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Sample records for rats undergoing withdrawal

  1. Acupuncture Attenuates Anxiety-Like Behavior by Normalizing Amygdaloid Catecholamines during Ethanol Withdrawal in Rats

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    Zheng Lin Zhao

    2011-01-01

    Full Text Available Previously, we demonstrated acupuncture at acupoint HT7 (Shen-Men attenuated ethanol withdrawal syndrome by normalizing the dopamine release in nucleus accumbens shell. In the present study, we investigated the effect of acupuncture on anxiety-like behavior in rats and its relevant mechanism by studying neuro-endocrine parameters during ethanol withdrawal. Rats were treated with 3 g kg−1day−1 of ethanol (20%, w/v or saline by intraperitoneal injections for 28 days. The rats undergoing ethanol withdrawal exhibited anxiety-like behavior 72 h after the last dose of ethanol characterized by the decrease of time spent in the open arms of the elevated plus maze compared with the saline-treated rats (P < .05. Radioimmunoassay exhibited there were notably increased concentrations of plasma corticosterone in ethanol-withdrawn rats compared with saline-treated rats (P < .05. Additionally, high performance liquid chromatography analysis also showed the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were markedly increased while the levels of dopamine and 3,4-dihydroxyphenylacetic acid were significantly decreased in the central nucleus of the amygdala of ethanol-withdrawn rats compared with saline-treated rats (P < .01. Acupuncture groups were treated with acupuncture at acupoint HT7 or PC6 (Nei-Guan. Acupuncture at HT7 but not PC6 greatly attenuated the anxiety-like behavior during ethanol withdrawal as evidenced by significant increases in the percentage of time spent in open arms (P < .05. In the meantime, acupuncture at HT7 also markedly inhibited the alterations of neuro-endocrine parameters induced by ethanol withdrawal (P < .05. These results suggest that acupuncture may attenuate anxiety-like behavior during ethanol withdrawal through regulation of neuro-endocrine system.

  2. Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats

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    Dencker, Ditte; Molander, Anna; Thomsen, Morgane

    2018-01-01

    , we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were...... maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms 'rigidity' and 'irritability'. CONCLUSION: Our preclinical pilot study suggests that a ketogenic...... diet may be a novel approach for treating alcohol withdrawal symptoms in humans. This article is protected by copyright. All rights reserved....

  3. Memantine reverses social withdrawal induced by ketamine in rats.

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    Uribe, Ezequiel; Landaeta, José; Wix, Richard; Eblen, Antonio

    2013-03-01

    The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.

  4. Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

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    Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

    2018-02-01

    Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

  5. Conditioned flavor avoidance as a measure of withdrawal in rats chronically exposed to a caffeine solution.

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    Dreumont-Boudreau, Sarah E; Dingle, Rachel N; Alcolado, Gillian M; Lolordo, Vincent M

    2008-09-03

    Rats were given 21 days of chronic oral caffeine. A novel flavor (Maintenance CS) was then paired with the continuation of caffeine, and a second flavor (Withdrawal CS) was paired with caffeine removal. Rats avoided the Withdrawal CS, and drank more of the Maintenance CS in a two-bottle test, suggesting that removing caffeine had induced withdrawal. The value of the Maintenance CS was investigated by comparing it to a novel flavor paired with water (Neutral CS). In a series of two-bottle tests, the Maintenance and Neutral CSs were equivalent when pitted against each other, and both were preferred to the Withdrawal CS. These results demonstrate that conditioned flavor avoidance is a useful procedure in assessing caffeine withdrawal, and by inference dependence, produced by chronic oral consumption.

  6. Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

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    Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

    2010-03-26

    In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification.

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    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.

  8. Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study

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    Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

    2017-01-01

    Objective: To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Materials and Methods: Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Results: Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. Conclusion: We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron. PMID:28553371

  9. Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

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    Khan, Munasib; Subhan, Fazal; Khan, Arif-Ullah; Abbas, Muzaffar; Ali, Gowhar; Rauf, Khalid; Gilani, Anwarul Hassan

    2014-05-01

    Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

  10. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

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    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  11. The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat

    International Nuclear Information System (INIS)

    Hemmingsen, R.; Braestrup, C.; Nielsen, M.; Barry, D.I.

    1982-01-01

    The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 31/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on 3 H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (Ksub(D)) and the maximal number of binding sites (Bsub(max)) for 3 H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causual part in physical ethanol dependence. (author)

  12. Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats.

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    Rudoy, C A; Van Bockstaele, E J

    2007-06-30

    Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on beta-adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)-adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 h following the last betaxolol injection. Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore

  13. Betaxolol, a selective β1-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats

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    Rudoy, C.A.; Van Bockstaele, E.J.

    2007-01-01

    Background Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on β-adrenergic receptor (β1 and β2) expression in the amygdala. Methods Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that β1–adrenergic receptor, but not β2–adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective β1–adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 hours following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 hours following the last betaxolol injection. Following behavioral testing, betaxolol effects on β1-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Results Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline

  14. Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.

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    Hemmingsen, R; Barry, D I; Hertz, M M; Klinken, L

    1979-09-14

    The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.

  15. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.

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    Wen, D; Sun, D; Zang, G; Hao, L; Liu, X; Yu, F; Ma, C; Cong, B

    2014-09-26

    Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

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    Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

    2008-12-01

    Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

  17. Complex plastic changes in the neuropeptide Y system during ethanol intoxication and withdrawal in the rat brain

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    Olling, J D; Ulrichsen, J; Christensen, D Z

    2009-01-01

    and NPY-stimulated [(35)S]GTPgammaS functional binding. Rats received intragastric ethanol repeatedly for 4 days, and the NPY system was studied in the hippocampal dentate gyrus (DG), CA3, CA1, and piriform cortex (PirCx) and neocortex (NeoCx) during intoxication, peak withdrawal (16 hr), late withdrawal...

  18. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    International Nuclear Information System (INIS)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-01-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[ 14 C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14 CO 2 excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an α 2 -adrenergic agonist

  19. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

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    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  20. Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia.

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    Seillier, Alexandre; Giuffrida, Andrea

    2017-10-01

    Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.

  1. Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.

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    Khaliq, Saima; Haider, Saida; Naqvi, Faizan; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

    2012-01-01

    Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (pcaffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression.

  2. Prediction of emergence agitation using withdrawal reaction following rocuronium injection in preschool-aged patients undergoing inguinal herniorrhaphy: a preliminary exploratory observational trial.

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    Kim, Dae Hee; Roh, Go Un; Lee, Young Bok; Choi, Chang Ik; Lee, Jae Moon; Chae, Yun Jeong

    2018-01-01

    The development of emergence agitation (EA) is associated with several factors including age, preoperative anxiety, postoperative pain, anesthesia method, and surgery type. No studies have investigated whether the withdrawal reaction following rocuronium injection can predict the occurrence of EA. Therefore, we investigated this relationship in preschool-aged children undergoing inguinal herniorrhaphy, and which grade of withdrawal reaction is appropriate for identifying patients at risk of experiencing EA. A total of 40 patients were enrolled in this study. During anesthesia induction, the withdrawal reaction after loss of consciousness following rocuronium injection was assessed using a 4-point scale. After surgery, EA was assessed using the Watcha scale. There was a correlation between withdrawal reaction and EA on admission to the postanesthesia care unit (PACU). Patients with a severe withdrawal reaction (grade 3) showed a significantly higher incidence of severe EA requiring medication on admission to the PACU. The findings of this preliminary exploratory observational study suggest that it is possible for withdrawal movement following rocuronium injection during anesthesia induction to reflect pain sensitivity of pediatric patients, which in turn may be useful in identifying those at risk of severe EA on admission to the PACU among preschool children undergoing inguinal herniorrhaphy. Further studies with a larger sample size are required to validate these findings. The exact correlation between pain reaction following rocuronium injection and postoperative pain or pain-related phenomenon should be elucidated.

  3. POTENTIAL USE OF MELATONIN IN PROCEDURAL ANXIETY AND PAIN IN CHILDREN UNDERGOING BLOOD WITHDRAWAL.

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    Marseglia, L; Manti, S; D'Angelo, G; Arrigo, T; Cuppari, C; Salpietro, C; Gitto, E

    2015-01-01

    The recognition of the value of pain, especially in the pediatric population, has increased over the last decade. It is known that pain-related anxiety can increase perceived pain intensity. There are several different approaches to the treatment of pre-procedural anxiety and procedural pain in children. Melatonin, a neurohormone with the profile of a novel hypnotic-anaesthetic agent, plays an important role in anxiolysis and analgesia. This study investigated the effects of oral melatonin premedication to reduce anxiety and pain in children having blood samples taken. The investigations were carried out on 60 children, aged 1-14 years, divided into 2 equal groups. Using a computer-generated randomization schedule, patients were given either melatonin orally (0.5 mg/kg BW, max 5 mg) or placebo 30 min before blood draw. Pre-procedural anxiety was assessed using the scale from the Children’s Anxiety and Pain Scales, while procedural pain used the Face, Legs, Activity, Cry and Consolability assessment tool for children under the age of 3 years, Faces Pain Scale-Revised for children aged 3-8 years and Numeric Rating Scale for children over the age of 8 years. Oral administration of melatonin before the blood withdrawal procedure significantly reduced both anxiety (pchildren under 3 years and pchildren over 3 years). These data support the use of melatonin for taking blood samples due to its anxiolytic and analgesic properties. Further studies are needed to support the routine use of melatonin to alleviate anxiety and pain in pediatric patients having blood samples taken.

  4. Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats.

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    Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

    2014-09-01

    Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats .

  5. A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal.

    Science.gov (United States)

    Gorodetzky, Charles W; Walsh, Sharon L; Martin, Peter R; Saxon, Andrew J; Gullo, Kristen L; Biswas, Kousick

    2017-07-01

    Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC 1-5 ), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms. Copyright © 2017. Published by Elsevier B.V.

  6. Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

    Science.gov (United States)

    Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

    2015-12-01

    Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

  7. Prediction of emergence agitation using withdrawal reaction following rocuronium injection in preschool-aged patients undergoing inguinal herniorrhaphy: a preliminary exploratory observational trial

    Directory of Open Access Journals (Sweden)

    Kim DH

    2018-01-01

    Full Text Available Dae Hee Kim,1 Go Un Roh,2 Young Bok Lee,3 Chang Ik Choi,3 Jae Moon Lee,3 Yun Jeong Chae1 1Department of Anesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, 2Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam, 3Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea Purpose: The development of emergence agitation (EA is associated with several factors including age, preoperative anxiety, postoperative pain, anesthesia method, and surgery type. No studies have investigated whether the withdrawal reaction following rocuronium injection can predict the occurrence of EA. Therefore, we investigated this relationship in preschool-aged children undergoing inguinal herniorrhaphy, and which grade of withdrawal reaction is appropriate for identifying patients at risk of experiencing EA. Methods: A total of 40 patients were enrolled in this study. During anesthesia induction, the withdrawal reaction after loss of consciousness following rocuronium injection was assessed using a 4-point scale. After surgery, EA was assessed using the Watcha scale. Results: There was a correlation between withdrawal reaction and EA on admission to the postanesthesia care unit (PACU. Patients with a severe withdrawal reaction (grade 3 showed a significantly higher incidence of severe EA requiring medication on admission to the PACU. Conclusion: The findings of this preliminary exploratory observational study suggest that it is possible for withdrawal movement following rocuronium injection during anesthesia induction to reflect pain sensitivity of pediatric patients, which in turn may be useful in identifying those at risk of severe EA on admission to the PACU among preschool children undergoing inguinal herniorrhaphy. Further studies with a larger sample size are required to validate these findings. The exact correlation between pain

  8. Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

    Science.gov (United States)

    Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

    2013-11-26

    Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

  9. Microinjection of Orexin-A into the Locus Coeruleus Area Induces Morphine Withdrawal Behaviors in Morphine Independent Rats

    Directory of Open Access Journals (Sweden)

    Hosin Azizi

    2012-02-01

    Full Text Available Introduction: Orexin neuropeptide has a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC. Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. LC neurons do not show withdrawal-induced hyperactivity in brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Method: Adult male Wistar rats were used in this study. Intra-LC microinjection of orexin-A or orexin-A vehicle was performed one week after LC cannulation. Thereafter, somatic signs of withdrawal were evaluated during a period of 25 min.Findings: Orexin-A induced several signs of morphine withdrawal. Conclusion: It may be concluded that orexin at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.

  10. Amlodipine decreases fibrosis and cardiac hypertrophy in spontaneously hypertensive rats: persistent effects after withdrawal.

    Science.gov (United States)

    Sevilla, María A; Voces, Felipe; Carrón, Rosalía; Guerrero, Estela I; Ardanaz, Noelia; San Román, Luis; Arévalo, Miguel A; Montero, María J

    2004-07-02

    Our objective was to examine the effect of chronic treatment with amlodipine on blood pressure, left ventricular hypertrophy, and fibrosis in spontaneously hypertensive rats and the persistence of such an effect after drug withdrawal. We investigated the effects of treatment with 2, 8 and 20 mg/kg/day of amlodipine given orally for six months and at three months after drug withdrawal. Systolic blood pressure was measured using the tail-cuff method. At the end of the study period, the heart was excised, the left ventricle was isolated, and the left ventricle weight/body weight ratio was calculated as a left ventricular hypertrophy index. Fibrosis, expressed as collagen volume fraction, was evaluated using an automated image-analysis system on sections stained with Sirius red. Age-matched untreated Wistar-Kyoto and SHR were used as normotensive and hypertensive controls, respectively. Systolic blood pressure was reduced in the treated SHR in a dose-dependent way and after amlodipine withdrawal it increased progressively, without reaching the values of the hypertensive controls. Cardiac hypertrophy was reduced by 8 and 20 mg/kg/day amlodipine, but when treatment was withdrawn only the group treated with 8 mg/kg/day maintained significant differences versus the hypertensive controls. All three doses of amlodipine reduced cardiac fibrosis and this regression persisted with the two highest doses after three months without treatment. We concluded that antihypertensive treatment with amlodipine is accompanied by a reduction in left ventricular hypertrophy and regression in collagen deposition. Treatment was more effective in preventing fibrosis than in preventing ventricular hypertrophy after drug withdrawal. Copyright 2004 Elsevier Inc.

  11. Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

    Science.gov (United States)

    Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

    2017-01-01

    Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

  12. Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

    Science.gov (United States)

    Sudakov, S K; Bogdanova, N G

    2016-10-01

    The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

  13. The Impact of Saffron on Symptoms of Withdrawal Syndrome in Patients Undergoing Maintenance Treatment for Opioid Addiction in Sabzevar Parish in 2017

    Directory of Open Access Journals (Sweden)

    Mohammad Nemat Shahi

    2017-01-01

    Full Text Available Background and Objective. Drug dependence is one of the serious problems around the world. Saffron is one of those beneficial medicinal plants which is embedded with a similar mechanism to methadone (e.g., inhibition of serotonin reuptake. Thus, it can be helpful in reducing the withdrawal symptoms. The aim of this study was to reduce the daily dose of methadone usage and reduce its side effects using saffron in the form of medicinal supplements. Methodology. This study was categorized as a clinical trial. Accordingly, 44 clients of addiction treatment centers in Sabzevar parish were randomly selected to participate in this study in 2016–2017. While the experimental group was treated with methadone syrup and self-made saffron capsules, the control group received methadone syrup and placebo capsules. Results. The results showed that the use of saffron and methadone alleviated the symptoms of withdrawal syndrome (p<0.001. Conclusion. Having reviewed the research participants, it was indicated that the introduction of saffron alleviated the symptoms of withdrawal syndrome in patients undergoing maintenance treatment for opioid addiction. Thus, it seems rational to make use of saffron in combination with methadone in order to alleviate the symptoms of withdrawal syndrome.

