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Sample records for delta opiate receptors

  1. Metabolic rate in different rat brain areas during seizures induced by a specific delta opiate receptor agonist.

    Science.gov (United States)

    Haffmans, J; De Kloet, R; Dzoljic, M R

    1984-06-04

    The glucose utilization during specific delta opiate agonist-induced epileptiform phenomena, determined by the [14C]2-deoxyglucose technique (2-DG), was examined in various rat brain areas at different time intervals. The peak in EEG spiking response and the most intensive 2-DG uptake occurred 5 min after intraventricular (i.v.t.) administration of the delta opiate receptor agonist. The most pronounced 2-DG uptake at this time interval can be observed in the subiculum, including the CA1 hippocampal area, frontal cortex and central amygdala. A general decrease of glucose consumption, compared to control values, is observed after 10 min, in all regions, with exception of the subiculum. Since functional activity and 2-DG uptake are correlated, we suggest that the subiculum and/or CA1 area, are probably the brain regions most involved in the enkephalin-induced epileptic phenomena.

  2. 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

  3. 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.

  4. 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 analysis...... in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity...... of [Leu]enkephalin and [Met]enkephalin to the known mu- and delta-type opiate receptors to which they bind as agonists. Other plausible consequences of these probability distributions are discussed in relation to the way in which they may influence the dynamics of the synapse....

  5. 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.)

  6. Opiate-induced seizures: a study of mu and delta specific mechanisms.

    Science.gov (United States)

    Snead, O C

    1986-08-01

    Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.

  7. Imaging opiate receptors with positron emission tomography

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    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.

  8. 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

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

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    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.

  10. Selective localization of different types of opiate receptors in hippocampus as revealed by in vitro autoradiography

    International Nuclear Information System (INIS)

    Duka, T.; Wuester, M.; Schubert, P.; Stoiber, R.; Herz, A.

    1981-01-01

    The visualization of opiate binding sites within the hippocampus of the rat has been achieved by means of an in vitro autoradiography. In line with the concept of multiple opiate receptors, different opioid agonists revealed a particular distribution pattern. Whereas the selective delta-receptor agonist [ 3 H]D-Ala 2 , D-Leu 5 -enkephalin specifically labelled binding sites in the CA 2 area, [ 3 H]etorphine grains displayed a uniform dense distribution throughout the pyramidal cell layers from CA 1 to CA 4 . (Auth.)

  11. 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)

  12. Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

    Science.gov (United States)

    Mayberg, H S; Sadzot, B; Meltzer, C C; Fisher, R S; Lesser, R P; Dannals, R F; Lever, J R; Wilson, A A; Ravert, H T; Wagner, H N

    1991-07-01

    Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.

  13. Photoaffinity labeling of opiate receptors using intrinsically photoactive 3H-opiates

    International Nuclear Information System (INIS)

    Kooper, G.N.; Levinson, N.R.; Copeland, C.F.; Bowen, W.D.

    1988-01-01

    Opiate receptors in rat and cow brain membranes have been labeled irreversibly using the intrinsic photolability of 3H-opiates. Membranes were incubated with 3H-ligand and then irradiated with UV light of 254 nm. Nonspecific binding was determined in the presence of 10 microM unlabeled levallorphan. Irreversible binding was defined as binding which survived heat or acid denaturation of membranes. Specific incorporation of label into denatured samples was observed only when unbound or loosely bound 3H-ligand was washed free from the membranes prior to irradiation. There was a general correlation between photosensitivity of the 3H-ligand and its ability to photolabel receptors. Hence, photolabeling presumably results by covalent attachment of highly reactive species generated during photochemical decomposition of ligand. With 3H-etorphine, optimal irradiation time was 5 min. In addition to 3H-etorphine, receptors could be labeled irreversibly with 3H-oxymorphone, 3H-dihydromorphine, and 3H-ethylketocyclazocine. Of the specific binding present in irradiated, nondenatured samples, 45-60% remained attached to receptors upon denaturation. 3H-Ethylketocyclazocine exhibited an 86% yield of incorporation. Signal-to-noise levels of 50-80% could be achieved in denatured samples. Therefore, this method provides a means of covalently labeling opiate receptors in high yield and with high signal-to-noise ratios. The opioid peptides, 3H-D-Ala2,D-Leu5-enkephalin, 3H-D-Ser2,Leu5,Thr6-enkephalin, 3H-D-Ala2,Met5-enkephalin amide, and 3H-D-Ala2,N-MePhe4,Gly-ol5-enkephalin, as well as the benzomorphan, 3H-bremazocine, apparently lack the structural characteristics which allow photolabeling

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

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    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.

  15. 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.

  16. Opiate receptor binding in the brain of the seizure sensitive Mongolian gerbil (Meriones unguiculatus).

    Science.gov (United States)

    Lee, R J; Olsen, R W; Lomax, P; McCabe, R T; Wamsley, J K

    1984-12-01

    Opiate receptor binding was studied in seizure sensitive (SS) and seizure resistant (SR) strains of the Mongolian gerbil. Cryostat sections of the brain were labeled with [3H]-dihydromorphine, subjected to autoradiography and analysed by microdensitometry. SS gerbils, prior to seizure induction, demonstrated overall greater brain opiate binding when compared to SR animals. Immediately following a seizure, binding in the interpeduncular nucleus fell to levels found in SR animals. The increased opiate binding in the SS (pre-seizure) compared to SR gerbils could reflect a deficit of endogenous ligand which could underlie the seizure diathesis in the gerbil.

  17. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy.

    Science.gov (United States)

    Frost, J J; Mayberg, H S; Fisher, R S; Douglass, K H; Dannals, R F; Links, J M; Wilson, A A; Ravert, H T; Rosenbaum, A E; Snyder, S H

    1988-03-01

    Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.

  18. Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus μ-opiate receptor dependent mechanisms.

    Science.gov (United States)

    Ahmad, Tasha; Lauzon, Nicole M; de Jaeger, Xavier; Laviolette, Steven R

    2013-09-25

    Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.

  19. 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.

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

    International Nuclear Information System (INIS)

    Edmondson, E.A.; Bonnet, K.A.; Friedhoff, A.J.

    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 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 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.

  3. The effect of various opiate receptor agonists on the seizure threshold in the rat. Is dynorphin an endogenous anticonvulsant?

    Science.gov (United States)

    Przewłocka, B; Stala, L; Lasoń, W; Przewłocki, R

    1983-01-01

    The effects of various opiate receptor agonists on the seizure threshold after an intravenous infusion of pentylenetetrazol were investigated in rats. The mu- and epsilon-receptor agonists, morphine (20-40 micrograms) and beta-endorphin (5-10 micrograms) show proconvulsant properties towards clonic and tonic seizures. The delta-receptor agonist (D-Ala2,D-Leu5-enkephalin, DADL 5-40 micrograms) and alpha-neoendorphin (20-40 micrograms) show pro- and anticonvulsant properties towards clonic and tonic seizures, respectively. Anticonvulsant properties of DADL are possibly due to its action on the spinal cord, since after the intrathecal injection this effect is still observed. Similarities between DADL and alpha-neoendorphin suggest that they may act through the same receptor. The kappa-receptor agonist dynorphin A (5-20 micrograms) and its degradation-resistant analogue D-Arg-dynorphin1-13 (10 micrograms) show significant anticonvulsant properties. Our present results suggest that the kappa-receptor agonist dynorphin may act physiologically as an endogenous anticonvulsant, in contrast to other opioid peptides.

  4. Opiate receptors in idiopathic generalised epilepsy measured with [11C]diprenorphine and positron emission tomography.

    Science.gov (United States)

    Prevett, M C; Cunningham, V J; Brooks, D J; Fish, D R; Duncan, J S

    1994-09-01

    The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.

  5. The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

    Science.gov (United States)

    Morisot, Nadège; Contarino, Angelo

    2016-06-01

    Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The epileptogenic spectrum of opiate agonists.

    Science.gov (United States)

    Snead, O C; Bearden, L J

    1982-11-01

    The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

  7. NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

    Science.gov (United States)

    Tan, Huibing; Rosen, Laura G; Ng, Garye A; Rushlow, Walter J; Laviolette, Steven R

    2014-12-01

    N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

  8. 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.

  9. Molecular identification of the mode of interaction of nitrous oxide with the opiate receptor system

    Energy Technology Data Exchange (ETDEWEB)

    Wallar, D D

    1985-01-01

    The discovery of the opioid receptors in 1973 has led to a great deal of in vivo and in vitro research in order to understand the mechanism of binding of endogenous and synthetic opiate ligands. The use of nitrous oxide (N/sub 2/O) in anaesthesia is well documented. However, at lower concentrations N/sub 2/O produces analgesia. In 1976, it was reported that N/sub 2/O analgesia in man could be modified by the opiate antagonist naloxone. This clearly linked nitrous oxide analgesia to the opioid receptor system. It is the purpose of this dissertation to examine the molecular mechanism of action of N/sub 2/O at the opioid receptor through the use of in vitro binding studies. In addition, a model of the opioid receptor will be proposed. The following radiolabelled ligands were used in classical competitive binding assays to determine K (sub D),B(sub max), and IC/sub 50/ values in the presence of nitrous oxide and other control gases: dihydromorphine, N-allyl-N-normetazocine (SKF 10,047), and ethylketocyclazocine, for putative ..mu.., sigma and kappa opioid binding sites, respectively. All assays were performed using rat forebrain homogenates suspended in buffer previously saturated with the gas. Results indicate that N/sub 2/O differentially affects the binding kinetics of dihydromorphine. The binding kinetics of SKF 10,047 or ethylketocyclazocine were not altered significantly by N/sub 2/O indicating that N/sub 2/O is specific in its effects for the putative ..mu..-binding site. It is suggested that N/sub 2/O exerts its analgesic effects by perturbation of protein/lipid interactions within a multiple binding site opioid receptor complex.

  10. Imaging dopamine and opiate receptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1986-01-01

    Chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its nature. In 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spipeone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress

  11. Synthesis of N-p-azidophenylethyl-7,8-dihydronormorphine and its 7,8-ditritio analogue. Potential opiate receptor photoaffinity labels

    International Nuclear Information System (INIS)

    Cooper, G.K.; Rapoport, Henry

    1985-01-01

    The morphine derivatives N-p-azidophenylethyl-7,8-dihydronormorphine and its 7,8-ditritio analogue were synthesized from morphine. This material, a potential photoaffinity label with high specific radio-activity and with opiate agonist activity comparable to morphine, may be useful for labeling of opiate receptors. (author)

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Dahren; 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.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with 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 [ 3 H]naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC 50 's against [ 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 [ 18 F]-6 was developed and the tissue distribution of [ 18 F]-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to 18 F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned. (author)

  15. 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.

  16. 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

  17. 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.

  18. 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...

  19. Stimulation of accumbal GABAA receptors 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.

  20. 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.

  1. Opiate and opioid withdrawal

    Science.gov (United States)

    ... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

  2. 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

  3. Striatal dopamine D2 receptor binding and dopamine release during cue-elicited craving in recently abstinent opiate-dependent males

    NARCIS (Netherlands)

    Zijlstra, Fleur; Booij, Jan; van den Brink, Wim; Franken, Ingmar H. A.

    2008-01-01

    Opiate addiction is a chronic disorder characterized by relapse behaviour, often preceded by craving and anhedonia. Chronic craving and anhedonia have been associated with low availability of dopamine D2 receptors (D2Rs) and cue-elicited craving has been linked with endogenous dopamine release. We

  4. 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.

  5. Imaging opiate receptors by positron tomography (PET): Evaluation by displacement of 3-Acetyl-6-Deoxy-6-Beta-/sup 18/F-flouronaltrexone with active and inactive naloxone

    International Nuclear Information System (INIS)

    Larson, S.M.; Channing, M.A.; Rice, K.R.; Pert, C.B.; Eckelman, W.C.; Burke, T.R.; Bennett, J.M.; Carson, R.E.; Di Chiro, G.

    1985-01-01

    We recently reported the development of a new radiopharmaceutical for in vivo PET imaging of opiate receptors, 3-acetyl-6-deoxy-6-Beta-/sup 18/F-fluoronaltrexone: 3-acetylcyclofoxy, or /sup 18/F-ACF. These studies involved displacement of /sup 18/F-ACF from sites of uptake in the baboon sub-cortical gray matter, and provided strong proof of the opiate receptor specificity of the tracer. We now report on the anatomic localization of /sup 18/F-ACF in the sub-cortical grapy matter of baboon, and the kinetics of uptake and displacement of the tracer. /sup 18/F-ACF was prepared from the known 3-acetyl-6-alpha-naltrexol via the triflate, using /sup 18/F produced by neutron bombardment of /sup 6/Li/sub 2/CO/sub 3/. Anesthetized baboons were imaged after injection of /sup 18/F-ACF (sp.ac.=20Ci/mmol), using the NIH NEUROPET, a high resolution PET scanner. After bolus injection, the initial distribution to brain was rapid with peak uptake at 6 minutes post-injection. Clearance from opiate receptor rich regions of thalamus and basal ganglia was gradual, but after injection of active (but not after inactive), naloxone, clearance from these regions more than doubled. In non-opiate rich regions, (e.g. cerebellum), the predominant component of clearance was equally rapid with or without the active naloxone. Displacement studies of positron labelled ligands provide a powerful tool for non-invasive study of opiate receptor in living primates

  6. 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.

  7. Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography

    International Nuclear Information System (INIS)

    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.

    1989-01-01

    [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

  8. Synthesis of [11C]-ohmefentanyl, a novel, highly potent and selective agonist for opiate μ-receptors

    International Nuclear Information System (INIS)

    Zhu, Y.C.; Academia Sinica, Shangha, SH; Prenant, C.; Crouzel, C.; Comar, D.; Chi, Z.Q.

    1992-01-01

    We describe the synthesis of 11 C-ohmefentanyl, a novel, highly potent and selective agonist for opiate μ-receptors, to be visualized by Positron Emission Tomography (PET). The unlabelled cis-A-ohmefentanyl was prepared in a nine-step synthesis and two-step fractional crystallization, and the OH-precursor for [ 11 C]-ohmefentanyl labelling was obtained by hydrolysis of the 4-N-propionyl group of cis-A-ohmefentanyl in 6 N hydrochloric acid. The [ 11 C]-propionyl chloride was prepared by carbonation of ethylmagnesium bromide with cyclotron-produced [ 11 C]-carbon dioxide followed by direct treatment of the intermediate complex with phthaloyl dichloride and 2,6-di-t-butylpyridine. Reaction of the OH-precursor with [ 11 C]-propionyl chloride yields [ 11 C]-ohmefentanyl separated by HPLC, with a high specific activity of 300-400 mCi μmol -1 . The keto-precursor prepared by hydrolysis of the 4-N-propionyl group of cis-10 in 8 N hydrochloric acid, was also used for [ 11 C]-ohmefentanyl labelling. Reaction of the [ 11 C]-propionyl chloride with keto-precursor, followed by addition of sodium borohydride, yields [ 11 C]-ohmefentanyl. The [ 11 C]-labelled ohmefentanyl obtained using the OH-precursor is a cis-A form, while that obtained using the keto-precursor is a mixture of cis-A and cis-B forms. (author)

  9. Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

    Science.gov (United States)

    Frenk, H

    1983-10-01

    The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.

  10. Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

    Science.gov (United States)

    Geiko, V V; Vorob'eva, T M; Berchenko, O G; Epstein, O I

    2003-01-01

    The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

  11. 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+

  12. 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

  13. GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity

    Directory of Open Access Journals (Sweden)

    Allison Doyle Brackley

    2016-09-01

    Full Text Available Opioids remain the standard for analgesic care; however, adverse effects of systemic treatments contraindicate long-term administration. While most clinical opioids target mu opioid receptors (MOR, those that target the delta class (DOR also demonstrate analgesic efficacy. Furthermore, peripherally restrictive opioids represent an attractive direction for analgesia. However, opioid receptors including DOR are analgesically incompetent in the absence of inflammation. Here, we report that G protein-coupled receptor kinase 2 (GRK2 naively associates with plasma membrane DOR in peripheral sensory neurons to inhibit analgesic agonist efficacy. This interaction prevents optimal Gβ subunit association with the receptor, thereby reducing DOR activity. Importantly, bradykinin stimulates GRK2 movement away from DOR and onto Raf kinase inhibitory protein (RKIP. protein kinase C (PKC-dependent RKIP phosphorylation induces GRK2 sequestration, restoring DOR functionality in sensory neurons. Together, these results expand the known function of GRK2, identifying a non-internalizing role to maintain peripheral DOR in an analgesically incompetent state.

  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. 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

  16. 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.

  17. 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

    AIMS: Hypoglycemia is the major limiting factor in achieving optimal glycemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counterregulation during hypoglycemia. Naloxone, an opiate receptor blocker, has been reported to enhance...... with a high risk for hypoglycemia. MATERIALS AND METHODS: We performed a randomized, placebo-controlled, double-blinded, cross-over study in which 9 intensively treated subjects with T1DM underwent a 2-step euglycemic-hypoglycemic-hyperinsulinemic clamp on two separate occasions. Twelve hours and 1 hour...

  18. 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...

  19. 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

    Peroxisome proliferator-activated receptor (PPAR) beta/delta is ubiquitously expressed, but the level of expression differs markedly between different cell types. In order to determine the molecular mechanisms governing PPARbeta/delta gene expression, we have isolated and characterized the mouse...

  20. 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

  1. 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

  2. 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.).

  3. 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.)

  4. 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.

  5. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  6. 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

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor....... 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...... deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue....

  7. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

    Science.gov (United States)

    Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

    2010-03-01

    Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior.

  8. 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.

  9. 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) ...

  10. 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

  11. 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.

  12. Characterization and autoradiographic visualization of (+)-[3H]SKF10,047 binding in rat and mouse brain: further evidence for phencyclidine/sigma opiate receptor commonality

    International Nuclear Information System (INIS)

    Sircar, R.; Nichtenhauser, R.; Ieni, J.R.; Zukin, S.R.

    1986-01-01

    The binding specificity of (+)-[ 3 H]N-allylnormetazocine, the dextrorotatory isomer of the prototypical sigma opiate SKF10,047, was determined in rat and mouse brain and the neuroanatomical distribution of its binding sites elucidated by quantitative autoradiography in sections of rat brain. Computer-assisted Scatchard analysis revealed an apparent two-site fit of the binding data in both species and in all rat brain regions examined. In whole rat brain, the Kd values were 3.6 and 153 nM and the maximum binding values were 40 fmol and 1.6 pmol/mg of protein for the apparent high- and low-affinity binding sites, respectively. (+)-SKF10,047, haloperidol and pentazocine were among the most potent inhibitors of 7 nM (+)-[ 3 H]SKF10,047 binding to the higher affinity sites; rank orders of ligand potencies at these sites differ sharply from those that have been reported for the [ 3 H]phencyclidine (PCP) site, or for eliciting PCP-like or SKF10,047-like behaviors. By contrast, rank orders of potency of sigma opiods, PCP derivatives and dioxolanes for displacement of 100 nM (+)-[ 3 H]SKF10,047 from the more numerous lower affinity sites in the presence of 100 nM haloperidol agreed closely with their potencies in the [ 3 H]PCP binding assay as well as their potencies in exerting PCP- or SKF10,047-like behavioral effects. In order to compare directly the anatomical localizations of PCP and (+)-SKF10,047 binding sites, quantitative light microscopy autoradiography utilizing tritium-labeled PCP and (+)-SKF10,047 was carried out in rat brain sections. (+)-[ 3 H]SKF10,047 binding was observed to follow the regional pattern of [3H]PCP binding but also to bind in other regions not associated with PCP receptors

  13. Structural insights into human peroxisome proliferator activated receptor delta (PPAR-delta selective ligand binding.

    Directory of Open Access Journals (Sweden)

    Fernanda A H Batista

    Full Text Available Peroxisome proliferator activated receptors (PPARs δ, α and γ are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328 in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design.

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

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    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.

  15. Opiate treatment for opiate withdrawal in newborn infants.

    Science.gov (United States)

    Osborn, David A; Jeffery, Heather E; Cole, Michael J

    2010-10-06

    Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. To assess the effectiveness and safety of using an opiate compared to a sedative or non-pharmacological treatment for treatment of NAS due to withdrawal from opiates. The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. Each author assessed study quality and extracted data independently. Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology.Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted.Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate.Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate.Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care

  16. 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

  17. New features of the delta opioid receptor: conformational properties of deltorphin I analogues.

    Science.gov (United States)

    Balboni, G; Marastoni, M; Picone, D; Salvadori, S; Tancredi, T; Temussi, P A; Tomatis, R

    1990-06-15

    Deltorphin I is an opioid peptide of sequence H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2, recently isolated from the skin of Phyllomedusa bicolor. Its enormous selectivity towards the delta opioid receptor and the similarity of the conformation of the N-terminal part of the sequence with that of dermorphin (H-Tyr-D-Ala-he-Gly-Tyr-Pro-Ser-NH2), a mu selective peptide, prompted the synthesis, biological evaluation and comparative conformational study of four analogs. A 1H-NMR study showed that the conformational preferences of the N-terminal sequences of all peptides are similar. The different selectivities towards opioid receptors have been interpreted in terms of charge effects in the interaction with the membrane and at the receptor site and of hydrophobicity of the C-terminal part, when structured in a folded conformation.

  18. Ionotropic glutamate receptors (iGluRs of the delta family (GluD1 and GluD2 and synaptogenesis

    Directory of Open Access Journals (Sweden)

    Muhammad Zahid Khan

    2017-08-01

    Full Text Available Glutamate delta-1 (GluD1 and glutamate delta-2 (GluD2 form the delta family of ionotropic glutamate receptors (iGluRs and are distinct from other (iGluRs in that they do not exhibit typical agonist-induced ion channel currents. Recent studies have demonstrated a crucial role of the delta receptors in synapse formation by interacting with presynaptic proteins 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.

  19. Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats.

    Science.gov (United States)

    Higley, Amanda E; Kiefer, Stephen W

    2006-11-01

    Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.

