for each group, were selected by the available sampling method. Young Schema Questionnaire (YSQ-RE2R, General Health Questionnaire (GHQ, and Personal Characteristic Questionnaire were administered among selected sample. The results were analyzed by ANOVA, chi square, MANOVA, and tukey test. Results: The findings of this research indicated that there was a significant difference on “Early Maladaptive Schema’s domains” between these three groups. Conclusion: The results have important clinical interpretations. It is assumed that medical interference with the aim of modifying and correcting the “Early Maladaptive Schema’s domains” can be effective on the level of success for opiate addicts to give up their addiction.

  11. Abraham Reef Stable Isotope Data (delta 13C, delta 18O, delta 14C) for 1635-1957

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Site: Abraham Reef, 22ó 06'S, 153ó 00'E, Porites australiensus, Radiocarbon (delta 14C) and Stable Isotope (del 18O and del 13C) results from bi-annual samples from...

  12. Deltas on the move. Making deltas cope with the effects of climate change

    International Nuclear Information System (INIS)

    Reker, J.; Van Winden, A.; Braakhekke, W.; Vermaat, J.; Eleveld, M.; Janssen, R.; De Reus, N.; Omzigt, N.

    2006-01-01

    This scoping study is the first phase of a study aimed at: (a) providing knowledge on the potential of a system-based approach to deal with the effects of climate change as an alternative for the more traditional technical measures such as dams, dikes and surge barriers. This should be shown for both rich and poor countries and should address hydrological, ecological as well as socio-economic aspects; and (b) identifying the potential to market these results worldwide. To reach these objectives four research steps are defined: (1) to make an inventory of deltas: their vulnerability to the effects of climate change; (2) development of indicators for successful use of a system-based approach; (3) to provide an overview of the potential of soft measures for these deltas; (4) to select a number of deltas with potential for marketing system-based measures and the development of strategies to link economic and ecological objectives. This scoping study addresses step 1 only. The results from step 1 will be used as a starting point for steps 2 and 3. The outputs of this scoping study are threefold: a background report (this report); a flyer with a brief description of the findings; a website with information on delta's and how these may be affected by climate change. The scoping study will roughly outline which deltas are still functioning in a more or less natural manner - or could be (re)developed in that direction - and thus would be good candidates for a system-based approach. Chapter 2 gives a description of the geomorphological and ecological processes in a delta. In addition, those aspects of climate change that can have an effect on deltas are described. The third chapter deals with human interventions in deltas and whether or not they fit within a system-based approach. In a system-based approach, as presented in Chapter 4, natural processes are given free reign where possible. Chapter 5 shows how available data on deltas could be used in such a system

  13. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing......- and heterodimerisation, let alone oligomerisation. Theoretically, this phenomenon adds a novel series of functional megareceptors/super-receptors, with varied pharmacological profiles, to the catalogue of monomeric receptor subtypes isolated and cloned in the past. SRIF analogues include both peptides and non......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  14. Mu Opioids and Their Receptors: Evolution of a Concept

    Science.gov (United States)

    Pan, Ying-Xian

    2013-01-01

    Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

  15. The Comparison of Attention Biases to Opiates in Substance Dependent and Treated Clients of Therapeutic Clinics and Narcotics Anonymous Memberships

    Directory of Open Access Journals (Sweden)

    Javad Enayat

    2012-11-01

    Full Text Available Aim: The purpose of this study was to compare the attention bias about tempting incentives related to opium materials in treated, addicted and normal people. Duration of consumption and treating were also considered. Method: In this causal-comparative study population was all addicted people who were referred to the rehabilitation offices, addiction treatment clinic, rebirthing centers and Narcotics Anonymous of East Azerbaijan. This study consisted of five groups of men, including addicted to opium materials which are divided into two groups namely: long consumption period and people with short consumption period, also, treated people including long term treated and short term treated, and a normal control group. Altogether, 103 selected people were studied. Sample groups were similar in terms of age, education, and sex. For measuring attention bias towards tempting stimuli related opiates, a words recognition test was used. This test included three subtests and one recognition test. The recognition scores for the three categories of words were measured. Results: The findings indicated that there was a difference in attention against opium material incentives between control group and the mild and severe consumers groups. Also there were significant differences between treated people with the short time distance and control group, and control group had less temptation and biases in comparison to the other groups. Finally, those who have mild consumption are threatened more in comparison with the control group. Conclusion: The findings have applied implications.

  16. Opiate-prostaglandin interactions in the regulation of insulin secretion from rat islets of Langerhans in vitro

    International Nuclear Information System (INIS)

    Green, I.C.; Tadayyon, M.

    1988-01-01

    The inadequate insulin secretory response to glucose stimulation in non-insulin dependent diabetes has been attributed to many factors including high PGE 2 levels blunting the secretory response, and to the existence of inhibitory opiate activity in vivo. The purpose of the present work was to see if there was a connection between these two independent theories. Radioimmunoassayable PGE 2 in islets of Langerhans was found to be proportional to islet number and protein content and was typically 4 to 5pg/μg islet protein. Indomethacin sodium salicylate and chlorpropamide all lowered islet PGE 2 levels and stimulated insulin release in vitro. Dynorphin stimulated insulin release at a concentration of 6 x 10 -9 M, while lowering islet PGE 2 . Conversely, at a higher concentration, dynorphin had no stimulatory effect on insulin secretion and did not lower PGE 2 levels in islets or in the incubation media. The stimulatory effects of dynorphin and sodium salicylate on insulin secretion were blocked by exogenous PGE 2 . PGE 2 at a lower concentration did not exert any inhibitory effect on dynorphin- or sodium salicylate-induced insulin release. This concentration of exogenous PGE 2 stimulated insulin release in the presence of 6mM glucose

  17. Multi-Family Therapy with a Reflecting Team: A Preliminary Study on Efficacy among Opiate Addicts in Methadone Maintenance Treatment.

    Science.gov (United States)

    Garrido-Fernández, Miguel; Marcos-Sierra, Juan A; López-Jiménez, Ana; Ochoa de Alda, Iñigo

    2017-04-01

    In this study, we evaluate the efficacy of multi-family therapy at reducing the addiction severity and at improving the psychological and family dynamics of opiate addicts receiving methadone treatment at a public treatment center. The study compares multi-family therapy with a reflecting team (MFT-RT) and a standard treatment following a methadone maintenance treatment program. The results show that multi-family therapy with a reflecting team effectively reduces the addiction severity in several of the areas evaluated and noted that this effect is superior to standard treatment. The psychotherapy patients showed improvement in the areas of employment and social support; their drug use diminished and their psychiatric condition improved. At the same time, they needed a lower daily dose of methadone. In addition, the group undergoing standard treatment showed a noteworthy deterioration in their medical condition. Both groups showed a significant increase in their alcohol use. When applied to family treatments, the systemic-constructivist approach by the reflecting team offers combined techniques that can help improve care for the families of patients with addiction problems. © 2016 American Association for Marriage and Family Therapy.