  14. Anabolic effects of clenbuterol after long-term treatment and withdrawal in t the rat.

    Science.gov (United States)

    Cartañà, J; Segués, T; Yebras, M; Rothwell, N J; Stock, M J

    1994-09-01

    Injection of rats with the beta 2-adrenoceptor agonist clenbuterol (1 mg/kg/d for 15 days) stimulated an increase in body weight (9%) and protein (8%) and water (7%) content, but reduced food intake (4%) and epididymal fat pad mass (39%). Nine days after termination of treatment, ex-clenbuterol rats were heavier (5%) and had a greater protein (7%) and water (6%) content and lower fat pad mass (32%) than controls. Clenbuterol-fed rats (2 mg/kg diet for 10 days, providing an average of 0.04 mg clenbuterol/kg/d) increased body weight (7%), muscle mass (15% to 21%), and muscle protein content (9% to 26%), whereas epididymal fat pad weight and muscle glycogen content were reduced. During the withdrawal period, the greater body weight of ex-clenbuterol rats was sustained overall (ANOVA, P < .00005), but by day 10 this difference was no longer significant. At this point, gastrocnemius muscle mass was still higher (11%) when compared with that of control animals, but soleus muscle mass, muscle glycogen concentration, and epididymal fat pad weight had reverted to control values. These results were corroborated in a subsequent experiment using older rats. It was concluded that, unlike other beta-adrenoceptor-mediated effects, muscle protein accumulated during clenbuterol treatment can be maintained in certain muscles after removal of the drug for a period of time that is at least equivalent to the duration of treatment. This could have implications for the potential therapeutic use of this class of compound, and differences in the response observed between muscle types may help to elucidate the mechanisms responsible for the muscle protein deposition induced by clenbuterol.

  15. Shortening Anesthesia Duration does not Affect Severity of Withdrawal Syndrome in Patients Undergoing Ultra Rapid Opioid Detoxification

    Directory of Open Access Journals (Sweden)

    Shoaleh Shami

    2010-02-01

    Full Text Available Ultra rapid opioid detoxification (UROD is one of the new methods of detoxification. This method of detoxification involves putting patients under general anesthesia and actively giving them opioid antagonists. The objective of this study was to evaluate effects of anesthesia duration in UROD on severity of withdrawal syndrome. Sixty addicted patients seeking UROD procedure assigned randomly to one of the 2hr, 4hr or 6hr anesthesia duration groups. Premedication and anesthesia procedure (induction and maintenance were the same for three groups. Detoxification was done for all patients with 50 mg oral naltroxane (prior to induction and 20 mg intravenous naloxane (8 mg/bolus and 12 mg/infusion. Blood pressure, heart rate and respiratory rate were automatically measured and recorded every 5 minutes. The severity of withdrawal syndrome was measured and recorded every one hour during anesthesia, 2hours post-anesthesia, and 12 and 24 hours following the induction of anesthesia according to the Wang Scale modified by Lomier (WSMBL. Patients aged 20-58 in three groups. Three cases experienced delirium after detoxification that lasted 24 hours in one. Severity of withdrawal syndrome in patients of groups 2, 4 and 6 hour were 8.7, 7.4 and 5.1 respectively during anesthesia and 12.3, 11.1 and 13.9 after 18 hours of anesthesia. Results of this study showed that, in standard settings, UROD is a safe method for detoxification and has low complications. The withdrawal symptoms during and after anesthesia are low. Shortening the duration of anesthesia has no affect on severity of withdrawal syndrome during and after anesthesia.

  16. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats

    OpenAIRE

    Der-Avakian, Andre; Markou, Athina

    2010-01-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent de...

  17. Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.

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    Bernadett Pintér-Kübler

    Full Text Available Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH, urocortin 2 (UCN2 and proopiomelanocortin (POMC compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY and arginine vasopressin (AVP mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.

  18. Effect of Short-term Forced Exercise on Naloxone Induced Withdrawal Symptoms in Morphine Addicted Male Rats

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    KH Saadipour

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. Materials & Methods: This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated (ip twice daily with increasing dose (5، 10، 20، 40, 50 mg/kg to addicted groups. Also single dose (50mg/kg of morphine was administrated to them on the 10th day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA (Tukey test. Results: The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group (p<0.05 , p<0.01. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group (p<0.01, p<0.001. Conclusion: The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

  19. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    Science.gov (United States)

    Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  20. Partial agonist of benzodiazepine receptors Ro 19-2088 elicits withdrawal symptoms after short-term administration in immature rats

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana; Mareš, Pavel

    2012-01-01

    Roč. 61, č. 3 (2012), s. 319-323 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/0846; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : Ro 19-2088 * iatrogenic withdrawal * pentylentetrazol-induced seizures * immature rats Subject RIV: FH - Neurology Impact factor: 1.531, year: 2012

  1. Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study.

    Directory of Open Access Journals (Sweden)

    Monica Grafals

    Full Text Available Rabbit antithymocyte globulin (ATG is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1 to our standard dose ATG (total dose 3.75 mg/kg(sATG vs. lower dose 2.25 mg/kg (lowATG. All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%, CMV (8% vs. 0 and BK (4% vs. 0 infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings.ClinicalTrials.gov NCT00548405.

  2. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    International Nuclear Information System (INIS)

    See, R.E.; Ellison, G.; Toga, A.W.

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2([ 3 H]spiperone and [ 3 H]raclopride), dopamine D1([ 3 H]SCH23390), GABA A ([ 3 H]muscimol), benzodiazepine ([ 3 H]RO15-1788), and muscarinic ACh receptors ([ 3 H]QNB). [ 3 H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [ 3 H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [ 3 H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [ 3 H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [ 3 H]QNB and [ 3 H]RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors)

  3. Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats.

    Science.gov (United States)

    Der-Avakian, Andre; Markou, Athina

    2010-07-01

    Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state.

  4. The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

    OpenAIRE

    Mohammad Allahtavakoli; Fatemeh Amin; Elham Hakimizadeh; Ali Roohbakhsh; Sayed Ali Haeri Rohani; Ahmad Taghavi Rafsanjani; Abbas Haghparast; Ali Shamsizadeh

    2012-01-01

    Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later t...

  5. Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.

    Science.gov (United States)

    Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W

    2016-09-01

    Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

  6. Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats

    Energy Technology Data Exchange (ETDEWEB)

    See, R E; Ellison, G; Toga, A W [California Univ., Los Angeles, CA (USA). School of Medicine

    1990-01-01

    Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2(({sup 3}H)spiperone and ({sup 3}H)raclopride), dopamine D1(({sup 3}H)SCH23390), GABA{sub A}(({sup 3}H)muscimol), benzodiazepine (({sup 3}H)RO15-1788), and muscarinic ACh receptors (({sup 3}H)QNB). ({sup 3}H)spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal ({sup 3}H)raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in ({sup 3}H)SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in ({sup 3}H)muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of ({sup 3}H)QNB and ({sup 3}H)RO15-1788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride. (Authors).

  7. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    Science.gov (United States)

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

    Science.gov (United States)

    Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

    2015-01-01

    Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

  9. Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy.

    Science.gov (United States)

    Zegre Cannon, Coralie; Kissling, Grace E; Goulding, David R; King-Herbert, Angela P; Blankenship-Paris, Terry

    2011-03-01

    In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model. The authors randomly assigned rats to undergo either surgery (abdominal laparotomy with visceral manipulation and anesthesia) or anesthesia only. Rats in each group were treated with tramadol (12.5 mg per kg body weight), carprofen (5 mg per kg body weight), a combination of tramadol and carprofen (12.5 mg per kg body weight and 5 mg per kg body weight, respectively) or saline (anesthesia control group only; 5 mg per kg body weight). The authors administered analgesia 10 min before anesthesia, 4 h after surgery or (for the rats that received anesthesia only) anesthesia and 24 h after surgery or anesthesia. They measured locomotor activity, running wheel activity, feed and water consumption, body weight and fecal corticosterone concentration of each animal before and after surgery. Clinical observations were made after surgery or anesthesia to evaluate signs of pain and distress. The authors found that carprofen, tramadol and a combination of carprofen and tramadol were all acceptable analgesia regimens for a rat laparotomy model.

  10. Opioid withdrawal for 4 days prevents synaptic depression induced by low dose of morphine or naloxone in rat hippocampal CA1 area in vivo.

    Science.gov (United States)

    Dong, Zhifang; Han, Huili; Cao, Jun; Xu, Lin

    2010-02-01

    The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (c) 2009 Wiley-Liss, Inc.

  11. Dansyl-PQRamide, a putative antagonist of NPFF receptors, reduces anxiety-like behavior of ethanol withdrawal in a plus-maze test in rats.

    Science.gov (United States)

    Kotlinska, Jolanta; Pachuta, Agnieszka; Bochenski, Marcin; Silberring, Jerzy

    2009-06-01

    Much evidence indicates that endogenous opioid peptides are involved in effects caused by ethanol. The aim of the present study was to determine whether dansyl-PQR amide, a putative antagonist of receptors for an anti-opioid peptide-neuropeptide FF (NPFF) could affect anxiety-like behavior measured during withdrawal from acute-, and chronic ethanol administration in the elevated plus maze test in rats. Our study indicated that intracerebroventricular (i.c.v.) administration of dansyl-PQRamide (2.4 and 4.8 nmol) reversed anxiety-like behavior measured as a percent time spent in the open arms, and a percent open arm entries onto the open arms in the elevated plus-maze test in rats. These effects were inhibited by NPFF (10 and/or 20 nmol, i.c.v.) in the experiments performed during withdrawal from acute- and chronic ethanol administration. During withdrawal from acute ethanol, naloxone (1mg/kg, i.p.), a nonselective opioid receptor antagonist, attenuated only an increased percent time spent in the open arms induced by dansyl-PQR amide (4.8 nmol). Dansyl-PQR amide, NPFF and naloxone given alone to naive rats did not have influence on spontaneous locomotor activity of animals. Furthermore, NPFF potentiated anxiety-like behavior during withdrawal from chronic, but not acute, ethanol administration in rats. Our data suggest that NPFF system is involved in regulation of affective symptoms of ethanol withdrawal. It seems that involvement of the NPFF system in ethanol withdrawal anxiety-like behavior is associated with regulation of the opioid system activity.

  12. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation.

    Science.gov (United States)

    Ruf, J C; Berger, J L; Renaud, S

    1995-01-01

    We investigated in rats fed a purified diet for 2 and 4 months whether wine drinking was associated with the rebound effect on thrombin-induced platelet aggregation observed after alcohol withdrawal. With 6% ethanol drinking or its equivalent in red or white wine, platelet aggregation was reduced similarly by 70% when the animals drank the alcoholic beverages up to the venipuncture. Depriving the rats of alcoholic beverages for 18 hours was associated with an increase in the platelet response of 124% in those receiving 6% ethanol, of 46% with white wine but a decrease of 59% in those with red wine. The protective effect of red wine on platelets could be reproduced by tannins (procyanidins) extracted from grape seeds or red wine and added to 6% ethanol, but not by glycerol or wine without alcohol. That was related to inhibition of the alcohol-induced lipid peroxidation as shown by the lowering of conjugated dienes, lipid peroxides, and the increase in vitamin E in plasma. Owing to tannins, the platelets of rats drinking red wine did not exhibit the rebound effect observed hours after alcohol drinking, eventually associated with sudden death and stroke in humans.

  13. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    OpenAIRE

    Desjardins , Stephane; Belkai , Emilie; Crete , Dominique; Cordonnier , Laurie; Scherrmann , Jean-Michel; Noble , Florence; Marie-Claire , Cynthia

    2008-01-01

    International audience; Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, th...

  14. Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

    Science.gov (United States)

    Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

    2014-09-01

    Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

  15. The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2012-07-01

    Full Text Available Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Findings. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Conclusion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

  16. ‌‌The effect of nicotine administration on physical and psychological signs of withdrawal syndrome induced by single or frequent doses of morphine in rats

    Directory of Open Access Journals (Sweden)

    Ali Shamsizadeh

    2012-07-01

    Full Text Available Introduction: Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Methods: Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Results: Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Discussion: The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

  17. Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats.

    Science.gov (United States)

    Sharma, Ajaykumar N; Pise, Ashish; Sharma, Jay N; Shukla, Praveen

    2015-06-01

    Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence.

  18. Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal

    Czech Academy of Sciences Publication Activity Database

    Drastichová, Z.; Škrabalová, J.; Jedelský, P.; Neckář, Jan; Kolář, František; Novotný, J.

    2012-01-01

    Roč. 7, č. 10 (2012), e47167 E-ISSN 1932-6203 R&D Projects: GA AV ČR(CZ) IAA501110901 Institutional support: RVO:67985823 Keywords : morphine * rat * heart * proteome Subject RIV: ED - Physiology Impact factor: 3.730, year: 2012

  19. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Maurício dos Santos Pereira

    Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

  20. Examining the effect of the CaMKII inhibitor administration in the locus coeruleus on the naloxone-precipitated morphine withdrawal signs in rats.

    Science.gov (United States)

    Navidhamidi, M; Semnanian, S; Javan, M; Goudarzvand, M; Rohampour, K; Azizi, H

    2012-01-15

    Drug addiction is an occurrence with physiological, psychological, and social outcomes. Repeated drug exposure causes neuronal adaptations and dependency. It has been shown that CaMKIIα enzyme contributes to morphine dependency. The locus coeruleus nucleus has been implied in the morphine withdrawal syndrome. This research focuses on the behavioral and molecular adaptations that occur in the locus coeruleus neurons in response to the chronic morphine exposure. Adult male Wistar rats were injected by morphine sulfate (10 mg/kg/s.c.) at an interval of 12 h for a period of nine subsequent days. On the tenth day, naloxone (1 mg/kg/i.p.) was injected 2 h after the morphine administration. Somatic withdrawal signs were investigated for 30 min. We concluded that the inhibition of CaMKIIα by administration of KN-93, the specific inhibitor of this enzyme, significantly attenuated some of the withdrawal signs. In molecular method, the expression of CaMKIIα protein has been enhanced in locus coeruleus of the morphine dependent rats. These findings indicate that CaMKIIα may be involved in the modulation of the naloxone-induced withdrawal syndrome, and treatment with KN-93 may have some effects on this system. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Age-related differences in anxiety-like behavior and amygdalar CCL2 responsiveness to stress following alcohol withdrawal in male Wistar rats.

    Science.gov (United States)

    Harper, Kathryn M; Knapp, Darin J; Park, Meredith A; Breese, George R

    2017-01-01

    Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats. Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays. Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults. Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.

  2. Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

    Science.gov (United States)

    Ragy, Merhan Mamdouh

    2015-01-01

    Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

  3. Loss and recovery of androgen receptor protein expression in the adult rat testis following androgen withdrawal by ethane dimethanesulfonate.