  20. Opiate and non-opiate aspects of morphine induced seizures.

    Science.gov (United States)

    Frenk, H; Liban, A; Balamuth, R; Urca, G

    1982-12-16

    The intraperitoneal administration of morphine hydrochloride at doses of 300 mg/kg produced analgesia, catalepsy, and electrographic spiking in rats that developed into electrographic seizure patterns after approximately 2.5 h. Whereas naltrexone (12 mg/kg) reversed analgesia and catalepsy, and diminished electrographic spiking, it precipitated electrographic seizure activity similar to that observed following intraperitoneal morphine alone. These seizures were accompanied by behavioral convulsions. No tolerance to these seizures developed with repeated paired administration of morphine and naltrexone or in morphine tolerant rats, but rather potentiation was observed. The epileptogenic effects were found to be potentiated in amygdaloid kindled rats, as well. It was concluded that morphine at these doses activates two different epileptogenic mechanisms, one mediated by opiate receptors, the other not. The possibility of the simultaneous activation of a morphine sensitive anticonvulsant mechanism is discussed.

  1. 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.

  2. Synthesis of triated N1'-alkyl derivatives of the delta opioid receptor ligand naltrindole

    International Nuclear Information System (INIS)

    Lever, J.R.; Johnson, S.M.

    1997-01-01

    Tritiated N1'-methyl and N1'-ethyl analogues of naltrindole (NTI) have been synthesized for evaluation as radioligands for studies of delta opioid receptors. The two N1'-alkyl-5',7'-dibromoNTI precursors for radiolabeling were prepared by base-promoted alkylation of 2,4-dibromophenylhydrazine with either iodomethane or iodoethane followed by condensation with naltrexone using the Fischer indole synthesis. Catalytic debromotritiation followed by HPLC purification afforded [ 3 H]MeNTI (17.3 Ci/mmol) and [ 3 H]EtNTI (22.5 Ci/mmol) with high chemical and radiochemical purities (≥ 99.8%). (author)

  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. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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, ...

  10. 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.

  11. 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

  12. sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes

    International Nuclear Information System (INIS)

    Tam, S.W.; Cook, L.

    1984-01-01

    The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[ 3 H]SKF 10,047 (N-allylnormetazocine) and to dopamine D 2 sites was investigated. In guinea pig brain membranes, (+)-[ 3 H]SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10 -8 M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from μ, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[ 3 H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[ 3 H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[ 3 H]SKF 10,047 binding sites did not correlate with those for [ 3 H]spiperone (dopamine D 2 ) sites. [ 3 H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-[ 3 H]SKF 10,047. In the striatum, about half of the saturable [ 3 H]haloperidol binding was to [ 3 H]spiperone (D 2 ) sites and the other half was to sites similar to (+)-[ 3 H]SKF 10,047 binding sites. 15 references, 4 figures, 1 table

  13. 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.

  14. Ventral tegmental area GABA neurons and opiate motivation

    Science.gov (United States)

    Vargas-Perez, Hector; Mabey, Jennifer K.; Shin, Samuel I.; Steffensen, Scott C.; van der Kooy, Derek

    2013-01-01

    Rational Past research has demonstrated that when an animal changes from a previously drug-naive to an opiate-dependent and withdrawn state, morphine’s motivational effects are switched from a tegmental pedunculopontine nucleus (TPP)-dependent to a dopamine-dependent pathway. Interestingly, a corresponding change is observed in ventral tegmental area (VTA) GABAA receptors, which change from mediating hyperpolarization of VTA GABA neurons to mediating depolarization. Objectives The present study investigated whether pharmacological manipulation of VTA GABAA receptor activity could directly influence the mechanisms underlying opiate motivation. Results Using an unbiased place conditioning procedure, we demonstrated that in Wistar rats, intra-VTA administration of furosemide, a Cl− cotransporter inhibitor, was able to promote a switch in the mechanisms underlying morphine’s motivational properties, one which is normally observed only after chronic opiate exposure. This behavioral switch was prevented by intra-VTA administration of acetazolamide, an inhibitor of the bicarbonate ion-producing carbonic anhydrase enzyme. Electrophysiological recordings of mouse VTA showed that furosemide reduced the sensitivity of VTA GABA neurons to inhibition by the GABAA receptor agonist muscimol, instead increasing the firing rate of a significant subset of these GABA neurons. Conclusion Our results suggest that the carbonic anhydrase enzyme may constitute part of a common VTA GABA neuron-based biological pathway responsible for controlling the mechanisms underlying opiate motivation, supporting the hypothesis that VTA GABAA receptor hyperpolarization or depolarization is responsible for selecting TPP- or dopamine-dependent motivational outputs, respectively. PMID:23392354

  15. Neuroscience of opiates for addiction medicine: From stress-responsive systems to behavior.

    Science.gov (United States)

    Zhou, Yan; Leri, Francesco

    2016-01-01

    Opiate addiction, similarly to addiction to other psychoactive drugs, is chronic relapsing brain disease caused by drug-induced short-term and long-term neuroadaptations at the molecular, cellular, and behavioral levels. Preclinical research in laboratory animals has found important interactions between opiate exposure and stress-responsive systems. In this review, we will discuss the dysregulation of several stress-responsive systems in opiate addiction: vasopressin and its receptor system, endogenous opioid systems (including proopiomelanocortin/mu opioid receptor and dynorphin/kappa opioid receptor), orexin and its receptor system, and the hypothalamic-pituitary-adrenal axis. A more complete understanding of how opiates alter these stress systems, through further laboratory-based studies, is required to identify novel and effective pharmacological targets for the long-term treatment of heroin addiction. © 2016 Elsevier B.V. All rights reserved.

  16. Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly selective delta-opioid receptor agonist.

    Science.gov (United States)

    Improta, G; Broccardo, M

    1992-01-01

    Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.

  17. 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.

  18. Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors.

    Science.gov (United States)

    Cignarella, G; Barlocco, D; Tranquillini, M E; Volterra, A; Brunello, N; Racagni, G

    1988-05-01

    A series of 3,8-diazabicyclo (3.2.1) octanes (DBO) (1) substituted at the nitrogen atoms by acyl and aralkenyl groups, were tested in in vitro binding assays towards mu and delta opioid receptors. The most representative terms (1a, 1d, 1g, 1j,) were also evaluated for the analgesic potency in vivo by the hot plate method. Among the compounds tested the most potent was the p.nitrocinnamyl DBO (1d) which displayed a mu/delta selectivity and an analgesic activity respectively 25 and 17 fold those of morphine. On the contrary, the m.hydroxycinnamyl DBO (1g) was markedly less active as agonist than the parent 1a, thus suggesting that structure 1 interacts with opioid receptors in a different fashion than morphine. Compound 1j isomer of 1a which is provided with high mu affinity, but lower analgesic potency, was found to possess a mixed agonist-antagonist activity.

  19. 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

  20. 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.

  1. 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

  2. Role of T cell receptor delta gene in susceptibility to celiac disease.

    Science.gov (United States)

    Roschmann, E; Wienker, T F; Volk, B A

    1996-02-01

    There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

  3. Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

    Science.gov (United States)

    Chao, Dongman; Donnelly, David F; Feng, Yin; Bazzy-Asaad, Alia; Xia, Ying

    2007-02-01

    Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.

  4. 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

  5. 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...

  6. Electrocardiographic abnormalities in opiate addicts.

    Science.gov (United States)

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P seizures less often (16 versus 27%, P opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation with methadone and benzodiazepines.

  7. Delta-opioid receptor analgesia is independent of microglial activation in a rat model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Joanna Mika

    Full Text Available The analgesic effect of delta-opioid receptor (DOR ligands in neuropathic pain is not diminished in contrast to other opioid receptor ligands, which lose their effectiveness as analgesics. In this study, we examine whether this effect is related to nerve injury-induced microglial activation. We therefore investigated the influence of minocycline-induced inhibition of microglial activation on the analgesic effects of opioid receptor agonists: morphine, DAMGO, U50,488H, DPDPE, Deltorphin II and SNC80 after chronic constriction injury (CCI to the sciatic nerve in rats. Pre-emptive and repeated administration of minocycline (30 mg/kg, i.p. over 7 days significantly reduced allodynia and hyperalgesia as measured on day 7 after CCI. The antiallodynic and antihyperalgesic effects of intrathecally (i.t. administered morphine (10-20 µg, DAMGO (1-2 µg and U50,488H (25-50 µg were significantly potentiated in rats after minocycline, but no such changes were observed after DPDPE (10-20 µg, deltorphin II (1.5-15 µg and SNC80 (10-20 µg administration. Additionally, nerve injury-induced down-regulation of all types of opioid receptors in the spinal cord and dorsal root ganglia was not influenced by minocycline, which indicates that the effects of opioid ligands are dependent on other changes, presumably neuroimmune interactions. Our study of rat primary microglial cell culture using qRT-PCR, Western blotting and immunocytochemistry confirmed the presence of mu-opioid receptors (MOR and kappa-opioid receptors (KOR, further we provide the first evidence for the lack of DOR on microglial cells. In summary, DOR analgesia is different from analgesia induced by MOR and KOR receptors because it does not dependent on injury-induced microglial activation. DOR agonists appear to be the best candidates for new drugs to treat neuropathic pain.

  8. 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.

  9. Interrogative suggestibility in opiate users.

    Science.gov (United States)

    Murakami, A; Edelmann, R J; Davis, P E

    1996-09-01

    The present study investigated interrogative suggestibility in opiate users. A group of patients undergoing a methadone detoxification programme in an in-patient drug treatment unit (Detox group, n = 21), and a group of residents who had come off drugs and were no longer suffering from withdrawal syndrome (Rehab group, n = 19) were compared on interrogative suggestibility and various other psychological factors. Significant differences were found between the two groups, with the Detox group having more physical and psychological problems, and a higher total suggestibility score in comparison with the Rehab group. These findings are discussed in relation to the context of police interrogations and the reliability of confessions made by suspects and witnesses dependent on opiates.

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, Saoirse E [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Tarling, Elizabeth J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Bennett, Andrew J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Kendall, David A [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Randall, Michael D [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom)

    2005-11-25

    Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.

  12. INTERACTION BETWEEN DELTA OPIOID RECEPTORS AND BENZODIAZEPINES IN CO2- INDUCED RESPIRATORY RESPONSES IN MICE

    Science.gov (United States)

    Borkowski, Anne H.; Barnes, Dylan C.; Blanchette, Derek R.; Castellanos, F. Xavier; Klein, Donald F.; Wilson, Donald A.

    2011-01-01

    The false-suffocation hypothesis of panic disorder (Klein, 1993) suggested δ-opioid receptors as a possible source of the respiratory dysfunction manifested in panic attacks occurring in panic disorder (Preter and Klein, 2008). This study sought to determine if a lack of δ-opioid receptors in a mouse model affects respiratory response to elevated CO2, and whether the response is modulated by benzodiazepines, which are widely used to treat panic disorder. In a whole-body plethysmograph, respiratory responses to 5% CO2 were compared between δ-opioid receptor knockout mice and wild-type mice after saline, diazepam (1 mg/kg), and alprazolam (0.3 mg/kg) injection. The results show that lack of δ-opioid receptors does not affect normal response to elevated CO2, but does prevent benzodiazepines from modulating that response. Thus, in the presence of benzodiazepine agonists, respiratory responses to elevated CO2 were enhanced in δ-opioid receptor knockout mice compared to wild-type mice. This suggests an interplay between benzodiazepine receptors and δ-opioid receptors in regulating the respiratory effects of elevated CO2, which might be related to CO2 induced panic. PMID:21561601

  13. 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

  14. 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

  15. Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

    Science.gov (United States)

    2016-07-01

    treat, and current opioids (i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered...treat, and current opioids that act on mu opioid receptors such as morphine generate significant side effects including addiction . War-related...al., J Neurosci Methods, 1994), starting with 0.1 g and ending with 2.0 g filament as cutoff value. As shown in Figure 2, our preliminary experiments

  16. 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

  17. 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

    δ-subunit containing extrasynaptic GABA(A) receptors are potential targets for modifying neuronal activity in a range of brain disorders. With the aim of gaining more insight in synaptic and extrasynaptic inhibition, we used a new positive modulator, AA29504, of δ-subunit containing GABA(A) recep......δ-subunit containing extrasynaptic GABA(A) receptors are potential targets for modifying neuronal activity in a range of brain disorders. With the aim of gaining more insight in synaptic and extrasynaptic inhibition, we used a new positive modulator, AA29504, of δ-subunit containing GABA......(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......-free environment using Ca²⁺ imaging in cultured neurons, AA29504 showed GABA(A) receptor agonism in the absence of agonist. Finally, AA29504 exerted dose-dependent stress-reducing and anxiolytic effects in mice in vivo. We propose that AA29504 potentiates δ-containing GABA(A) receptors to enhance tonic inhibition...

  18. {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.

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

    African Journals Online (AJOL)

    Muhammad Zahid Khan

    2016-10-20

    Oct 20, 2016 ... GluD1 knockout mice (GluD1 KO) have normal learning in the Morris water maze .... could bind and activate the receptor.5,6 D-Ser and glycine have now been identified as .... English editing of this manuscript. References. 1.

  20. 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...

  1. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    Science.gov (United States)

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  2. Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

    Science.gov (United States)

    2017-07-01

    i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered most frequently by active...slides. The slides were then processed for fluorescent in situ hybridization with RNAscope technology (ACD Biosystems) to detect Oprd1 mRNA, as...tissue as done in Bardoni et al., Neuron, 2014) and negative controls (no probe). Controls indicated that the technology and reagents work as expected

  3. Sedatives for opiate withdrawal in newborn infants.

    Science.gov (United States)

    Osborn, David A; Jeffery, Heather E; Cole, Michael J

    2010-10-06

    Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings. Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. Each author assessed study quality and extracted data independently. Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group.One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure.In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study

  4. 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...

  5. Achalasia and chronic opiate use: innocent bystanders or associated conditions?

    Science.gov (United States)

    Ravi, K; Murray, J A; Geno, D M; Katzka, D A

    2016-01-01

    High-resolution manometry identifies three subtypes of achalasia. However, type 3 differs from classic achalasia. Although opiates affect esophageal motility, opiate use and achalasia have not been studied. Patients with a new diagnosis of achalasia at Mayo Clinic Rochester between June 1, 2012 and January 3, 2014 were identified. Clinical records were reviewed to assess symptoms, opiate use, and therapy. Fifty-six patients with achalasia were identified, 14 (25%) were on opiates. Opiate prescription was unrelated to achalasia in all cases, with chronic back and joint pain constituting the majority. Of patients on opiates, five (36%) had type 3 achalasia compared with four (10%) not on opiates (P = 0.02). No patients on opiates had type 1 achalasia. Clinical presentation did not differ with opiates, although those on opiates were more likely to report chest pain (39 vs. 14%, P = 0.05) and less likely to have esophageal dilation (62 vs. 82%, P = 0.13), none with greater than 5-cm diameter. Contractile vigor was greater with opiate use, with distal contractile integral of 7149 versus 2615.5 mmHg/cm/second (P = 0.08). Treatment response was inferior on opiates, with persistent symptoms in 22% compared with 3% without opiates (P = 0.06). Opiate use is common in type 3 achalasia, with the majority of patients on opiates. No patients on opiates were diagnosed with type 1 achalasia. Manometric findings of type 3 achalasia mimic those induced by opiates, suggesting a physiologic mechanism for opiate induced type 3 achalasia. Treatment outcome is inferior with opiates, with opiate cessation perhaps preferable. Further studies assessing opiate use and achalasia are needed. © 2014 International Society for Diseases of the Esophagus.

  6. 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

  7. Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by ligand-biased antagonism.

    Directory of Open Access Journals (Sweden)

    Laura Milan-Lobo

    Full Text Available Delta (DOR and mu opioid receptors (MOR can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED50 for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED50 had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment.

  8. 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.

  9. 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

    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...

  10. Pregabalin abuse among opiate addicted patients.

    Science.gov (United States)

    Grosshans, Martin; Lemenager, Tagrid; Vollmert, Christian; Kaemmerer, Nina; Schreiner, Rupert; Mutschler, Jochen; Wagner, Xenija; Kiefer, Falk; Hermann, Derik

    2013-12-01

    Pregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds. Urine specimens from 124 patients with opiate dependency syndrome and from 111 patients with other addiction disorders (alcohol, benzodiazepines, cannabis, amphetamines) were screened for pregabalin by means of a mass spectrometer analysis. We found 12.1 % of all urine specimens from patients with opiate addiction to be positive for pregabalin. None of the patients concerned had a medical indication for using pregabalin. In the control group, 2.7 % of the patients were tested positively for pregabalin, due to their taking it regularly for chronic pain or general anxiety. Our data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.

  11. 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.

  12. Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

    Science.gov (United States)

    Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

    2006-07-01

    The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of signaling molecules, in contributing to protection of cardiac myocytes from ischemic damage.

  13. 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.

  14. 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

  15. Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System.

    Science.gov (United States)

    Hauser, Kurt F; Knapp, Pamela E

    2017-01-01

    The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS) regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance) during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

  16. 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.

  17. 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

  18. 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).

  19. Autoradiographic analysis of mu1, mu2, and delta opioid binding in the central nervous system of C57BL/6BY and CXBK (opioid receptor-deficient) mice

    International Nuclear Information System (INIS)

    Moskowitz, A.S.

    1985-01-01

    In this study the authors used semi-quantitative in vitro autoradiography to compare the levels of binding to central mu 1 , mu 2 , and delta opioid sites in two strains of mice, C57BL/6BY and CXBK. The CXBK strain is known to be deficient in whole brain opioid binding sites and to be less sensitive than the C57 strain to the analgesic and locomotor stimulatory effects of opiates and opioids. Delta sites were visualized using [ 3 H][D-Ala 2 -D-Leu 5 ]-enkephalin (DADL) plus a low concentration of morphine, total mu sites (mu 1 and mu 2 ) were visualized using [ 3 H]dihydromorphine (DHM), and mu 2 sites were visualized using [ 3 H]DHM plus a low concentration of DADL. Binding to mu 1 sites was determined by subtracting mu 2 binding from total mu binding. The authors found that the two strains did not consistently differ in the levels of delta sites. The CXBK strain, however, either had less or the same amount of mu binding as the C57 strain in all areas studied. The CXBK strain was especially deficient in mu 1 binding, particularly in areas involved in pain processing. (Auth.)

  20. 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.

  1. 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...

  2. 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

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

    OpenAIRE

    Jovanović Tatjana; Lazarević Dušan; Nikolić Gordana

    2012-01-01

    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 opioi...

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

    International Nuclear Information System (INIS)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N.

    1991-01-01

    The binding of 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. 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 3 H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B max value) and apparent dissociation constant (K d value) values of 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 max value of 3 H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K d values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Endogenous Opiates and Behavior: 2006

    Science.gov (United States)

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 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 (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  10. Endogenous opiates and behavior: 2012.

    Science.gov (United States)

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 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 (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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

  12. 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.

  13. Opiate addiction - current trends and treatment options

    OpenAIRE

    Achal Bhatt; Aminder Gill

    2016-01-01

    Opioids are widely used drugs for treatment of pain and related disorders. Opiate addiction is a major public health concern in the United States causing significant increase in healthcare expenditure. They produce euphoria and sense of well-being which makes them addictive to some people. Used in higher doses they can lead to cardiac or respiratory compromise. They also impair cognition leading to impaired decision making. Opioids exert their effects by acting on three different types of re...

  14. 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.

  15. 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.

  16. Synthesis of N1'-([11C]methyl)naltrindole ([11C]MeMNTI): a radioligand for positron emission tomographic studies of delta opioid receptors

    International Nuclear Information System (INIS)

    Lever, J.R.; Dannals, R.F.; Kinter, C.M.; Mathews, W.B.

    1995-01-01

    A delta opioid receptor antagonist, Nl'-methylnaltrindole (MeNTI), has been labeled with carbon-11. The precursor for radiolabeling was prepared in 71% yield by benzylation of the phenolic moiety of naltrindole. Alkylation of the indole nitrogen using [ 11 C]iodomethane and aqueous tetra(n-butyl)ammonium hydroxide at 80 o C in dimethylformamide followed by hydrogenolysis (H 2 , 10% Pd-C) of the benzyl protecting group gave [ 11 C]MeNTI. The average (n = 10) time for radiosynthesis, HPLC purification and formulation was 24 min from end-of-bombardment. [ 11 C]MeNTI of high radiochemical purity was obtained at end-of-synthesis with an average specific activity of 2050 mCi/μmol and radiochemical yield, based on [ 11 C]iodomethane, of 6%. (Author)

  17. Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4

    NARCIS (Netherlands)

    Gascan, H.; Aversa, G. G.; Gauchat, J. F.; van Vlasselaer, P.; Roncarolo, M. G.; Yssel, H.; Kehry, M.; Spits, H.; de Vries, J. E.

    1992-01-01

    In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell

  18. Infusion of opiates into substantia nigra protects against maximal electroshock seizures in rats.

    Science.gov (United States)

    Garant, D S; Gale, K

    1985-07-01

    Microinfusion of morphine sulfate (50 nmol), [d-Ala2]-Met-enkephalin (35 nmol) or dynorphin A 1-13 (1 nmol) bilaterally into the substantia nigra significantly attenuated seizures induced by maximal electroshock in rats. This action was accompanied by stereotyped behavioral hyperactivity. These anticonvulsant and behavioral effects were antagonized by systemic naloxone administration; neither effect was observed after intranigral microinjection of dynorphin A 1-17 amide (1 nmol). These results are consistent with a mu opiate receptor-mediated inhibition of substantia nigra efferent neurons, and with the proposal that bilateral inhibition of nigral efferents attenuates seizure propagation. However, intranigral morphine failed to alter the severity of i.v. bicuculline seizures, indicating that opiate-mediated inhibition in substantia nigra is distinct from that produced by gamma-aminobutyric acid.

  19. Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

    Science.gov (United States)

    Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly As; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2013-09-01

    Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.

  20. Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides

    Science.gov (United States)

    2013-01-01

    Leu-enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-enkephalin. Findings from the present study further revealed that the hydrogen-bond donor properties of the fourth amide of Leu-enkephalin are not important for its biological activity on DOPr. Our results show that the systematic replacement of amide bonds by isosteric functions represents an efficient way to design and synthesize novel peptide analogues with enhanced stability. Our findings further suggest that such a strategy can also be useful to study the biological roles of amide bonds. PMID:23650868

  1. Opiate Drugs with Abuse Liability Hijack the Endogenous Opioid System to Disrupt Neuronal and Glial Maturation in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kurt F. Hauser

    2018-01-01

    Full Text Available The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.