  18. Comparison of personality traits in pedophiles, abstinent opiate addicts, and healthy controls: considering pedophilia as an addictive behavior.

    Science.gov (United States)

    Cohen, Lisa J; Grebchenko, Yuli F; Steinfeld, Matthew; Frenda, Steven J; Galynker, Igor I

    2008-11-01

    To investigate the model of pedophilia as a disorder of addictive behavior, pedophiles and chemically addicted individuals were compared on personality traits potentially associated with impaired behavioral inhibition. Twenty-nine pedophiles, 25 opiate addicts (OA's), and 27 healthy controls were administered the Barratt Impulsivity Scale, Hare Psychopathy Checklist-Revised (PCL-R), and Structured Clinical Interview for DSM-V for Axis-II. OA's scored higher than either pedophiles or controls on the Barratt. Pedophiles and OA's scored higher than controls on all 3 Psychopathy Checklist-Revised scores but OA's scored marginally higher than pedophiles on factor 2 (behavioral) and total scores. On Structured Clinical Interview for DSM-V for Axis-II, pedophiles scored higher than controls on paranoid and schizoid scores whereas OA's did so on paranoid scores. Thus, both pedophiles and OA's may have elevated psychopathic traits and propensity toward cognitive distortions, as reflected in cluster A traits. Such similarities support the conceptualization of pedophilia as a behavioral addiction. Pedophiles may be less impulsive than OA's, however, and more prone toward cognitive distortions.

  19. Statistical Delta-V Tool for Pre-proposal Studies

    Data.gov (United States)

    National Aeronautics and Space Administration — For any space mission proposal it is essential to provide an accurate, defensible estimate of the total propellant ("Delta-V") budget, including the Delta-V required...

  20. Induction of CD3 delta epsilon omega by phorbol 12-myristate 13-acetate

    DEFF Research Database (Denmark)

    Vangsted, A; Neisig, A; Wallin, H

    1993-01-01

    The effect of phorbol 12-myristate 13-acetate (PMA) on the synthesis, assembly and processing of the components of the T cell receptor (TcR) was studied with special focus on the CD3 omega chain. Treatment of the human leukemic T cell line Jurkat with PMA increased the synthesis of the Ti alpha, CD......3 gamma and CG3 zeta chains two- to threefold and the synthesis of Ti beta and CD3 delta epsilon omega complexes five- to sevenfold as assessed by metabolic labeling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by scanning densitometry. The amount...... of TcR complexes expressed on the cell surface was decreased after 16 h of PMA treatment. Based on these results we propose a role of CD3 omega in retention of TcR complexes. From PMA-treated CEM cells more than 50-fold the amount of CD3 delta epsilon omega complexes was immunoprecipitated as compared...

  1. The Delta Team: Empowering Adolescent Girls.

    Science.gov (United States)

    Hood, Marian White

    1994-01-01

    In response to adolescent girls' concerns about teen violence, rumors, grooming, careers, and equity, four women teachers and a woman administrator at a Maryland middle school developed the Delta Program. The program provides positive learning experiences, teaches social skills and conflict management techniques, empowers girls through mentoring…

  2. ECOSYSTEM SERVICES OF THE NIGER DELTA FORESTS ...

    African Journals Online (AJOL)

    This research aimed to appraise the Niger Delta forest ecosystem services. The. Millennium Ecosystem ... Despite the good knowledge of ecosystem services by the urban respondents, only 42.5% were aware of fresh .... and in planning for government and other interventions such as conservation actions (Isoun, 2006).

  3. Bioluminescent hydrocarbonclastic bacteria of the Niger Delta

    African Journals Online (AJOL)

    Administrator

    2007-02-19

    Feb 19, 2007 ... Utilization of three petroleum hydrocarbons (Mobil SAE 40 Engine Oil, Diesel and Bonny light Crude. Oil) by four ... growth of hydrocarbonoclastic bioluminescent bacteria which could serve as a potential tool for the remediation of petroleum ... lized TNT. In the Niger Delta, increasing petroleum exploration.

  4. AMNESTY IN THE NIGER DELTA: VERTICAL MOVEMENT ...

    African Journals Online (AJOL)

    OLAWUYI

    opportunities, promises of infrastructure development in the region and direct payments of oil revenues ..... 38 See generally, the Petroleum Act, P10 Laws of the Federation of Nigeria (LFN), 2004; Territorial. Waters Act, Chapter T4 LFN ..... Grant amnesty to all Niger Delta militants willing and ready to participate in the DDR ...

  5. Solubility of hydrogen in delta iron

    International Nuclear Information System (INIS)

    Shapovalov, V.I.; Trofimenko, V.V.

    1979-01-01

    The solubility of hydrogen in iron (less than 0.002 % impurities) at temperatures of 800-1510 deg C and a pressure of 100 atm was measured. The heat of solution of hydrogen in delta-Fe, equal to 73 kJ/g-atom, is by far greater than the corresponding values for α- and γ-Fe

  6. Kinematic Analysis 6dof Delta Manipulator

    Directory of Open Access Journals (Sweden)

    Dawid PIETRALA

    2014-12-01

    Full Text Available In the paper the solid and kinematic model of delta type parallel manipulator with six degrees of freedom is proposed. Method of determining the manipulator kinematics equations using the notation of Denavitt – Hartenberg is presented. For given movements of manipulator platform the trajectory of drives are illustrated. Also working space for various platform orientations are showed.

  7. Delta 9-tetrahydrocannabinol produced discrimination in pigeons.

    Science.gov (United States)

    Henriksson, B G; Johansson, J O; Järbe, T U

    1975-01-01

    In an operant situation pigeons learned to peck one response key 90 min after an injection of 0.25mg/kg delta9-tetrahydrocannabinol (delta9-THC) and another key when trained nondrugged. When tested with doses of delta9-THC lwer than the training dose the birds disciminated 0.20 mg/kg of the drug from the nondrugged state but not 0.15 mg/kg or lower doses. The animals were able to discriminate the drug state from the nondrugged 180 min but not 360 min after the injection At a shorter interval (45 min) both drug and nondrug responding appeared. Cannabinol and cannabidiol (4.0 - 8.0 mg/kg) did not elicit any drug responses, nor did pentobarbital, ditran or amphetamine. Tests with LSD resulted in both drug and nondrug responding. When administering noncannabinoid drugs in combination with delta9-THC 0.15 mg/kg the birds responded at the key associated with the drug state, suggesting interactional effects.

  8. 2016 Rose Ojowhoh Delta State Polytechnic, Ozoro

    African Journals Online (AJOL)

    OJOHWOH ROSE

    Staff training and development are reoccurring. Staff development and library services in academic libraries in Bayelsa and Delta States. Information Impact: ... managers. A culture of group and individual learning is created through the use of critique, feedback and teaching at all levels of the training and development.

  9. Bioluminescent hydrocarbonclastic bacteria of the Niger Delta ...

    African Journals Online (AJOL)

    Utilization of three petroleum hydrocarbons (Mobil SAE 40 Engine Oil, Diesel and Bonny light Crude Oil) by four bioluminescent bacteria (Vibrio harveyi, V. fisheri, Photobacterium leiognathi and P. Phosphoreum isolated from the Bonny estuary in the Niger Delta, Nigeria was investigated. Microbial utilization was monitored ...