    Directory of Open Access Journals (Sweden)

    Boycho Nikolov

    2006-06-01

    Full Text Available Androgens are especially important for the maintenance of spermatogenesis in adulthood and the experimental withdrawal of testosterone (T production by ethane dimenthanesulfonate (EDS is a valuable tool for studying androgen-dependent events of spermatogenesis. The aim of the present study was to investigate the specific changes in immunoexpression of androgen receptor (AR in the testis in relation to degeneration and regeneration of Leydig cell (LC population and seminiferous epithelium. Immunohistochemistry for AR and 3beta-hydroxysteroid dehydrogenase (3beta-HSD as well as TUNEL assay for apoptosis were performed on testicular sections of control and EDS-treated rats. Serum LH and T levels were measured by RIA. Our results revealed a total loss of AR immunoexpression from the nuclei of Sertoli (SCs, LCs and peritubular cells during the first week after EDS administration and that coincided with severe drop in T levels. Two weeks after EDS administration, the AR expression was recovered in these cells but normal stage-specificity in SCs was replaced by uniform intensity of AR immunostaining at all the stages of the spermatogenic cycle. The stage-specific pattern of androgen expression in SCs with a maximum at stages VII-VIII appeared 5 weeks after treatment. LC immunoreactivity for 3beta-HSD at different time points after EDS administration correlated with values of T concentration. The maximal germ cell apoptosis on day 7 was followed by total loss of elongated spermatids 2 weeks after EDS treatment. Regeneration of seminiferous epithelium 3 weeks after EDS administration and onwards occurred in tandem with the development of new LC population indicated by the appearance of 3beta-HSD-positive cells and gradual increase in T production. The specific changes in AR after EDS including their loss and recovery in Sertoli cells paralleled with degenerative and regenerative events in Leydig and germ cell populations, confirming close functional

  4. Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats.

    Science.gov (United States)

    Rylkova, Daria; Boissoneault, Jeffrey; Isaac, Shani; Prado, Melissa; Shah, Hina P; Bruijnzeel, Adrie W

    2008-06-01

    Tobacco addiction is a chronic disorder that is characterized by dysphoria upon smoking cessation and relapse after periods of abstinence. Previous research suggests that Neuropeptide Y (NPY) and Y1 receptor agonists attenuate negative affective states and somatic withdrawal signs. The aim of the present experiments was to investigate the effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. The intracranial self-stimulation procedure was used to assess the effects of nicotine withdrawal on brain reward function as this procedure can provide a quantitative measure of emotional states in rodents. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In the first experiment, NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Similar to NPY, [D-His(26)]-NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Neither NPY nor [D-His(26)]-NPY affected the response latencies. In a separate experiment, it was demonstrated that the specific Y1 receptor antagonist BIBP-3226 prevented the NPY-induced elevations in brain reward thresholds. NPY attenuated the overall somatic signs associated with precipitated nicotine withdrawal. [D-His(26)]-NPY did not affect the overall somatic signs associated with precipitated nicotine withdrawal, but decreased the number of abdominal constrictions. Both NPY and [D-His(26)]-NPY attenuated the overall somatic signs associated with spontaneous nicotine withdrawal. These findings indicate that NPY and [D-His(26)]-NPY attenuate somatic nicotine withdrawal signs, but do not prevent the deficit in brain reward function associated

  5. Phosphodiesterase 2A Inhibitor TAK-915 Ameliorates Cognitive Impairments and Social Withdrawal in N-Methyl-d-Aspartate Receptor Antagonist-Induced Rat Models of Schizophrenia.

    Science.gov (United States)

    Nakashima, Masato; Imada, Haruka; Shiraishi, Eri; Ito, Yuki; Suzuki, Noriko; Miyamoto, Maki; Taniguchi, Takahiko; Iwashita, Hiroki

    2018-04-01

    The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N -methyl-d-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain-penetrant PDE2A inhibitor, ( N -{(1 S )-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3- b ]pyrazine-4(1 H )-carboxamide) (TAK-915) as a novel treatment of schizophrenia. Oral administration of TAK-915 at 3 and 10 mg/kg significantly increased cGMP levels in the frontal cortex, hippocampus, and striatum of rats. TAK-915 at 10 mg/kg significantly upregulated the phosphorylation of α -amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor subunit GluR1 in the rat hippocampus. TAK-915 at 3 and 10 mg/kg significantly attenuated episodic memory deficits induced by the NMDA receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in the rat passive avoidance test. TAK-915 at 10 mg/kg significantly attenuated working memory deficits induced by MK-801 in the rat radial arm maze test. Additionally, TAK-915 at 10 mg/kg prevented subchronic phencyclidine-induced social withdrawal in social interaction in rats. In contrast, TAK-915 did not produce antipsychotic-like activity; TAK-915 had little effect on MK-801- or methamphetamine-induced hyperlocomotion in rats. These results suggest that TAK-915 has a potential to ameliorate cognitive impairments and social withdrawal in schizophrenia. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

    Science.gov (United States)

    Hughes, Robert N; Hancock, Nicola J

    2017-03-15

    For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Effects of an alkaloid-rich extract from Mitragyna speciosa leaves and fluoxetine on sleep profiles, EEG spectral frequency and ethanol withdrawal symptoms in rats.

    Science.gov (United States)

    Cheaha, Dania; Keawpradub, Niwat; Sawangjaroen, Kitja; Phukpattaranont, Pimpimol; Kumarnsit, Ekkasit

    2015-10-15

    Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance. Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms. The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity. The present study

  8. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors.

    Science.gov (United States)

    Bocarsly, Miriam E; Berner, Laura A; Hoebel, Bartley G; Avena, Nicole M

    2011-10-24

    Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague-Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet or a sweet, high-fat diet supplemented with standard rodent chow. Naloxone-precipitated withdrawal was also not seen in rats fed a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substances of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize "food addiction" may be subtyped based on the nutritional composition of the food consumed. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats.

    Science.gov (United States)

    Li, Ming; He, Wei; Munro, Rebecca

    2012-06-01

    Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

  10. Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex.

    Science.gov (United States)

    Sadakierska-Chudy, Anna; Frankowska, Małgorzata; Jastrzębska, Joanna; Wydra, Karolina; Miszkiel, Joanna; Sanak, Marek; Filip, Małgorzata

    2017-07-01

    Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required.

  11. Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.

    Science.gov (United States)

    Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali

    2014-09-01

    Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine.

    Science.gov (United States)

    Bai, Yunjing; Belin, David; Zheng, Xigeng; Liu, Zhengkui; Zhang, Yue

    2017-06-01

    Negative affective states, e.g., anhedonia, are suggested to be involved in the long-lasting motivational processes associated with relapse. Here, we investigated whether anhedonic behaviors could be elicited by an acute stress after protracted abstinence from morphine. The behavioral responses to natural stimuli following exposure to an acute stress were examined after 14 days of withdrawal from morphine. Male rats were pretreated with either a binge-like morphine regimen or daily saline injections for 5 days. The motivation for two natural stimuli, i.e., a social stimulus (male rat) and a sexual stimulus (estrous female rat), was measured, following exposure to an acute stress (intermittent foot shock, 0.5 mA * 0.5 s * 10 min; mean inter-shock interval 40 s), under three conditions: free approach and effort- and conflict-based approaches. Foot-shock-induced stress did not influence free-approach behavior (sniffing time) towards the social or sexual stimulus. However, in the effort-based approach task, the stressed morphine-withdrawn rats demonstrated an attenuated motivation to climb over a partition to approach the social stimulus while the stressed saline-pretreated rats showed an increased motivation to approach the social stimulus. When an aversive stimulus (pins) was introduced in order to induce an approach-avoidance conflict, both drug-withdrawn and drug-naïve groups exhibited a bimodal distribution of approach behavior towards the sexual stimulus after the stress was introduced, i.e., the majority of rats had low risky appetitive behaviors but a minority of them showed rather highly "risky" approach behavior. The acute stress induces differential motivational deficits for social and sexual rewards in protracted drug-abstinent rats.

  13. Administration of memantine during withdrawal mitigates overactivity and spatial learning impairments associated with neonatal alcohol exposure in rats.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

    2014-02-01

    Prenatal alcohol exposure can disrupt central nervous system development, manifesting as behavioral deficits that include motor, emotional, and cognitive dysfunction. Both clinical and animal studies have reported binge drinking during development to be highly correlated with an increased risk of fetal alcohol spectrum disorders (FASD). We hypothesized that binge drinking may be especially damaging because it is associated with episodes of alcohol withdrawal. Specifically, we have been investigating the possibility that NMDA receptor-mediated excitotoxicity occurs during alcohol withdrawal and contributes to developmental alcohol-related neuropathology. Consistent with this hypothesis, administration of the NMDA receptor antagonists MK-801 or eliprodil during withdrawal attenuates behavioral alterations associated with early alcohol exposure. In this study, we investigated the effects of memantine, a clinically used NMDA receptor antagonist, on minimizing ethanol-induced overactivity and spatial learning deficits. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol via intubation on postnatal day (PD) 6, a period of brain development that models late gestation in humans. Controls were intubated with a calorically matched maltose solution. During withdrawal, 24 and 36 hours after ethanol exposure, subjects were injected with a total of either 0, 20, or 30 mg/kg memantine. The subjects' locomotor levels were recorded in open field activity monitors on PDs 18 to 21 and on a serial spatial discrimination reversal learning task on PDs 40 to 43. Alcohol exposure induced overactivity and impaired performance in spatial learning. Memantine administration significantly attenuated the ethanol-associated behavioral alterations in a dose-dependent manner. Thus, memantine may be neuroprotective when administered during ethanol withdrawal. These data have important implications for the treatment of EtOH's neurotoxic effects and provide further support that ethanol withdrawal

  14. Irradiation effects on the adrenal gland of rats undergoing inanition stress

    International Nuclear Information System (INIS)

    Hasan, S.S.; Chaturvedi, P.K.

    1985-01-01

    The effect of total body x-irradiation was studied on rats under inanition stress. In response to irradiation an increase in the activity of cortex and medulla was noted in inanition stress administered rats rather than in the normally fed animals. Similarly, rising levels of urinary catecholamines and 5-hydroxytryptamine were observed in the starved animals after irradiation. (author)

  15. Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

    Science.gov (United States)

    Cruz, Catarina; Meireles, Manuela; Silva, Susana M

    2017-05-01

    Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

    Science.gov (United States)

    Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

    2015-11-01

    Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

    Science.gov (United States)

    Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

    2014-01-01

    This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

  18. Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

    Science.gov (United States)

    Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

    2010-01-07

    We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

  19. Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

    Science.gov (United States)

    Gomez, Gimena; Saborido, Mariano D; Bernardi, M Alejandra; Gershanik, Oscar S; Taravini, Irene R; Ferrario, Juan E

    2018-02-14

    L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Cardiac impairment evaluated by transesophageal echocardiography and invasive measurements in rats undergoing sinoaortic denervation.

    Directory of Open Access Journals (Sweden)

    Raquel A Sirvente

    Full Text Available BACKGROUND: Sympathetic hyperactivity may be related to left ventricular (LV dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE using intracardiac echocardiographic catheter. METHODS AND RESULTS: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD. The rats (n = 32 were divided into 4 groups: 16 Wistar (W with (n = 8 or without SAD (n = 8 and 16 spontaneously hypertensive rats (SHR with (n = 8 or without SAD (SHRSAD (n = 8. Blood pressure (BP and heart rate (HR did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. CONCLUSIONS: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.

  1. 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

  2. The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats.

    Science.gov (United States)

    Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

    2016-03-01

    Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain, and its abnormalities have been linked to schizophrenia. The present study was designed to investigate the ability of the NO donor sodium nitroprusside (SNP) to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. The ability of SNP to reverse ketamine-induced memory deficits and social withdrawal were assessed using the novel object recognition task (NORT) and the social interaction test, respectively. Furthermore, since anxiety disorders are noted to occur commonly in schizophrenics, the effects of SNP on anxiety-like behaviour were examined using the light/dark test. Locomotor activity was also assessed as an independent measure of the potential motoric effects of this NO donor. SNP (0.3 and 1 mg/kg) reversed ketamine (3 mg/kg)-induced short-term recognition memory deficits. SNP (1 mg/kg) counteracted the ketamine (8 mg/kg)-induced social isolation in the social interaction test. The anxiolytic-like effects in the light/dark test of SNP (1 mg/kg) cannot be attributed to changes in locomotor activity. Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia-like behavioural deficits. The data also suggest a role of NO in anxiety.

  3. Biomechanical findings in rats undergoing fascial reconstruction with graft materials suggested as an alternative to polypropylene.

    Science.gov (United States)

    Konstantinovic, M L; Ozog, Y; Spelzini, F; Pottier, C; De Ridder, D; Deprest, J

    2010-03-01

    Graft materials used for pelvic floor reinforcement should still be considered as investigational and, therefore, evaluated experimentally and within clinical trials. The present report describes our biomechanical findings in rats implanted with selected novel implant materials, which in recent years have been suggested as alternatives to plain polypropylene (PP) meshes. Full thickness abdominal wall defects were primarily repaired by the implant of interest. Experiments involved eight different implant materials: two partly degradable synthetic implants, that is, a hybrid of polyglactin 910 with PP (Vypro II) and collagen coated PP (Pelvitex); two non-cross linked (Surgisis, InteXēn LP) and two cross-linked materials (Pelvicol, Pelvisoft) and two porous modifications of InteXēn LP and Pelvicol implants. At different time points (7, 14, 30, and 90 days), the implants and surrounding host tissue (explant) were harvested and tensiometry was performed. Tensile strength and location of breakage were recorded. In general resorbable non-cross linked collagen matrices and porous materials were weaker after 90 days; similar behavior was seen for implant materials alone and their construction with the surrounding native tissue. Both non-porous and porous modification of InteXēn LP appeared at 90 days as a very thin layer of collagen that was two-thirds, respectively one-third of the initial thickness. In experimental conditions, sufficient strength was obtained only after 3 months, and PP containing constructs appeared as the strongest though reconstruction with Pelvicol showed comparable outcomes. Lower values for strength of non-cross linked and porous collagen materials are questioning their efficacy for pelvic floor reconstruction. (c) 2009 Wiley-Liss, Inc.

  4. 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. ...

  5. Withdrawal from high-carbohydrate, high-saturated-fat diet changes saturated fat distribution and improves hepatic low-density-lipoprotein receptor expression to ameliorate metabolic syndrome in rats.