  2. 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

  3. 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

    Telmisartan shows antihypertensive and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that telmisartan prevents adipogenesis in vitro and weight gain in vivo through activation of peroxisome proliferator-activated receptor (PPAR)-d...

  4. 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

  5. (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.

  6. Delta Dynamics

    DEFF Research Database (Denmark)

    Bendixen, Mette

    . The warming air temperature affects the soil temperature and permafrost thaws and destabilizes the material in the coastal zone. In Greenland, the warming temperature lowers the surface mass balance of the Greenland Ice Sheet and more material is transported to the coastal zone. The sea ice extent is thinning...... 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...... deltas are prograding, contrary to the global trend showing eroding Arctic coasts. Moreover, it is revealed that the increasing proglacial freshwater runoff, caused by a lowering of the surface mass balance of the Greenland Ice Sheet is the main determining agent in delta progradation. The final part...

  7. β-Endorphin via the Delta Opioid Receptor is a Major Factor in the Incubation of Cocaine Craving

    Science.gov (United States)

    Dikshtein, Yahav; Barnea, Royi; Kronfeld, Noam; Lax, Elad; Roth-Deri, Ilana; Friedman, Alexander; Gispan, Iris; Elharrar, Einat; Levy, Sarit; Ben-Tzion, Moshe; Yadid, Gal

    2013-01-01

    Cue-induced cocaine craving intensifies, or ‘incubates', during the first few weeks of abstinence and persists over extended periods of time. One important factor implicated in cocaine addiction is the endogenous opioid β-endorphin. In the present study, we examined the possible involvement of β-endorphin in the incubation of cocaine craving. Rats were trained to self-administer cocaine (0.75 mg/kg, 10 days, 6 h/day), followed by either a 1-day or a 30-day period of forced abstinence. Subsequent testing for cue-induced cocaine-seeking behavior (without cocaine reinforcement) was performed. Rats exposed to the drug-associated cue on day 1 of forced abstinence demonstrated minimal cue-induced cocaine-seeking behavior concurrently with a significant increase in β-endorphin release in the nucleus accumbens (NAc). Conversely, exposure to the cue on day 30 increased cocaine seeking, while β-endorphin levels remained unchanged. Intra-NAc infusion of an anti-β-endorphin antibody (4 μg) on day 1 increased cue-induced cocaine seeking, whereas infusion of a synthetic β-endorphin peptide (100 ng) on day 30 significantly decreased cue response. Both intra-NAc infusions of the δ opioid receptor antagonist naltrindole (1 μg) on day 1 and naltrindole together with β-endorphin on day 30 increased cue-induced cocaine-seeking behavior. Intra-NAc infusion of the μ opioid receptor antagonist CTAP (30 ng and 3 μg) had no behavioral effect. Altogether, these results demonstrate a novel role for β-endorphin and the δ opioid receptor in the development of the incubation of cocaine craving. PMID:23800967

  8. 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

  9. 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.

  10. Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Kvien Tore K

    2007-06-01

    Full Text Available Abstract Background The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Δ32 and rheumatoid arthritis (RA has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA, an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Δ32 polymorphism is associated with RA or JIA in Norwegian cohorts. Methods 853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Δ32 polymorphism. Results The CCR5Δ32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36 and 9.7% in JIA patients (OR = 0.85; P = 0.20. No decreased homozygosity was observed for CCR5Δ32, as previously suggested. Conclusion Our data do not support an association between the CCR5Δ32 allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5Δ32 in RA, albeit substantially weaker than the effect first reported.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Probes for narcotic receptor mediated phenomena 22. Pt.1: Synthesis and characterization of optically pure [{sup 3}H](+)-4-[({alpha}R)-{alpha}-((2S,5R)-4-propyl-2,5-dimethyl-1-pi perazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, [{sup 3}H]SNC 121, a novel high affinity and selective ligand for delta opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Calderon, S.N.; Bertha, C.M.; Rice, K.C. [National Inst. of Diabetes and Digestive and Kidney Diseases, Medicinal Chemistry Lab., Bethesda, MD (United States); Gutkind, J.S. [National Inst. of Dental Research, Bethesda, MD (United States); Heng Xu; Partilla, J.S.; Rothman, R.B. [National Inst. on Drug Abuse, Clinical Psychopharmacology Section, Baltimore, MD (United States)

    1996-09-01

    The synthesis of unlabelled and labelled SNC 121, a selective nonpeptide ligand for the delta opioid receptor is reported. [{sup 3}H]SNC 121 of specific activity of 26.8 Ci/mmol, was synthesized by catalytic tritiation of the optically pure precursor SNC 80. (author).

  16. Probes for narcotic receptor mediated phenomena 22. Pt.1: Synthesis and characterization of optically pure [3H](+)-4-[(αR)-α-((2S,5R)-4-propyl-2,5-dimethyl-1-pi perazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, [3H]SNC 121, a novel high affinity and selective ligand for delta opioid receptors

    International Nuclear Information System (INIS)

    Calderon, S.N.; Bertha, C.M.; Rice, K.C.; Gutkind, J.S.; Heng Xu; Partilla, J.S.; Rothman, R.B.

    1996-01-01

    The synthesis of unlabelled and labelled SNC 121, a selective nonpeptide ligand for the delta opioid receptor is reported. [ 3 H]SNC 121 of specific activity of 26.8 Ci/mmol, was synthesized by catalytic tritiation of the optically pure precursor SNC 80. (author)

  17. Elaboración de un modelo 3D del receptor Humano de NK1 a partir del receptor delta Opiode

    OpenAIRE

    Vílchez Cruz, Ángela

    2015-01-01

    La publicación de la primera estructura cristalográfica de resolución atómica de un miembro de la familia de los receptores acoplados a proteínas G (GPCR) como es la Rodopsina Bovina (Rho) (1)marcó el comienzo de los estudios sobre la relación entre la actividad biológica y la estructura de estas proteínas (1,2). Si bien se han llevado a cabo numerosos estudios de difracción de rayos X de las estructuras de GPCRs desde ese momento, dada la dificultad de cristalización de es...

  18. Peroxisome proliferator-activated receptor delta (PPARdelta) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis.

    Science.gov (United States)

    Pesant, Matthieu; Sueur, Stéphanie; Dutartre, Patrick; Tallandier, Mireille; Grimaldi, Paul A; Rochette, Luc; Connat, Jean-Louis

    2006-02-01

    Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied. We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we also showed that the selective PPARdelta agonist GW501516 protected cells from H(2)O(2)-induced cell death. The protective effect of GW501516 was due to an inhibition of H(2)O(2)-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARdelta that the protection induced by GW501516 was totally dependent on PPARdelta. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H(2)O(2)-triggered apoptosis, as evidenced by annexin-V labeling. Taken together, our results account for an important role of PPARdelta in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARdelta appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences.

  19. 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.

  20. Craving by imagery cue reactivity in opiate dependence following detoxification

    OpenAIRE

    Behera, Debakanta; Goswami, Utpal; Khastgir, Udayan; Kumar, Satindra

    2003-01-01

    Background: Frequent relapses in opioid addiction may be a result of abstinentemergent craving. Exposure to various stimuli associated with drug use (drug cues) may trigger craving as a conditioned response to ?drug cues?. Aims: The present study explored the effects of imagery cue exposure on psychophysiological mechanisms of craving, viz. autonomic arousal, in detoxified opiate addicts. Methodology: Opiate dependent subjects (N=38) following detoxification underwent imagery cue reactivity t...

  1. 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

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

    Science.gov (United States)

    Jovanović, Tatjana; Lazarević, Dusan; Nikolić, Gordana

    2012-04-01

    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. 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. 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. The opioid relapse behavior is associated with a

  3. Source-receptor relationships for PM2.5 during typical pollution episodes in the Pearl River Delta city cluster, China

    Science.gov (United States)

    Fan, Q.; Liu, Y.; Hong, Y.; Wang, X.; Chan, P.; Chen, X.; Lai, A.; Wang, M.; Chen, X.

    2017-12-01

    Located in the Southern China monsoon region, pollution days in Pearl River Delta (PRD) were classified into "Western type", "Central type" or "Eastern type", with a relative percentage of 67%, 24% and 9%, respectively. Using this classification system, three typical pollution events were selected for numerical simulations using the WRF-Chem model. The source sensitivity method for anthropogenic emissions of PM2.5 and its precursors was applied to identify the source-receptor relationships for PM2.5 among 9 cities in PRD. For "Western type" case, the PRD region was under control of a high-pressure system with easterly prevailing winds. The PM2.5 concentrations in the western PRD region were higher than those in the eastern region, with emissions from cities in the eastern PRD region having higher contributions. Within the PRD's urban cluster, PM2.5 in Huizhou, Dongguan and Shenzhen was mainly derived from local emissions, whereas the PM2.5 in the other cities was primarily derived from external transport. For "Eastern type" case, the PRD was influenced by Typhoon Soulik with westerly prevailing winds. Emissions from cities in the western PRD region had the highest impacts on the overall PM2.5 concentration. PM2.5 in Jiangmen and Foshan was primarily derived from local emissions. Regarding "Central type" case, the PRD region was under control of a uniform pressure field with low wind speed. PM2.5 concentrations of each city were primarily caused by local emissions. Overall, wind flows played a significant role in the transport and spatial distribution of PM2.5 across the PRD region. Ideally, local governments would be wise to establish joint prevention and control measures to reduce regional atmospheric pollution, especially for "Western type" pollution.

  4. ( 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.

  5. Effects of naloxone opiate blockade on the immunomodulation induced by exercise in rats.

    Science.gov (United States)

    Bouix, O; elMezouini, M; Orsetti, A

    1995-01-01

    The purpose of this study was to examine the possible involvement of the endogenous opiate system in the changes in immune competence induced by isolated exercise. Male untrained rats were subjected to a 2.5 hours swimming exercise bout. Animals were killed 15 min after the end of the exercise. The concentration of leukocytes, lymphocytes, monocytes and granulocytes and T4 (T-helper), T8 (T-suppressor/cytotoxic), interleukin-2 receptor (IL-2R) and transferrin receptor (TrfR) positive lymphocytes were determined both in peripheral blood and spleen by flow cytometric analysis. Exercise resulted in a significant decrease in 1) blood lymphocyte and splenic granulocyte number (p exercising rats induced a decrease in the concentration and proportion of T8 positive lymphocytes, thereby restoring a normal T4/T8 ratio both in peripheral blood and spleen. Naloxone had no effect in control animals. The concentration and proportion of IL-2R and TrfR positive lymphocytes were not affected by naloxone. The mechanisms of the immunomodulation induced by isolated intense exercise are unclear. These data suggest that endogenous opiates participate in the alteration of cell-mediated immunity associated with exercise by modulating the T8 (suppressor/cytotoxic)-cell activity.

  6. 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.

  7. Enhanced bioavailability of opiates after intratracheal administration

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. General, kappa, delta and mu opioid receptor antagonists mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: reciprocal and regional interactions.

    Science.gov (United States)

    Miner, Patricia; Shimonova, Lyudmila; Khaimov, Arthur; Borukhova, Yaffa; Ilyayeva, Ester; Ranaldi, Robert; Bodnar, Richard J

    2012-03-14

    Food intake is significantly increased following administration of agonists of GABA and opioid receptors into the nucleus accumbens shell (NACs) and ventral tegmental area (VTA). GABA-A or GABA-B receptor antagonist pretreatment within the VTA or NACs differentially affects mu-opioid agonist-induced feeding elicited from the same site. Correspondingly, general or selective opioid receptor antagonist pretreatment within the VTA or NACs differentially affects GABA agonist-induced feeding elicited from the same site. Regional interactions have been evaluated in feeding studies by administering antagonists in one site prior to agonist administration in a second site. Thus, opioid antagonist-opioid agonist and GABA antagonist-GABA agonist feeding interactions have been identified between the VTA and NACs. However, pretreatment with GABA-A or GABA-B receptor antagonists in the VTA failed to affect mu opioid agonist-induced feeding elicited from the NACs, and correspondingly, these antagonists administered in the NACs failed to affect mu opioid-induced feeding elicited from the VTA. To evaluate whether regional and reciprocal VTA and NACs feeding interactions occur for opioid receptor modulation of GABA agonist-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen microinjected into the NACs was dose-dependently blocked by pretreatment with general (naltrexone: NTX), mu (beta-funaltrexamine: BFNA), kappa (nor-binaltorphamine: NBNI) or delta (naltrindole: NTI) opioid antagonists in the VTA, and correspondingly, whether VTA baclofen-induced feeding was dose-dependently blocked by NACs pretreatment with NTX, BFNA, NBNI or NTI in rats. Bilateral pairs of cannulae aimed at the VTA and NACs were stereotaxically implanted in rats, and their food intakes were assessed following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NACs treatment. Baclofen

  13. Suboxone misuse along the opiate maintenance treatment pathway.

    Science.gov (United States)

    Furst, R Terry

    2013-01-01

    This study explores strategies that Suboxone misusers utilize while in drug treatment. Ethnographic interviews were conducted with 14 patients who had cycled in and out of Suboxone treatment. The objective of the study is to identify strategies implemented by patients who intermittently use opiates/opioids while in Suboxone treatment. Findings indicate that some patients serially stop and start treatment in a Harm Reduction setting in New York City. Many patients suggest that they manage their opiate/opioid dependency through a sequential use of Suboxone and heroin to avoid withdrawal and to continue their misuse of opiates/opioids. Results are discussed in conjunction with the difficulties inherent to substance abuse treatment and suggestions for improvement are offered.

  14. 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

  15. 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).

  16. The Neuropsychology of Amphetamine and Opiate Dependence: Implications for Treatment

    Science.gov (United States)

    Sahakian, Barbara J

    2013-01-01

    Chronic use of amphetamines and/or opiates has been associated with a wide range of cognitive deficits, involving domains of attention, inhibitory control, planning, decision-making, learning and memory. Although both amphetamine and opiate users show marked impairment in various aspects of cognitive function, the impairment profile is distinctly different according to the substance of abuse. In light of evidence showing that cognitive impairment in drug users has a negative impact on treatment engagement and efficacy, we review substance-specific deficits on executive and memory function, and discuss possibilities to address these during treatment intervention. PMID:17690986

  17. Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

    Science.gov (United States)

    Cone, Katherine; Lanpher, Janell; Kinens, Abigail; Richard, Philomena; Couture, Sarah; Brackin, Rebecca; Payne, Emily; Harrington, Kylee; Rice, Kenner C; Stevenson, Glenn W

    2018-05-01

    Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior. A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects. The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.

  18. Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

    Science.gov (United States)

    Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

    2009-09-01

    The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

  19. Changes in reward-induced brain activation in opiate addicts.

    Science.gov (United States)

    Martin-Soelch, C; Chevalley, A F; Künig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, K L

    2001-10-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

  20. Changes in reward-induced brain activation in opiate addicts

    NARCIS (Netherlands)

    Martin-Soelch, C; Chevalley, AF; Kunig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, KL

    2001-01-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with

  1. 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.

  2. [Hospital morbidity and mortality of acute opiate intoxication].

    Science.gov (United States)

    Larpin, R; Vincent, A; Perret, C

    1990-09-22

    The records of 188 consecutive patients admitted for acute opiate intoxication were analyzed retrospectively to evaluate the morbidity and mortality of opiates. The most frequently used of these drugs were heroin (127 cases) and methadone (41 cases). In 79 cases the opiate was associated with another psychodepressant, usually benzodiazepines, alcohol or barbiturates. Forty-seven percent of the patients were admitted in deep coma, with respiratory arrest in almost every case. The complications observed in 49 patients were: aspiration of gastric contents (n = 24), rhabdomyolysis (n = 22), often associated with myocarditis (n = 13), pulmonary edema (n = 16), convulsions (n = 10), left ventricular dysfunction (n = 5) and lesions of the peripheral nervous system (n = 4). All patients survived, except one who died of cardiac arrest before admission. It is concluded that acute opiate intoxication treated in hospital has an excellent prognosis for life provided no cardiac arrest occurs prior to admission. One quarter of the patients require prolonged stay in an intensive care unit because of complications. The other patients, even when deeply comatose on admission, spend less than 1 day in hospital owing to the specific antagonist available.

  3. 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.

  4. Enlarged cavum septum pellucidum as a neurodevelopmental marker in adolescent-onset opiate dependence.

    Directory of Open Access Journals (Sweden)

    Jaeuk Hwang

    Full Text Available Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP, a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.The overall length of the CSP and the prevalence of abnormal enlargement of the CSP were assessed and compared in 65 opiate-dependent subjects (41 adolescent-onset opiate users and 24 adult-onset opiate users and 67 healthy subjects.Opiate-dependent subjects showed a greater prevalence of abnormal CSP enlargement relative to healthy subjects (odds ratio [OR]=3.64, p=0.034. The overall CSP length of adolescent-onset opiate-dependent subjects was greater, as compared not only with healthy subjects (F₁,₁₀₄=11.03, p=0.001 but also with those who began opiate use during adulthood (F₁,₆₁=4.43, p=0.039.The current findings provide the first evidence that abnormal CSP enlargement, which reflects limbic system dysgenesis of neurodevelopmental origin, may be linked to later development of opiate dependence. In addition, a greater CSP length, which indicates more severe limbic abnormalities, appears to confer higher risk for earlier onset of opiate use.

  5. 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.

  6. Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

    Science.gov (United States)

    Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

    2017-06-01

    Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

  7. 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

  8. 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.

  9. [Reimbursement of opiate substitution drugs to militaries in 2007].

    Science.gov (United States)

    d'Argouges, F; Desjeux, G; Marsan, P; Thevenin-Garron, V

    2012-09-01

    The use of psychoactive drugs by militaries is not compatible with the analytical skills and self-control required by their jobs. Military physicians take this problem into consideration by organising systematic drugs screening in the French forces. However, for technical reasons, opiates are not concerned by this screening with the agreement of the people concerned. The estimated number of militaries who use an opiate substitute may be an approach of heroin consumption in the French forces. This study describes buprenorphine and methadone reimbursements made during 2007 by the national military healthcare centre to French militaries. Each French soldier is affiliated to a special health insurance. The national military healthcare centre has in its information system, all the data concerning drug reimbursement made to French military personnel. This is a retrospective study of buprenorphine and methadone reimbursements made during 2007 by the military healthcare centre, to militaries from the three sectors of the French forces, and from the gendarmerie and joint forces. Only one reimbursement of one of these two drugs during this period allowed the patient to be included in our study. Daily drug dose and treatment steadiness profile have been calculated according to the criteria of the French monitoring centre for drugs and drug addiction. The criteria of the National guidelines against frauds have been used to identify misuse of these drugs. Doctors' shopping behaviour has also been studied. Finally, the nature of the prescriber and the consumption of other drugs in combination with opiate substitute have been analysed. One hundred and eighty-one military consumers of opiate substitute drugs (167 men and 14 women) participated. This sample included people from the three sectors of the French forces as well as from the gendarmerie and from the joint forces. The average age of the consumers was 26.6 years (20-42 years). The average length of service was 6.1 years

  10. The opiate addiction test: a clinical evaluation of a quick test for physical dependence on opiate drugs.

    OpenAIRE

    Ghodse, H; Taylor, D R; Greaves, J L; Britten, A J; Lynch, D

    1995-01-01

    1. Mydriasis (pupil dilation) in response to conjunctivally applied naloxone hydrochloride has been demonstrated using an innovative electronic binocular pupillometer in 40 opiate dependent patients, on maintenance methadone treatment. 2. No pupillary response to naloxone was seen when an identical procedure was carried out in a control population of 12 healthy volunteers. 3. After a baseline measurement of pupil size, two drops of naloxone hydrochloride were instilled into the conjunctival s...

  11. Systemic morphine blocks the seizures induced by intracerebroventricular (i.c.v.) injections of opiates and opioid peptides.

    Science.gov (United States)

    Urca, G; Frenk, H

    1982-08-19

    Intracerebroventricular (i.c.v.) injections of the endorphins and of morphine in rats produce highly characteristic, naloxone sensitive, electrographic seizures. In contrast, systemic injections of morphine have been shown to exert a marked anticonvulsant effect. The present study demonstrates that systemic morphine pretreatment can prevent the occurrence of electrographic seizures injected by i.c.v. morphine, Leu-enkephalin and beta-endorphin and that the anti-epileptic effect of morphine can be reversed by naloxone. Male albino rats, previously prepared for chronic i.c.v. injections and EEG recordings, were pretreated with 0--100 mg/kg of intraperitoneal (i.p.) morphine. Thirty five minutes later morphine (520 nmol), Leu-enkephalin (80 nmol) or beta-endorphin (5 nmol) were injected i.c.v. Pretreatment with i.p. morphine blocked the occurrence of seizures induced by morphine and both endogenous opioids. Lower doses of systemic morphine (50 mg/kg) were necessary to block i.c.v. morphine seizures than the dose (100 mg/kg) necessary to block seizures induced by i.c.v. Leu-enkephalin and beta-endorphin. Naloxone (1 mg/kg) administered 25 min following 50 mg/kg of i.p. morphine and preceding the injections of i.c.v. morphine reversed the antiepileptic effect of systemic morphine. These results demonstrate the possible existence of two opiate sensitive systems, one with excitatory-epileptogenic effects and the other possessing inhibitory-antiepileptic properties. The possible relationship between these findings and the known heterogeneity of opiate receptors and opiate actions is discussed.

  12. 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) -Isoxazol...

  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. delta-vision

    Data.gov (United States)

    California Natural Resource Agency — Delta Vision is intended to identify a strategy for managing the Sacramento-San Joaquin Delta as a sustainable ecosystem that would continue to support environmental...

  15. 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.

  16. 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…

  17. Estimating the number of opiate users in amsterdam by capture-recapture: the importance of case definition

    NARCIS (Netherlands)

    Buster, M. C.; van Brussel, G. H.; van den Brink, W.

    2001-01-01

    One of the objectives of Amsterdam's methadone maintenance treatment is maximising its coverage among problematic opiate users. In order to evaluate what proportion is reached, the capture-recapture method is conducted to estimate the prevalence of problematic opiate use. Samples of opiate users in

  18. 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.