  10. Error Minimization of Polynomial Approximation of Delta

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... The difference between Universal time (UT) and Dynamical time (TD), known as Delta ( ) is tabulated for the first day of each year in the Astronomical Almanac. During the last four centuries it is found that there are large differences between its values for two consecutive years. Polynomial ...

  11. Strong decays of nucleon and delta resonances

    International Nuclear Information System (INIS)

    Bijker, R.; Leviatan, A.

    1996-01-01

    We study the strong couplings of the nucleon and delta resonances in a collective model. In the ensuing algebraic treatment we derive closed expressions for decay widths which are used to analyze the experimental data for strong decays into the pion and eta channels. (Author)

  12. Water quality in the Okavango Delta

    African Journals Online (AJOL)

    2010-03-12

    Mar 12, 2010 ... The Okavango Delta ecosystem sustains a large number of plant and animal species as well as providing resources for the livelihood of the riparian human population. Despite changes in flow patterns, rainfall and other climatic conditions over the past decades, the system has responded well to maintain ...

  13. Ethnic Minority Problems in the Niger Delta

    African Journals Online (AJOL)

    As a conceptual background typical types of minorities and typical sources of minority conflict are outlined. A historical overview is given of the problems. Niger Delta minorities have been experiencing. Their grievances and demands are highlighted, and the responses of different Nigerian governments are discussed.

  14. S-Nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner

    Directory of Open Access Journals (Sweden)

    Mönkkönen Kati S

    2005-04-01

    Full Text Available Abstract Background Recent studies indicate that the G protein-coupled receptor (GPCR signaling machinery can serve as a direct target of reactive oxygen species, including nitric oxide (NO and S-nitrosothiols (RSNOs. To gain a broader view into the way that receptor-dependent G protein activation – an early step in signal transduction – might be affected by RSNOs, we have studied several receptors coupling to the Gi family of G proteins in their native cellular environment using the powerful functional approach of [35S]GTPγS autoradiography with brain cryostat sections in combination with classical G protein activation assays. Results We demonstrate that RSNOs, like S-nitrosoglutathione (GSNO and S-nitrosocysteine (CysNO, can modulate GPCR signaling via reversible, thiol-sensitive mechanisms probably involving S-nitrosylation. RSNOs are capable of very targeted regulation, as they potentiate the signaling of some receptors (exemplified by the M2/M4 muscarinic cholinergic receptors, inhibit others (P2Y12 purinergic, LPA1lysophosphatidic acid, and cannabinoid CB1 receptors, but may only marginally affect signaling of others, such as adenosine A1, μ-opioid, and opiate related receptors. Amplification of M2/M4 muscarinic responses is explained by an accelerated rate of guanine nucleotide exchange, as well as an increased number of high-affinity [35S]GTPγS binding sites available for the agonist-activated receptor. GSNO amplified human M4 receptor signaling also under heterologous expression in CHO cells, but the effect diminished with increasing constitutive receptor activity. RSNOs markedly inhibited P2Y12 receptor signaling in native tissues (rat brain and human platelets, but failed to affect human P2Y12 receptor signaling under heterologous expression in CHO cells, indicating that the native cellular signaling partners, rather than the P2Y12 receptor protein, act as a molecular target for this action. Conclusion These in vitro studies

  15. Morphodynamics of a cyclic prograding delta: the Red River, Vietnam

    NARCIS (Netherlands)

    Maren, D.S. van

    2004-01-01

    River deltas are inhabited by over 60% of the world population, and are, consequently, of paramount agricultural and economical importance. They constitute unique wetland envi ronments which gives river deltas ecological importance as well. Additionally, many deltas contain large accumulations of

  16. Wastewater disposal at safari lodges in the Okavango Delta, Botswana

    African Journals Online (AJOL)

    driniev

    2004-01-01

    Jan 1, 2004 ... their wastewater via soak-aways, creating a potential risk of contamination of their water supply. Most islands in the Delta ... in the Okavango Delta. Key words: Okavango Delta; wastewater disposal; field bacteriological screening ... groundwater 183 m from a wastewater point source. Viruses in particular ...

  17. Surface water quality in the Okavango Delta panhandle, Botswana ...

    African Journals Online (AJOL)

    The Okavango Delta, a Ramsar and a World Heritage Site, is an important source of food and water in the Kalahari Desert of southern Africa. Although the eastern delta fan is a protected area, the rest, including the upstream panhandle, is unprotected. Water quality in the Okavango Delta panhandle from Popa Falls, ...

  18. Amnesty to Niger Delta Militants: Challenges and Opportunities for ...

    African Journals Online (AJOL)

    The Niger Delta militants' disposition against the Federal government of Nigeria and the oil firms coupled with international pressures, compelled the Federal Government to grant amnesty to the Niger Delta Militants. The amnesty deal is a desperate effort by the Nigeria State to end the Niger Delta crisis, and thereby restore ...

  19. enhancing stakeholder participation in the niger delta region

    African Journals Online (AJOL)

    RAYAN_

    Nigeria's indigenous people, found in the Niger Delta area, have for many years experienced developmental challenges associated with oil exploration. The region has been .... Delta Petroleum System: Niger Delta Province, Nigeria, Cameroon, and. Equatorial .... grant injunctions or provisional measures. Therefore, to ...

  20. Farmers' perception of extension services of the Delta Stat ...

    African Journals Online (AJOL)

    The paper investigated farmers' perception of Extension Services Provided by Delta State Agricultural Development Programme (DTADP) in Delta North Agricultural Zone, Delta State, Nigeria. Data for the study was obtained with the aid of an interview schedule from 90 respondents in the study area. Findings from the study ...

  1. Environmental challenges in Nigeria's Delta Region and Agriculture ...

    African Journals Online (AJOL)

    The paper discussed the environmental challenges in the Niger-Delta region of Nigeria with emphasis on the impacts on agricultural production. It thus discussed the concepts of Niger-Delta, Environmental pollution, Niger-Delta crises and Agriculture. The paper posits that there are positive relationships between these ...

  2. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  3. delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.