    Science.gov (United States)

    Hazarika, Ankita; Kalita, Himadri; Kalita, Mohan Chandra; Devi, Rajlakshmi

    2017-06-01

    The "lipid hypothesis" determined that saturated fatty acid (SFA) raises low-density lipoprotein cholesterol, thereby increasing the risk for metabolic syndrome (MetS). The aim of this study was to investigate the effect of subchronic withdrawal from a high-carbohydrate, high-saturated fat (HCHF) diet during MetS with reference to changes in deleterious SFA (C12:0, lauric acid; C14:0, myristic acid; C16:0, palmitic acid; C18:0, stearic acid) distribution in liver, white adipose tissue (WAT), and feces. MetS induced by prolonged feeding of an HCHF diet in Wistar albino rat is used as a model of human MetS. The MetS-induced rats were withdrawn from the HCHF diet and changed to a basal diet for final 4 wk of the total experimental duration of 16 wk. SFA distribution in target tissues and hepatic low-density lipoprotein receptor (LDLr) expression were analyzed. Analyses of changes in SFA concentration of target tissues indicate that C16:0 and C18:0 reduced in WAT and liver after withdrawal of the HCHF diet. There was a significant (P < 0.001) decrease in fecal C12:0 with HCHF feeding, which significantly (P < 0.01) increased after withdrawal of this diet. Also, an improvement in expression of hepatic LDLr was observed after withdrawal of HCHF diet. The prolonged consumption of an HCHF diet leads to increased SFA accumulation in liver and WAT, decreased SFA excretion, and reduced hepatic LDLr expression during MetS, which is prominently reversed after subchronic withdrawal of the HCHF diet. This can contribute to better understanding of the metabolic fate of dietary SFA during MetS and may apply to the potential reversal of complications by the simple approach of nutritional modification. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal

    International Nuclear Information System (INIS)

    Kobayashi, Haruo; Suzuki, Tadahiko; Sakamoto, Maki; Hashimoto, Wataru; Kashiwada, Keiko; Sato, Itaru; Akahori, Fumiaki; Satoh, Tetsuo

    2007-01-01

    Activity of acetylcholinesterase (AChE) and specific binding of [ 3 H]quinuclidinyl benzilate (QNB), [ 3 H]pirenzepine (PZP) and [ 3 H]AF-DX 384 to muscarinic acetylcholine receptor (mAChR) preparations in the striatum, hippocampus and cortex of rats were determined 1, 6 and 11 days after the last treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly decreased in the three regions 1 day after the treatment with DDVP for 7 and 14 days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11 days after the treatment with propoxur for 7 days but not for 14 days in the hippocampus and cortex. The binding of [ 3 H]-QNB, PZP and AF-DX 384 in the three regions was generally decreased by the treatment with DDVP for 7 and 14 days. Such down-regulations were generally restored 6 or 11 days after the treatment for 7 but not for 14 days. The down-regulation or up-regulation as measured by [ 3 H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced similar effects except AChE activity to DDVP. These results suggest that repeated inhibition of AChE activity may usually cause down-regulation of mAChRs with some exception in the hippocampus when a reversible antiChE propoxur is injected

  7. Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

    2011-02-01

    Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine whether administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. Copyright © 2010 by the Research Society on Alcoholism.

  8. Determination of μ-, δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal.

    Science.gov (United States)

    Ujcikova, Hana; Hlouskova, Martina; Cechova, Kristina; Stolarova, Katerina; Roubalova, Lenka; Svoboda, Petr

    2017-01-01

    Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC) of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on μ-, δ- and κ-OR protein levels in FBC. Rats were exposed to increasing doses of morphine (10-40 mg/kg) for 10 days and sacrificed either 24 h (group +M10) or 20 days (group +M10/-M20) after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20). Post-nuclear supernatant (PNS) fraction was prepared from forebrain cortex, resolved by 1D-SDS-PAGE under non-dissociated (-DTT) and dissociated (+DTT) conditions, and analyzed for the content of μ-, δ- and κ-OR by immunoblotting with C- and N-terminus oriented antibodies. Significant down-regulation of δ-OR form exhibiting Mw ≈ 60 kDa was detected in PNS prepared from both (+M10) and (+M10/-M20) rats. However, the total immunoblot signals of μ-, δ- and κ-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10) rats and this increase was reversed back to control level in (+M10/-M20) rats. In FBC, prolonged exposure of rats to morphine results in minor (δ-OR) or no change (μ- and κ-OR) of opioid receptor content. The reversible increases

  9. Determination of μ-, δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal.

    Directory of Open Access Journals (Sweden)

    Hana Ujcikova

    Full Text Available Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold and II (2.5-fold. The other isoforms of AC (III-IX were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on μ-, δ- and κ-OR protein levels in FBC.Rats were exposed to increasing doses of morphine (10-40 mg/kg for 10 days and sacrificed either 24 h (group +M10 or 20 days (group +M10/-M20 after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20. Post-nuclear supernatant (PNS fraction was prepared from forebrain cortex, resolved by 1D-SDS-PAGE under non-dissociated (-DTT and dissociated (+DTT conditions, and analyzed for the content of μ-, δ- and κ-OR by immunoblotting with C- and N-terminus oriented antibodies.Significant down-regulation of δ-OR form exhibiting Mw ≈ 60 kDa was detected in PNS prepared from both (+M10 and (+M10/-M20 rats. However, the total immunoblot signals of μ-, δ- and κ-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10 rats and this increase was reversed back to control level in (+M10/-M20 rats.In FBC, prolonged exposure of rats to morphine results in minor (δ-OR or no change (μ- and κ-OR of opioid receptor content. The reversible increases

  10. Evaluation of Pulmonary Reperfusion Injury in Rats Undergoing Mesenteric Ischemia and Reperfusion and Protective Effect of Postconditioning on this Process

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Marques dos Santos

    2015-10-01

    Full Text Available ABSTRACT INTRODUCTION: Some publications have demonstrated the presence of lung reperfusion injury in mesenteric ischemia and reperfusion (I/R, but under to diverse methods. Postconditioning has been recognized as effective in preventing reperfusion injury in various organs and tissues. However, its effectiveness has not been evaluated in the prevention of lung reperfusion injury after mesenteric ischemia and reperfusion. OBJECTIVE: To evaluate the presence of pulmonary reperfusion injury and the protective effect of ischemic postconditioning on lung parenchyma in rats submitted to mesenteric ischemia and reperfusion. METHODS: Thirty Wistar rats were distributed into three groups: group A (10 rats, which was held mesenteric ischemia (30 minutes and reperfusion (60 minutes; group B (10 rats, ischemia and reperfusion, interspersed by postconditioning with two alternating cycles of reperfusion and reocclusion, for two minutes each; and group C (10 rats, ischemia and reperfusion interleaved by postconditioning with four alternating cycles of reperfusion and reocclusion of 30 seconds each. Finally, it was resected the upper lung lobe for histological analysis. RESULTS: There were mild lung lesions (grade 1 in all samples. There was no statistical difference between groups 1 and 2 (P >0.05. CONCLUSION: The mesenteric ischemia and reperfusion in rats for thirty and sixty minutes, respectively, caused mild reperfusion injury in lung. Postconditioning was not able to minimize the remote reperfusion injury and there was no difference comparing two cycles of two minutes with four cycles of 30 seconds.

  11. Neonatal opioid withdrawal syndrome.

    Science.gov (United States)

    Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

    2014-06-01

    Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The Acute Administration of the Selective Dopamine D3 Receptor Antagonist SB-277011A Reverses Conditioned Place Aversion Produced by Naloxone Precipitated Withdrawal From Acute Morphine Administration in Rats

    Science.gov (United States)

    RICE, ONARAE V.; GARDNER, ELIOT L.; HEIDBREDER, CHRISTIAN A.; ASHBY, CHARLES R.

    2014-01-01

    We examined the effect of SB-277011A, a selective D3 receptor antagonist, on the conditioned place aversion (CPA) response associated with naloxone-induced withdrawal from acute morphine administration in male Sprague-Dawley rats. Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg i.p.) and prior to placing the animals in one specific chamber of the test apparatus. All animals were subjected to 2 of these trials. A significant CPA occurred in animals that received an i.p. injection of vehicle 30 minutes prior to the measurement of chamber preference. The pretreatment of animals (30 minutes prior to testing) with 3 mg/kg i.p. of SB-277011A did not significantly alter the CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg i.p. of SB-277011A significantly decreased the CPA compared to vehicle-treated animals. In fact, the 12 and 24 mg/kg doses of SB-277011A significantly increased the time spent in the chamber where animals were paired with morphine and naloxone. These results suggest that the selective antagonism of D3 receptors attenuates the CPA produced by a model of naloxone-induced withdrawal from acute morphine dependence. PMID:21905128

  13. Treatment for amphetamine withdrawal.

    Science.gov (United States)

    Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

    2009-04-15

    Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine

  14. Analysis of activity and motor coordination in rats undergoing stereotactic surgery and implantation of a cannula into the dorsal hippocampus.

    Science.gov (United States)

    Hernández-López, F; Rodríguez-Landa, J F; Puga-Olguín, A; Germán-Ponciano, L J; Rivadeneyra-Domínguez, E; Bernal-Morales, B

    Stereotactic surgery is used to place electrodes or cannulas in the brain in order to study the function of several brain structures in preclinical research. The hippocampus has been extensively studied with this methodology due to its involvement in a wide range of neurological, cognitive, emotional, and affective disorders. However, the effects of stereotactic surgery on coordination and motor activity should be evaluated in order to determine whether this surgical procedure causes any neurological alterations that may bias the results of studies incorporating this technique. We evaluated the effects of stereotactic surgery and implantation of a cannula into the hippocampus of female Wistar rats on the motor activity, forced swim, and rotarod tests. The stage of the oestrous cycle was included in the statistical analysis. Stereotactic surgery had no impact on any of the motor activity variables assessed in the open field (squares crossed, time spent in grooming, and rearing), forced swim (turning behaviour, lateral swimming, latency to first immobility, and time spent immobile), and rotarod (latency to fall) tests, compared with intact rats. Regardless of surgical manipulation, rats in the metestrus and diestrus stages crossed a greater number of squares and displayed longer immobility times than those in the proestrus and estrus stages. Stereotactic surgery for cannula placement in the dorsal hippocampus does not affect coordination and motor activity in rats. We can therefore conclude that this procedure has no neurological complications that may interfere in the interpretation of results of studies applying this technique. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

    Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  16. Vagal withdrawal during endoscopic retrograde cholangiopancreatography

    DEFF Research Database (Denmark)

    Christensen, M; Rasmussen, Verner; Schulze, S

    2000-01-01

    BACKGROUND: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk of developing cardiorespiratory complications, but the mechanism is still unknown. Treatment with metoprolol 2 h before the endoscopy has been shown to decrease the incidence of myocardial ischaemia......: The existence of a defence-like reaction ('vagal withdrawal') during ERCP has been shown. Metoprolol given 2 h before the procedure did not affect the occurrence of this phenomenon. The interaction of other periendoscopic factors is still unclear and should be studied further....

  17. Psychosis following Tramadol Withdrawal

    OpenAIRE

    Rajabizadeh, Ghodratolah; Kheradmand, Ali; Nasirian, Mansoureh

    2009-01-01

    Background: Tramadol is a centrally acting opioid analgesic used to treat moderate to sever pain. It has more advantage and less opioid adverse effects than conventional opioid analgesia. Case Report: This article reports a patient with tramadol dependency that had psychosis after tramadol withdrawal. Conclusion: By the increase of tramadol usage for relief of chronic pain, tramadol abuse and dependency is increased. Some of tramadol withdrawal symptoms are not related to opioid, for example ...

  18. Comparative analysis of the number of neurofilaments in rat sciatic nerve undergoing neuropraxia treated by low-level laser and therapeutic ultrasound

    International Nuclear Information System (INIS)

    Matamala, F; Cornejo, R; Paredes, M; Farfan, E; Garrido, O. S; Alves, N

    2014-01-01

    Therapy by low-level laser (LLL) or ultrasound (US) are commonly used as treatment after nerve crush. The aim of this study was to determine the effectiveness of such treatments to repair the neuronal cytoskeleton evaluating the variation in the number of neurofilaments. For this an experimental design was performed, which involved 30 rats divided into 6 groups: 1 - control healthy; 2 - control injured; 3 - irradiated by LLL 2 J/cm2; 4 - irradiated by LLL 10 J/cm2; 5 - irradiated by US 0.5 W/cm2 and 6 - irradiated by US 1W/cm2. With the exception of group 1 all specimens were anesthetized and underwent right sciatic nerve compression using 40N pressure for 45 seconds. Twenty-four hours after compression irradiation was started by LLL and US according protocol. In our research we found that the increase in the number of neurofilaments was related to the applied dose of LLL and US. The average value of neurofilaments / 0.25 mm2 obtained in each group was: 1 - 128; 2-100; 3-156; 4-140; 5-100; 6-148. We concluded that the application of LLL and therapeutic US increases the number of neurofilaments in rat sciatic nerve undergoing neuropraxia, with LLL being more effective compared to the US. Furthermore we concluded that the effectiveness of therapies to induce regeneration of injured nerve is related to the type of protocol used, demonstrating the need to establish an adequate radiation dose with the purpose of obtaining the best therapeutic response, thus achieving successful treatment [es

  19. Impact of different analgesic depths and abdominal trauma of different severities on stress and recovery of rats undergoing total intravenous anesthesia

    Directory of Open Access Journals (Sweden)

    Huang HM

    2017-05-01

    Full Text Available Hai-ming Huang,1,2 Jun Cao,3 Lin-mei Zhu,4 Yu-qing Chen,2 Fu-ding Lu,2 Hong-wei Cai1 1Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 2Department of Anesthesiology, 3Department of Hepatic and Biliary Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 4Department of Obstetrics and Gynecology, Clifford Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China Abstract: A number of animal models have been developed to examine the pathophysiological consequences of surgical procedures, but anesthetic methods, monitoring, and management measures in these models are very different from those used in humans. This study was designed to create a rat model of abdominal surgery using anesthetic methods and perioperative treatment similar to those used in the clinic and to investigate the effects of different injury severities and depths of anesthesia and analgesia on surgical stress and postoperative recovery. Abdominal skin/muscle incision was compared with exploratory laparotomy in rats under propofol intravenous anesthesia, accompanied by perioperative measures such as oxygen inhalation, fluid infusion, warmth, blood gas analysis, and infection prevention. Stress indices (mean arterial pressure, heart rate, blood glucose, and plasma corticosterone were monitored during anesthesia and surgery, and recovery indicators (body weight, food consumption, and pain were measured after surgery. In addition, animals undergoing laparotomy were subjected to low and high dosages of propofol and sufentanil, in order to examine the relationship between anesthetic and analgesic depth and stress on recovery. Exploratory laparotomy induced a greater stress response and caused slower postoperative recovery as measured than somatic injury. High-dose sufentanil downregulated plasma corticosterone and improved postoperative recovery more effectively than high-dose propofol (P<0

  20. Effect of Hydro Alcoholic Ginger Extracts on the Body Weight, Testis Weight and Spermatogenesis in Male Rats Undergoing Chemotherapy with Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    E Sharifi

    2010-03-01

    Full Text Available Introduction: Cyclophosphamide is used as an anti cancer medicine in chemotherapy. This is an alkalizing medicine and causes the binding of DNA strands, breaking of DNA and control of protein synthesis and RNA. The side effects of this medicine include lack of appetite, nausea, reduction in activity of sexual lymph nodes, causing amenorrhea, azoospermia and oligospermia. Ginger includes many compounds, some of which are shogaols, gingerols, pyrogallols and sesquiterpenes. Ginger has anti nauseating, anti cancer, anti oxidant effects and eliminates free radicals. This medicine is used along with cyclophosphamide to reduce its destructive side effects in the body. Methods: For 21 days, the rats were fed with ginger and cyclophosphamide. After 21 days, the animals were weighed and rendered unconscious. Their testes were removed and tissue samples were provided from their testes. Results: The results showed that cyclophosphamide alone reduces body weight, testes weight and spermatogenesis as compared to the control group. In other experimental groups that were fed with ginger and cyclophosphamide, increased dosage of ginger increased the body weight, the testes weight and spermatogenesis in comparison to the other experimental groups. Conclusion: It seems that compounds present in ginger are anti tumoral and control the production of active metabolites. Therefore, if administered together with Cyclophosphamide, it can be useful and effective in patients undergoing chemotherapy.