  19. Effective medical treatment of opiate addiction. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction.

    Science.gov (United States)

    1998-12-09

    To provide clinicians, patients, and the general public with a responsible assessment of the effective approaches to treat opiate dependence. A nonfederal, nonadvocate, 12-member panel representing the fields of psychology, psychiatry, behavioral medicine, family medicine, drug abuse, epidemiology, and the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 600. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in the areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of a third day. The conference was organized and supported by the Office of Medical Applications of Research, National Institutes of Health. The literature was searched through MEDLINE and other National Library of Medicine and online databases from January 1994 through September 1997 and an extensive bibliography of 941 references was provided to the panel and the conference audience. Experts prepared abstracts for their presentations as speakers at the conference with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its

  20. Binding of kappa- and sigma-opiates in rat brain

    International Nuclear Information System (INIS)

    Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

    1982-01-01

    Detailed displacements of [ 3 H]dihydromorphine by ketocyclazocine and SKF 10,047, [ 3 H]ethylketocyclazocine by SKF 10,047, and [ 3 H]SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of 3 H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of [ 3 H]dihydromorphine (KD . 3 nM), [ 3 H]ethylketocyclazocine (KD . 4 nM), [ 3 H]SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-[ 3 H]enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin

  1. Continuous subcutaneous infusion of opiates at end-of-life.

    Science.gov (United States)

    Anderson, Stacey L; Shreve, Scott T

    2004-06-01

    To review pertinent controlled trials using the continuous subcutaneous infusion of opioids (CSIO) at end-of-life and offer insight to pharmacists and clinicians into the appropriate use of this route of administration. A MEDLINE search for information regarding the subcutaneous administration of opioids in terminally ill patients (1975-December 2002) was conducted using the key words subcutaneous, narcotics, morphine, hydromorphone, fentanyl, pain, hospices, and palliative care. Additional references were located through review of bibliographies of the articles cited. Case reports and postsurgical studies were excluded. Searches were limited to English-language studies using humans. Experimental and observational studies were evaluated, using prospective trials as the evidence base for conclusions and including pertinent retrospective trials as they relate to the subcutaneous infusion of opioids at end-of-life. CSIO is effective and safe for use in terminal illness. Appropriate situations for consideration of CSIO are when difficulties arise in using the oral route, standard oral opiate therapy has failed adequate trials, the patient has limited intravenous access, adequate supervision of the CSIO is present, and CSIO will not unduly limit the functional activity of the patient. CSIO has a proven role in the management of pain at end-of-life. CSIO should not be considered the first route for administration of opiates, but does offer distinct advantages in the appropriate setting. CSIO continues to be a choice for end-of-life patients and is gradually becoming a standard practice in palliative medicine.

  2. Neuropsychological predictors of clinical outcome in opiate addiction.

    Science.gov (United States)

    Passetti, F; Clark, L; Mehta, M A; Joyce, E; King, M

    2008-04-01

    A growing literature supports a role for neurocognitive deficits such as impaired decision-making in the development and maintenance of addictive behaviour. On the basis of these findings, it has been suggested that measures of neurocognitive functioning may be applied to the task of predicting clinical outcome in drug addiction. This in turn may have relevance for differentiating treatment based on individual patient needs. To explore this hypothesis we obtained neurocognitive measures of planning, impulsivity and decision-making from 37 opiate dependent individuals within 6 weeks of starting a community drug treatment programme and we followed them up 3 months into the programme. Performance on two tests of decision-making, but not on tests of planning, motor inhibition, reflection impulsivity or delay discounting, was found to predict abstinence from illicit drugs at 3 months with high specificity and moderate sensitivity. In particular, two thirds of the participants performing normally on the Cambridge Gamble Task and the Iowa Gambling Task, but none of those impaired on both, were abstinent from illicit drugs at follow up. Other neuropsychological, psychiatric or psychosocial factors measured in this sample did not explain this finding. The results are discussed in terms of the brain circuitry involved and the potential implications for the planning of treatment services for opiate dependence.

  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(D)J recombinations

    Science.gov (United States)

    Baum, Thierry-Pascal; Hierle, Vivien; Pasqual, Nicolas; Bellahcene, Fatena; Chaume, Denys; Lefranc, Marie-Paule; Jouvin-Marche, Evelyne; Marche, Patrice Noël; Demongeot, Jacques

    2006-01-01

    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(D)J 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 . 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(D)J gene rearrangements and their applications in immune response analysis. PMID:16640788

  5. 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.

  6. In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    International Nuclear Information System (INIS)

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-01-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states

  7. Craving and drug reward: A comparison of celecoxib and ibuprofen in detoxifying opiate addicts

    Directory of Open Access Journals (Sweden)

    sara jafari

    2017-10-01

    Full Text Available OBJECTIVE: Craving for substance abuse is a usual and complicated problem in patients, with opioid addiction, who are in their opioid cessation process. Craving has been added as one of the diagnostic criteria of substance use disorders in DSM-5. AIM: The present trial was intended to compare effects of celecoxib versus ibuprofen in reducing pain and in decreasing the desire to use opiates in patients undergoing opiate detoxification. (n=32. PATIENTS AND METHOD: A total of 32 patients (both inpatients and outpatients, who were undergoing opiate detoxification procedure entered this 4 week study. Subjects who suffered pain due to opiate withdrawal were randomized into two groups; group one received celecoxib 200 milligrams once daily and group two received ibuprofen 400 milligrams four times per day.  Self-reported Desire for Drug Questionnaire (DDQ was utilized at baseline and at the end of the study to evaluate changes in opiate craving. RESULTS: After 4 weeks of treatment, with either ibuprofen or celecoxib, significant improvements in pain and craving were noted in each group. However no significant difference between the two groups was observed after 4 weeks of treatment with celecoxib and ibuprofen. CONCLUSION: The study noted that both celecoxib and ibuprofen, reduce craving in patients with opiate craving after 4 weeks of treatment without any significant difference between the two groups. The results suggest further study of celecoxib and other NSAIDs in the maintenance treatment of opiate craving.

  8. 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.

  9. Delta antibody radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Kselikova, M; Urbankova, J

    1985-11-15

    The principle and procedure are described of the radioimmunoassay of delta antibody (delta-Ab) using the ABBOTT ANTI-DELTA kit by Abbott Co. A description is given of the kit, the working procedure and the method of evaluation. The results are reported of the incidence of delta-Ab in sera of patients with viral hepatitis B, in haemophiliacs, carriers of the hepatitis B virus surface antigen (HBsAg) and blood donors. The presence was detected of delta-Ab in one HBsAg carrier. The necessity is emphasized of delta-Ab determinations in the blood of donors in view of the antibody transfer with blood and blood preparations.

  10. 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.

  11. 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”.

  12. Neuron-specific deletion of peroxisome proliferator-activated receptor delta (PPARδ in mice leads to increased susceptibility to diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Heidi E Kocalis

    Full Text Available Central nervous system (CNS lipid accumulation, inflammation and resistance to adipo-regulatory hormones, such as insulin and leptin, are implicated in the pathogenesis of diet-induced obesity (DIO. Peroxisome proliferator-activated receptors (PPAR α, δ, γ are nuclear transcription factors that act as environmental fatty acid sensors and regulate genes involved in lipid metabolism and inflammation in response to dietary and endogenous fatty acid ligands. All three PPAR isoforms are expressed in the CNS at different levels. Recent evidence suggests that activation of CNS PPARα and/or PPARγ may contribute to weight gain and obesity. PPARδ is the most abundant isoform in the CNS and is enriched in the hypothalamus, a region of the brain involved in energy homeostasis regulation. Because in peripheral tissues, expression of PPARδ increases lipid oxidative genes and opposes inflammation, we hypothesized that CNS PPARδ protects against the development of DIO. Indeed, genetic neuronal deletion using Nes-Cre loxP technology led to elevated fat mass and decreased lean mass on low-fat diet (LFD, accompanied by leptin resistance and hypothalamic inflammation. Impaired regulation of neuropeptide expression, as well as uncoupling protein 2, and abnormal responses to a metabolic challenge, such as fasting, also occur in the absence of neuronal PPARδ. Consistent with our hypothesis, KO mice gain significantly more fat mass on a high-fat diet (HFD, yet are surprisingly resistant to diet-induced elevations in CNS inflammation and lipid accumulation. We detected evidence of upregulation of PPARγ and target genes of both PPARα and PPARγ, as well as genes of fatty acid oxidation. Thus, our data reveal a previously underappreciated role for neuronal PPARδ in the regulation of body composition, feeding responses, and in the regulation of hypothalamic gene expression.

  13. Opioid receptor desensitization: mechanisms and its link to tolerance

    Directory of Open Access Journals (Sweden)

    Stéphane eAllouche

    2014-12-01

    Full Text Available Opioid receptors are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization and post-endocytic fate of the receptor.

  14. 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

    cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes...... 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...

  15. 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...

  16. Connectivity in river deltas

    Science.gov (United States)

    Passalacqua, P.; Hiatt, M. R.; Sendrowski, A.

    2016-12-01

    Deltas host approximately half a billion people and are rich in ecosystem diversity and economic resources. However, human-induced activities and climatic shifts are significantly impacting deltas around the world; anthropogenic disturbance, natural subsidence, and eustatic sea-level rise are major causes of threat to deltas and in many cases have compromised their safety and sustainability, putting at risk the people that live on them. In this presentation, I will introduce a framework called Delta Connectome for studying connectivity in river deltas based on different representations of a delta as a network. Here connectivity indicates both physical connectivity (how different portions of the system interact with each other) as well as conceptual (pathways of process coupling). I will explore several network representations and show how quantifying connectivity can advance our understanding of system functioning and can be used to inform coastal management and restoration. From connectivity considerations, the delta emerges as a leaky network that evolves over time and is characterized by continuous exchanges of fluxes of matter, energy, and information. I will discuss the implications of connectivity on delta functioning, land growth, and potential for nutrient removal.

  17. 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...

  18. The Relationship between Motivational Structure, Mental Health and Attitude to Opiate Substances in University Students

    Directory of Open Access Journals (Sweden)

    Ali akbar Soliemanian

    2012-02-01

    Full Text Available Introduction: This study was carried out with the aim of evaluating the relationship between motivational structure, mental health and attitude to opiate substances in a sample of North-Khorasan's university students. Method: In a descriptive cross-sectional study, 400 participants (200 males and 200 females were selected by stratified random sampling of three universities of north khorasan. All participants completed the SCL-90-R, Personal Concerns Inventory and Attitude to Opiate Substances questionnaire. Findings: The results revealed that there was a significant difference between participants with maladaptive motivational structure and adaptive motivational structure on GSI and subscales of SCL-90-R. In addition, the comparison of two groups showed that participants with maladaptive motivational structure had significant more positive attitude to opiate Substances than participants with adaptive motivational structure. Conclusion: There is a significant relationship between motivational structure, mental health and attitude to opiate substances.

  19. 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.

  20. Use of Opiates to Manage Pain in the Seriously and Terminally Ill Patient

    Science.gov (United States)

    ... and misconceptions about the use of opiates for pain management, among health care professionals as well as among ... class that are commonly used by experts in pain management are: Single drugs (used for control of moderate ...

  1. Implicit and Explicit Memory Bias in Opiate Dependent, Abstinent and Normal Individuals

    Directory of Open Access Journals (Sweden)

    Jafar Hasani

    2013-07-01

    Full Text Available Objective: The aim of current research was to assess implicit and explicit memory bias to drug related stimuli in opiate Dependent, abstinent and normal Individuals. Method: Three groups including opiate Dependent, abstinent and normal Individuals (n=25 were selected by available sampling method. After matching on the base of age, education level and type of substance use all participants assessed by recognition task (explicit memory bias and stem completion task (implicit memory bias. Results: The analysis of data showed that opiate dependent and abstinent groups in comparison with normal individual had implicit memory bias, whereas in explicit memory only opiate dependent individuals showed bias. Conclusion: The identification of explicit and implicit memory governing addiction may have practical implications in diagnosis, treatment and prevention of substance abuse.

  2. [{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.

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

    OpenAIRE

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

    2011-01-01

    Background 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. Methods 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 Questionnair...

  4. Comparison of buprenorphine and methadone effects on opiate self-administration in primates.

    Science.gov (United States)

    Mello, N K; Bree, M P; Mendelson, J H

    1983-05-01

    The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

  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. Preclinical Assessment of a Strategy to Minimize the Abuse Liability of Opiate Medications for Pain

    Science.gov (United States)

    2016-09-01

    plans (3). In fact, Bray and colleagues found that pain medication is the most highly abused of all prescribed drugs in the military (4). Prescription...the drug gamma-vinyl GABA (GVG) prior to morphine treatment effectively eliminates the highly addictive nature of this opiate . In these studies, we...widespread risk of opiate addiction in this population. Preclinical imaging studies aim to build a foundation for effective clinical drug development, and the

  7. 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.

  8. 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.

  9. Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users.

    Science.gov (United States)

    Ahn, Woo-Young; Vasilev, Georgi; Lee, Sung-Ha; Busemeyer, Jerome R; Kruschke, John K; Bechara, Antoine; Vassileva, Jasmin

    2014-01-01

    Substance dependent individuals (SDI) often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively "pure" amphetamine-dependent (N = 38) and heroin-dependent individuals (N = 43) who were currently in protracted abstinence, and in 48 healthy controls (HC). A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1) Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI), (2) PVL with delta learning rule (PVL-Delta), and (3) Value-Plus-Perseverance (VPP) model based on Win-Stay-Lose-Switch (WSLS) strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL) and a heuristic strategy of perseverance had the best post-hoc model fit, but the two PVL models showed better simulation and parameter recovery performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to HC across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing) and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to HC with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI) revealed increased reward sensitivity relative to HC. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users.

  10. Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users

    Directory of Open Access Journals (Sweden)

    Woo-Young eAhn

    2014-08-01

    Full Text Available Substance dependent individuals (SDI often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively pure amphetamine-dependent (N=38 and heroin-dependent individuals (N=43 who were currently in protracted abstinence, and in 48 healthy controls. A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1 Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI, (2 PVL with delta learning rule (PVL-Delta, and (3 Value-Plus-Perseverance (VPP models based on Win-Stay-Lose-Switch (WSLS strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL and a heuristic strategy of perseverance had the best post hoc model fit, but the two PVL models showed better simulation performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to healthy controls across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to healthy controls with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI revealed increased reward sensitivity relative to healthy controls. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users.

  11. The Niger Delta Crisis

    African Journals Online (AJOL)

    chifaou.amzat

    2013-09-28

    Sep 28, 2013 ... Department of History & International Studies, Delta State University, Abraka,. Nigeria. .... democracy implies popular power. That is ... Okonta (2006:5) draws attention to Anna Zalik's treatise called 'Petro-Vio- lence' and ...

  12. Delta agent (Hepatitis D)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  13. 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. DELTA...... 2.0 behandler mere generelle matematikdidaktiske problemstillinger såsom læringsteoretiske overvejelser i forbindelse med matematik, centrale aspekter af det at undervise i matematik og digitale teknologier som værktøj til at støtte elevers faglige læring af matematik....

  14. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Opiate modification of amygdaloid-kindled seizures in rats.

    Science.gov (United States)

    Stone, W S; Eggleton, C E; Berman, R F

    1982-05-01

    Male Long-Evans rats were stereotaxically implanted bilaterally with bipolar electrodes in the central amygdala. Rats were then kindled once daily for 1 sec until 3 consecutive Stage V [25] kindled seizures were elicited. On the following day, animals were injected (IP) with either saline, naloxone (10 mg/kg), naltrexone (10mg/kg) or morphine sulfate (10 mg/kg) and again stimulated at the kindling stimulation parameters. Saline injected animals continued to show long bilateral AD's and behaviors (i.e., forelimb clonus, rearing, falling) typical of Stage V kindled animals. In contrast, rats injected with naloxone or naltrexone showed reduced behavioral seizures. Potentiation of post-ictal spiking by morphine in amygdaloid-kindled rats was also observed supporting previous reports [7,21]. In a second experiment, the reduction of kindled seizure serverity by naloxone was systematically replicated. It is concluded that opiates can significantly modify amygdaloid-kindled seizures, and that brain endorphins may play a role in the development or maintenance of an amygdaloid-kindled seizure focus.

  16. Decision-making, somatic markers and emotion processing in opiate users.

    Science.gov (United States)

    Biernacki, Kathryn; Terrett, Gill; McLennan, Skye N; Labuschagne, Izelle; Morton, Phoebe; Rendell, Peter G

    2018-01-01

    Opiate use is associated with deficits in decision-making. A possible explanation for these deficits is provided by the somatic marker hypothesis, which suggests that substance users may experience abnormal emotional responses during decision-making involving reward and punishment. This in turn may interfere with the brief physiological arousal, i.e. somatic markers that normally occur in anticipation of risky decisions. To date, the applicability of the somatic marker hypothesis to explain decision-making deficits has not been investigated in opiate users. This study assessed whether decision-making deficits in opiate users were related to abnormal emotional responses and reduced somatic markers. Opiate users enrolled in an opiate substitute treatment program (n = 28) and healthy controls (n = 32) completed the Iowa Gambling Task (IGT) while their skin conductance responses (SCRs) were recorded. Participants' emotional responses to emotion-eliciting videos were also recorded using SCRs and subjective ratings. Opiate users displayed poorer decision-making on the IGT than did controls. However, there were no differences between the groups in SCRs; both groups displayed stronger SCRs following punishment than following reward, and both groups displayed stronger anticipatory SCRs prior to disadvantageous decisions than advantageous decisions. There were no group differences in objective or subjective measures of emotional responses to the videos. The results suggest that deficits in emotional responsiveness are not apparent in opiate users who are receiving pharmacological treatment. Thus, the somatic marker hypothesis does not provide a good explanation for the decision-making deficits in this group.

  17. The delta-opioid receptor agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists, in rats.

    Science.gov (United States)

    Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

    2008-02-01

    The nonpeptidic delta-opioid agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known whether cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine whether SNC80 produced cross-tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three-hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation but also augmented greatly amphetamine-stimulated locomotor activity in a dose-dependent manner. Pretreatments with other delta-opioid agonists, (+)BW373U86 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide] and oxymorphindole (17-methyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'-indolomorphinan), also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine (1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinanmine maleate salt), but not the direct dopamine receptor agonists SKF81297 [R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] and quinpirole [trans-(-)-(4alphaR)-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline

  18. 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.

  19. Women Opiate Users' Perception Toward MMT: A Qualitative Study in Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Zarei

    2016-09-01

    Full Text Available Background: Methadone maintenance therapy (MMT is an evidence-based approach for opiate addiction treatment. While its effectiveness in reducing opiate use has been evidently verified, unanswered questions with respect to the cultural scenarios for MMT programs remain unanswered. This study was conducted to explore understanding address MMT initiation among a women-recruited sample of persons who use Opiate. Methods: Qualitative in-depth interviews were used in purposeful and maximum variation sampling. All participants recruited for interview in 60-90 minutes were 17 women with opiate addiction experience from three MMT clinics in Sari capital city of Mazandaran, Iran. We applied a content analysis with a conventional approach for analyzing and finding addicted women perception towards MMT. Results: To answer the main concern of the research team about how Iranian Opiate- addicted women perceived the MMT. The results were categorized into six main themes including Service Providers’ Support, Stigma in Society, Fear of Rejection, Long waiting time, Family Support, and Methadone’ Side Effects. Conclusion: The results revealed that there are several perceived reasons beyond personal and psychological factors. The contextual experience acts as important cues that might encourage or deter drug users toward MMT.

  20. The specifics of opiate abuse in women as a basis of prevention programs and treatment

    Directory of Open Access Journals (Sweden)

    Raketić Diana

    2013-01-01

    Full Text Available The aim of this research is to determine the specifics of opiate addiction in women in our environment, so as to create a specific plan of action in preventing and treatment opiate addiction in women based on the conducted description and results analysis. The sample consists of 32 examinees. Sociodempgraphic questionnaire and widely applied ASI structured interview (McLellan, Cacciola, 1982 were used. The results are in accordance with foreign research. 62.5% of opiate addicted women live with someone who is a drug addict, either as a family member or a partner. 40.6% of the examinees were physically abused, 21.9% were sexually abused as well, and 43.7% were positive for HCV. Positive criminal status and doing illegal business were present in 56% of the examinees. 56.3% of the examinees reported depression, while 84.4% are anxious. 65.6% are unemployed. Research results indicate some significant specifics of opiate addiction in women, with regard to which valuable recommendations for prevention and treatment can be made in our environment. Prevention and treatment must be multidisciplinary with the emphasis on the preserved capacities and the development of positive behavior in opiate addicted women.

  1. Executive functions and risky decision-making in patients with opiate dependence.

    Science.gov (United States)

    Brand, Matthias; Roth-Bauer, Martina; Driessen, Martin; Markowitsch, Hans J

    2008-09-01

    Recent evidence suggests that individuals with opiate dependence may have cognitive dysfunctions particularly within the spectrum of executive functioning and emotional processing. Such dysfunctions can also compromise daily decisions associated with risk-taking behaviors. However, it remains unclear whether patients addicted to opiates show impaired decision-making on gambling tasks that specify explicit rules for rewards and punishments and provide information about probabilities associated with different long-term outcomes. In this study, we examined 18 individuals with opiate dependence and 18 healthy comparison subjects, matched for age, gender, and education with the Game of Dice Task (GDT). The GDT is a gambling task with explicit rules for gains and losses and fix winning probabilities. In addition, all subjects completed a neuropsychological test battery that primarily focused on executive functions and a personality questionnaire. On the GDT, patients chose the risky alternatives more frequently than the control group. Patients' GDT performance was related to executive functioning but not to other neuropsychological constructs, personality or dependence specific variables with one exception that is the number of days of abstinence. Thus, patients with opiate dependence demonstrate abnormalities in decision-making that might be neuropsychologically associated with dysfunctional behavior in patients' daily lives. Decision-making and other neuropsychological functioning should be considered in the treatment of opiate dependence.

  2. Clinical pharmacokinetics of non-opiate abused drugs.

    Science.gov (United States)

    Busto, U; Bendayan, R; Sellers, E M

    1989-01-01

    The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.