    Science.gov (United States)

    Little, M J; Zappia, C; Gilles, N; Connor, M; Tyler, M I; Martin-Eauclaire, M F; Gordon, D; Nicholson, G M

    1998-10-16

    delta-Atracotoxins from the venom of Australian funnel-web spiders are a unique group of peptide toxins that slow sodium current inactivation in a manner similar to scorpion alpha-toxins. To analyze their interaction with known sodium channel neurotoxin receptor sites, we studied their effect on [3H]batrachotoxin and 125I-Lqh II (where Lqh is alpha-toxin II from the venom of the scorpion Leiurus quinquestriatus hebraeus) binding and on alkaloid toxin-stimulated 22Na+ uptake in rat brain synaptosomes. delta-Atracotoxins significantly increased [3H]batrachotoxin binding yet decreased maximal batrachotoxin-activated 22Na+ uptake by 70-80%, the latter in marked contrast to the effect of scorpion alpha-toxins. Unlike the inhibition of batrachotoxin-activated 22Na+ uptake, delta-atracotoxins increased veratridine-stimulated 22Na+ uptake by converting veratridine from a partial to a full agonist, analogous to scorpion alpha-toxins. Hence, delta-atracotoxins are able to differentiate between the open state of the sodium channel stabilized by batrachotoxin and veratridine and suggest a distinct sub-conductance state stabilized by delta-atracotoxins. Despite these actions, low concentrations of delta-atracotoxins completely inhibited the binding of the scorpion alpha-toxin, 125I-Lqh II, indicating that they bind to similar, or partially overlapping, receptor sites. The apparent uncoupling between the increase in binding but inhibition of the effect of batrachotoxin induced by delta-atracotoxins suggests that the binding and action of certain alkaloid toxins may represent at least two distinguishable steps. These results further contribute to the understanding of the complex dynamic interactions between neurotoxin receptor site areas related to sodium channel gating.

  4. Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection

    NARCIS (Netherlands)

    Mulherin, Stephanie A.; O'Brien, Thomas R.; Ioannidis, John P.; Goedert, James J.; Buchbinder, Susan P.; Coutinho, Roel A.; Jamieson, Beth D.; Meyer, Laurence; Michael, Nelson L.; Pantaleo, Giuseppe; Rizzardi, G. Paolo; Schuitemaker, Hanneke; Sheppard, Haynes W.; Theodorou, Ioannis D.; Vlahov, David; Rosenberg, Philip S.

    2003-01-01

    OBJECTIVE: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. DESIGN: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. METHODS:

  5. Crystal structure of a Gammadelta T-cell Receptor Specific for the Human MHC class I Homolog MICA

    Energy Technology Data Exchange (ETDEWEB)

    B Xu; J Pizarro; M Holmes; C McBeth; V Groh; T Spies; R Strong

    2011-12-31

    {gamma}{delta} T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human {gamma}{delta} T cells of the V{sub {delta}}1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V{sub {delta}}1 {gamma}{delta} T-cell receptor (TCR) showed expected overall structural homology to antibodies, {alpha}{beta}, and other {gamma}{delta} TCRs, but complementary determining region conformations and conservation of V{sub {delta}}1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on {gamma}{delta} T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of {gamma}{delta} T-cell/target cell interfaces.

  6. Isomerization of delta-9-THC to delta-8-THC when tested as trifluoroacetyl-, pentafluoropropionyl-, or heptafluorobutyryl- derivatives.

    Science.gov (United States)

    Holler, Justin M; Smith, Michael L; Paul, Shom N; Past, Marilyn R; Paul, Buddha D

    2008-05-01

    For GC-MS analysis of delta-9-tetrahydrocannabinol (delta-9-THC), perfluoroacid anhydrides in combination with perfluoroalcohols are commonly used for derivatization. This reagent mixture is preferred because it allows simultaneous derivatization of delta-9-THC and its acid metabolite, 11-nor-delta-9-THC-9-carboxylic acid present in biological samples. When delta-9-THC was derivatized by trifluoroacetic anhydride/hexafluoroisopropanol (TFAA/HFIPOH) and analyzed by GC-MS using full scan mode (50-550 amu), two peaks (P1 and P2) with an identical molecular mass of 410 amu were observed. On the basis of the total ion chromatogram (TIC), P1 with a shorter retention time (RT) was the major peak (TIC 84%). To identify the peaks, delta-8-THC was also tested under the same conditions. The RT and spectra of the major peak (TIC 95%) were identical with that of P1 for delta-9-THC. A minor peak (5%) present also correlated well with the latter peak (P2) for the delta-9-THC derivative. The fragmentation pathway of P1 was primarily demethylation followed by retro Diels-Alder fragmentation (M - 15-68, base peak 100%) indicating P1 as a delta-8-THC-trifluoroacetyl compound. This indicated that delta-9-THC isomerized to delta-8-THC during derivatization with TFAA/HFIPOH. Similar results were also observed when delta-9-THC was derivatized with pentafluoropropionic anhydride/pentafluoropropanol or heptafluorobutyric anhydride/heptafluorobutanol. No isomerization was observed when chloroform was used in derivatization with TFAA. In this reaction, the peaks of delta-8-THC-TFA and delta-9-THC-TFA had retention times and mass spectra matching with P1 and P2, respectively. Because of isomerization, perfluoroacid anhydrides/perfluoroalcohols are not suitable derivatizing agents for analysis of delta-9-THC; whereas the TFAA in chloroform is suitable for the analysis.

  7. Topography of inland deltas: Observations, modeling, and experiments

    Science.gov (United States)

    Seybold, H. J.; Molnar, P.; Akca, D.; Doumi, M.; Cavalcanti Tavares, M.; Shinbrot, T.; Andrade, J. S.; Kinzelbach, W.; Herrmann, H. J.

    2010-04-01

    The topography of inland deltas is influenced by the water-sediment balance in distributary channels and local evaporation and seepage rates. In this letter a reduced complexity model is applied to simulate inland delta formation, and results are compared with the Okavango Delta, Botswana and with a laboratory experiment. We show that water loss in inland deltas produces fundamentally different dynamics of water and sediment transport than coastal deltas, especially deposition associated with expansion-contraction dynamics at the channel head. These dynamics lead to a systematic decrease in the mean topographic slope of the inland delta with distance from the apex following a power law with exponent α = -0.69 ± 0.02 where the data for both simulation and experiment can be collapsed onto a single curve. In coastal deltas, on the contrary, the slope increases toward the end of the deposition zone.

  8. Changes in psychological well-being among heroin-dependent adolescents during psychologically supported opiate substitution treatment.

    Science.gov (United States)

    Smyth, Bobby P; Ducray, Kevin; Cullen, Walter

    2016-01-23

    Heroin-dependent adolescents demonstrate high rates of comorbid psychological problems. Among heroin-dependent adults, opiate substitution treatment (OST) programmes appear to reduce mental health problems. We sought to examine the impact of OST on psychological well-being in adolescents, as this is unknown. We conducted a prospective study examining psychological well-being in heroin dependent adolescents, aged 18 years or younger, engaged in outpatient psychologically supported OST. Patients were treated with either methadone or buprenorphine. This was complimented with individual key working, counselling (motivational interviewing and cognitive behavioral therapy) and group work focusing on life skills. The Beck Youth Inventory was used to measure psychological well-being at treatment entry and repeated after 4 months of treatment. Among 55 consecutive treatment episodes, we examined the 32 episodes where the patient persisted with the OST programme. Polysubstance use was the norm at treatment entry. At follow-up, the median doses of methadone and buprenorphine were 50 mgs and 8 mgs, respectively. Only three patients were treated with antidepressant medication. There was significant improvement in the mean depression (65.0 to 57.9, P = 0.001), anxiety (61.7 to 57.0, P = 0.006) and anger (57.8 to 54.6, P = 0.009) subscale scores. The self-concept and disruptive behaviour subscale scores did not improve significantly. In this relatively short-term follow-up, psychosocially assisted OST appears to be associated with improved psychological well-being in heroin-dependent adolescents, especially in the area of depressive and anxiety symptoms. © 2016 John Wiley & Sons Australia, Ltd.