  1. The alcohol withdrawal syndrome.

    LENUS (Irish Health Repository)

    McKeon, A

    2008-08-01

    The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

  2. Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

    OpenAIRE

    Breese, George R; Knapp, Darin J; Overstreet, David H

    2004-01-01

    Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposur...

  3. Conducting a Withdrawal Survey.

    Science.gov (United States)

    Aldridge, Sue; Rowley, Jennifer

    2001-01-01

    A survey at Edge Hill College of Higher Education in Canada, designed to be part of the mechanism for monitoring and evaluating the quality of the student experience, revealed that key factors influencing withdrawal were: course not as expected, traveling difficulties, institution not as expected, domestic difficulties, and financial difficulties.…

  4. Anticonvulsants for alcohol withdrawal.

    Science.gov (United States)

    Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

    2010-03-17

    Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. Two authors independently screened and extracted data from studies. Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results

  5. Is this ?complicated? opioid withdrawal?

    OpenAIRE

    Parkar, S.R.; Seethalakshmi, R; Adarkar, S; Kharawala, S

    2006-01-01

    Seven patients with opioid dependence admitted in the de-addiction centre for detoxification developed convulsions and delirium during the withdrawal phase. After ruling out all other possible causes of these complications, opioid withdrawal seemed to emerge as the most likely explanation. The unpredictability of the course of opioid dependence and withdrawal needs to be considered when treating patients with opioid dependence.

  6. Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential.

    Directory of Open Access Journals (Sweden)

    Eleonora Bassino

    Full Text Available Catestatin (Cst is a 21-amino acid peptide deriving from Chromogranin A. Cst exerts an overall protective effect against an excessive sympathetic stimulation of cardiovascular system, being able to antagonize catecholamine secretion and to reduce their positive inotropic effect, by stimulating the release of nitric oxide (NO from endothelial cells. Moreover, Cst reduces ischemia/reperfusion (I/R injury, improving post-ischemic cardiac function and cardiomyocyte survival. To define the cardioprotective signaling pathways activated by Cst (5 nM we used isolated adult rat cardiomyocytes undergoing simulated I/R. We evaluated cell viability rate with propidium iodide labeling and mitochondrial membrane potential (MMP with the fluorescent probe JC-1. The involvement of Akt, GSK3β, eNOS and phospholamban (PLN cascade was studied by immunofluorescence. The role of PI3K-Akt/NO/cGMP pathway was also investigated by using the pharmacological blockers wortmannin (Wm, L-NMMA and ODQ. Our experiments revealed that Cst increased cell viability rate by 65% and reduced cell contracture in I/R cardiomyocytes. Wm, L-NMMA and ODQ limited the protective effect of Cst. The protective outcome of Cst was related to its ability to maintain MMP and to increase AktSer473, GSK3βSer9, PLNThr17 and eNOSSer1179 phosphorylation, while treatment with Wm abolished these effects. Thus, the present results show that Cst is able to exert a direct action on cardiomyocytes and give new insights into the molecular mechanisms involved in its protective effect, highlighting the PI3K/NO/cGMP pathway as the trigger and the MMP preservation as the end point of its action.

  7. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

    Directory of Open Access Journals (Sweden)

    Beng-Siang Khor

    Full Text Available A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.

  8. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2011-01-01

    Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

  9. CONSUMER'S RIGHT TO WITHDRAW

    Directory of Open Access Journals (Sweden)

    ANCA NICOLETA GHEORGHE

    2013-05-01

    Full Text Available The right of withdrawal (of a contract belongs to the consumer, and is an essential means for the improvement of regulations that protect the consumer.. Right of withdrawal is not a recent creation and is not even specific to the consumer field. He was previously recognized in civil and commercial law (without special regulation. The right to withdraw may even have as ground the parties will. Thus, based on the contractual freedom, the parties may agree that one of them has the right to terminate the contract unilaterally The possibility of unilateral denunciation of the contract, gives the consumer, added protection by being able to reflect the decision and to check how the trader fulfil its obligations. In this context, through its effects, the right of denunciation, forces the professional parties to conduct themselves as fair as possible to the consumer and to execute the contract properly. In the study of the consumer protection, the time of conclusion is essential because in this stage is manifested, the inequality between the consumer and professional. Thus, the lack of information, the major of products and activities, commercial practices, influence the formation of consumer will, preventing the expression of a freely and knowingly consent.

  10. Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates

    Directory of Open Access Journals (Sweden)

    Haspel Gal

    2010-12-01

    Full Text Available Abstract Background Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy. Results RTX was injected into rat hind paws (mid-plantar to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm, high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm, long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin are upregulated in the dorsal root ganglia (DRG when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG, although induced

  11. Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease

    International Nuclear Information System (INIS)

    Kubota, Sumihisa; Ohye, Hidemi; Yano, Genichiro; Nishihara, Eijun; Kudo, Takumi; Ito, Mitsuru; Fukata, Shuji; Amino, Nobuyuki; Kuma, Kanji; Miyauchi, Akira

    2006-01-01

    The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy. (author)

  12. Narp regulates long-term aversive effects of morphine withdrawal

    Science.gov (United States)

    Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

    2008-01-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

  13. Acupuncture for alcohol withdrawal: a randomized controlled trial.

    Science.gov (United States)

    Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

    2003-01-01

    Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

  14. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

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    Robin W. Rockhold

    2002-10-01

    Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

  15. Afghanistan after NATO Withdrawal

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    Bojor Laviniu

    2015-06-01

    Full Text Available The conclusion of a conflict, called by some American analysts as “America’s Longest War”, after the withdrawal of the majority of NATO military forces, requires a careful analysis of the conditions and security environment that ISAF mission, International Security Afghan Forces, leaves as legacy to the Afghan military forces. The transfer of authority towards a strong government, recognized by most Afghan provinces, and benefiting from the support of national military forces able to cope with terrorist and insurgent threats on its own, are the minimum and necessary conditions leading the country towards a stable and secure environment and towards a sustainable development. Given these realities, any approach on the consequences of the transition towards self-sustainable governance becomes interesting and timely for any military political study. These are the prospects that we propose in our paper.

  16. The function of androgen/androgen receptor and insulin growth factor‑1/insulin growth factor‑1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise.

    Science.gov (United States)

    Wu, Yin; Yang, Hongfang; Wang, Xiaohui

    2017-09-01

    Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment. The rats of the E and E+TT groups underwent high intensity exercise with a progressively increasing load for 5 weeks, and TT extracts were intragastrically administered in the TT and E+TT rats 30 min prior to training. TT extract composition was analyzed using ultra‑high performance liquid chromatography‑quadrupole‑time of flight mass spectrometry. Testosterone and IGF‑1 plasma levels and AR, IGF‑1R and myosin heavy chain (MHC) protein levels in muscles were determined by ELISA and western blotting, respectively. The saponins tigogenin and diosgenin comprised ~71.35% of the total peak area. Compared with the E group, TT extracts increased the testosterone and IGF‑1 plasma levels, and AR, IGF‑1R and MHC protein levels in the gastrocnemius of rats undergoing high intensity exercise, accompanied with increased body weight and gastrocnemius weight. In conclusion, the effect of TT extracts on the performance of high intensity exercise rats may be attributed to increased levels of circulating testosterone and IGF‑1 and increased AR and IGF‑1R protein expression levels in the gastrocnemius, resulting in increased muscle weight and increased MHC in the gastrocnemius. The present study provided preliminary evidence supporting the use of TT extracts as a dietary supplement for the promotion of skeletal muscle mass increase and the

  17. Control rod withdrawal monitoring device

    International Nuclear Information System (INIS)

    Ebisuya, Mitsuo.

    1984-01-01

    Purpose: To prevent the power ramp even if a plurality of control rods are subjected to withdrawal operation at a time, by reducing the reactivity applied to the reactor. Constitution: The control rod withdrawal monitoring device is adapted to monitor and control the withdrawal of the control rods depending on the reactor power and the monitoring region thereof is divided into a control rod group monitoring region a transition region and a control group monitoring not interfere region. In a case if the distance between a plurality of control rods for which the withdrawal positions are selected is less than a limiting value, the coordinate for the control rods, distance between the control rods and that the control rod distance is shorter are displayed on a display panel, and the withdrawal for the control rods are blocked. Accordingly, even if a plurality of control rods are subjected successively to the withdrawal operation contrary to the control rod withdrawal sequence upon high power operation of the reactor, the power ramp can be prevented. (Kawakami, Y.)

  18. Ethical Analysis of Withdrawing Total Artificial Heart Support.

    Science.gov (United States)

    DeMartino, Erin S; Wordingham, Sara E; Stulak, John M; Boilson, Barry A; Fuechtmann, Kayla R; Singh, Nausheen; Sulmasy, Daniel P; Pajaro, Octavio E; Mueller, Paul S

    2017-05-01

    To describe the characteristics of patients who undergo withdrawal of total artificial heart support and to explore the ethical aspects of withdrawing this life-sustaining treatment. We retrospectively reviewed the medical records of all adult recipients of a total artificial heart at Mayo Clinic from the program's inception in 2007 through June 30, 2015. Management of other life-sustaining therapies, approach to end-of-life decision making, engagement of ethics and palliative care consultation, and causes of death were analyzed. Of 47 total artificial heart recipients, 14 patients or their surrogates (30%) requested withdrawal of total artificial heart support. No request was denied by treatment teams. All 14 patients were supported with at least 1 other life-sustaining therapy. Only 1 patient was able to participate in decision making. It is widely held to be ethically permissible to withdraw a life-sustaining treatment when the treatment no longer meets the patient's health care-related goals (ie, the burdens outweigh the benefits). These data suggest that some patients, surrogates, physicians, and other care providers believe that this principle extends to the withdrawal of total artificial heart support. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  19. Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

    Science.gov (United States)

    Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

    2018-03-27

    The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

  20. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

    Science.gov (United States)

    Kreipke, R E; Birren, S J

    2015-12-01

    Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  1. Neuro, cardio, and reno protective activities of rosuvastatin in streptozotocin-induced type 2 diabetic rats undergoing treatment with metformin and glimepiride

    Directory of Open Access Journals (Sweden)

    Shailaja Rondi

    2014-01-01

    Full Text Available Diabetes is associated with complications like neuropathy, nephropathy, cardiomyopathy, and retinopathy due to increased oxidative stress and serum lipids. In the present study, rosuvastatin, a HMG-CoA inhibitor, was investigated for its protective effect in neuropathy, nephropathy, and cardiomyopathy based on the lipid-lowering property along with its pleiotropic effects such as improved blood flow to the organ and antioxidant defense. Type 2 diabetes was induced in Wistar rats by single i.p. administration of streptozotocin (50 mg/kg. These diabetic rats were treated with daily doses of rosuvastatin (10 mg/kg alone, metformin (120 mg/kg and glimepiride (1 mg/kg and rosuvastatin in combination with metformin (120 mg/kg and glimepiride (1 mg/kg for a period of 6 weeks. The biochemical parameters involved in neuropathy, renopathy, and cardiopathy were estimated. Treatment resulted in significant (P < 0.05 decrease in thiobarbituric acid reactive substances (TBARS and increase in levels of glutathione peroxidise and catalase in brain and kidney homogenates. Significant (P < 0.05 increase in high-density lipoproteins and decrease in creatinine kinase, triglycerides, total serum cholesterol represents the cardioprotective action, whereas significant (P < 0.05 increase in the latency in the hotplate model shows the neuroprotective activity, and significant (P < 0.05 decrease in blood urea nitrogen, creatinine levels and increase in serum total protein levels suggested the renoprotective actions. The unique properties of rosuvastatin such as antioxidant defense and lipid-lowering nature might have resulted in cardio, neuro, and renoprotective activity in type 2 diabetic rats treated with metformin and glimepiride.

  2. NMDA receptor subunits in the adult rat hippocampus undergo similar changes after 5 minutes in an open field and after LTP induction.

    Directory of Open Access Journals (Sweden)

    Maria Veronica Baez

    Full Text Available NMDA receptor subunits change during development and their synaptic expression is modified rapidly after synaptic plasticity induction in hippocampal slices. However, there is scarce information on subunits expression after synaptic plasticity induction or memory acquisition, particularly in adults. GluN1, GluN2A and GluN2B NMDA receptor subunits were assessed by western blot in 1 adult rats that had explored an open field (OF for 5 minutes, a time sufficient to induce habituation, 2 mature rat hippocampal neuron cultures depolarized by KCl and 3 hippocampal slices from adult rats where long term potentiation (LTP was induced by theta-burst stimulation (TBS. GluN1 and GluN2A, though not GluN2B, were significantly higher 70 minutes--but not 30 minutes--after a 5 minutes session in an OF. GluN1 and GluN2A total immunofluorescence and puncta in neurites increased in cultures, as evaluated 70 minutes after KCl stimulation. Similar changes were found in hippocampal slices 70 minutes after LTP induction. To start to explore underlying mechanisms, hippocampal slices were treated either with cycloheximide (a translation inhibitor or actinomycin D (a transcription inhibitor during electrophysiological assays. It was corroborated that translation was necessary for LTP induction and expression. The rise in GluN1 depends on transcription and translation, while the increase in GluN2A appears to mainly depend on translation, though a contribution of some remaining transcriptional activity during actinomycin D treatment could not be rouled out. LTP effective induction was required for the subunits to increase. Although in the three models same subunits suffered modifications in the same direction, within an apparently similar temporal course, further investigation is required to reveal if they are related processes and to find out whether they are causally related with synaptic plasticity, learning and memory.

  3. A 'symptom-triggered' approach to alcohol withdrawal management.

    Science.gov (United States)

    Murdoch, Jay; Marsden, Janet

    In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms.

  4. Alcohol Withdrawal Mimicking Organophosphate Poisoning

    Directory of Open Access Journals (Sweden)

    Nezihat Rana Disel

    2014-02-01

    Full Text Available Organophosphates, which can cause occupational poisoning due to inappropriate personal protective measures, are widely used insecticides in agricultural regions of southern Turkey. Therefore, the classical clinical findings of this cholinergic poisoning are myosis, excessive secretions, bradicardia and fasciculations are easy to be recognized by local medical stuff. Diseases and conditions related to alcoholism such as mental and social impairments, coma, toxicity, withdrawal, and delirium are frequent causes of emergency visits of chronic alcoholic patients. Here we present a case diagnosed and treated as organophosphate poisoning although it was an alcohol withdrawal in the beginning and became delirium tremens, due to similar symptoms.

  5. Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

    Science.gov (United States)

    Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

    2018-01-01

    A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

  6. MALDI-TOF mass spectrometry analysis of small molecular weight compounds (under 10 KDa) as biomarkers of rat hearts undergoing arecoline challenge.

    Science.gov (United States)

    Chen, Tung-Sheng; Chang, Mu-Hsin; Kuo, Wei-Wen; Lin, Yueh-Min; Yeh, Yu-Lan; Day, Cecilia Hsuan; Lin, Chien-Chung; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang

    2013-04-01

    Statistical and clinical reports indicate that betel nut chewing is strongly associated with progression of oral cancer because some ingredients in betel nuts are potential cancer promoters, especially arecoline. Early diagnosis for cancer biomarkers is the best strategy for prevention of cancer progression. Several methods are suggested for investigating cancer biomarkers. Among these methods, gel-based proteomics approach is the most powerful and recommended tool for investigating biomarkers due to its high-throughput. However, this proteomics approach is not suitable for screening biomarkers with molecular weight under 10 KDa because of the characteristics of gel electrophoresis. This study investigated biomarkers with molecular weight under 10 KDa in rats with arecoline challenge. The centrifuging vials with membrane (10 KDa molecular weight cut-off) played a crucial role in this study. After centrifuging, the filtrate (containing compounds with molecular weight under 10 KDa) was collected and spotted on a sample plate for MALDI-TOF mass spectrometry analysis. Compared to control, three extra peaks (m/z values were 1553.1611, 1668.2097 and 1740.1832, respectively) were found in sera and two extra peaks were found in heart tissue samples (408.9719 and 524.9961, respectively). These small compounds should play important roles and may be potential biomarker candidates in rats with arecoline. This study successfully reports a mass-based method for investigating biomarker candidates with small molecular weight in different types of sample (including serum and tissue). In addition, this reported method is more time-efficient (1 working day) than gel-based proteomics approach (5~7 working days).