  3. 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.

  4. Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

    Science.gov (United States)

    da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

    1999-03-01

    To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

  5. 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.

  6. Opiate Users' Perceived Barriers Against Attending Methadone Maintenance Therapy: A Qualitative Study in China

    Science.gov (United States)

    Lin, Chunqing; Wu, Zunyou; Detels, Roger

    2012-01-01

    Methadone maintenance therapy (MMT) in China is facing challenges such as high relapse rates and low coverage. The study assessed factors influencing MMT utilization among opiate users. In-depth interviews were conducted among 30 opiate users in 2008 to ascertain the barriers against seeking MMT. Data were analyzed using ATLAS.ti. Barriers to the treatment included requirement of registration with police, perceived discrimination, logistic difficulties, side effects, fear of being addicted to another drug, lack of additional services, and economic burden. The result suggests the need for structural changes such as improving comprehensive services, simplifying application procedure, and enhancing referral system. The study's limitations are noted. PMID:21417558

  7. Post-radiation analgesia at rats and function of endogenous opiates

    International Nuclear Information System (INIS)

    Slivkova, E.; Smajda, B.; Paulikova, E.; Lackova, M.

    2002-01-01

    In this work post-radiation analgesia at rats as well as the function of endogenous opiates were tested. Males of rats were irradiated all-body dose 6 Gy. Hot-plate test was used. Dose of 8 mg of naloxone per kg of animal blocked perception of ache. This dose blocked analgetic effect of ionising radiation. Activity of phagocyte activity and phagocyte index were enhanced at rats which obtained naloxone. Authors stated that opiate system play a significant role at analgesia induced by radiation at rats and can modify response of immunity system on the stress

  8. Pheromones and pheromone receptors are required for proper sexual development in the homothallic ascomycete Sordaria macrospora.

    Science.gov (United States)

    Mayrhofer, Severine; Weber, Jan M; Pöggeler, Stefanie

    2006-03-01

    The homothallic, filamentous ascomycete Sordaria macrospora is self-fertile and produces sexual fruiting bodies (perithecia) without a mating partner. Even so, S. macrospora transcriptionally expresses two pheromone-precursor genes (ppg1 and ppg2) and two pheromone-receptor genes (pre1 and pre2). The proteins encoded by these genes are similar to alpha-factor-like and a-factor-like pheromones and to G-protein-coupled pheromone receptors of the yeast Saccharomyces cerevisiae. It has been suggested that in S. macrospora, PPG1/PRE2 and PPG2/PRE1 form two cognate pheromone-receptor pairs. To investigate their function, we deleted (delta) pheromone-precursor genes (delta ppg1, delta ppg2) and receptor genes (delta pre1, delta pre2) and generated single- as well as double-knockout strains. No effect on vegetative growth, fruiting-body, and ascospore development was seen in the single pheromone-mutant and receptor-mutant strains, respectively. However, double-knockout strains lacking any compatible pheromone-receptor pair (delta pre2/delta ppg2, delta pre1/delta ppg1) and the double-pheromone mutant (delta ppg1/delta ppg2) displayed a drastically reduced number of perithecia and sexual spores, whereas deletion of both receptor genes (delta pre1/delta pre2) completely eliminated fruiting-body and ascospore formation. The results suggest that pheromones and pheromone receptors are required for optimal sexual reproduction of the homothallic S. macrospora.

  9. Women of Niger Delta

    African Journals Online (AJOL)

    Religion Dept

    The Indispensability of Women in Conflict Resolution in the Niger Delta ... The situation leads to a shift in gender roles with a dramatic increase in the number of women .... organization is to work in partnership with the Nigerian Government and the .... that “women are the impartial arbitrators in family or clan disputes or.

  10. Conservative Delta Hedging

    Science.gov (United States)

    1997-09-01

    an exact method for converting such intervals into arbitrage based prices of financial derivatives or industrial or contractual options. We call this...procedure conservative delta hedging . As existing procedures are of an ad hoc nature, the proposed approach will permit an institution’s man agement a greater oversight of its exposure to risk.

  11. /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.

  12. Mystery of the delta(980)

    International Nuclear Information System (INIS)

    Cahn, R.N.; Landshoff, P.V.

    1986-01-01

    The apparent conflict between the dominance of the decay delta->etaπ in D->deltaπ and its absence in iota->deltaπ is analyzed. Explicit models are presented in which the nearby Kanti K threshold plays an important role in resolving the conflict. (orig.)

  13. 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

  14. 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

  15. Nonmedical Abuse of Benzodiazepines in Opiate-Dependent Patients in Tehran, Iran

    Science.gov (United States)

    Babakhanian, Masuade; Sadeghi, Maliheh; Mansoori, Nader; Alam Mehrjerdi, Zahra; Tabatabai, Mahmood

    2012-01-01

    Objective: The purpose of the present preliminary study was to explore the prevalence of nonmedical abuse of benzodiazepines in a group of opiate-dependent patients who were on methadone maintenance treatment (MMT) program in outpatient clinics in the south-west of Tehran, Iran. Methods: 114 male and female opiate-dependent clients who met DSM.IV-TR criteria for opiate dependence with mean age 36.5 years participated in the study from 16 clinics and completed a self-report questionnaire on demographics and substance use details. Then the participants were interviewed on the details of nonmedical abuse of benzodiazepines. Results: The study findings indicated that the current nonmedical abuse of benzodiazepines was commonly prevalent among participants. The most common current benzodiazepines abused were alprazolam (100%) followed by chlordiazepoxide (96.5%), clonazepam (94.7%), diazepam (86.8%), lorazepam (79.8%) and oxazepam (73.7%) respectively. Depression (77%) and anxiety (72.8%) were frequently reported as the most important reasons associated with consuming benzodiazepines followed by problem in anger control (44.7%), suicide thought (12.3%), self-injury (7.9%), and suicide commitment (5.3%) respectively. Conclusion: Nonmedical abuse of benzodiazepines is an important problem among opiate addicts which should be considered in treatment interventions during MMT program. PMID:24644471

  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. 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

    BACKGROUND: To evaluate if an opiate sparing multimodal regimen of dexamethasone, gabapentin, ibuprofen and paracetamol had better analgesic effect, less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery. METHODS: Open-label, prospective...

  18. 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

  19. 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 .

  20. 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.

  1. 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

  2. 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.

  3. The adhesion force of Notch with Delta and the rate of Notch signaling.

    Science.gov (United States)

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-12-20

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

  4. 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

  5. Molecular pharmacology of cell receptors for cardiac glycosides, opiates, ACTH and ion channel modulators

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, M R

    1986-01-01

    The influence of light and oxygen on molecular interactions between the artificial food dye, erythrosine (ERY), and (/sup 3/H)ouabain ((/sup 3/H)OUA) binding sites on (Na/sup +/ + K/sup +/)-ATPase in rat brain and guinea pig heart was investigated. Putative endogenous digitalis-like factors (DLF's) were studied in four in vitro assays for cardiac glycosides. (/sup 3/H)Etorphine binding was characterized in rat brain homogenates, depleted of opioids, from animals acutely and chronically treated with morphine and naloxone, and either unstressed or cold-restraint-stressed. Binding sites for the ion channel modulators (/sup 3/H)verapamil ((/sup 3/H)VER) and (/sup 3/H) phencyclidine ((/sup 3/H)PCP) were characterized in rat brain.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.

    Science.gov (United States)

    Byrnes, John J; Johnson, Nicole L; Carini, Lindsay M; Byrnes, Elizabeth M

    2013-05-01

    The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generations) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression within the nucleus accumbens. These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.

  11. 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

  12. People of the Delta

    Energy Technology Data Exchange (ETDEWEB)

    Gregoire, L.

    2007-09-15

    The potential impacts of both global warming and the $16 billion Mackenzie pipeline project on communities in the Mackenzie Delta were discussed. A consortium of oil and gas developers is now planning to exploit the natural gas reserves located near the mouth of the Delta, whose largest town is Inuvik. The project is expected to place a significant burden on the resources and infrastructure of the town, which currently has a population of 6000. The community, comprised of a diverse international population and an Inuit majority, is largely in favour of the pipeline project. The Inuvialuit people have invested a significant amount of time to ensure that the project, which was stalled due to land claims in 1977, benefits their communities. Public hearings are now being held to consider the potential environmental and socio-economic impacts of the project. Separate hearings are also being held to consider the project's design. The pipeline project includes 3 natural gas production facilities, a gas-processing facility, a pipeline gathering system, a 480 km natural gas liquids pipeline to the Northwest Territories, and a 1220 km natural gas pipeline to northern Alberta. The pipeline will be buried to minimize environmental impacts. The project is expected to create 8200 jobs at the height of its construction. However, communities located near the site of the natural gas reserves, such as the town of Tuktoyaktuk are now threatened by soil erosion that has been attributed to global warming. 21 figs.

  13. Peat compaction in deltas : implications for Holocene delta evolution

    NARCIS (Netherlands)

    van Asselen, S.

    2010-01-01

    Many deltas contain substantial amounts of peat, which is the most compressible soil type. Therefore, peat compaction potentially leads to high amounts of subsidence in deltas. The main objective of this research was to quantify subsidence due to peat compaction in Holocene fluvial-deltaic settings

  14. Implicit motive profile of treatment-seeking opiate users: high affiliation and low achievement.

    Science.gov (United States)

    Bársonya, Katalin; Martos, Tamás; Ehmann, Bea; Balázs, Hedvig; Demetrovics, Zsolt

    2013-01-01

    Research on basic human motives (achievement, affiliation, and power) encoded at the emotional level recently returned to the forefront of scientific research. To date, there are only a few studies on the pattern of implicit motives of substance users, so the present study examined opiate users participating in methadone maintenance treatment (N = 80) along these dimensions, comparing them to 40 non-substance users. Participants were asked to create stories on the basis of the pictures of the Thematic Apperception Test. The stories were analyzed using the content analysis method of David Winter (1991). Like other substance user groups, opiate-dependent persons used less achievement and more affiliation notions in creating stories, while there was no significant difference between the two groups concerning power notions. The results proved to be independent of the presence of anxiety and depression symptoms, despite substance users reporting higher levels of these, and suggest that motivational factors are worth considering in treatment planning.

  15. Septal co-infusions of glucose with the benzodiazepine agonist chlordiazepoxide impair memory, but co-infusions of glucose with the opiate morphine do not.

    Science.gov (United States)

    Krebs-Kraft, Desiree L; Parent, Marise B

    2010-03-30

    We have found repeatedly that medial septal (MS) infusions of glucose impair memory when co-infused with the gamma-amino butyric acid (GABA) agonist muscimol. The present experiments sought to determine whether the memory-impairing effects of this concentration of glucose would generalize to another GABA(A) receptor agonist and to an agonist from another neurotransmitter system that is known to impair memory. Specifically, we determined whether the dose of glucose that produces memory deficits when combined with muscimol in the MS would also impair memory when co-infused with the GABA(A) receptor modulator chlordiazepoxide (CDP) or the opiate morphine. Male Sprague-Dawley rats were given MS co-infusions and then 15 min later tested for spontaneous alternation or given shock avoidance training (retention tested 48 h later). The results showed that MS infusions of the higher dose of glucose with morphine did not produce memory deficits, whereas, the performance of rats given MS co-infusions of CDP with glucose was impaired. These findings suggest that the memory-impairing effects of brain glucose administration may involve an interaction with the GABA(A) receptor. (c) 2009 Elsevier Inc. All rights reserved.

  16. 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.

  17. Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

    Science.gov (United States)

    Ersche, Karen D; Clark, Luke; London, Mervyn; Robbins, Trevor W; Sahakian, Barbara J

    2007-01-01

    Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices. PMID:16160707

  18. 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.

  19. 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.

  20. 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

  1. [Opiate dependence type II or antisocial: Cloninger's Psychobiological Model and its usefullness in addictions].

    Science.gov (United States)

    Benito, Ana; Haro, Gonzalo; Orengo, Teresa; González, Marisa; Fornés, Teresa; Mateu, César

    2012-01-01

    The aim was to analyze the relationship between Cloninger's dimensions and Personality Disorders (PD) (with DSM-IV criteria) in opiate dependents. The study was Cross-sectional. The sampling of 196 patients with opiate dependence was consecutive. All were receiving treatment in an inpatient detoxification unit. Cloninger's Temperament and Character Inventory (TCI), International Personality Disorders Examination (IPDE) and a Substance Use Questionnaire were used. Character's dimensions as Self-directness and Cooperation were related with PD when scored low. Opposite to Cloninger descriptions, high scores of Self-transcendence were related with presence of PD. Related to temperamental dimensions, cluster A was related with low scores of Reward Dependence (RD) and cluster C with high scores of Harm Avoidance (HA). Otherwise, in cluster B, while Borderline PD had high scores of Novelty Seeking (as high HA), the Antisocial PD only were related to low scores of RD. RD dimension seems useful to differ from presence or absence of Antisocial PD, also when alcohol consumption is considered. Cloninger's Model of Personality is useful in drug dependents for the definition of the different PD, as well as for probable PD's aggregation. This model also helps to create subtypes in opiate dependents as the antisocial or type II.

  2. 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.

  3. NCK2 Is Significantly Associated with Opiates Addiction in African-Origin Men

    Directory of Open Access Journals (Sweden)

    Zhifa Liu

    2013-01-01

    Full Text Available Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs have led to discoveries of numerous genetic variants for complex diseases including substance dependence. Most of the GWAS discoveries were only based on single nucleotide polymorphisms (SNPs and a single dichotomized outcome. By employing both SNP- and gene-based methods of analysis, we identified a strong (odds ratio = 13.87 and significant (P value = 1.33E−11 association of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African-origin men. Codependence analysis also identified a genome-wide significant association between NCK2 and comorbidity of substance dependence (P value = 3.65E−08 in African-origin men. Furthermore, we observed that the association between the NCK2 gene (P value = 3.12E−10 and opiates addiction reached the gene-based genome-wide significant level. In summary, our findings provided the first evidence for the involvement of NCK2 in the susceptibility to opiates addiction and further revealed the racial and gender specificities of its impact.

  4. Challenges, Approaches and Experiences from Asian Deltas and the Rhine-Meuse Delta : Regional Training Workshop on Delta Planning and Management

    NARCIS (Netherlands)

    Wosten, J.H.M.; Douven, W.; Long Phi, H.; Fida Abdullah Khan, M.

    2013-01-01

    River delta's, like the Mekong Delta (Vietnam), Ganges-Brahmaputra Delta (Bangladesh), Ayeyarwady Delta (Myanmar), Nile (Egypt) and Ciliwung Delta (Indonesia) are developing rapidly and are characterised by large-scale urbanisation and industrialization processes. They are facing serious planning

  5. 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

  6. Delta isobars in neutron stars

    Directory of Open Access Journals (Sweden)

    Pagliara Giuseppe

    2015-01-01

    Full Text Available The appearance of delta isobars in beta-stable matter is regulated by the behavior of the symmetry energy at densities larger than saturation density. We show that by taking into account recent constraints on the density derivative of the symmetry energy and the theoretical and experimental results on the excitations of delta isobars in nuclei, delta isobars are necessary ingredients for the equations of state used for studying neutron stars. We analyze the effect of the appearance of deltas on the structure of neutron stars: as in the case of hyperons, matter containing delta is too soft for allowing the existence of 2M⊙ neutron stars. Quark stars on the other hand, could reach very massive configurations and they could form from a process of conversion of hadronic stars in which an initial seed of strangeness appears through hyperons.

  7. 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.

  8. 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.

  9. 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.

  10. The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis.

    Science.gov (United States)

    Marsch, L A

    1998-04-01

    To provide empirically based evaluation data regarding the efficacy of psychopharmacological interventions in opiate substance abuse, the present study employed meta-analytic statistical procedures to determine the effectiveness of methadone hydrochloride as a pharmacotherapeutic agent. Empirical research findings from 11 studies investigating the effect of methadone maintenance treatment (MMT) on illicit opiate use, and eight and 24 studies investigating the effect of MMT on HIV risk behaviors and criminal activities, respectively, by individuals in such treatment were addressed. Results demonstrate a consistent, statistically significant relationship between MMT and the reduction of illicit opiate use, HIV risk behaviors and drug and property-related criminal behaviors. The effectiveness of MMT is most apparent in its ability to reduce drug-related criminal behaviors. MMT had a moderate effect in reducing illicit opiate use and drug and property-related criminal behaviors, and a small to moderate effect in reducing HIV risk behaviors. Results clarify discrepancies in the literature and are useful in predicting the outcomes of individuals in treatment. The treatment's effectiveness is evident among opiate-dependent individuals across a variety of contexts, cultural and ethnic groups, and study designs.

  11. 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.

  12. 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

  13. Fast delta Hadamard transform

    International Nuclear Information System (INIS)

    Fenimore, E.E.; Weston, G.S.

    1981-01-01

    In many fields (e.g., spectroscopy, imaging spectroscopy, photoacoustic imaging, coded aperture imaging) binary bit patterns known as m sequences are used to encode (by multiplexing) a series of measurements in order to obtain a larger throughput. The observed measurements must be decoded to obtain the desired spectrum (or image in the case of coded aperture imaging). Decoding in the past has used a technique called the fast Hadamard transform (FHT) whose chief advantage is that it can reduce the computational effort from N 2 multiplies of N log 2 N additions or subtractions. However, the FHT has the disadvantage that it does not readily allow one to sample more finely than the number of bits used in the m sequence. This can limit the obtainable resolution and cause confusion near the sample boundaries (phasing errors). Both 1-D and 2-D methods (called fast delta Hadamard transforms, FDHT) have been developed which overcome both of the above limitations. Applications of the FDHT are discussed in the context of Hadamard spectroscopy and coded aperture imaging with uniformly redundant arrays. Special emphasis has been placed on how the FDHT can unite techniques used by both of these fields into the same mathematical basis

  14. Energy deposition by delta rays

    International Nuclear Information System (INIS)

    Weigand, F.C.; Braby, L.A.

    1983-01-01

    Monte Carlo calculations for proton tracks were extended to projectile with more complex electronic structures which add additional delta ray production processes. An experimental apparatus was used to detect gas gain and resolution for H 2+ and 3 He ++

  15. Niger Delta Development Commission and Sustainable ...

    African Journals Online (AJOL)

    Niger Delta Development Commission and Sustainable Development of Niger Delta Region of Nigeria: The Case of Rivers State. Goddey Wilson. Abstract. 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 ...

  16. The adhesion force of Notch with Delta and the rate of Notch signaling

    OpenAIRE

    Ahimou, Francois; Mok, Lee-Peng; Bardot, Boris; Wesley, Cedric

    2004-01-01

    Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of ...

  17. 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.

  18. 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.

  19. 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.

  20. 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.)

  1. Opiates in poppy seed: effect on urinalysis results after consumption of poppy seed cake-filling.

    Science.gov (United States)

    Pettitt, B C; Dyszel, S M; Hood, L V

    1987-07-01

    We report the analysis of poppy seed filling for morphine and codeine content. Concentrations in the range 17.4 to 18.6 micrograms/g (morphine) and 2.3 to 2.5 micrograms/g (codeine) were found in different lots of the filling, which is widely used in baking. The effect of consumption of poppy seed filling on opiate urinalysis results is discussed. Morphine concentrations as high as 4.5 mg/L are reported, with persistence of concentrations greater than 0.3 mg/L as long as 35 h after consumption.

  2. Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly.

    Science.gov (United States)

    LaBella, F S; Havlicek, V; Pinsky, C

    1979-01-12

    Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.

  3. Assessing Need for Medication-Assisted Treatment for Opiate-Dependent Prison Inmates

    Science.gov (United States)

    Albizu-García, Carmen E.; Caraballo, José Noel; Caraballo-Correa, Glorimar; Hernández-Viver, Adriana; Román-Badenas, Luis

    2012-01-01

    Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitute standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a needs assessment was conducted at the Department of Correction and Rehabilitation (DCR) of Puerto Rico (PR). We report on the research process, the findings that informed our recommendations for the PCR to expand MAT for eligible inmates, and lessons learned. PMID:22263714

  4. $\\delta$-Expansion at Finite Temperature

    OpenAIRE

    Ramos, Rudnei O.

    1996-01-01

    We apply the $\\delta$-expansion perturbation scheme to the $\\lambda \\phi^{4}$ self-interacting scalar field theory in 3+1 D at finite temperature. In the $\\delta$-expansion the interaction term is written as $\\lambda (\\phi^{2})^{ 1 + \\delta}$ and $\\delta$ is considered as the perturbation parameter. We compute within this perturbative approach the renormalized mass at finite temperature at a finite order in $\\delta$. The results are compared with the usual loop-expansion at finite temperature.

  5. Anaerobic Transformation of Furfural by Methanococcus deltae (Delta)LH

    Science.gov (United States)

    Belay, N.; Boopathy, R.; Voskuilen, G.

    1997-01-01

    Methanococcus deltae (Delta)LH was grown on H(inf2)-CO(inf2) in the presence of various concentrations of furfural. Furfural at higher concentrations, namely, 20 and 25 mM, inhibited growth of this organism. At concentration of 5 and 10 mM, no inhibition of growth was observed. The other methanogens in this study were not inhibited by 10 mM furfural. Among the methanogens tested, M. deltae was capable of transforming furfural, whereas Methanobacterium thermoautotrophicum Marburg, Methanosarcina barkeri 227, Methanococcus thermolithotrophicus, and Methanobrevibacter ruminantium lacked this capability. One hundred percent removal of furfural was observed within 48 h of incubation in M. deltae cultures. The end product observed during furfural metabolism was furfuryl alcohol. An almost stoichiometric amount of furfuryl alcohol was produced by M. deltae. This transformation is likely to be of value in the detoxification of furfural and in its ultimate conversion to methane and CO(inf2) by anaerobic digestion. PMID:16535618

  6. 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

  7. 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.

  8. 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.