  9. Development, optimization, and validation of a novel extraction procedure for the removal of opiates from human hair's surface.

    Science.gov (United States)

    Restolho, José; Barroso, Mário; Saramago, Benilde; Dias, Mário; Afonso, Carlos A M

    2015-05-01

    Room temperature ionic liquids (ILs) have proved to be efficient extraction media for several systems, and their ability to capture volatile compounds from the atmosphere is well established. We report herein a contactless extraction procedure for the removal of opiate drugs from the surface of human hair. The compounds were chosen as a model drug, particularly due to their low volatility. Equal amounts of IL and hair (about 100 mg) were introduced in a customized Y-shaped vial, and the process occurred simply by heating. After testing several ILs, some of them (e.g. 1-methyl-3-ethanol-imidazolium tetrafluoroborate, phenyl-trimethyl-ammonium triflate or bis(dimethyl) diheptylguanidinium iodide) showed extraction efficiencies higher than 80% for the two studied compounds, morphine and 6-monoacetylmorphine. Using the design of experiments (DOE) approach as an optimization tool, and bearing in mind the hygroscopic properties of the ILs (in particular, 1-methyl-3-ethanol-imidazolium tetrafluoroborate), the process was optimized concerning the following variables: temperature (50-120 ºC), extraction time (8-24 h), IL amount (50-200 mg) and water content of the IL (0.01-60%). This study not only provided the optimum conditions for the process (120 ºC, 16 h, 100 mg of IL containing 40% of water), but has also showed that the water content of the IL represents the variable with the most significant effect on the extraction efficiency. Finally, we validated our method through the comparison of the results obtained by treating hair samples with the described procedure to those obtained using a standard washing method and criteria for positivity. Copyright © 2014 John Wiley & Sons, Ltd.

  10. The politics of place(ment): problematising the provision of hepatitis C treatment within opiate substitution clinics.

    Science.gov (United States)

    Rance, Jake; Newland, Jamee; Hopwood, Max; Treloar, Carla

    2012-01-01

    The hepatitis C virus (HCV) epidemic is a significant public health challenge in Australia. Current initiatives to expand access to HCV treatment focus on opiate substitution therapy (OST) settings where the prevalence of hepatitis C among clients is high. In Australia, the provision of OST for many clients is via large clinics, with an estimated median of 150 clients per service. Conceptually informed by the work of Michel Foucault, our analysis of the proposed integrated treatment model focuses on the critical but overlooked question of organisational culture and power operating within OST. We argue that the specific context of OST not merely reflects but actively participates in the political economy of social exclusion via which the socio-spatial segregation and stigmatisation of the service user as 'drug user' is enacted. This paper analyses data collected from two samples during 2008/9: OST clients living in New South Wales, Australia and a range of OST health professionals working in Australian settings. In total, 27 interviews were conducted with current OST clients; 19 by phone and 8 face-to-face. One focus group and 16 telephone interviews were conducted with OST health professionals. Our analysis of key themes emerging from the interview data suggests that the successful introduction of HCV treatment within the OST clinic is not a given. We are concerned that particular areas of tension, if not explicit contradiction, have been overlooked in current research and debates informing the proposed combination treatment model. We question the appropriateness of co-locating a notoriously arduous, exacting treatment (HCV) within the highly surveillant and regulatory environment of OST. While applauding the intention to improve access to HCV care and treatment for people who inject drugs we caution against a treatment model that risks further entrenching (socio-spatial) stigmatisation amongst those already experiencing significant marginalisation. Copyright

  11. Delta-nucleus dynamics: proceedings of symposium

    International Nuclear Information System (INIS)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P.

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta Δ(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe Δ-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented

  12. Adaptive Delta Management: cultural aspects of dealing with uncertainty

    Science.gov (United States)

    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

  13. THIP, a hypnotic and antinociceptive drug, enhances a tonic GABAA receptor mediated conductance in mouse neocortex

    DEFF Research Database (Denmark)

    Drasbek, Kim Ryun; Jensen, Kimmo

    2006-01-01

    THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Sinc...... suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity....

  14. Central Delta languages: An overview1

    African Journals Online (AJOL)

    Kate H

    The Central. Delta languages on or about which linguistic research materials were available for this study are Abuan, Oḍual (Sạkạ), Ọgbi ̣ạ (Ọgbi ̣nyạ), Ogbrọnụagum (Ḅukuma), Obulom (Abuloma), and Ogbogolo (Obogolo). Due to a lack of research materials or adequate research materials at the time of writing this paper, ...

  15. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity

    International Nuclear Information System (INIS)

    James, I.F.; Goldstein, A.

    1984-01-01

    A method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites is reported. Radioligands are used that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands. After enrichment for mu receptors, [ 3 H] dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for [ 3 H] [D-Ala2, D-Leu5]enkephalin and [3H]ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but no evidence for residual mu or delta sites in kappa-enriched membranes were found. This method was used to identify ligands that are highly selective for each of the three types of sites

  16. Understanding delta-sigma data converters

    CERN Document Server

    Pavan, Shanti; Temes, Gabor C

    2017-01-01

    This new edition introduces novel analysis and design techniques for delta-sigma (ΔΣ) converters in physical and conceptual terms, and includes new chapters that explore developments in the field over the last decade. This book explains the principles and operation of delta-sigma analog-to-digital converters (ADCs) in physical and conceptual terms in accordance with the most recent developments in the field. The interest of ΔΣ converter designers has shifted significantly over the past decade, due to many new applications for data converters at the far ends of the frequency spectrum. Continuous-time delta-sigma A/D converters with GHz clocks, of both lowpass and bandpass types, are required for wireless applications. At the other extreme, multiplexed ADCs with very narrow (sometimes 10 Hz wide) signal bandwidths, but very high accuracy are needed in the interfaces of biomedical and environmental sensors. To reflect the changing eeds of designers, the second edition includes significant new material on bo...

  17. Delta: Data Reduction for Integrated Application Workflows.

    Energy Technology Data Exchange (ETDEWEB)

    Lofstead, Gerald Fredrick [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jean-Baptiste, Gregory [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Oldfield, Ron A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-06-01

    Integrated Application Workflows (IAWs) run multiple simulation workflow components con- currently on an HPC resource connecting these components using compute area resources and compensating for any performance or data processing rate mismatches. These IAWs require high frequency and high volume data transfers between compute nodes and staging area nodes during the lifetime of a large parallel computation. The available network band- width between the two areas may not be enough to efficiently support the data movement. As the processing power available to compute resources increases, the requirements for this data transfer will become more difficult to satisfy and perhaps will not be satisfiable at all since network capabilities are not expanding at a comparable rate. Furthermore, energy consumption in HPC environments is expected to grow by an order of magnitude as exas- cale systems become a reality. The energy cost of moving large amounts of data frequently will contribute to this issue. It is necessary to reduce the volume of data without reducing the quality of data when it is being processed and analyzed. Delta resolves the issue by addressing the lifetime data transfer operations. Delta removes subsequent identical copies of already transmitted data during transfers and restores those copies once the data has reached the destination. Delta is able to identify duplicated information and determine the most space efficient way to represent it. Initial tests show about 50% reduction in data movement while maintaining the same data quality and transmission frequency.