  7. Water withdrawals in Florida, 2012

    Science.gov (United States)

    Marella, Richard L.

    2015-09-01

    In 2012, the total amount of water withdrawn in Florida was estimated to be 14,237 million gallons per day (Mgal/d). Saline water accounted for 7,855 Mgal/d (55 percent), and freshwater accounted for 6,383 Mgal/d (45 percent). Groundwater accounted for 4,167 Mgal/d (65 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,216 Mgal/d (35 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. Freshwater withdrawals were greatest in Palm Beach County (682 Mgal/d), and saline-water withdrawals were greatest in Pasco County (1,822 Mgal/d). Fresh groundwater provided drinking water (through either public supply or private domestic wells) for 17.699 million residents (93 percent of Florida’s population), and fresh surface water provided drinking water for 1.375 million residents (7 percent). The statewide public-supply gross per capita water use for 2012 was estimated at 136 gallons per day.

  8. Buprenorphine for managing opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M; Mbewe, Dalitso

    2017-02-21

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. To assess the effects of buprenorphine versus tapered doses of methadone, alpha 2 -adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha 2 -adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. We used standard methodological procedures expected by Cochrane. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to

  9. Prediction of withdrawal symptoms during opioid detoxification

    NARCIS (Netherlands)

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

    2008-01-01

    OBJECTIVE: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of

  10. The benzodiazepine withdrawal syndrome and its management.

    OpenAIRE

    Onyett, S R

    1989-01-01

    The literature on benzodiazepine dependence and withdrawal is reviewed with an emphasis on social and psychological considerations. The problems of when to prescribe, identifying withdrawal symptoms, effective communication with the patient, the structure of withdrawal programmes, and the use of drugs, psychological approaches and other services are discussed.

  11. Prediction of withdrawal symptoms during opioid detoxification

    NARCIS (Netherlands)

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

    2008-01-01

    Objective: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of

  12. Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

    Science.gov (United States)

    Choi, Byung In; Choi, Seung Ho; Shin, Yang-Sik; Lee, Sung Jin; Yoon, Kyung Bong; Shin, Seo Kyung

    2008-01-01

    Purpose The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. Materials and Methods Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n = 30), 0.5 µg/kg remifentanil (Group II, n = 30) or 1 µg/kg remifentanil (Group III, n = 30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. Results The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. Conclusion The pretreatment with 0.5 and 1.0 µg/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation. PMID:18452256

  13. Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

    Directory of Open Access Journals (Sweden)

    M Julia García-Fuster

    Full Text Available Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

  14. Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents.

    Science.gov (United States)

    de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

    2017-01-01

    Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

  15. The Combination Very Low-Dose Naltrexone–Clonidine in the Management of Opioid Withdrawal

    Science.gov (United States)

    Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A.; Gorelick, David A.

    2013-01-01

    Background The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives We investigated the effects of a VLNTX–clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1–.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal. PMID:22233189

  16. Scaffold-Free Tubular Tissues Created by a Bio-3D Printer Undergo Remodeling and Endothelialization when Implanted in Rat Aortae

    Science.gov (United States)

    Itoh, Manabu; Nakayama, Koichi; Noguchi, Ryo; Kamohara, Keiji; Furukawa, Kojirou; Uchihashi, Kazuyoshi; Toda, Shuji; Oyama, Jun-ichi; Node, Koichi; Morita, Shigeki

    2015-01-01

    Background Small caliber vascular prostheses are not clinically available because synthetic vascular prostheses lack endothelial cells which modulate platelet activation, leukocyte adhesion, thrombosis, and the regulation of vasomotor tone by the production of vasoactive substances. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system. This system enables the creation of pre-designed three-dimensional structures using a computer controlled robotics system. With this system, we created a tubular structure and studied its biological features. Methods and Results Using a “Bio-3D printer,” we made scaffold-free tubular tissues (inner diameter of 1.5 mm) from a total of 500 MCSs (2.5× 104 cells per one MCS) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%), and normal human dermal fibroblasts (50%). The tubular tissues were cultured in a perfusion system and implanted into the abdominal aortas of F344 nude rats. We assessed the flow by ultrasonography and performed histological examinations on the second (n = 5) and fifth (n = 5) day after implantation. All grafts were patent and remodeling of the tubular tissues (enlargement of the lumen area and thinning of the wall) was observed. A layer of endothelial cells was confirmed five days after implantation. Conclusions The scaffold-free tubular tissues made of MCS using a Bio-3D printer underwent remodeling and endothelialization. Further studies are warranted to elucidate the underlying mechanism of endothelialization and its function, as well as the long-term results. PMID:26325298

  17. Scaffold-Free Tubular Tissues Created by a Bio-3D Printer Undergo Remodeling and Endothelialization when Implanted in Rat Aortae.

    Science.gov (United States)

    Itoh, Manabu; Nakayama, Koichi; Noguchi, Ryo; Kamohara, Keiji; Furukawa, Kojirou; Uchihashi, Kazuyoshi; Toda, Shuji; Oyama, Jun-Ichi; Node, Koichi; Morita, Shigeki

    2015-01-01

    Small caliber vascular prostheses are not clinically available because synthetic vascular prostheses lack endothelial cells which modulate platelet activation, leukocyte adhesion, thrombosis, and the regulation of vasomotor tone by the production of vasoactive substances. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a "Bio-3D printer"-based system. This system enables the creation of pre-designed three-dimensional structures using a computer controlled robotics system. With this system, we created a tubular structure and studied its biological features. Using a "Bio-3D printer," we made scaffold-free tubular tissues (inner diameter of 1.5 mm) from a total of 500 MCSs (2.5× 104 cells per one MCS) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%), and normal human dermal fibroblasts (50%). The tubular tissues were cultured in a perfusion system and implanted into the abdominal aortas of F344 nude rats. We assessed the flow by ultrasonography and performed histological examinations on the second (n = 5) and fifth (n = 5) day after implantation. All grafts were patent and remodeling of the tubular tissues (enlargement of the lumen area and thinning of the wall) was observed. A layer of endothelial cells was confirmed five days after implantation. The scaffold-free tubular tissues made of MCS using a Bio-3D printer underwent remodeling and endothelialization. Further studies are warranted to elucidate the underlying mechanism of endothelialization and its function, as well as the long-term results.

  18. Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB₁ receptors: implications for schizophrenia.

    Science.gov (United States)

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-08-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.

  19. Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

    OpenAIRE

    Self, David W.; Choi, Kwang-Ho; Simmons, Diana; Walker, John R.; Smagula, Cynthia S.

    2004-01-01

    Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydro...

  20. Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

    Directory of Open Access Journals (Sweden)

    Michal eBajo

    2014-06-01

    Full Text Available The central amygdala (CeA plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 M had mixed effects (> 20% change from baseline on mIPSCs in placebo and WD rats. In most CeA neurons (64% from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R-adenosine, cyclic 3’,5’-(hydrogenphosphorothioate triethylammonium (RP, prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence.

  1. Withdrawal: Expanding a Key Addiction Construct.

    Science.gov (United States)

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  3. Withdrawal: Plews and Laursen (2017).

    Science.gov (United States)

    2018-03-01

    We, the Editors and Publishers of the International Journal of Sports Physiology and Performance, have withdrawn the following article in whole: Plews, DJ, Laursen, PB. Training intensity distribution over a four-year cycle in Olympic champion rowers: different roads lead to Rio [version of record published online ahead of print September 27, 2017]. Int J Sports Physiol Perform. doi: 10.1123/ijspp.2017-0343 . The Editorial Office was contacted with the request to withdraw this article informing the Editor-in-Chief that the data in this article were not permissible to use due to undisclosed contractual obligations.

  4. Heavy Alcohol Consumption Effects on Blood Pressure and on Kidney Structure Persist After Long-Term Withdrawal

    Directory of Open Access Journals (Sweden)

    Sandra Leal

    2017-11-01

    Full Text Available Background/Aims: Heavy ethanol consumption is a risk factor for hypertension and prompts organ damage. There is no information regarding the impact of long-term heavy ethanol consumption on kidney structure and function linking to their hypertensive effects nor the repercussions after withdrawal. Methods: Rats were exposed to ethanol for 24 weeks and, afterwards, a group was assigned to withdrawal for 8 weeks. Blood pressure (BP was measured and serum biochemical parameters were quantified. Glomerular volume density, areal density of glomerular tuft and renal corpuscles were determined. Angiotensin II type 1 receptor (AT1R protein expression was evaluated. Results: Twenty-four weeks of ethanol consumption causes atrophy of renal corpuscles and glomeruli and reduces the volume of glomeruli. Glomerular changes induced by ethanol consumption were still evident after withdrawal. Renal AT1R levels were increased in ethanol-treated rats and returned to control levels during withdrawal. Ethanol consumption also induced an increase in BP, uric acid and albumin levels. Upon withdrawal, systolic and mean arterial pressures decreased, but were still higher than in controls rats. Conclusion: Ethanol consumption induces changes in glomerular morphology associated with increased BP and AT1R expression. Long-term withdrawal was inefficient to restore the structural integrity of renal corpuscles and in lowering systolic pressure.

  5. 42 CFR 457.170 - Withdrawal process.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review process...

  6. Perinatal risk factors and social withdrawal behaviour.

    Science.gov (United States)

    Guedeney, Antoine; Marchand-Martin, Laetitia; Cote, Sylvana J; Larroque, Béatrice

    2012-04-01

    The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies. © Springer-Verlag 2012

  7. 75 FR 7526 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-02-19

    ...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

  8. In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

    Science.gov (United States)

    Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

    2015-01-01

    Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

  9. Withdrawal of food and fluid.

    Science.gov (United States)

    Daly, B J

    1990-05-01

    John S. is a 72-year-old patriarch of a large, extended family. He underwent a mitral and aortic valve replacement, followed by a complicated postoperative course. His recovery was complicated by hemodynamic instability, several cardiac arrests, acute renal failure, and sepsis. He has been in the ICU for 14 weeks and has been unable to wean from mechanical ventilation. After many conferences between the patient's family and the ICU staff, a decision was made to remove ventilator support. This was done 3 days ago. John's condition seems stable now, but it is clear that he will not regain his former state of health. He is very debilitated, may require chronic dialysis, and has suffered some anoxic brain damage during his arrests. The nursing and medical staff are now faced with the question of further withdrawal of treatment and are considering whether or not to discontinue his parenteral nutrition and all IV fluids.

  10. Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

    Science.gov (United States)

    Lee, Ho Jun; Han, Sung Jin; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon; Kim, Nan Suk; Lim, Sang Ho

    2009-01-01

    The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection. PMID:19794987

  11. [An examination of the determinants of social withdrawal and affinity for social withdrawal].

    Science.gov (United States)

    Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

    2010-12-01

    This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

  12. Adult attachment and male aggression in couple relationships: the demand-withdraw communication pattern and relationship satisfaction as mediators.

    Science.gov (United States)

    Fournier, Benoit; Brassard, Audrey; Shaver, Phillip R

    2011-07-01

    This study examines men's domestic aggression as a function of attachment insecurities, considering the mediating roles of the demand-withdraw communication pattern and relationship satisfaction. The sample included 55 Canadian men undergoing counseling for relationship difficulties including aggression. The men completed questionnaires assessing physical and psychological aggression, the two dimensions of attachment insecurity (anxiety over abandonment and avoidance of intimacy), the demand-withdraw communication pattern, relationship satisfaction, and social desirability (a control measure). As predicted, there was an association between attachment anxiety and aggression (both physical and psychological), which was mediated by the man demands/woman withdraws (MD/WW) pattern (as reported by the men). There was no evidence of mediation by the woman demands/man withdraws pattern, as reported by the men. Relationship satisfaction mediated the association between attachment anxiety and psychological (but not physical) aggression, but did not mediate the link between avoidance and aggression (physical or psychological). Limitations and clinical implications are discussed.

  13. Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

    Science.gov (United States)

    Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

    2017-08-02

    Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

  14. Quantifying the Clinical Significance of Cannabis Withdrawal

    Science.gov (United States)

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  15. Quantifying the clinical significance of cannabis withdrawal.

    Directory of Open Access Journals (Sweden)

    David J Allsop

    Full Text Available Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001.Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

  16. Adult Attachment and Male Aggression in Couple Relationships: The Demand-Withdraw Communication Pattern and Relationship Satisfaction as Mediators

    Science.gov (United States)

    Fournier, Benoit; Brassard, Audrey; Shaver, Phillip R.

    2011-01-01

    This study examines men's domestic aggression as a function of attachment insecurities, considering the mediating roles of the demand-withdraw communication pattern and relationship satisfaction. The sample included 55 Canadian men undergoing counseling for relationship difficulties including aggression. The men completed questionnaires assessing…

  17. Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

    Science.gov (United States)

    Greenberg, G D; Huang, L C; Spence, S E; Schlumbohm, J P; Metten, P; Ozburn, A R; Crabbe, J C

    2016-04-01

    Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice. Published by Elsevier B.V.

  18. Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

    Science.gov (United States)

    Gates, Sharon A; Brown, James R

    Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process. Nine groups of 8-10 students participated in a 2.5-hour simulation event that included an alcohol withdrawal seizure, team meeting, and discharge of the patient. Students recognized the importance of all the professional roles and how each professional benefits patient care. Before the simulation, students thought they were prepared to care for patients experiencing alcohol withdrawal; however, the crisis of an alcohol seizure decreased the student's ability to perform skills and communicate effectively. These findings suggest that new nurses and social workers may not be prepared to care for the acute alcohol withdrawal patient.

  19. Pseudopheochromocytoma induced by anxiolytic withdrawal.

    Science.gov (United States)

    Páll, Alida; Becs, Gergely; Erdei, Annamária; Sira, Lívia; Czifra, Arpád; Barna, Sándor; Kovács, Péter; Páll, Dénes; Pfliegler, György; Paragh, György; Szabó, Zoltán

    2014-10-08

    Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.

  20. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    Science.gov (United States)

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

    Science.gov (United States)

    Gupta, N; Bhargava, V K; Pandhi, P

    2000-05-01

    The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

  2. 21 CFR 314.530 - Withdrawal procedures.

    Science.gov (United States)

    2010-04-01

    ... Serious or Life-Threatening Illnesses § 314.530 Withdrawal procedures. (a) For new drugs approved under... benefit; (2) The applicant fails to perform the required postmarketing study with due diligence; (3) Use...

  3. MITS Feed and Withdrawal Subsystem: operating procedures

    International Nuclear Information System (INIS)

    Brown, W.S.