  9. Effectiveness of Positive Psychotherapy in Improving Opiate Addicts’ Quality of Life

    Directory of Open Access Journals (Sweden)

    P Porzoor

    2016-02-01

    Full Text Available Objective: This study was aimed to assess the effectiveness of positive psychotherapy based on quality of life in improving opiate addicts’ quality of life. Method: A quasi experimental research design long with control group and pre-test, post-test and follow-up was employed for the conduct of this study. All the opiate addicts referring to treatment centers of Ardebil city in 2013 constituted the statistical population of the study and the number of 36 participants was selected as the sample via purposive sampling and randomly assigned into experimental and control groups. Quality-of-life-based psychotherapy was conducted on the experimental group in 8 sessions while the control group received no intervention. Quality of life questionnaire was used for data collection purposes. Results: The results suggested the effectiveness of the intervention in quality of life. Conclusion: This intervention, which is formed from the combination positive psychology and cognitive-behavioral approach, can be used as an effective treatment method.

  10. 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.

  11. 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

  12. 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...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  13. Four new Delta Scuti stars

    Science.gov (United States)

    Schutt, R. L.

    1991-01-01

    Four new Delta Scuti stars are reported. Power, modified into amplitude, spectra, and light curves are used to determine periodicities. A complete frequency analysis is not performed due to the lack of a sufficient time base in the data. These new variables help verify the many predictions that Delta Scuti stars probably exist in prolific numbers as small amplitude variables. Two of these stars, HR 4344 and HD 107513, are possibly Am stars. If so, they are among the minority of variable stars which are also Am stars.

  14. 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.

  15. Tunable detection sensitivity of opiates in urine via a label-free porous silicon competitive inhibition immunosensor.

    Science.gov (United States)

    Bonanno, Lisa M; Delouise, Lisa A

    2010-01-15

    Currently, there is need for laboratory-based high-throughput and reliable point-of-care drug screening methodologies. We demonstrate here a chip-based label-free porous silicon (PSi) photonic sensor for detecting opiates in urine. This technique provides a cost-effective alternative to conventional labeled drug screening immunoassays with potential for translation to multiplexed analysis. Important effects of surface chemistry and competitive binding assay protocol on the sensitivity of opiate detection are revealed. Capability to tune sensitivity and detection range over approximately 3 orders of magnitude (18.0 nM to 10.8 muM) was achieved by varying the applied urine specimen volume (100-5 muL), which results in systematic shifts in the competitive binding response curve. A detection range (0.36-4.02 muM) of morphine in urine (15 muL) was designed to span the current positive cutoff value (1.05 muM morphine) in medical opiate urine screening. Desirable high cross-reactivity to oxycodone, in addition to other common opiates, morphine, morphine-3-glucuronide, 6-acetyl morphine, demonstrates an advantage over current commercial screening assays, while low interference with cocaine metabolite was maintained. This study uniquely displays PSi sensor technology as an inexpensive, rapid, and reliable drug screening technology. Furthermore, the versatile surface chemistry developed can be implemented on a range of solid-supported sensors to conduct competitive inhibition assays.

  16. 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 increase (p intelligence measures were not changed significantly, their short-term 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.

  17. 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.

  18. 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

  19. The possible role of opiates in women with chronic urinary retention: observations from a prospective clinical study.

    Science.gov (United States)

    Panicker, Jalesh N; Game, Xavier; Khan, Shahid; Kessler, Thomas M; Gonzales, Gwen; Elneil, Sohier; Fowler, Clare J

    2012-08-01

    Urinary retention in women often presents a diagnostic difficulty, and the etiology may remain unidentified even after excluding structural and neurological causes. We evaluated a group of women referred to a specialist center with unexplained urinary retention. A total of 61 consecutive women with complete urinary retention were evaluated. Urological and neurological investigations locally had failed to identify a cause. Urethral pressure profile, sphincter volume measurement and in some cases urethral sphincter electromyography were performed to diagnose a primary disorder of sphincter relaxation (Fowler's syndrome). Mean patient age was 39 years (range 18 to 88). Following investigations, a probable etiology was identified in 25 (41%) women, the most common being Fowler's syndrome. Of the women 24 (39%) were being treated with opiates for various pain syndromes and in 13 no other cause of retention was identified. Opiates could be discontinued in only 2 patients, and both demonstrated improved sensations and voiding. The cause of urinary retention may remain unknown in spite of extensive investigations. Young women regularly using prescription opiates for various undiagnosed pain syndromes present a challenging clinical problem and this study suggests that iatrogenic causes should be considered if voiding difficulties emerge. An association between opiate use and constipation is well-known and, although urinary retention is a listed adverse event, it appears to be often overlooked in clinical practice. It is hypothesized that Fowler's syndrome is due to an up-regulation of spinal cord enkephalins and that exogenous opiates may compound any functional abnormalities predisposing young women to urinary retention. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. Hydrological and Climatic Significance of Martian Deltas

    Science.gov (United States)

    Di Achille, G.; Vaz, D. A.

    2017-10-01

    We a) review the geomorphology, sedimentology, and mineralogy of the martian deltas record and b) present the results of a quantitative study of the hydrology and sedimentology of martian deltas using modified version of terrestrial model Sedflux.

  2. Adaptive delta management : Roots and branches

    NARCIS (Netherlands)

    Timmermans, J.S.; Haasnoot, M.; Hermans, L.M.; Kwakkel, J.H.; Rutten, M.M.; Thissen, W.A.H.

    2015-01-01

    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,

  3. Adaptive Delta Management : Roots and Branches

    NARCIS (Netherlands)

    Timmermans, Jos; Haasnoot, Marjolijn; Hermans, Leon; Kwakkel, Jan H.; Rutten, Maarten; Thissen, Wil A.H.; Mynett, Arthur

    2015-01-01

    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,

  4. 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....

  5. The geographic spread of the CCR5 Delta32 HIV-resistance allele.

    Directory of Open Access Journals (Sweden)

    John Novembre

    2005-11-01

    Full Text Available The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10% for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation. When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

  6. 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.

  7. 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

  8. about the Dirac Delta Function(?)

    Indian Academy of Sciences (India)

    V Balakrishnan is in the. Department of ... and sweet as befits this impatient age. It said (in its en- ... to get down to real work by shutting down the system and reverting to ... the Dirac delta function" - but do note the all-important question mark in ...

  9. Rapid qualitative and quantitative analysis of opiates in extract of poppy head via FTIR and chemometrics: towards in-field sensors.

    Science.gov (United States)

    Turner, Nicholas W; Cauchi, Michael; Piletska, Elena V; Preston, Christopher; Piletsky, Sergey A

    2009-07-15

    Identification and quantification of the opiates morphine and thebaine has been achieved in three commercial poppy cultivars using FTIR-ATR spectroscopy, from a simple and rapid methanolic extraction, suitable for field analysis. The limits of detection were 0.13 mg/ml (0.013%, w/v) and 0.3 mg/ml (0.03%, w/v) respectively. The concentrations of opiates present were verified with HPLC-MS. The chemometrics has been used to identify specific "signature" peaks in the poppy IR spectra for characterisation of cultivar by its unique fingerprint offering a potential forensic application in opiate crop analysis.

  10. 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

  11. An analytical framework for strategic delta planning

    NARCIS (Netherlands)

    Seijger, C.; Douven, W.; Halsema, van G.; Hermans, L.; Evers, J.; Phi, H.L.; Khan, M.F.; Brunner, J.; Pols, L.; Ligtvoet, W.; Koole, S.; Slager, K.; Vermoolen, M.S.; Hasan, S.; Thi Minh Hoang, Vo

    2017-01-01

    Sectoral planning on water, agriculture and urban development has not been able to prevent increased flood risks and environmental degradation in many deltas. Governments conceive strategic delta planning as a promising planning approach and develop strategic delta plans. Such plans are linked to

  12. 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...

  13. Cocaine and opiates use in pregnancy: detection of drugs in neonatal meconium and urine.

    Science.gov (United States)

    López, P; Bermejo, A M; Tabernero, M J; Cabarcos, P; Alvarez, I; Fernández, P

    2009-09-01

    In this study, the case of a newborn with symptoms of hyperexcitability was analyzed. After it was confirmed in the hospital that the mother had consumed drugs during pregnancy using an enzyme multiplied immunoassay technique, samples of the newborn's urine and meconium were sent to our laboratory to observe the evolution in the distribution of cocaine and opiates during the days following birth. For urine analysis, screening was done with an immunoassay technique, and the confirmation was done by gas chromatography-mass spectrometry (GC-MS) according to a published method. A GC-MS method for simultaneous analysis of cocaine, benzoylecgonine, codeine, morphine, and 6-acetylmorphine in meconium is described. GC-MS confirmation of urine and meconium results showed consumption of cocaine and codeine during pregnancy and also showed the levels of drugs gradually declined, totally disappearing by the third day.

  14. Cause and motivation in cases of non-fatal drug overdoses in opiate addicts.

    Science.gov (United States)

    Pfab, R; Eyer, F; Jetzinger, E; Zilker, Thomas

    2006-01-01

    Drug overdose (OD) is a frequent incident among opiate addicts. Survivors of ODs are at risk for additional and eventually fatal ODs. ODs may be classified as accidental (aOD) or deliberate (dOD). Investigations into the connection between OD and suicide attempts have led to insconsistent results. (1) to determine how many non-fatal ODs were dODs and how many were aODs; (2) to determine how many cases of dODs were motivated by explicit or by ambivalent suicidal intentions; (3) to determine how many cases of aODs had causes that might respond to preventative measures; (4) to compare the addiction histories of dODs and aODs; (5) to compare the drugs causing the ODs; and (6) to compare the severity of the ODs in both groups. Prospective study utilizing a standardized questionnaire to evaluate opiate-addicted patients admitted to our treatment unit for OD. All cases underwent standardized drug testing to identify drug use patterns. Seventy-four cases of OD underwent standardized interviews after awakening. Forty-three percent of the cases were dOD. Cases of dOD had significantly more OA in substitution programs, more previous ODs, and more often consumed methadone and cocaine. Among dODs, 22.5% had suicidal intention and 9.6% were ambivalent about committing suicide; background motivations were most often conflicts with spouses. Fifty-seven percent of the cases were aOD. Cases of aODs had significantly more potential lethal intoxications and had heroin detected more frequently. aODs happened with unexpected pure heroin (46%), in combination with alcohol (36%), as relapse after abstinence (40%) or after institutionalized treatment (19%). This group should be accessible for targeted education.

  15. Social learning and peer education in responding to opiate overdose among injection drug users in Ukraine

    Directory of Open Access Journals (Sweden)

    Anna Tokar

    2014-06-01

    Full Text Available BACKGROUND: Opiate overdoses (OD constitute one of the leading causes of avoidable deaths among people aged 20-40 years old. As peer-administered help in cases of overdose was found to be effective, we aimed to explore how much the subjects of the intervention are able to learn from one another and from their own experience. METHODS: Secondary data analysis was performed with the 2008 dataset of peer-driven intervention among IDUs who were not involved in harm reduction programs earlier; recruiting was performed with respondent driven sampling methodology combined with peer education covering overdose response. Subsample of 6667 opiate users was considered. Data on overdose response strategies experienced by respondents were considered predictors and data on intended response strategies as outcomes. To reveal relationships between the experienced and intended responses, binary logistic regression analysis was performed. RESULTS: With recommended strategies including calling ambulance, putting a person in recovery position, fixing the tongue, applying mouth-to-mouth resuscitation and cardiac massage, percentages of those planning to apply them was considerably higher (on average, 2.3 times higher than the percentage of those having experienced them. With other strategies including applying cold, pain, ammonia, percentages of those who experienced the strategy and those who planned to practice it were rather close and on average differed just by 1.1. With all the strategies, the intention to apply a particular response in future was strongly associated with personal experience of having had this applied when having an overdose episode. Peer-education to larger extent determines the intentions of those who have not experienced particular overdose responses themselves. On the other hand, social learning contributes to persisting of those experienced strategies which cannot be recommended. CONCLUSIONS: Social learning can impact intended overdose

  16. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine

    OpenAIRE

    Xia, Yan; Portugal, George S.; Fakira, Amanda K.; Melyan, Zara; Neve, Rachael; Lee, H. Thomas; Russo, Scott J.; Liu, Jie; Morón, Jose A.

    2011-01-01

    Glutamatergic systems, including α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic...

  17. Future Change to Tide-Influenced Deltas

    Science.gov (United States)

    Nienhuis, Jaap H.; Hoitink, A. J. F. (Ton); Törnqvist, Torbjörn E.

    2018-04-01

    Tides tend to widen deltaic channels and shape delta morphology. Here we present a predictive approach to assess a priori the effect of fluvial discharge and tides on deltaic channels. We show that downstream channel widening can be quantified by the ratio of the tide-driven discharge and the fluvial discharge, along with a second metric representing flow velocities. A test of our new theory on a selection of 72 deltas globally shows good correspondence to a wide range of environments, including wave-dominated deltas, river-dominated deltas, and alluvial estuaries. By quantitatively relating tides and fluvial discharge to delta morphology, we offer a first-order prediction of deltaic change that may be expected from altered delta hydrology. For example, we expect that reduced fluvial discharge in response to dam construction will lead to increased tidal intrusion followed by enhanced tide-driven sediment import into deltas, with implications for navigation and other human needs.

  18. 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).

  19. Deformation characteristics of {delta} phase in the delta-processed Inconel 718 alloy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H.Y., E-mail: haiyanzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, S.H., E-mail: shzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Cheng, M. [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Z.X. [Beijing Institute of Aeronautica1 Materials, Beijing 100095 (China)

    2010-01-15

    The hot working characteristics of {delta} phase in the delta-processed Inconel 718 alloy during isothermal compression deformation at temperature of 950 deg. C and strain rate of 0.005 s{sup -1}, were studied by using optical microscope, scanning electron microscope and quantitative X-ray diffraction technique. The results showed that the dissolution of plate-like {delta} phase and the precipitation of spherical {delta} phase particles coexisted during the deformation, and the content of {delta} phase decreased from 7.05 wt.% to 5.14 wt.%. As a result of deformation breakage and dissolution breakage, the plate-like {delta} phase was spheroidized and transferred to spherical {delta} phase particles. In the center with largest strain, the plate-like {delta} phase disappeared and spherical {delta} phase appeared in the interior of grains and grain boundaries.

  20. 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

  1. 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

  2. Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry

    Science.gov (United States)

    Manicke, Nicholas E.; Belford, Michael

    2015-05-01

    One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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 (pprice elasticity=0.00, p>0.10). Opium consumption (βˆ1=0.47 to 0.49, pprice (βˆ2=-0.34 to -0.35, pprice and wage income responsiveness (inelasticity) consistent with an addictive substance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. 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

  9. 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

  10. COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Tina; Ke, Ying; Ly, Kevin [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand); McDonald, Fiona J., E-mail: fiona.mcdonald@otago.ac.nz [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand)

    2011-08-05

    Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

  11. 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.

  12. 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.

  13. Penelope Delta, recently discovered writer

    OpenAIRE

    MALAPANI A.

    2015-01-01

    The aim of this article is to present a Greek writer, Penelope Delta. This writer has recently come up in the field of the studies of the Greek literature and, although thereare neither many translations of her works in foreign languages nor many theses or dissertations, she was chosen for the great interest for her works. Her books have been read by many generations, so she is considered a classical writer of Modern Greek Literature. The way she uses the Greek language, the unique characters...

  14. 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

  15. From Natural to Design River Deltas

    Science.gov (United States)

    Giosan, Liviu

    2016-04-01

    Productive and biologically diverse, deltaic lowlands attracted humans since prehistory and may have spurred the emergence of the first urban civilizations. Deltas continued to be an important nexus for economic development across the world and are currently home for over half a billion people. But recently, under the double whammy of sea level rise and inland sediment capture behind dams, they have become the most threatened coastal landscape. Here I will address several deceptively simple questions to sketch some unexpected answers using example deltas from across the world from the Arctic to the Tropics, from the Danube to the Indus, Mississippi to Godavari and Krishna, Mackenzie to Yukon. What is a river delta? What is natural and what is not in a river delta? Are the geological and human histories of a delta important for its current management? Is maintaining a delta the same to building a new one? Can we design better deltas than Nature? These answers help us see clearly that survival of deltas in the next century depends on human intervention and is neither assured nor simple to address or universally applicable. Empirical observations on the hydrology, geology, biology and biochemistry of deltas are significantly lagging behind modeling capabilities endangering the applicability of numerical-based reconstruction solutions and need to be ramped up significantly and rapidly across the world.

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

    Science.gov (United States)

    Dijkstra, Boukje A G; Krabbe, Paul F M; Riezebos, Truus G M; van der Staak, Cees P F; De Jong, Cor A J

    2007-01-01

    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. The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addiction treatment centers during rapid detoxification with or without general anesthesia. Examination of the psychometric properties of the SOWS included exploratory factor analysis, internal consistency, test-retest reliability, and criterion validity. Exploratory factor analysis of the SOWS revealed a general pattern of four factors with three items not always clustered in the same factors at different points of measurement. After excluding these items from factor analysis four factors were identified during detoxification (temperature dysregulation, tractus locomotorius, tractus gastro-intestinalis and facial disinhibition). The 13-item SOWS shows high internal consistency and test-retest reliability and good validity at different stages of withdrawal. The 13-item SOWS is a reliable and valid instrument to assess opioid withdrawal during rapid detoxification. Three items were deleted because their content does not correspond directly with opioid withdrawal symptoms. Copyright (c) 2007 S. Karger AG, Basel.

  17. 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.

  18. Skin conductance at baseline and postheel lance reflects sympathetic activation in neonatal opiate withdrawal.

    Science.gov (United States)

    Oji-Mmuo, Christiana N; Michael, Eric J; McLatchy, Jacqueline; Lewis, Mary M; Becker, Julie E; Doheny, Kim Kopenhaver

    2016-03-01

    Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). Fourteen term (mean, SE: 38.8 ± 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/seconds and mean of peaks) was measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). Nonparametric tests were used to determine group differences, phase differences from baseline to HLS and HLS to recovery, and associations between MFNSS and SC measures. Neonates that would later require morphine treatment for NAS (n = 6) had higher baseline SC mean of peaks than those that did not require treatment (n = 8) (p < 0.05). Moreover, there were unique phase differences between groups and SC positively correlated with MFNSS (p < 0.05). SC provides early identification of NAS severity. However, a larger sample is needed to determine sensitivity and specificity of SC for early identification of NAS and treatment effectiveness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. [Opiate addiction in gravidity - consequences for the newborn. Results of an interdisciplinary treatment concept].

    Science.gov (United States)

    Rohrmeister, K; Bernert, G; Langer, M; Fischer, G; Weninger, M; Pollak, A

    2001-01-01

    To evaluate the outcome of infants of drug dependent mothers (IDM) after establishing an interdisciplinary attention concept at the University Hospital in Vienna. To compare the influence of different maintenance agents on neonatal morbidity. All newborns of opiate dependent mothers were prospectively included from III 1995 to IX 1999. The following data were collected: maintenance agent (methadone, slow release morphine, buprenorphine), infectious status, demographic data, congenital malformations, perinatal complications, as well as incidence and duration of the neonatal abstinence syndrome (NAS). Medical treatment with phenobarbital (1995 - 96) or morphine hydrochloride (MoHCl) (1997 - 99), respectively, was indicated when Finnegan score exceeded 10. 88 neonates (38 females/50 males) with a median gestational age of 39 weeks were included, 18 (20.5 %) were born prematurely. The median birthweight was 2905 g, 24 (27.3 %) infants were small for date (methadone group 76 %, in the morphine group 93 %, but in the buprenorphine group 19 % only (p methadone and morphine exposure (8.3 d versus 15 d and 16.5 d respectively). In neonates treated with phenobarbital duration of NAS was 17.6 d, whereas NAS in infants with MoHCl therapy lasted 12.8 d (p methadone and morphine exposure. Withdrawal time under morphin-hydrochloride therapy was reduced by one third compared to treatment with phenobarbital.

  20. [Quality of life among people addicted to psychoactive substances participating in the opiate substitution treatment].

    Science.gov (United States)

    Kotwas, Artur; Karakiewicz, Beata; Sein Anand, Jacek

    2014-01-01

    Opiate addiction remains a major threat to public health worldwide. It also had a number of negative consequences for the psychosocial and economic functioning of abusers. One of the most common addiction treatment method is maintenance methadone therapy. An important part of evaluating the effectiveness of the participation of a person addicted to methadone treatment is to assess the quality of life determined by participation in substitution therapy. Quality of life of persons addicted to psychoactive substances determined by socio-demographic situation. The study involved 234 outpatient addicts included in the methadone maintenance treatment programs in Szczecin, Warsaw and Lublin. It was based on a diagnostic survey performed using an original questionnaire and the SF-36 v2. In a research of subjective qual- ity of life, respondents obtained results at the level sufficient, higher values were obtained in the domains of physical than mental health. Respondents from Szczecin and Warszawa scored higher, statistically significant, the assessment than patients from Lublin. 1. Variation of respondents quality of life was conditioned by the place of performance of therapy. 2. Respondents had the greatest disparity in the subjective evaluation of physical and mental health. 3. Age was an important factor affecting the marks obtained by the respondents in the SF-36 v2.

  1. Temporal correlation between opiate seizures in East/Southeast Asia and B.C. heroin deaths: a transoceanic model of heroin death risk.

    Science.gov (United States)

    McLean, Mark E

    2003-01-01

    Because heroin supply changes cannot be measured directly, their impact on populations is poorly understood. British Columbia has experienced an injection drug use epidemic since the 1980s that resulted in 2,590 illicit drug deaths from 1990-1999. Since previous work indicates heroin seizures can correlate with supply and B.C. receives heroin only from Southeast Asia, this study examined B.C. heroin deaths against opiate seizures in East/Southeast Asia. Opiate seizures in East/Southeast Asia and data from two B.C. mortality datasets containing heroin deaths were examined. The Pearson correlation coefficient for seizures against each mortality dataset was determined. Opiate seizures, all illicit drug deaths and all opiate deaths concurrently increased twice and decreased twice from 1989-1999, and all reached new peak values in 1993. Three B.C. sub-regions exhibited illicit drug deaths rate trends concurrent with the three principal datasets studied. The Pearson correlation coefficient for opiate-induced deaths against opiate seizures from 1980-1999 was R=0.915 (popiate seizures from 1987-1999 was R=0.896 (popiate seizures in East/Southeast Asia were very strongly correlated with B.C. opiate and illicit drug deaths. The number of B.C. heroin-related deaths may be strongly linked to heroin supply. Enforcement services are not effective in preventing harm caused by heroin in B.C.; therefore, Canada should examine other methods to prevent harm. The case for harm reduction is strengthened by the ineffectiveness of enforcement and the unlikelihood of imminent eradication of heroin production in Southeast Asia.