  18. Delta count-rate monitoring system

    International Nuclear Information System (INIS)

    Van Etten, D.; Olsen, W.A.

    1985-01-01

    A need for a more effective way to rapidly search for gamma-ray contamination over large areas led to the design and construction of a very sensitive gamma detection system. The delta count-rate monitoring system was installed in a four-wheel-drive van instrumented for environmental surveillance and accident response. The system consists of four main sections: (1) two scintillation detectors, (2) high-voltage power supply amplifier and single-channel analyzer, (3) delta count-rate monitor, and (4) count-rate meter and recorder. The van's 6.5-kW generator powers the standard nuclear instrument modular design system. The two detectors are mounted in the rear corners of the van and can be run singly or jointly. A solid-state bar-graph count-rate meter mounted on the dashboard can be read easily by both the driver and passenger. A solid-state strip chart recorder shows trends and provides a permanent record of the data. An audible alarm is sounded at the delta monitor and at the dashboard count-rate meter if a detected radiation level exceeds the set background level by a predetermined amount

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

    Science.gov (United States)

    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.

  20. Muscarinic cholinergic receptor antagonists in the VTA and RMTg have opposite effects on morphine-induced locomotion in mice.

    Science.gov (United States)

    Steidl, Stephan; Dhillon, Ekamjeet S; Sharma, Natasha; Ludwig, Jessica

    2017-04-14

    The ventral tegmental area (VTA) and the rostromedial tegmental nucleus (RMTg) each contribute to opiate reward and each receive inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic cell groups. We compared the contributions of VTA or RMTg muscarinic cholinergic receptors to locomotion induced by morphine infusions into the same sites. VTA co-infusion of atropine completely blocked VTA morphine-induced locomotion providing additional support for the important role of VTA muscarinic cholinergic receptors in the stimulant effects of opiates. By contrast, RMTg co-infusion of atropine increased RMTg morphine-induced locomotion. Furthermore, RMTg co-infusion of the M3-selective antagonist 4-DAMP, but not the M4-selective antagonist Tropicamide, strongly increased RMTg morphine-induced locomotion. RMTg infusions of 4-DAMP, but not of Tropicamide, by themselves strongly increased drug-free locomotion. Muscarinic cholinergic receptors in the RMTg thus also contribute to the stimulant effects of morphine, but in a way opposite to those in VTA. We suggest that the net effect of endogenous cholinergic input to the RMTg on drug-free and on RMTg morphine-induced locomotion is inhibitory. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  2. A pilot feasibility randomised controlled trial of an adjunct brief social network intervention in opiate substitution treatment services.

    Science.gov (United States)

    Day, Ed; Copello, Alex; Seddon, Jennifer L; Christie, Marilyn; Bamber, Deborah; Powell, Charlotte; Bennett, Carmel; Akhtar, Shabana; George, Sanju; Ball, Andrew; Frew, Emma; Goranitis, Ilias; Freemantle, Nick

    2018-01-15

    Approximately 3% of people receiving opioid substitution therapy (OST) in the UK manage to achieve abstinence from prescribed and illicit drugs within three years of commencing treatment. Involvement of families and wider social networks in supporting psychological treatment may be an effective strategy in facilitating recovery, and this pilot study aimed to evaluate the impact of a social network-focused intervention for patients receiving OST. A two-site, open feasibility trial randomised patients receiving OST for at least 12 months but still reporting illicit opiate use in the past 28 days to one of three treatments: 1) treatment as usual (TAU), 2) Brief Social Behaviour and Network Therapy (B-SBNT) + TAU, or 3) Personal Goal Setting (PGS) + TAU. The two active interventions consisted of 4 sessions. There were 3 aims: 1) test the feasibility of recruiting OST patients to a trial of B-SBNT, and following them up over 12 months; 2) test the feasibility of training clinicians to deliver B-SBNT; 3) test whether B-SBNT reduces heroin use 3 and 12 months after treatment, and to explore potential mediating factors. The primary outcome for aim 3 was number of days of heroin use in the past month, and a range of secondary outcome measures were specified in advance (level of drug dependence, mental health, social satisfaction, therapist rapport, treatment satisfaction, social network size and support). A total of 83 participants were randomised, and 70 (84%) were followed-up at 12 months. Fidelity analysis of showed that B-SBNT sessions were clearly distinguishable from PGS and TAU sessions, suggesting it was possible to train clinical staff to an adequate level of competence. No significant differences were found between the 3 intervention arms in the primary or secondary outcome measures. Attendance at psychosocial treatment intervention sessions was low across all three arms (44% overall). Patients receiving OST can be recruited into a trial of a social

  3. Evaluation of the Counter-regulatory Responses to Hypoglycemia in Patients with Type 1 Diabetes during Opiate Receptor Blockade with Naltrexone

    DEFF Research Database (Denmark)

    Naik, Sarita; Belfort-DeAguiar, Renata; Sejling, Anne-Sophie

    2017-01-01

    visits; as well as the glucose infusion rates required to keep glucose levels at target. During hypoglycemia, naltrexone, in comparison to the placebo group, induced an increase in epinephrine levels (P=0.05). However, no statistically significant differences in glucagon, cortisol, and growth hormone...... before the clamp study the participants received 100 mg of naltrexone or placebo orally. Counterregulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinemic-clamp. RESULTS: Glucose and insulin levels did not differ significantly between the naltrexone and placebo...

  4. An audit of the use of an opiate sparing, multimodal analgesic regime in children with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing adenotonsillectomy.