    1980-01-01

    This procedure details the steps required to provide continuous feed flow and withdrawal of process product and waste flows in support of thruput operation in the cascade or its elements. It particularly requires operator attention to safety considerations

  4. Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

    Science.gov (United States)

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-01-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

  5. Tobacco withdrawal among opioid-dependent smokers.

    Science.gov (United States)

    Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

    2018-04-01

    Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. 20 CFR 408.355 - Can you withdraw your application?

    Science.gov (United States)

    2010-04-01

    ... Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your application? (a) Request for withdrawal filed before a determination is made. You may withdraw your application...

  7. 19 CFR 144.38 - Withdrawal for consumption.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for consumption. 144.38 Section 144.38... Withdrawal for consumption. (a) Form. Withdrawals for consumption of merchandise in bonded warehouses shall... considered a withdrawal for consumption pursuant to § 181.53 of this chapter. (c) Information to be shown on...

  8. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the time...

  9. Comparison of randomized preemptive dexketoprofen trometamol or placebo tablets to prevent withdrawal movement caused by rocuronium injection.

    Science.gov (United States)

    Aydın, Gözde Bumin; Polat, Reyhan; Ergil, Julide; Sayın, Murat; Caparlar, Ceyda Ozhan

    2014-06-01

    Rocuronium is a non-depolarizing neuromuscular blocking agent which is associated with injection pain and induces withdrawal movement of the injected hand or arm or generalized movements of the body after intravenous injection. The aim of this randomized study was to compare the efficacy of pretreatment with oral dexketoprofen trometamol (Arvelles(®); Group A) with placebo (Group P) without tourniquet to prevent the withdrawal response caused by rocuronium injection. The study cohort comprised 150 American Society of Anaesthesiologists class I-III patients aged 18-75 years who were scheduled to undergo elective surgery with general anesthesia. The patients response to rocuronium was graded using a 4-point scale [0 = no response; 1 = movement/withdrawal at the wrist only, 2 = movement/withdrawal involving the arm only (elbow/shoulder); 3 = generalized response]. The overall incidence of withdrawal movement after rocuronium injection was significantly lower in Group A (30.1 %) than in Group P (64.6 %) (p  0.05). These results demonstrate that the preemptive administration of dexketoprofen trometamol can attenuate the degree of withdrawal movements caused by the pain of the rocuronium injection.

  10. Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.

    Science.gov (United States)

    Madden, Kate; Burns, Michele M; Tasker, Robert C

    2017-06-01

    To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children. Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms "delirium," "substance withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical illness," "ICU," and "intensive care." Review article references were also searched. Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded. References cataloged by study type, population, and screening process. Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains. Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.

  11. Control rod excess withdrawal prevention device

    International Nuclear Information System (INIS)

    Takayama, Yoshihito.

    1992-01-01

    Excess withdrawal of a control rod of a BWR type reactor is prevented. That is, the device comprises (1) a speed detector for detecting the driving speed of a control rod, (2) a judging circuit for outputting an abnormal signal if the driving speed is greater than a predetermined level and (3) a direction control valve compulsory closing circuit for controlling the driving direction of inserting and withdrawing a control rod based on an abnormal signal. With such a constitution, when the with drawing speed of a control rod is greater than a predetermined level, it is detected by the speed detector and the judging circuit. Then, all of the direction control valve are closed by way of the direction control valve compulsory closing circuit. As a result, the operation of the control rod is stopped compulsorily and the withdrawing speed of the control rod can be lowered to a speed corresponding to that upon gravitational withdrawal. Accordingly, excess withdrawal can be prevented. (I.S)

  12. Effect of Nifedipine on Reproductive Functions in Male Rats ...

    African Journals Online (AJOL)

    Effect of Nifedipine on Reproductive Functions in Male Rats. ... Background: After life itself, fertility is probably the most highly prized human possession. ... Animals in Group 3 were allowed another 30 days after drug withdrawal for recovery.

  13. Withdrawal-oriented therapy for smokers.

    Science.gov (United States)

    Hajek, P

    1989-06-01

    The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

  14. [Treatment of gamma-hydroxybutyrate withdrawal].

    Science.gov (United States)

    Strand, Niels August Willer; Petersen, Tonny Studsgaard; Nielsen, Lars Martin; Boegevig, Soren

    2017-12-11

    Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

  15. Children's judgements of social withdrawal behaviours.

    Science.gov (United States)

    Watling, Dawn

    2015-06-01

    Ding et al. (Brit. J. Dev. Psychol., 2015; 33, 159-173) demonstrated that Chinese children discriminate between the three subtypes of social withdrawal: Shyness, unsociability, and social avoidance. This commentary on the Ding et al.'s paper highlights the need to further explore the following: (1) children's understanding of the implications of being shy, unsociable, or socially avoidant, including assessing these which we know are associated with outcomes for socially withdrawn children; (2) what additional subtypes might exist naturally within the Chinese culture; and (3) consider the implications of social withdrawal on children's developing social skills. © 2015 The British Psychological Society.

  16. Effects of Nicotine Withdrawal in Adult Male and Female Rats

    Science.gov (United States)

    2008-01-01

    the planning and organization strategies required of the experimentalist. I am also indebted to Manuel Marwein, Alberta Nyarko, Becca Dieffenbach, Juan ...no difference in self-administration behavior between women who were randomly assigned to placebo and nicotine (Perkins, Grobe, D’Amico, Fonte

  17. Modulation of histone deacetylase attenuates naloxone-precipitated opioid withdrawal syndrome.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Nirmal; Rachamalla, Mahesh; Tikoo, Kulbhushan

    2012-06-01

    The present study has been designed to investigate the effect of selective inhibitors of histone deacetylase and/or N-acetyl-Asp-Glu-Val-Asp-al (Ac-DEVD-CHO), a selective interleukin-1β converting enzyme inhibitor, on the development of naloxone-induced opioid withdrawal syndrome both in vitro and in vivo and the effect of histone deacetylase inhibition on histone H3 acetylation in brain. Sub-acute morphine administration followed by a single injection of naloxone (8 mg/kg, i.p.) was used to precipitate opioid withdrawal syndrome in mice. Behavioral observations were made immediately after naloxone treatment. Withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and frequency of jumping, rearing, fore paw licking and circling. Separately naloxone-induced contraction in morphine-dependent isolated rat ileum was employed as an in vitro model. An isobolographic study design was employed to assess potential synergistic activity between trichostatin A and Ac-DEVD-CHO. Brain histone acetylation status was examined by western blotting. Injection of naloxone precipitated a severe form of abstinence syndrome in morphine-dependent mice along with strong contracture in isolated rat ileum. Administration of tributyrin (1.5, 3 and 6 g/kg, p.o.), trichostatin A (0.3, 1.0 and 3.0 mg/kg, p.o.) and Ac-DEVD-CHO (0.3, 1.0 and 3.0 mg/kg, p.o.) markedly and dose dependently attenuated naloxone-induced morphine withdrawal syndrome in vivo as well as in vitro in rat ileum. Trichostatin A was also observed to exert a synergistic interaction with Ac-DEVD-CHO. Western blot analysis revealed that multiple administration with the effective dose of tributyrin or trichostatin A in the in vivo experiments induced hyperacetylation of histone H3 in the mouse brain. Thus, it is proposed that histone deacetylase activation linked mechanism might be involved in the development of opioid dependence and the precipitation of its withdrawal syndrome.

  18. Progesterone Withdrawal-Evoked Plasticity of Neural Function in the Female Periaqueductal Grey Matter

    Directory of Open Access Journals (Sweden)

    T. A. Lovick

    2009-01-01

    Full Text Available Cyclical changes in production of neuroactive steroids during the oestrous cycle induce significant changes in GABAA receptor expression in female rats. In the periaqueductal grey (PAG matter, upregulation of α4β1δ GABAA receptors occurs as progesterone levels fall during late dioestrus (LD or during withdrawal from an exogenous progesterone dosing regime. The new receptors are likely to be extrasynaptically located on the GABAergic interneurone population and to mediate tonic currents. Electrophysiological studies showed that when α4β1δ GABAA receptor expression was increased, the excitability of the output neurones in the PAG increased, due to a decrease in the level of ongoing inhibitory tone from the GABAergic interneurones. The functional consequences in terms of nociceptive processing were investigated in conscious rats. Baseline tail flick latencies were similar in all rats. However, acute exposure to mild vibration stress evoked hyperalgesia in rats in LD and after progesterone withdrawal, in line with the upregulation of α4β1δ GABAA receptor expression.

  19. Teachers' Withdrawal Behaviors: Integrating Theory and Findings

    Science.gov (United States)

    Shapira-Lishchinsky, Orly

    2012-01-01

    Purpose: The article aims to investigate the relationships between different dimensions of organizational ethics and different withdrawal symptoms--lateness, absence, and intent to leave work. Design/methodology/approach: Participants were 1,016 school teachers from 35 high schools in Israel. A joint model of Glimmix procedure of SAS was used for…

  20. Withholding and withdrawing treatment: practical applications of ...

    African Journals Online (AJOL)

    Withholding and withdrawing treatment: practical applications of ethical principles in end-of-life care. L Gwyther. Abstract. No Abstract South African Journal of Bioethics and Law Vol. 1 (1) 2008: pp. 24-26. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  1. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    Science.gov (United States)

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  2. 75 FR 22868 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-04-30

    ...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

  3. Recent advances in alcohol withdrawal states.

    Science.gov (United States)

    Fialkov, M J

    1977-11-26

    Recent advances in alcohol withdrawal states are described. New concepts of classification, the development of the syndrome and its management are outlined. In the light of recent research, more optimistic results for this much maligned but common condition may be achieved.

  4. MITS Feed and Withdrawal Subsystem: operating procedures

    International Nuclear Information System (INIS)

    Brown, W.S.

    1980-01-01

    This document details procedures for the operation of the MITS (Machine Interface Test System) Feed and Withdrawal Subsystem (F and W). Included are fill with UF 6 , establishment of recycle and thruput flows, shutdown, UF 6 makeup, dump to supply container, Cascade dump to F and W, and lights cold trap dump, all normal procedures, plus an alternate procedure for trapping light gases

  5. MITS Feed and Withdrawal Subsystem: operating procedures

    International Nuclear Information System (INIS)

    Brown, W.S.

    1980-01-01

    This procedure details the steps involved in filling two of the four MITS (Machine Interface Test System) Feed and Withdrawal subsystem main traps and the Sample/Inventory Make-up Pipette with uranium hexafluoride from the ''AS RECEIVED'' UF 6 supply

  6. Evaluation of Ashwagandha in alcohol withdrawal syndrome

    Directory of Open Access Journals (Sweden)

    Ruby B

    2012-10-01

    Full Text Available Objective: To evaluate the effect of Ashwagandha (ASW in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg in comparison with diazepam (1 mg/kg in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ kindling test for seizure threshold, forced swim test (FST for depression and locomotor activity (LCA in open field test (OFT. 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p. In FST, mice were forced to swim and the total duration of immobility (seconds was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions.

  7. A psychometric validation of the Short Alcohol Withdrawal Scale (SAWS)

    DEFF Research Database (Denmark)

    Elholm, Bjarne; Larsen, Klaus; Hornnes, Nete

    2010-01-01

    The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS).......The study aimed to evaluate psychometrically a Danish translation of the Short Alcohol Withdrawal Scale (SAWS) in an outpatient setting in patients with Alcohol Dependence (AD) and Alcohol Withdrawal Symptoms/Syndrome (AWS)....

  8. An overview of research on social withdrawal in childhood

    OpenAIRE

    野村, あすか; NOMURA, Asuka

    2013-01-01

    In recent years, “HIKIKOMORI” in adolescence or adulthood has grown into a serious problem in Japan and the need for early intervention and support has been emphasized. Among the risk factors of “HIKIKOMORI” is social withdrawal in childhood. With this in mind, I reviewed previous studies on the social withdrawal in children living abroad. The review commences with an examination of definitions of social withdrawal, which showed that in some foreign countries, social withdrawal refers to the ...

  9. 19 CFR 144.36 - Withdrawal for transportation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

  10. 19 CFR 144.37 - Withdrawal for exportation.

    Science.gov (United States)

    2010-04-01

    ...) Class 9 warehouse withdrawals for exportation—(1) Applicability of sales ticket procedure. Merchandise... be eligible for withdrawal under the sales ticket procedure specified in this paragraph. (2) Sales ticket content and handling. Sales ticket withdrawals must be made only under a blanket permit to...

  11. 47 CFR 1.8 - Withdrawal of papers.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw an...

  12. 5 CFR 362.207 - Withdrawal and readmission.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Withdrawal and readmission. 362.207... PRESIDENTIAL MANAGEMENT FELLOWS PROGRAM Program Administration § 362.207 Withdrawal and readmission. (a...) An agency must notify OPM when a Fellow or Senior Fellow withdraws from the Program. (b) Readmission...

  13. 45 CFR 400.301 - Withdrawal from the refugee program.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Withdrawal from the refugee program. 400.301... Waivers and Withdrawals § 400.301 Withdrawal from the refugee program. (a) In the event that a State... assistance, social services, preventive health, and an unaccompanied minors program if appropriate. A State...

  14. 20 CFR 404.640 - Withdrawal of an application.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of an application. 404.640 Section 404.640 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Filing of Applications and Other Forms Withdrawal of Application § 404.640 Withdrawal of...

  15. 20 CFR 416.355 - Withdrawal of an application.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of an application. 416.355 Section 416.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Filing of Applications Withdrawal of Application § 416.355 Withdrawal of an...

  16. 29 CFR 102.104 - Withdrawal of petition.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Withdrawal of petition. 102.104 Section 102.104 Labor... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion. ...

  17. 15 CFR 10.13 - Withdrawal of a published standard.

    Science.gov (United States)

    2010-01-01

    ...) Before withdrawing a standard published under these procedures, the Director will review the relative... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Withdrawal of a published standard. 10... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.13 Withdrawal of a published standard. (a) Standards published...

  18. 21 CFR 171.7 - Withdrawal of petition without prejudice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Withdrawal of petition without prejudice. 171.7... Withdrawal of petition without prejudice. (a) In some cases the Commissioner will notify the petitioner that... clarification or the obtaining of additional data. This withdrawal will be without prejudice to a future filing...

  19. 21 CFR 571.7 - Withdrawal of petition without prejudice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Withdrawal of petition without prejudice. 571.7... Withdrawal of petition without prejudice. (a) In some cases the Commissioner will notify the petitioner that... clarification or the obtaining of additional data. This withdrawal will be without prejudice to a future filing...

  20. Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.

    Science.gov (United States)

    Hooten, W Michael; Warner, David O

    2015-03-01

    The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

    2015-09-01

    The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis

    Directory of Open Access Journals (Sweden)

    Mir Priya S

    2012-02-01

    Full Text Available Abstract Background Adipocyte numbers and peroxisome proliferators activated receptorγ (PPARγ expression of retroperitoneal tissue increased while area under the curve (AUC during the glucose tolerance test (GTT was reduced in rats subjected to certain feed withdrawal (FW regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control. Methods Growth, body composition, adipocyte numbers, PPARγ expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM and subcutaneous (SQ fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum. Results Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively in pigs in FW treatments. In OM fat; cell numbers, glucose Universal14C [U14C] incorporation into fat and rate of incorporation per 104 cells was greatest for cells with diameters of 90-119 μm. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191% number of adipocytes, increased (p = 0.0234 glucose U14C incorporation into adipocytes and greater (p = 0.0872 rate of glucose uptake into cells of 119-150 μm diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 μm diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively than for those in FWx4 treatment, yet PPARγ expression and total cell number were not affected by treatment. Conclusions Results suggest that FW regimens influence fat cell function or

  3. Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC.