  2. An analytical framework for strategic delta planning : negotiating consent for long-term sustainable delta development

    NARCIS (Netherlands)

    Seijger, C.; Douven, W; Hermans, L.M.; Evers, J.; Phi, H. L.; Brunner, J.; Pols, L.; Ligtvoet, W.; Koole, S.; Slager, K.; Vermoolen, M.S.; Hasan, S.; Hoang, V. T M; van Halsema, G

    2016-01-01

    Sectoral planning on water, agriculture and urban development has not been able to prevent increased flood risks and environmental degradation in many deltas. Governments conceive strategic delta planning as a promising planning approach and develop strategic delta plans. Such plans are linked to

  3. 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

  4. 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.

  5. 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.

  6. A Modal Logic for Abstract Delta Modeling

    NARCIS (Netherlands)

    F.S. de Boer (Frank); M. Helvensteijn (Michiel); J. Winter (Joost)

    2012-01-01

    htmlabstractAbstract Delta Modeling is a technique for implementing (software) product lines. Deltas are put in a partial order which restricts their application and are then sequentially applied to a core product in order to form specific products in the product line. In this paper we explore the

  7. Tidal controls on river delta morphology

    NARCIS (Netherlands)

    Hoitink, A.J.F.; Wang, Z.B.; Vermeulen, B.; Huismans, Y.; Kästner, K.

    2017-01-01

    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

  8. Tidal controls on river delta morphology

    NARCIS (Netherlands)

    Hoitink, A.J.F.; Wang, Zhengbing; Vermeulen, B.; Huismans, Y; Kästner, K

    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

  9. 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

  10. 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.

  11. 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

  12. Entendiendo Delta desde las Humanidades

    Directory of Open Access Journals (Sweden)

    José Calvo Tello

    2016-05-01

    Full Text Available Stylometry is one of the research areas in greater development within Digital Humanities. However, few studies have worked until recently with texts in Spanish and even less so from Spanish-speaking countries. The aim of this paper is to present in Spanish, and without prior statistical knowledge from the reader, one of the main methods used in stylometry, the measure of textual distance Burrows’ Delta. This paper explains this measure using a very small corpus of proverbs and then checks the results in a corpus of Spanish novels. Both data and Python scripts are available to the community through GitHub, commented step by step so that you can play and visualize each step.

  13. EEHG at FLASH and DELTA

    Energy Technology Data Exchange (ETDEWEB)

    Molo, Robert; Hoener, Markus; Huck, Holger; Hacker, Kirsten; Khan, Shaukat; Schick, Andreas; Ungelenk, Peter; Zeinalzadeh, Maryam [Center for Synchrotron Radiation (DELTA), TU Dortmund University (Germany); Meulen, Peter van der; Salen, Peter [Stockholm University (Sweden); Angelova Hamberg, Gergana; Ziemann, Volker [Uppsala University (Sweden)

    2013-07-01

    The echo-enabled harmonic generation (EEHG) scheme utilizes two modulators with two magnetic chicanes in order to generate an electron density modulation with high harmonic content. In contrast to free-electron lasers (FEL) based on self-amplified spontaneous emission (SASE), the radiation of an EEHG FEL has better longitudinal coherence and is naturally synchronized with an external laser, which is advantageous for pump-probe applications. At the free-electron laser in Hamburg (FLASH), an EEHG experiment is currently under preparation. The short-pulse facility at DELTA (a 1.5-GeV synchrotron light source operated by the TU Dortmund University) based on coherent harmonic generation (CHG) will be upgraded using the EEHG technique in order to reach shorter wavelengths.

  14. 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.

  15. Growth laws for delta crevasses in the Mississippi River Delta: observations and modeling

    Science.gov (United States)

    Yocum, T. A.; Georgiou, I. Y.

    2016-02-01

    River deltas are accumulations of sedimentary deposits delivered by rivers via a network of distributary channels. Worldwide they are threatened by environmental changes, including subsidence, global sea level rise and a suite of other local factors. In the Mississippi River Delta (MRD) these impacts are exemplified, and have led to proposed solutions to build land that include sediment diversions, thereby reinitiating the delta cycle. While economically efficient, there are too few analogs of small deltas aside from laboratory studies, numerical modeling studies, theoretical approaches, and limited field driven observations. Anthropogenic crevasses in the modern delta are large enough to overcome limitations of laboratory deltas, and small enough to allow for "rapid" channel and wetland development, providing an ideal setting to investigate delta development mechanics. Crevasse metrics were obtained using a combination of geospatial tools, extracting key parameters (bifurcation length and width, channel order and depth) that were non-dimensionalized and compared to river-dominated delta networks previously studied. Analysis showed that most crevasses in the MRD appear to obey delta growth laws and delta allometry relationships, suggesting that crevasses do exhibit similar planform metrics to larger Deltas; the distance to mouth bar versus bifurcation order demonstrated to be a very reasonable first order estimate of delta-top footprint. However, some crevasses exhibited different growth metrics. To better understand the hydrodynamic and geomorphic controls governing crevasse evolution in the MRD, we assess delta dynamics via a suite of field observations and numerical modeling in both well-established and newly constructed crevasses. Our analysis suggests that delta development is affected by the relative influence of external (upstream and downstream) and internal controls on the hydrodynamic and sediment transport patterns in these systems.

  16. 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

  17. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. [Neuropsychopharmacology of delta-9-tetrahydrocannabinol].

    Science.gov (United States)

    Costentin, J

    2008-08-01

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

  19. 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.

  20. Opiate sensitization induces FosB/ΔFosB expression in prefrontal cortical, striatal and amygdala brain regions.

    Directory of Open Access Journals (Sweden)

    Gary B Kaplan

    Full Text Available Sensitization to the effects of drugs of abuse and associated stimuli contributes to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate exposure produces behavioral sensitization that is hypothesized to result from neural plasticity in specific limbic, striatal and cortical systems. ΔFosB and FosB are members of the Fos family of transcription factors that are implicated in neural plasticity in addiction. This study examined the effects of intermittent morphine treatment, associated with motor sensitization, on FosB/ΔFosB levels using quantitative immunohistochemistry. Motor sensitization was tested in C57BL/6 mice that received six intermittent pre-treatments (on days 1, 3, 5, 8, 10, 12 with either subcutaneous morphine (10 mg/kg or saline followed by a challenge injection of morphine or saline on day 16. Mice receiving repeated morphine injections demonstrated significant increases in locomotor activity on days 8, 10, and 12 of treatment (vs. day 1, consistent with development of locomotor sensitization. A morphine challenge on day 16 significantly increased locomotor activity of saline pre-treated mice and produced even larger increases in motor activity in the morphine pre-treated mice, consistent with the expression of opiate sensitization. Intermittent morphine pre-treatment on these six pre-treatment days produced a significant induction of FosB/ΔFosB, measured on day 16, in multiple brain regions including prelimbic (PL and infralimbic (IL cortex, nucleus accumbens (NAc core, dorsomedial caudate-putamen (CPU, basolateral amygdala (BLA and central nucleus of the amygdala (CNA but not in a motor cortex control region. Opiate induced sensitization may develop via Fos/ΔFosB plasticity in motivational pathways (NAc, motor outputs (CPU, and associative learning (PL, IL, BLA and stress pathways (CNA.

  1. Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study

    Directory of Open Access Journals (Sweden)

    Khan Riaz

    2011-08-01

    Full Text Available Abstract Background Despite the importance of heavy drinking and alcohol dependence among patients with opiate and cocaine dependence, few studies have evaluated specific interventions within this group. The aim of the present study was to evaluate the impact of screening with the Alcohol Use Disorders Identification Test (AUDIT and of brief intervention (BI on alcohol use in a sample of patients treated for opioid or cocaine dependence in a specialized outpatient clinic. Methods Adult outpatients treated for opioid or cocaine dependence in Switzerland were screened for excessive alcohol drinking and dependence with the AUDIT. Patients with AUDIT scores that indicated excessive drinking or dependence were randomized into two groups--treatment as usual or treatment as usual together with BI--and assessed at 3 months and 9 months. Results Findings revealed a high rate (44% of problematic alcohol use (excessive drinking and dependence among patients with opiate and cocaine dependence. The number of drinks per week decreased significantly between T0 (inclusion and T3 (month 3. A decrease in average AUDIT scores was observed between T0 and T3 and between T0 and T9 (month 9. No statistically significant difference between treatment groups was observed. Conclusions In a substance abuse specialized setting, screening for alcohol use with the AUDIT, followed by feedback on the score, and use of alcohol BI are both possibly useful strategies to induce changes in problematic alcohol use. Definitive conclusions cannot, however, be drawn from the study because of limitations such as lack of a naturalistic group. An important result of the study is the excellent internal consistency of AUDIT in a population treated for opiate or cocaine dependence.

  2. Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck).

    Science.gov (United States)

    Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco

    2010-03-24

    To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

  3. Immunological screening of drugs of abuse and gas chromatographic-mass spectrometric confirmation of opiates and cocaine in hair.

    Science.gov (United States)

    Segura, J; Stramesi, C; Redón, A; Ventura, M; Sanchez, C J; González, G; San, L; Montagna, M

    1999-03-05

    The work presents an analytical strategy to detect drugs of abuse in hair. It involves two sequential steps: a screening by a simple enzyme-linked immunosorbent assay (ELISA) methodology to detect opiates, cocaine and its metabolites, and benzodiacepines, followed by confirmation of opiates and cocaine metabolites in positive samples by gas chromatography coupled to mass spectrometry (GC-MS). In the same GC-MS run other drugs for substitution therapy (e.g. methadone and its main metabolite) can also be detected. After a double washing of hair samples with dichloromethane, hair specimens were cut into small pieces and 10 mg samples were incubated in 2 ml of methanol-trifluoroacetic acid (9:1) mixture, overnight at 37 degrees C. Aliquots of the extract were then evaporated, reconstituted in buffer and analysed according to the ELISA procedure. Confirmation involved solid-phase extraction of another fraction of the extract kept at -20 degrees C, derivatization with heptafluorobutyric anhydride and hexafluoroisopropanol and detection of cocaine, benzoylecgonine, ecgonine methylester, cocaethylene, morphine, codeine, 6-monoacetylmorphine, methadone and 2-ethylidene-1.5-dimethyl-3,3-diphenylpirrolidine (methadone metabolite) by selective ion monitoring after gas chromatographic separation. During the development of the method it was verified that no more than 10% of cocaine, opiates and benzodiacepines were lost when dichloromethane was used to wash real samples. The results also confirmed the increase of extractability power of TFA when it was added to methanol: the recovery for the analytes (cocaine and its metabolites and opiates) added to methanol-TFA alone was of the order of 90% except for benzoylecgonine (75%), and the recovery for the analytes added to methanol-TFA extract of drug-free hair was about 90% for all analytes except for benzoylecgonine and 6-MAM (around 70%). Regarding the stability of labile compounds, only small amounts of ecgonine methylester (2

  4. 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.

  5. 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.

  6. Contingency Management interventions for non-prescribed drug use during treatment for opiate addiction: A systematic review and meta-analysis.

    Science.gov (United States)

    Ainscough, Tom S; McNeill, Ann; Strang, John; Calder, Robert; Brose, Leonie S

    2017-09-01

    Use of non-prescribed drugs during treatment for opiate addiction reduces treatment success, creating a need for effective interventions. This review aimed to assess the efficacy of contingency management, a behavioural treatment that uses rewards to encourage desired behaviours, for treating non-prescribed drug use during opiate addiction treatment. A systematic search of the databases Embase, PsychInfo, PsychArticles and Medline from inception to March 2015 was performed. Random effects meta-analysis tested the use of contingency management to treat the use of drugs during opiate addiction treatment, using either longest duration of abstinence (LDA) or percentage of negative samples (PNS). Random effects moderator analyses were performed for six potential moderators: drug targeted for intervention, decade in which the study was carried out, study quality, intervention duration, type of reinforcer, and form of opiate treatment. The search returned 3860 papers; 22 studies met inclusion criteria and were meta-analysed. Follow-up data was only available for three studies, so all analyses used end of treatment data. Contingency management performed significantly better than control in reducing drug use measured using LDA (d=0.57, 95% CI: 0.42-0.72) or PNS (d=0.41) (95% CI: 0.28-0.54). This was true for all drugs other than opiates. The only significant moderator was drug targeted (LDA: Q=10.75, p=0.03). Contingency management appears to be efficacious for treating most drug use during treatment for opiate addiction. Further research is required to ascertain the full effects of moderating variables, and longer term effects. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2009-12-01

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

  8. 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...

  9. 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.

  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. Legal Delta Boundary, 2001, DWR [ds586

    Data.gov (United States)

    California Natural Resource Agency — The original topographic maps containing the drawn delta border were scanned from the Department of Water Resources. Images were registered to 1:24,000 USGS DRG's in...

  12. sheltered creeks in Niger Delta, Nigeria

    African Journals Online (AJOL)

    user

    2015-03-18

    Mar 18, 2015 ... 273 and 115,000 barrels, respectively, making the delta. *Corresponding author. .... content was transferred to savillex digestion bombs and concen- trated hydrochloric ... metals (Zn, Pb and Cu) by flame atomic absorption.

  13. South Local Government Area, Delta S

    African Journals Online (AJOL)

    ADOWIE PERE

    environs, Aniocha- South Local Government Area of Delta State, Nigeria was carried out with a view to determining the ... supply for physical industrial development to achieve maximum human .... the Schlumberger O' Neil software package.

  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. 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.

  16. 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.)

  17. 2016 Rose Ojowhoh Delta State Polytechnic, Ozoro

    African Journals Online (AJOL)

    OJOHWOH ROSE

    The study examined staff development and library services in academic libraries in Bayelsa and Delta States. ... academic libraries, whose responsibility will be to cater for the development of staff in all ramifications. ..... Human resource.

  18. AMNESTY IN THE NIGER DELTA: VERTICAL MOVEMENT ...

    African Journals Online (AJOL)

    OLAWUYI

    federal government, the Niger Delta communities claim that they are entitled to ... instability, macroeconomic challenges, inconsistent policy regimes to ..... continues they cannot threaten the stability of the country nor affect its continued.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung D. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Seo, Kwang W. [Department of Internal Medicines, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Lee, Eun A.; Quang, Nguyen N. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Cho, Hong R. [Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Kwon, Byungsuk, E-mail: bskwon@mail.ulsan.as.kr [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of)

    2011-07-01

    Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

  7. 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.

  8. Delta infection evidenced by radioimmunoanalysis in selected collectives

    Energy Technology Data Exchange (ETDEWEB)

    Kselikova, M; Horejsi, J; Urbankova, J

    1987-01-01

    The presence of the Delta agent within the population was tested by means of the Delta-antibody radioimmunoassay using competitive kits of the firms ABBOTT (ABBOTT-ANTI-DELTA) and SORIN (AB-DELTAK). The Delta-antibody was found in 3.2% HBV patients, 5% HBsAg carriers, and in 20.8% of specific anti-Hbs-immunoglobulin. In hemophiliacs and blood donors no Delta-antibody was seen.

  9. Delta infection evidenced by radioimmunoanalysis in selected collectives

    International Nuclear Information System (INIS)

    Kselikova, M.; Horejsi, J.; Urbankova, J.

    1987-01-01

    The presence of the Delta agent within the population was tested by means of the Delta-antibody radioimmunoassay using competitive kits of the firms ABBOTT (ABBOTT-ANTI-DELTA) and SORIN (AB-DELTAK). The Delta-antibody was found in 3.2% HBV patients, 5% HBsAg carriers, and in 20.8% of specific anti-Hbs-immunoglobulin. In hemophiliacs and blood donors no Delta-antibody was seen. (author)

  10. 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

  11. [The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling].

    Science.gov (United States)

    Kryzhanovskiĭ, G N; Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Nguyen, T T

    1991-03-01

    It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.

  12. A preliminary, controlled investigation of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-maintained patients.

    Science.gov (United States)

    Margolin, Arthur; Kantak, Kathleen; Copenhaver, Michael; Avants, S Kelly

    2003-01-01

    Based on pre-clinical studies suggesting that magnesium (Mg) reduces cocaine self-administration and potentiates the antinociceptive effects of morphine, we conducted a preliminary randomized clinical trial investigating Mg for the treatment of illicit cocaine and opiate use. Eighteen methadone-maintained patients who used illicit opiates and cocaine received either Mg (732 mg/day) or placebo for 12 weeks. Overall, findings showed that the percentage of urine screens testing positive for opiates in the Mg group (22.6%) was half that of the placebo group (46.4%), p = .04; the difference was even greater in the "medication compliant" sample (Mg: 16.3%, placebo: 47.9%), p = .02. Cocaine craving was lower in the Mg compared to the placebo group, but there was no difference between groups in cocaine use. These preliminary findings suggest that Mg may have a beneficial effect for reducing illicit opiate use. It is possible that a higher dose of Mg than was used in this study may be needed to decrease cocaine use.

  13. Antagonism of the morphine-induced locomotor activation of mice by fructose: comparison with other opiates and sugars, and sugar effects on brain morphine.

    Science.gov (United States)

    Brase, D A; Ward, C R; Bey, P S; Dewey, W L

    1991-01-01

    The mouse locomotor activation test of opiate action in a 2+2 dose parallel line assay was used in a repeated testing paradigm to determine the test, opiate and hexose specificities of a previously reported antagonism of morphine-induced antinocociception by hyperglycemia. In opiate specificity studies, fructose (5 g/kg, i.p.) significantly reduced the potency ratio for morphine and methadone, but not for levorphanol, meperidine or phenazocine when intragroup comparisons were made. In intergroup comparisons, fructose significantly reduced the potencies of levorphanol and phenazocine, but not methadone or meperidine. In hexose/polyol specificity studies, tagatose and fructose significantly reduced the potency ratio for morphine, whereas glucose, galactose, mannose and the polyols, sorbitol and xylitol, caused no significant decrease in potency. Fructose, tagatose, glucose and mannose (5 g/kg, i.p.) were tested for effects on brain morphine levels 30 min after morphine (60 min after sugar), and all four sugars significantly increased brain morphine relative to saline-pretreated controls. It is concluded that the antagonism of morphine by acute sugar administration shows specificity for certain sugars and occurs despite sugar-induced increases in the distribution of morphine to the brain. Furthermore, the effects of fructose show an opiate specificity similar to that of glucose on antinociception observed previously in our laboratory, except that methadone was also significantly inhibited in the present study, when a repeated-testing experimental design was used.

  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. 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....

  16. 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

  17. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-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...

  18. 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.

  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. How to find non-dependent opiate users: a comparison of sampling methods in a field study of opium and heroin users.

    Science.gov (United States)

    Korf, Dirk J; van Ginkel, Patrick; Benschop, Annemieke

    2010-05-01

    The first aim is to better understand the potentials and limitations of different sampling methods for reaching a specific, rarely studied population of drug users and for persuading them to take part in a multidisciplinary study. The second is to determine the extent to which these different methods reach similar or dissimilar segments of the non-dependent opiate-using population. Using ethnographic fieldwork (EFW) and targeted canvassing (TARC; small newspaper advertisements and website announcements), supplemented by snowball referrals, we recruited and interviewed 127 non-dependent opiate users (lifetime prevalence of use 5-100 times; 86.6% had used heroin and 56.7% opium). Average age was 39.0; 66.1% were male and 33.9% female. In addition to opiates, many respondents had wide experience with other illicit drugs. The majority had non-conventional lifestyles. Both EFW and TARC yielded only limited numbers of snowball referrals. EFW requires specific skills, is labour-intensive, thus expensive, but allows unsuitable candidates to be excluded faster. Respondents recruited through EFW were significantly more likely to have experience with opium and various drugs other than opiates. TARC resulted in larger percentages of women and respondents with conventional lifestyles. TARC is less labour-intensive but requires more time for screening candidates; its cost-effectiveness depends on the price of advertising for the recruitment. Different methods reach different segments of the population of non-dependent opiate users. It is useful to employ a multi-method approach to reduce selectivity. Copyright 2009 Elsevier B.V. All rights reserved.

  1. 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.

  2. Opioid receptor imaging and displacement studies with [6-O-[11C]methyl]buprenorphine in baboon brain

    International Nuclear Information System (INIS)

    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.

    1996-01-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[ 11 C]methyl]buprenorphine ([ 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 [ 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 ( 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

  3. Open source integrated modeling environment Delta Shell

    Science.gov (United States)

    Donchyts, G.; Baart, F.; Jagers, B.; van Putten, H.

    2012-04-01

    In the last decade, integrated modelling has become a very popular topic in environmental modelling since it helps solving problems, which is difficult to model using a single model. However, managing complexity of integrated models and minimizing time required for their setup remains a challenging task. The integrated modelling environment Delta Shell simplifies this task. The software components of Delta Shell are easy to reuse separately from each other as well as a part of integrated environment that can run in a command-line or a graphical user interface mode. The most components of the Delta Shell are developed using C# programming language and include libraries used to define, save and visualize various scientific data structures as well as coupled model configurations. Here we present two examples showing how Delta Shell simplifies process of setting up integrated models from the end user and developer perspectives. The first example shows coupling of a rainfall-runoff, a river flow and a run-time control models. The second example shows how coastal morphological database integrates with the coastal morphological model (XBeach) and a custom nourishment designer. Delta Shell is also available as open-source software released under LGPL license and accessible via http://oss.deltares.nl.