    Science.gov (United States)

    Hack, Henrik

    2014-01-01

    Children with Sleep Disordered Breathing/Obstructive Sleep Apnoea have an increased incidence of respiratory complications following adenotonsillectomy. This may be partly related to an increase in sensitivity to opiates. An audit of such cases undergoing adenotonsillectomy was performed with the following aims: All patients had Sleep Disordered Breathing/Obstructive Sleep Apnoea confirmed preoperatively by Overnight Oximetry Studies. Oximetry data was expressed as the lowest recorded saturation (SpO2 Low %) and number of significant desaturations (see text) per hour (ODI4%). Case notes and oximetry studies were scrutinized for relevant perioperative anaesthetic and analgesic data, risk factors and complications. The overall incidence of major and minor respiratory complications was low (1.6% and 27% respectively). Children who suffered any complication were more likely to be younger (p=0.0078), have a lower SpO2 Low (p=0.004) and higher ODI4% (p=8 may be the best cut off point in predicting complications (AUC=0.78, sensitivity=0.90) but it showed a poor specificity (0.57). Primary/secondary haemorrhage occurred in 0.4%/1.2% respectively and postoperative nausea and vomiting in 4.4%. A low dose opiate-based, multi modal analgesic regime appears to be effective and safe in children with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing adenotonsillectomy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. The Effectiveness of Cognitive-Behavioral Group Therapy on Reduction of Craving, Depression and Anxiety Symptoms among the Opiate Abusers Under MMT

    Directory of Open Access Journals (Sweden)

    Fereshtwh Momeni

    2009-10-01

    Full Text Available Introduction: The aim of this study was to examine the effectiveness of cognitive behavior group therapy on reduction of craving, depression and anxiety symptoms among the Opiate abusers under MMT. Method: In this experimental research, 36 addicts on MMT were selected between the entire opiate addicts referred to Iranian national center for addiction studies (INCAS by convenience sampling and were randomly assigned into experimental and control groups. In experimental group, cognitive behavior group therapy was performed in 8 sessions, one each week. Sessions were performed for craving, depression and anxiety management. Data was gathered by demographic questionnaire, scale of relapse predicts craving assessment, BDI-II and BAI for depression and anxiety symptoms assessment. The data was analyzed, independent and paired samples t test. Results: Data analysis revealed that craving index was decreased in post- test and follow-up and it was statistically significant. Also beck depression and anxiety symptoms were decreased significantly in post-test and follow-up. Conclusion: The results show that cognitive-behavior group therapy was efficient on reduction of drug craving, depression, and anxiety symptoms in post-test and follow-up, and it can apply as a method of treatment.

  6. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

    Directory of Open Access Journals (Sweden)

    Dalton Richard

    2007-01-01

    Full Text Available Abstract Background In the United Kingdom (UK, there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. Methods/Design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

  7. Vitreous fluid quantification of opiates, cocaine, and benzoylecgonine: comparison of calibration curves in both blood and vitreous matrices with corresponding concentrations in blood.

    Science.gov (United States)

    Antonides, Heather M; Kiely, Elizabeth R; Marinetti, Laureen J

    2007-10-01

    Vitreous fluid specimens are often used in the Montgomery County Coroner's Office as a second matrix confirmation for both cocaine and opiate analyses. In this manuscript, calibration curves constructed for both vitreous and blood were used to quantify vitreous specimens to evaluate if any matrix effects occur when measuring vitreous specimens using a calibration curve in blood. Cases that screened positive by ELISA for cocaine metabolite and opiates were confirmed by solid-phase extraction. Gas chromatography with mass spectral detection in the positive electron impact mode was used for the detection and quantification of oxycodone, free morphine, codeine, 6-monoacetylmorphine, hydrocodone, cocaine, and benzoylecgonine. For interpretive purposes, no significant matrix effects were found in concentrations of vitreous specimens quantified with a calibration curve constructed in a blood matrix. After determining that vitreous fluid can be accurately measured with blood calibrators, a comparison was made between blood and vitreous concentrations for the above analytes. Concentration differences between blood and vitreous specimens for each drug are evaluated with selected case histories included.

  8. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    Science.gov (United States)

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Delta robots – robots for high speed manipulation

    OpenAIRE

    Poppeová, Viera; Uríček, Juraj; Bulej, Vladimír; Šindler, Peter

    2011-01-01

    This paper is oriented to parallel kinematic robots definition, description of their specific application, comparison of robots made by different producers and determination of velocity and acceleration parameters, kinematic analysis – inverse and forward kinematic. It brings information about development of Delta robots at Academia, including the University of Žilina and Delta robots in the market. Two models of Delta robots called M-1iA and M-3iA have been developed by FANUC Robotics during...

  10. THE RURAL TOURISM IN DANUBE DELTA

    Directory of Open Access Journals (Sweden)

    Ionica SOARE

    2014-06-01

    Full Text Available Purpose - the purpose of this paper is to evaluate the rural areas has market size and forecast its development as an economic activity. The present paper aims at analyzing the rural areas has in Danube Delta. In an enviable BAs which have responsibility for their particular isolated, such as the Danube Delta and the Danube that used, fishing and rural areas has the main activities that provide jobs and income sources for local populations. Design/methodology/approach - A survey was administered to customers’ rural hostel accommodation in Danube Delta. Descriptive statistics method was mainly adopted to calculate the mean with standard deviation of entry assumes variable, and to examine the different levels of consumers' awareness. The index values of product familiarity, the ratio between entries assumes product's familiarity value and the average value. Findings - the research results show hash has rural consumers have different perception and accomplished through behaviour. The information channels of brand hash mainly from friends, relatives and neighbours, so word of mouth spreading is very important for a brand. Women show a higher sensitivity in health and are currently operating the propensity than referred to follow the recommendations for nutrition. Research limitations/implications - This item is intended to synthesize developments and challenges," on June 13th rural market growth has. The results of this paper should be considered tentatively until has also features replicated by larger has rural consumers. Originality/value - members of rural areas has consumer's behavior would improve marketing and the development of rural areas has products, in order to reduce consumer confusion.

  11. Neuroreceptor imaging in epilepsy

    International Nuclear Information System (INIS)

    Frost, J.J.

    1991-01-01

    The neurochemical processes that mediate seizures in humans are not fully understood. PET has contributed to our understanding of the neurochemical abnormalities of epilepsy with studies of cerebral metabolism and, more recently, regional neuroreceptor binding. We have focused on inhibitory neurotransmitter receptors that may (1) be decreased, thus facilitating seizure initiation, or (2) increase in response to seizure activity. Opiate receptors are believed to mediate anticonvulsant effects of the endogenous opioids. Accordingly, [ 11 C]carfentanil, a ligand selective for the mu-opiate receptor, displays increased binding in temporal neocortex ipsilateral to seizure foci in complex partial epilepsy. This finding is consistent with activation of the endogenous opiate system in response to seizure activity. [ 11 C]diprenorphine, a ligand that labels mu-, delta- and kappa-opiate receptors with equal affinity, shows little or no change in temporal cortex. Together, these findings suggest a decrease in delta- or kappa-receptors. The development of delta- and kappa-selective receptor ligands will help to elucidate the involvement of these opiate receptors in human epilepsy. The benzodiazepine-GABA receptor complex is the most prevalent in mediating inhibitory brain processes. Use of the benzodiazepine (BZD) receptor ligand [ 11 C]RO 15-1788 has shown decreases in BZD receptors in human epilepsy in one study, but this has not been observed in a current study. Thus, the existence of reduced inhibitory processes that might enhance seizure initiation remains uncertain at present. Future studies of receptors for excitatory transmitters will provide additional insight into alternate factors potentially responsible for the initiation of seizures

  12. Tracks, spurs, blobs and delta-rays

    International Nuclear Information System (INIS)

    Magee, J.L.; Chatterjee, A.