  4. QCD in the {delta}-regime

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, W. [Universidad Nacional Autonoma de Mexico, Mexico City (Mexico). Inst. de Ciencias Nucleares; Cundy, N. [Seoul National Univ. (Korea, Republic of). Lattice Gauge Theory Research Center; Goeckeler, M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Horsley, R.; Zanotti, J.M. [Edinburgh Univ. (United Kingdom). School of Physics; Nakamura, Y. [Tsukuba Univ., Ibaraki (Japan). Center for Computational Sciences; Pleiter, D. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-03-15

    The {delta}-regime of QCD is characterised by light quarks in a small spatial box, but a large extent in (Euclidean) time. In this setting a specific variant of chiral perturbation theory - the {delta}-expansion - applies, based on a quantum mechanical treatment of the quasi onedimensional system. In particular, for vanishing quark masses one obtains a residual pion mass M{sup R}{sub {pi}}, which has been computed to the third order in the {delta}-expansion. A comparison with numerical measurements of this residual mass allows for a new determination of some Low Energy Constants, which appear in the chiral Lagrangian. We first review the attempts to simulate 2-flavour QCD directly in the {delta}-regime. This is very tedious, but results compatible with the predictions for M{sup R}{sub {pi}} have been obtained. Then we show that an extrapolation of pion masses measured in a larger volume towards the {delta}-regime leads to good agreement with the theoretical predictions. From those results, we also extract a value for the (controversial) sub-leading Low Energy Constant anti l{sub 3}. (orig.)

  5. 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.

  6. Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

    2012-10-01

    Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

  7. Increased thermolability of benzodiazepine receptors in cerebral cortex of a baboon with spontaneous seizures: a case report.

    Science.gov (United States)

    Squires, R; Naquet, R; Riche, D; Braestrup, C

    1979-06-01

    The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Large old trees influence patterns of delta13C and delta15N in forests.

    Science.gov (United States)

    Weber, Pascale; Bol, Roland; Dixon, Liz; Bardgett, Richard D

    2008-06-01

    Large old trees are the dominant primary producers of native pine forest, but their influence on spatial patterns of soil properties and potential feedback to tree regeneration in their neighbourhood is poorly understood. We measured stable isotopes of carbon (delta(13)C) and nitrogen (delta(15)N) in soil and litter taken from three zones of influence (inner, middle and outer zone) around the trunk of freestanding old Scots pine (Pinus sylvestris L.) trees, to determine the trees' influence on below-ground properties. We also measured delta(15)N and delta(13)C in wood cores extracted from the old trees and from regenerating trees growing within their three zones of influence. We found a significant and positive gradient in soil delta(15)N from the inner zone, nearest to the tree centre, to the outer zone beyond the tree crown. This was probably caused by the higher input of (15)N-depleted litter below the tree crown. In contrast, the soil delta(13)C did not change along the gradient of tree influence. Distance-related trends, although weak, were visible in the wood delta(15)N and delta(13)C of regenerating trees. Moreover, the wood delta(15)N of small trees showed a weak negative relationship with soil N content in the relevant zone of influence. Our results indicate that large old trees control below-ground conditions in their immediate surroundings, and that stable isotopes might act as markers for the spatial and temporal extent of these below-ground effects. John Wiley & Sons, Ltd

  14. Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia).

    Science.gov (United States)

    Cotrina, M; Buti, M; Jardi, R; Quer, J; Rodriguez, F; Pascual, C; Esteban, R; Guardia, J

    1998-06-01

    Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

  15. 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...

  16. 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

  17. Deltorphins: a family of naturally occurring peptides with high affinity and selectivity for delta opioid binding sites.

    Science.gov (United States)

    Erspamer, V; Melchiorri, P; Falconieri-Erspamer, G; Negri, L; Corsi, R; Severini, C; Barra, D; Simmaco, M; Kreil, G

    1989-07-01

    Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affinity for delta receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phyllomedusa skin, dermorphin, which is highly selective for mu-opioid receptors. These peptides all have the N-terminal sequence Tyr-D-Xaa-Phe, where D-Xaa is either D-alanine or D-methionine. While this structure seems to be capable of activating both mu and delta opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.

  18. The Economic Dimensions of the Niger Delta Ethnic Conflicts (Pp ...

    African Journals Online (AJOL)

    User

    1970, the price of international oil stepped upwards following the Middle. Eastern Yom Kippur .... Over the years, the pleas of the Niger Delta people for accommodation are ignored or .... In a labour surplus region like the Niger Delta, budget.

  19. Conceptualizing delta forms and processes in Arctic coastal environments

    DEFF Research Database (Denmark)

    Bendixen, Mette; Kroon, Aart

    2017-01-01

    Climate warming in the Arctic directly causes two opposite changes in Arctic coastal systems: increased melt-water discharge through rivers induces extra influx of sediments and extended open water season increases wave impact which reworks and erodes the shores. A shoreline change analysis along...... and popped up as hotspots. The Tuapaat delta and Skansen delta showed large progradation rates (1.5 and 7m/yr) and migration of the adjacent barriers and spits. The dynamic behavior at the delta mouths was mainly caused by classic delta channel lobe switching at one delta (Tuapaat), and by a breach...... of the fringing spit at the other delta (Skansen). The longshore and cross-shore transports are responsible for reworking the sediment with a result of migrating delta mouths and adjacent subaqueous mouth bars. Seaward progradation of the deltas is limited due to the steep nature of the bathymetry in Disko Bay...

  20. Binding energies of two deltas bound states

    International Nuclear Information System (INIS)

    Sato, Hiroshi; Saito, Koichi.

    1982-06-01

    Bound states of the two-deltas system are investigated by employing the realistic one boson exchange potential. It is found that there exist many bound states in each isospin channel and also found that the tensor interaction plays important role in producing these bound states. Relationship between these bound states and dibaryon resonances is discussed. (J.P.N.)

  1. 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

  2. Applications of Dirac's Delta Function in Statistics

    Science.gov (United States)

    Khuri, Andre

    2004-01-01

    The Dirac delta function has been used successfully in mathematical physics for many years. The purpose of this article is to bring attention to several useful applications of this function in mathematical statistics. Some of these applications include a unified representation of the distribution of a function (or functions) of one or several…

  3. Managing flood risks in the Mekong Delta

    NARCIS (Netherlands)

    Hoang, Long Phi; Biesbroek, Robbert; Tri, Van Pham Dang; Kummu, Matti; Vliet, van Michelle T.H.; Leemans, Rik; Kabat, Pavel; Ludwig, Fulco

    2018-01-01

    Climate change and accelerating socioeconomic developments increasingly challenge flood-risk management in the Vietnamese Mekong River Delta—a typical large, economically dynamic and highly vulnerable delta. This study identifies and addresses the emerging challenges for flood-risk management.

  4. 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 ...

  5. 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…

  6. delta. -isobars and photodisintegration at intermediate energies

    Energy Technology Data Exchange (ETDEWEB)

    Suzumura, Jun-ichi; Futami, Yasuhiko [Science Univ. of Tokyo, Noda, Chiba (Japan). Faculty of Science and Technology

    1982-12-01

    The dynamics of the peak considered to be due to the two-nucleon process in the reaction /sup 9/Be(gamma, p) anything is investigated with the quasi-deuteron model. We show that the process is dominated by a two-nucleon mechanism with pion and rho-meson exchange through virtual delta-isobar formation (author).

  7. 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...

  8. 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

  9. 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 ...

  10. Chronic effects of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors

    International Nuclear Information System (INIS)

    Wong, D.T.; Reid, L.R.; Bymaster, F.P.; Threlkeld, P.G.

    1985-01-01

    Fluoxetine administration to rats dose of 10mg/kg i.p. daily up to 12 or 24 days failed to change the concentration-dependent binding of [ 3 H]WB4101, [ 3 H]clonidine and [ 3 H]dihydroalprenolol to α 1 -, α 2 - and β-adrenergic receptors, respectively; [ 3 H]quinuclidinyl benzilate to muscarinic receptors; [ 3 H]pyrilamine to histamine H 1 receptors and [ 3 H]naloxone to opiate receptors. Persistent and significant decreases in receptor number (Bsub(max) value) without changes in the dissociation constant (Ksub(D) value) of [ 3 H]5-HT binding in cortical membranes were observed upon chronic treatment with fluoxetine administered either by intraperitoneal injection or incorporation in the diet. A detectable reduction of 5-HT 1 receptor number occured after once-daily injections of fluoxetine at 10mg/kg i.p. within 49 hours. After pretreatment for 3 days with p-chlorophenylalanine, an inhibitor of 5-HT synthesis, followed by repeated administration of fluoxetine, 5-HT 1 receptor numbers were higher than those of normal rats, suggesting a dependence on synaptic concentration of 5-HT for fluoxetine to affect a receptor down-regulation. These studies provide further evidence for the selectivity of fluoxetine as an inhibitor of 5-HT reuptake, resulting in a selective down-regulation of 5-HT 1 receptors in the cerebal cortex of rat brain. (Author)

  11. [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.

  12. deltaPlotR: An R Package for Di?erential Item Functioning Analysis with Ango? s Delta Plot

    OpenAIRE

    David Magis; Bruno Facon

    2014-01-01

    Angoff's delta plot is a straightforward and not computationally intensive method to identify differential item functioning (DIF) among dichotomously scored items. This approach was recently improved by proposing an optimal threshold selection and by considering several item purification processes. Moreover, to support practical DIF analyses with the delta plot and these improvements, the R package deltaPlotR was also developed. The purpose of this paper is twofold: to outline the delta plot ...

  13. Severe, childhood-onset, idiopathic, life-long insomnia responding selectively to opiate therapy: case report with 19 year follow-up.

    Science.gov (United States)

    Schenck, C H; Mahowald, M W

    2001-11-01

    Idiopathic (primary) insomnia can be difficult to treat; only two prior cases responsive to opiate therapy have been reported. A case is now presented of severe, idiopathic, childhood-onset, familial insomnia, with increased libido, absence of psychopathology, tardive emergence of restless legs syndrome (RLS), and selective response to opiate therapy. A 39-year-old woman was referred in 1981 by her physician who had discovered 3 years earlier that propoxyphene treatment of migraines also controlled her chronic insomnia. She had experienced severe insomnia since childhood, and during early adulthood the insomnia intensified, as she would sleep 0-3 h nightly and never napped. Daily generalized motor restlessness resulted in her frequently walking around the house while feeling exhausted. The quality of her life was considerably compromised by her insomnia, motor restlessness, and by an increased libido that was present since puberty and that was only partially relieved by having sex repeatedly with her husband. Nightly opiate therapy for 19 years has controlled the insomnia, motor restlessness, and excessive libido without affecting her normal libido. The insomnia had not responded to treatment with >25 agents covering >10 pharmacologic categories. During her first (unmedicated) polysomnographic (PSG) study in 1981, she slept 0 min while spending 436 min in bed. In 1984, four consecutive PSG studies were conducted in a design that confirmed the efficacy of propoxyphene therapy of her insomnia. In 1990, an ambulatory PSG revealed two runs of EEG rhythmic paroxysmal activity arising from sleep and wakefulness, without clinical correlate. Neurologic history was negative for seizures, but positive for complete right carotid artery occlusion and three transient ischemic attacks. At age 55 years, typical RLS emerged that was controlled with levodopa therapy, and a concurrent relapse of insomnia was controlled with oxycodone replacing propoxyphene. Nightly opiate therapy of

  14. Pilot study of a social network intervention for heroin users in opiate substitution treatment: study protocol for a randomized controlled trial

    OpenAIRE

    Day, E.; Copello, A.; Seddon, J. L.; Christie, M.; Bamber, D.; Powell, C.; George, S.; Ball, A.; Frew, E.; Freemantle, N.

    2013-01-01

    Background Research indicates that 3% of people receiving opiate substitution treatment (OST) in the UK manage to achieve abstinence from all prescribed and illicit drugs within 3 years of commencing treatment, and there is concern that treatment services have become skilled at engaging people but not at helping them to enter a stage of recovery and drug abstinence. The National Treatment Agency for Substance Misuse recommends the involvement of families and wider social networks in suppo...

  15. The effectiveness of mindfulness-based relapse prevention on the prevention of relapse, craving and self-control in opiate-dependent individuals

    OpenAIRE

    alireza maredpour; Mahmmod Najafy; Farangiss amiri

    2015-01-01

    Abstract Objective: the aim of this study is to investigate the effectiveness of mindfulness-based relapse prevention on the prevention of relapse, craving and self-control in opiate-dependent individuals in Yasuj. Methodology: This quasi-experimental study applied pretest - posttest and a control group. The sample included 30 male patients with drug addiction in Yasuj who were chosen from addiction clinics based on criterion sampling. To collect the required data the short form of Self-Co...

  16. 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.

  17. 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...

  18. 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

  19. Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol.

    Science.gov (United States)

    Warner, W; Harris, L S; Carchman, R A

    1977-12-01

    ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

  20. Determination of the positions and residues of the. delta. /sup + +/ and. delta. /sup 0/ poles. [Phase shifts,coulomb corrections

    Energy Technology Data Exchange (ETDEWEB)

    Vasan, S S [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics

    1976-04-19

    The poles and the associated residues in the ..pi..N P/sub 33/ amplitude corresponding to the resonances ..delta../sup + +/ and ..delta../sup 0/ are determined by fitting the ..pi../sup +/p and ..pi../sup -/p hadronic phase shifts from the Carter 73 analysis. The ..delta../sup + +/ and ..delta../sup 0/ pole positions are determined also from the nuclear phase shifts, these being the phase shifts made up of the hadronic phase shifts plus the Coulomb corrections. The pole positions obtained from the two sets of phase shifts are different, the differences being larger in the case of the ..delta../sup + +/.

  1. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  2. 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

  3. 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

  4. The sensitivity of the ESA DELTA model

    Science.gov (United States)

    Martin, C.; Walker, R.; Klinkrad, H.

    Long-term debris environment models play a vital role in furthering our understanding of the future debris environment, and in aiding the determination of a strategy to preserve the Earth orbital environment for future use. By their very nature these models have to make certain assumptions to enable informative future projections to be made. Examples of these assumptions include the projection of future traffic, including launch and explosion rates, and the methodology used to simulate break-up events. To ensure a sound basis for future projections, and consequently for assessing the effectiveness of various mitigation measures, it is essential that the sensitivity of these models to variations in key assumptions is examined. The DELTA (Debris Environment Long Term Analysis) model, developed by QinetiQ for the European Space Agency, allows the future projection of the debris environment throughout Earth orbit. Extensive analyses with this model have been performed under the auspices of the ESA Space Debris Mitigation Handbook and following the recent upgrade of the model to DELTA 3.0. This paper draws on these analyses to present the sensitivity of the DELTA model to changes in key model parameters and assumptions. Specifically the paper will address the variation in future traffic rates, including the deployment of satellite constellations, and the variation in the break-up model and criteria used to simulate future explosion and collision events.

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

    Science.gov (United States)

    Ortí, E; Coirini, H; Pico, J C

    1999-04-01

    In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

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

    Science.gov (United States)

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

    2001-01-26

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

  11. Biomass co-firing for Delta Electricity

    International Nuclear Information System (INIS)

    Anon

    2014-01-01

    Electricity generator Delta Electricity has implemented a biomass co-firing program at its Vales Point power station on the Central Coast to reduce its reliance on coal and emissions of CO 2 . The program comprises two parts: direct co-firing with coal of up to 5% biomass; and development of Continuous Biomass Converter (CBC) technology with the Crucible Group to remove technology constraints and enable much higher rates of biomass co-firing. It is talking industrial scale tests. Delta increased biomass co-firing in 2013/14 to 32,000 tonnes, up from just 3,000 tonnes the previous year, and conducted biochar co-firing trials at a rate equivalent to 400,000 tonnes per annum to demonstrate the potential of CBC technology. It reduced CO 2 emissions in 2013/14 by more than 32,000 tonnes. 'Legislation and regulations define biomass as renewable,' said Delta Electricity sustainability manager Justin Flood. 'By preferring biomass over coal, the carbon in the coal is not burnt and remains locked up.' One biomass source is wood waste that would normally go to landfill, but the primary driver of Delta's recent increase in co-firing is sawmill residues. 'Previously there was a higher value market for the residues for paper pulp. However, when that market evaporated the timber industry was left with a sizable problem in terms of what to do with its residues and the loss of revenue,' said Flood. The way greenhouse gas accounting is conducted in Australia, with carbon emissions based on site activities, makes it difficult to undertake a life cycle assessment of the program. 'However, some of the international studies looking at this issue have concluded that the net carbon emissions of the biomass system are significantly lower than the coal system because of the uptake of carbon during biomass growth,' said Flood. Delta identified two challenges, sourcing the feedstock and that biomass conversion to electricity is slightly less

  12. Serial EEG findings in anti-NMDA receptor encephalitis: correlation between clinical course and EEG.

    Science.gov (United States)

    Ueda, Jun; Kawamoto, Michi; Hikiami, Ryota; Ishii, Junko; Yoshimura, Hajime; Matsumoto, Riki; Kohara, Nobuo

    2017-12-01

    Anti-NMDA receptor encephalitis is a paraneoplastic encephalitis characterised by psychiatric features, involuntary movement, and autonomic instability. Various EEG findings in patients with anti-NMDA receptor encephalitis have been reported, however, the correlation between the EEG findings and clinical course of anti-NMDA receptor encephalitis remains unclear. We describe a patient with anti-NMDA receptor encephalitis with a focus on EEG findings, which included: status epilepticus, generalised rhythmic delta activity, excess beta activity, extreme delta brush, and paroxysmal alpha activity upon arousal from sleep, which we term"arousal alpha pattern". Initially, status epilepticus was observed on the EEG when the patient was comatose with conjugate deviation. The EEG then indicated excess beta activity, followed by the emergence of continuous slow activity, including generalised rhythmic delta activity and extreme delta brush, in the most severe phase. Slow activity gradually faded in parallel with clinical amelioration. Excess beta activity persisted, even after the patient became almost independent in daily activities, and finally disappeared with full recovery. In summary, our patient with anti-NMDA receptor encephalitis demonstrated slow activity on the EEG, including extreme delta brush during the most severe phase, which gradually faded in parallel with clinical amelioration, with excess beta activity persisting into the recovery phase.

  13. Evidence of morphine like substance and μ-opioid receptor expression in Toxacara canis (Nematoda: Ascaridae).

    Science.gov (United States)

    Golabi, Mostafa; Naem, Soraya; Imani, Mehdi; Dalirezh, Nowruz

    2016-01-01

    Toxocara canis (Nematoda: Ascaridae) is an intestinal nematode parasite of dogs, which can also cause disease in humans. Transmission to humans usually occurs because of direct contact with T. canis eggs present in soil contaminated with the feces of infected dogs. This nematode has extraordinary abilities to survive for many years in different tissues of vertebrates, and develop to maturity in the intestinal tract of its definitive host. Survival of parasitic nematodes within a host requires immune evasion using complicated pathways. Morphine-like substance, as well as opioids, which are known as down regulating agents, can modulate both innate and acquired immune responses, and let the parasite survives in their hosts. In the present study, we aimed to find evidences of morphine-like substance and µ-opiate receptor expression in T. canis , using high performance liquid chromatography (HPLC) and reverse transcription polymerase chain reaction (RT-PCR). The results indicated that T. canis produced morphine-like substances at the level of 2.31± 0.26 ng g -1 wet weight, and expressed µ-opiate receptor as in expected size of 441 bp. According to our findings, it was concluded that T. canis , benefits using morphine-like substance to modulate host immunity.

  14. 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

  15. Improved γ-linolenic acid production in Mucor circinelloides by homologous overexpressing of delta-12 and delta-6 desaturases.

    Science.gov (United States)

    Zhang, Yao; Luan, Xiao; Zhang, Huaiyuan; Garre, Victoriano; Song, Yuanda; Ratledge, Colin

    2017-06-21

    γ-Linolenic acid (GLA) is important because of its nutritional value and medicinal applications. Although the biosynthetic pathways of some plant and microbial GLA have been deciphered, current understanding of the correlation between desaturases and GLA synthesis in oleaginous fungi is incomplete. In previous work, we found that a large amount of oleic acid (OA) had not been converted to linoleic acid (LA) or GLA in Mucor circinelloides CBS 277.49, which may be due to inadequate activities of the delta-12 or delta-6 desaturases, and thus leading to the accumulation of OA and LA. Thus, it is necessary to explore the main contributing factor during the process of GLA biosynthesis in M. circinelloides. To enhance GLA production in M. circinelloides, homologous overexpression of delta-12 and two delta-6 desaturases (named delta-6-1 and delta-6-2, respectively) were analyzed. When delta-6 desaturase were overexpressed in M. circinelloides, up to 43% GLA was produced in the total fatty acids, and the yield of GLA reached 180 mg/l, which were, respectively, 38 and 33% higher than the control strain. These findings revealed that delta-6 desaturase (especially for delta-6-1 desaturase) plays an important role in GLA synthesis by M. circinelloides. The strain overexpressing delta-6-1 desaturase may have potential application in microbial GLA production.

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

    DEFF Research Database (Denmark)

    Grarup, Niels; 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. Th...

  17. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero

    2011-10-01

    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  18. Synoptic Lithostratigraphy of The Niger Delta

    International Nuclear Information System (INIS)

    Nwajide, C.S.

    2002-01-01

    The Tertiary Niger Delta is stratigraphically framed by the Dahomey, Anambra, Abakaliki, Afikpo and Calabar Flank basins. From the apex at Onitsha a fluvial plain splays southwards and translates progressively into a freshwater swamp, succeeded by a mangrove swamp belt. Along the coast is a strip of wave-washed barrier bars indented by large estuaries, fronted by submerged moth bars. Habitation in the delta is on levees, point bars, and barrier bars. These landforms provided the firm salients for buildings the ports that facilitated international trade from the pre-colonial times.There are four lithofacies-clean, pebbly, and muddy sandstones, and mudstones. Their subdivision, based on sedimentary structures, textures and fossil content yields twenty reservoir and seven nonreservoir classes. Their environments of deposition, identified using facies associations, fall into fluvial, wave-and tide-dominated, marginal, and shallow marine, with localised canyons incised into the delta front and filled with deeper marine facies.The reservoirs are composed of 70 90% quartz, 4 15% feldspar, and 3 13% clay matrix, with minor mica, bioclasts, carbonaceous debris, glauconite, and heavy minerals. Grain size varies from very fine to coarse and pebbly, implying the presence of sands of varying textural and compositional maturities. Silica, K-feldspar, and carbonates constitute the cements.Porosity in the reservoirs has remained about the same as at deposition due to low mechanical compaction occasioned by shallow burial. Meteoric water-flushed progradational sequence are characterised by cementation with quartz and kaolinite. In contrast, marine water-flushed transgressive sands show grain coating illite-smectite, chlorite and K-feldspar overgrowths

  19. 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.

  20. 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.