    1983-01-01

    The track of a high-energy particle is the collection of all transient species created by the particle in the total degradation of its energy. Visible electron tracks are called delta rays. A microscopic description of the track with all its knocked-out electrons leads to spurs, blobs, and short tracks. Energy deposition criteria for these three track entities are 6 to 100 eV, 100 to 500 eV, and 500 eV to 5 keV, respectively

  13. The situation in the Niger Delta

    International Nuclear Information System (INIS)

    Vitalis, E.

    2007-01-01

    An energy issue for the United States and a political challenge for Europe, Nigeria is experiencing growing instability and is on the verge of civil war; the ecosystem and the population of the Niger Delta are the main victims. The State, corrupt, is powerless to contain the rising violence and redistribute the proceeds of oil sales. It is high time for oil-consuming countries, starting with the United States, to concern themselves with stabilizing the region. Europe must contribute to the lasting development of this country. (author)

  14. Subsurface Miocene sequence stratigraphic framework in the Nile Delta, Egypt

    Science.gov (United States)

    Farouk, Sherif; Ziko, Abdelmohsen; Eweda, Shehtta A.; Said, Ali E.

    2014-03-01

    The Miocene depositional history of the Nile Delta is dominated by fluvial-deltaic, marginal marine and marine shelf sedimentation. It exhibits radical lateral facies changes due to its tectonic setting. Different attributions in age assignments characterise the Miocene Nile Delta due to the lack of large vertical facies changes, which consists mainly of siliciclastic with different environments. This study uses integrating lithologic, biostratigraphic, gamma-ray log and benthic foraminiferal biofacies, at four boreholes (Tanta-1, Rommana-1X, El-Fayrouz and Rosetta-7) in the Nile Delta, Egypt. Planktonic foraminifera allow subdivision of the Miocene Nile Delta succession into 12 planktonic biozones and benthic species are used in paleobathymetic estimates.

  15. Upper-division student difficulties with the Dirac delta function

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2015-03-01

    Full Text Available The Dirac delta function is a standard mathematical tool that appears repeatedly in the undergraduate physics curriculum in multiple topical areas including electrostatics, and quantum mechanics. While Dirac delta functions are often introduced in order to simplify a problem mathematically, students still struggle to manipulate and interpret them. To characterize student difficulties with the delta function at the upper-division level, we examined students’ responses to traditional exam questions and a standardized conceptual assessment, and conducted think-aloud interviews. Our analysis was guided by an analytical framework that focuses on how students activate, construct, execute, and reflect on the Dirac delta function in the context of problem solving in physics. Here, we focus on student difficulties using the delta function to express charge distributions in the context of junior-level electrostatics. Common challenges included invoking the delta function spontaneously, translating a description of a charge distribution into a mathematical expression using delta functions, integrating 3D or non-Cartesian delta function expressions, and recognizing that the delta function can have units. We also briefly discuss implications of these difficulties for instruction.

  16. Optimality and self-organization in river deltas

    Science.gov (United States)

    Tejedor, A.; Longjas, A.; Edmonds, D. A.; Zaliapin, I. V.; Georgiou, T. T.; Rinaldo, A.; Foufoula-Georgiou, E.

    2017-12-01

    Deltas are nourished by channel networks, whose connectivity constrains, if not drives, the evolution, functionality and resilience of these systems. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. However, in contrast to tributary channel networks, to date, no theory has been proposed to explain how deltas self-organize to distribute water and sediment to the delta top and the shoreline. Here, we hypothesize the existence of an optimality principle underlying the self-organized partition of fluxes in delta channel networks. Specifically, we hypothesize that deltas distribute water and sediment fluxes on a given delta topology such as to maximize the diversity of flux delivery to the shoreline. By introducing the concept of nonlocal Entropy Rate (nER) and analyzing ten field deltas in diverse environments, we present evidence that supports our hypothesis, suggesting that delta networks achieve dynamically accessible maxima of their nER. Furthermore, by analyzing six simulated deltas using the Delf3D model and following their topologic and flux re-organization before and after major avulsions, we further study the evolution of nER and confirm our hypothesis. We discuss how optimal flux distributions in terms of nER, when interpreted in terms of resilience, are configurations that reflect an increased ability to withstand perturbations.

  17. CMS: Aboveground Biomass for Mangrove Forest, Zambezi River Delta, Mozambique

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset provides several estimates of aboveground biomass from various regressions and allometries for mangrove forest in the Zambezi River Delta, Mozambique....

  18. Delta9-tetrahydrocannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain.

    Science.gov (United States)

    Porcella, A; Gessa, G L; Pani, L

    1998-05-01

    Delta-9-tetrahydrocannabinol (delta9-THC), the psychoactive principle of marijuana, has been shown to upregulate the mRNA levels of immediate-early genes in the rat brain. Using electrophoretic mobility-shift assay and one-dimensional Western blot, we here report that delta9-THC increases Activator protein-1 (AP-1) DNA-binding and Fos-related antigen activity in discrete areas of the rat brain. One hour after the intraperitoneal administration of delta9-THC at a dose of 10 or 15 mg/kg, AP-1 DNA-binding activity in the nucleus accumbens increased by 33 and 49%, respectively, while Western blot showed an increase in both c-Fos, FosB, Fra-1 (Fos-related antigen) and Fra-2. In the cingulate cortex and caudate-putamen, delta9-THC significantly increased AP-1 DNA-binding activity only at the highest dose used (57 and 71%, respectively). While in the caudate-putamen the increase in AP-1 DNA binding was mainly due to an elevation of the c-Fos and FosB proteins, the same phenomenon depended on the FosB, Fra-1 and Fra-2 peptides in the cingulate cortex. The effect of delta9-THC on the AP-1 DNA binding and the Fos-related antigens in the nucleus accumbens was blocked by the specific cannabinoid antagonist SR141716 A (3 mg/kg i.p.). delta9-THC failed to modify Specificity protein 1 (Sp1) DNA-binding activity. The results indicate that delta9-THC activates gene coding for AP-1 DNA-binding proteins by acting on cannabinoid receptors, and induces a different transcriptional program on the early-immediate gene of the Fos family, in different areas in the rat brain, suggesting that this mechanism might be involved in the central actions of cannabinoids.

  19. Delta Alliance Young Professionals Award: Innovative solutions for delta challenges worldwide

    NARCIS (Netherlands)

    Krueger, I.; Miguel Ayala, L.; Driel, van W.F.

    2012-01-01

    Deltas are fragile, dynamic landforms at the boundary of land and ocean. They belong to the most valuable, but at the same time also to the most vulnerable areas in the world. With increasing pressure from population growth, industrialization and changing climate, it is more important than ever that

  20. Adaptive delta management: a comparison between the Netherlands and Bangladesh Delta Program

    NARCIS (Netherlands)

    Zevenbergen, Chris; Khan, Shah Alam; Alphen, van Jos; Terwisscha van Scheltinga, Catharien; Veerbeek, William

    2018-01-01

    In the Netherlands, the central government, water authorities, provinces and municipalities are working together on a new Delta Program on Flood Risk Management and Fresh Water Supply (DP). Its primary goal is to protect the Netherlands against floods and ensure the availability of fresh water, now