    Science.gov (United States)

    Miller, Bailey W; Wroten, Melissa G; Sacramento, Arianne D; Silva, Hannah E; Shin, Christina B; Vieira, Philip A; Ben-Shahar, Osnat; Kippin, Tod E; Szumlinski, Karen K

    2017-05-01

    In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular signal-regulated kinase observed in cocaine-seeking rats. Further, the impact of inhibiting PKCε translocation within the vmPFC using TAT infusion proteins upon cue-elicited responding was determined and inhibition coinciding with the period of testing attenuated cocaine-seeking behavior, with an effect also apparent the next day. In contrast, inhibitor pretreatment prior to testing during early withdrawal was without effect. Thus, a history of excessive cocaine taking influences the cue reactivity of important intracellular signaling molecules within the vmPFC, with PKCε playing a critical role in the manifestation of cue-elicited cocaine seeking during protracted drug withdrawal. © 2016 Society for the Study of Addiction.

  4. Radionuclide withdrawal from animal and human body

    International Nuclear Information System (INIS)

    Arkhipov, A.S.; Sidorova, T.F.

    1995-01-01

    The authors review the history of the problem of radionuclide withdrawal from animal and human body and discuss methodological approaches to it. Results of studies of radionuclide elimination by means of chemical and bioactive substances are analyzed. Special attention is paid to decorporation of radioactive elements which are the most hazardous as regards intoxication in connection with the Chernobyl accident: 131 I, 89 St and 90 Sr, 137 Cs, 238 Pu, and 241 Am. The authors analyze the results of studies of radionuclide withdrawal based on the dissolution effect, ionic antagonism, and by means of complexons, carried out in humans and animals. Efficacies of alimentary fibers and other adsorbents, foodstuffs and drinks are demonstrated. 48 refs

  5. SSRI and SNRI withdrawal symptoms reported on an internet forum.

    Science.gov (United States)

    Stockmann, Tom; Odegbaro, Dolapo; Timimi, Sami; Moncrieff, Joanna

    2018-05-09

    Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

  6. Moves to withdraw nuclear weapons from NATO?

    International Nuclear Information System (INIS)

    Dumoulin, A.

    2008-01-01

    The American nuclear landscape in Europe could change in the coming months. The signs are already there, and a new strategic posture will have major implications for the Europeans as well as for the visibility of France deterrent force. Nonetheless, the Georgian crisis, tensions with Iran, Russian muscle flexing and NATO's line cast doubt on the idea that a partial or even complete withdrawal of American B-61 bombs could be on the agenda at the Alliance's 60. anniversary in April 2009. (author)

  7. Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner.

    Science.gov (United States)

    Spahn, Viola; Fischer, Oliver; Endres-Becker, Jeannette; Schäfer, Michael; Stein, Christoph; Zöllner, Christian

    2013-04-01

    Hyperalgesia is a cardinal symptom of opioid withdrawal. The transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated ion channel expressed on sensory neurons responding to noxious heat, protons, and chemical stimuli such as capsaicin. TRPV1 can be inhibited via μ-opioid receptor (MOR)-mediated reduced activity of adenylyl cyclases (ACs) and decreased cyclic adenosine monophosphate (cAMP) levels. In contrast, opioid withdrawal following chronic activation of MOR uncovers AC superactivation and subsequent increases in cAMP and protein kinase A (PKA) activity. Here we investigated (1) whether an increase in cAMP during opioid withdrawal increases the activity of TRPV1 and (2) how opioid withdrawal modulates capsaicin-induced nocifensive behavior in rats. We applied whole-cell patch clamp, microfluorimetry, cAMP assays, radioligand binding, site-directed mutagenesis, and behavioral experiments. Opioid withdrawal significantly increased cAMP levels and capsaicin-induced TRPV1 activity in both transfected human embryonic kidney 293 cells and dissociated dorsal root ganglion (DRG) neurons. Inhibition of AC and PKA, as well as mutations of the PKA phosphorylation sites threonine 144 and serine 774, prevented the enhanced TRPV1 activity. Finally, capsaicin-induced nocifensive behavior was increased during opioid withdrawal in vivo. In summary, our results demonstrate an increased activity of TRPV1 in DRG neurons as a new mechanism contributing to opioid withdrawal-induced hyperalgesia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  8. Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

    Science.gov (United States)

    Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

    2010-07-06

    Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

  9. 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

  10. Pathophysiology of metabolic syndrome: The onset of natural recovery on withdrawal of a high-carbohydrate, high-fat diet.

    Science.gov (United States)

    Hazarika, Ankita; Kalita, Himadri; Chandra Boruah, Dulal; Chandra Kalita, Mohan; Devi, Rajlakshmi

    2016-10-01

    Chronic consumption of high-carbohydrate, high-fat (HCHF) diet induces metabolic syndrome (MetS) and markedly impairs the ultra-structure of organs. To our knowledge, no scientific study has yet to report the effect of withdrawal of an HCHF diet on MetS-associated ultra-structural abnormalities in affected organs and tissues. Therefore, the aim of this study was to investigate the effects of subchronic withdrawal of the HCHF diet, specifically with a pathophysiological approach. Wister albino rats (N = 72) were divided into three groups: Groups A and B were fed a standard basal diet and an HCHF diet, respectively, for 16 wk. Group C was on an HCHF diet for the initial 12 wk and then returned to basal diet for 4 wk. Histopathological changes in the heart, lungs, liver, spleen, pancreas, small intestine, kidney, white adipose tissue (WAT), skeletal muscle, and hippocampus of the brain were monitored at 4, 8, 12, and 16 wk. Lipid droplets (LDs) in liver, fibrosis in the pancreas, abnormalities in the glomerulus of the kidney, and an increase in the size of adipocytes were observed in groups B and C at week 12. Withdrawal of the HCHF diet in group C showed the onset of regenerative features at the ultra-structural level. HCHF diet-fed rats in group B had higher body weights; raised lipid profiles, blood glucose levels, and insulin resistance than basal diet-fed rats in group A and HCHF to basal diet-fed rats in group C at week 16. An HCHF diet induces ultra-structural abnormalities, which are significantly reversed by subchronic withdrawal of a MetS-inducing HCHF diet, indicating the onset of natural recovery at the ultra-structural level of affected organs. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

    Science.gov (United States)

    Pereira, Pedro A; Neves, João; Vilela, Manuel; Sousa, Sérgio; Cruz, Catarina; Madeira, M Dulce

    2014-01-01

    Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Caffeine dependence in rats: effects of exposure duration and concentration.

    Science.gov (United States)

    Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

    2008-09-03

    Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

  13. Recognition and management of iatrogenically induced opioid dependence and withdrawal in children.

    Science.gov (United States)

    Galinkin, Jeffrey; Koh, Jeffrey Lee

    2014-01-01

    Opioids are often prescribed to children for pain relief related to procedures, acute injuries, and chronic conditions. Round-the-clock dosing of opioids can produce opioid dependence within 5 days. According to a 2001 Consensus Paper from the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, dependence is defined as "a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist." Although the experience of many children undergoing iatrogenically induced withdrawal may be mild or goes unreported, there is currently no guidance for recognition or management of withdrawal for this population. Guidance on this subject is available only for adults and primarily for adults with substance use disorders. The guideline will summarize existing literature and provide readers with information currently not available in any single source specific for this vulnerable pediatric population.

  14. Clinical management of alcohol withdrawal: A systematic review

    Directory of Open Access Journals (Sweden)

    Shivanand Kattimani

    2013-01-01

    Full Text Available Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed.

  15. Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

    Science.gov (United States)

    Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

    2017-07-01

    In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  16. A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

    Science.gov (United States)

    Yu, Elmer; Miotto, Karen; Akerele, Evaristo; Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Fischman, Marian W.; Collins, Joseph; McSherry, Frances; Boardman, Kathy; Davies, David K.; O’Brien, Charles P.; Ling, Walter; Kleber, Herbert; Herman, Barbara H.

    2008-01-01

    Context Lofexidine is an alpha-2-A noradrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally-defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. Design An inpatient, Phase 3, placebo-controlled, double blind, randomized multi-site trial with three phases: (1) Opioid Agonist Stabilization Phase (days 1–3), (2) Detoxification/Medication or Placebo Phase (days 4–8), and (3) Post Detoxification/Medication Phase (days 9–11). Subjects Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main Outcome Measure Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (2nd opioid detoxification treatment day). Results Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 ± 2.1 versus 30.9 ± 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Registration trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, registration number NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/NCT00032942?order=4. PMID:18508207

  17. New Drugs of Abuse and Withdrawal Syndromes.

    Science.gov (United States)

    Andrabi, Sara; Greene, Spencer; Moukaddam, Nidal; Moukkadam, Nidal; Li, Benjamin

    2015-11-01

    New drugs of abuse continue to emerge, including synthetic cannabinoids, synthetic cathinones, and hallucinogens. It is important to recognize their individual psychopharmacologic properties, symptoms of intoxication, and symptoms of withdrawal. Providers must be vigilant of acute medical or psychiatric complications that may arise from use of these substances. Treatment of the patient also includes recognition of any substance use disorders as well as comorbid psychiatric disorders. Although pharmacologic treatments for substance use disorder (of the drugs included in this article) are limited, there are a variety of psychotherapeutic modalities that may be of some benefit. Published by Elsevier Inc.

  18. Spontaneous reduction of prolactinoma post cabergoline withdrawal

    Directory of Open Access Journals (Sweden)

    Sampath Kumar Venkatesh

    2012-01-01

    Full Text Available Prolactinomas are common pituitary tumors usually highly responsive to dopamine agonists. Around 70-90% of the prolactinomas exhibit decrease in tumor size, though variably with these agents. Uncommonly, there may be little or no shrinkage in pituitary tumor. In the absence of medical therapy, pituitary apoplexy may also result in tumor shrinkage, albeit rarely. We report here a case showing only modest reduction in prolactinoma with cabergoline given for a period of one and a half years. Surprisingly, this tumor showed a 40% reduction in the tumor size 3 months after cabergoline withdrawal in the absence of clinical or radiological evidence of apoplexy.

  19. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  20. Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

    Science.gov (United States)

    Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

    2017-08-01

    Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

  1. Smartphone Restriction and its Effect on Subjective Withdrawal Related Scores

    OpenAIRE

    Aarestad, Sarah Helene; Eide, Tine Almenning

    2017-01-01

    Smartphone overuse is associated with a number of negative consequences for the individual and the environment. In the right end of the distribution of smartphone usage, concepts such as smartphone addiction seem warranted. An area that so far lacks research concerns the effect of smartphone restriction generally and specifically on subjective withdrawal related scores across different degrees of smartphone usage. The present study examined withdrawal related scores on the Smartphone Withdraw...

  2. Demand-Withdraw Patterns in Marital Conflict in the Home

    OpenAIRE

    Papp, Lauren M.; Kouros, Chrystyna D.; Cummings, E. Mark

    2009-01-01

    The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that con...

  3. Predictors of withdrawal: possible precursors of avoidant personality disorder.

    Science.gov (United States)

    Eggum, Natalie D; Eisenberg, Nancy; Spinrad, Tracy L; Valiente, Carlos; Edwards, Alison; Kupfer, Anne S; Reiser, Mark

    2009-01-01

    Relations of avoidant personality disorder (AvPD) with shyness and inhibition suggest that a precursor of AvPD is withdrawal. Using a sample of 4.5- to 7-year-olds studied four times, 2 years apart, four and three classes of children differing in trajectories of mother- and teacher-reported withdrawal, respectively, were identified. Mothers and teachers generally did not agree on children's trajectories but the pattern of findings in the two contexts did not differ markedly. The mother-identified high and declining withdrawal class, in comparison with less withdrawn classes, and the teacher-identified high and declining class compared with low withdrawal classes, were associated with relatively high levels of anger and low levels of attentional control and resiliency. The mother-identified moderate and increasing withdrawal class was distinguished from less problematic withdrawal classes by higher anger, lower resiliency, and sometimes, lower attentional control. The teacher-identified low and increasing withdrawal class was distinguished from less problematic withdrawal classes by lower resiliency and lower attentional control. Findings are discussed in terms of the developmental precursors to social withdrawal and avoidant behavior.

  4. Withdrawal symptoms in internet gaming disorder: A systematic review.

    Science.gov (United States)

    Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

    2016-02-01

    Internet gaming disorder (IGD) is currently positioned in the appendix of the DSM-5 as a condition requiring further study. The aim of this review was to examine the state of current knowledge of gaming withdrawal symptomatology, given the importance of withdrawal in positioning the disorder as a behavioral addiction. A total of 34 studies, including 10 qualitative studies, 17 research reports on psychometric instruments, and 7 treatment studies, were evaluated. The results indicated that the available evidence on Internet gaming withdrawal is very underdeveloped. Internet gaming withdrawal is most consistently referred to as 'irritability' and 'restlessness' following cessation of the activity. There exists a concerning paucity of qualitative studies that provide detailed clinical descriptions of symptoms arising from cessation of internet gaming. This has arguably compromised efforts to quantify withdrawal symptoms in empirical studies of gaming populations. Treatment studies have not reported on the natural course of withdrawal and/or withdrawal symptom trajectory following intervention. It is concluded that many more qualitative clinical studies are needed, and should be prioritised, to develop our understanding of gaming withdrawal. This should improve clinical descriptions of problematic internet gaming and in turn improve the quantification of IGD withdrawal and thus treatments for harmful internet gaming. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. [Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

    Science.gov (United States)

    Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

    2018-01-01

    To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

  6. The Non-Proliferation Treaty and the Withdrawal Clause

    International Nuclear Information System (INIS)

    Boutherin, Gregory

    2008-01-01

    Like any international agreement, the NPT includes a withdrawal clause. The North Korean withdrawal, which was announced in 1993 and became effective in 2003, shows how difficult it is to preserve this possibility, while guaranteeing compliance with signed agreements. To achieve this target, two conditions are required: first, enhancing the means by which the reasons for withdrawals can be made clear and second, to allow the Security Council to draw all the consequences of withdrawals that could imply that a treaty has been violated

  7. Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.

    Science.gov (United States)

    Kim, Ronald; Sepulveda-Orengo, Marian T; Healey, Kati L; Williams, Emily A; Reissner, Kathryn J

    2018-01-01

    Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2008-01-01

    Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

  9. 12 CFR 563g.11 - Withdrawal or abandonment.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Withdrawal or abandonment. 563g.11 Section 563g.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.11 Withdrawal or abandonment. (a) Any offering circular, amendment, or exhibit may be withdrawn...

  10. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Science.gov (United States)

    2010-01-01

    ... type. (d) OPM also considers a disability retirement application to be withdrawn when the agency... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of...

  11. 49 CFR 450.16 - Withdrawal of delegation.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Withdrawal of delegation. 450.16 Section 450.16... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS GENERAL Procedure for Delegation to Approval Authorities § 450.16 Withdrawal of delegation. (a) The Chief, Office of Operating and Environmental Standards (CG-522...

  12. Social Withdrawal, Friendship, and Depressed Mood in Adolescents

    NARCIS (Netherlands)

    Aleva, A.E.|info:eu-repo/dai/nl/141299789; van Beek, Y.|info:eu-repo/dai/nl/107292300

    2017-01-01

    Social withdrawal in children may develop into a depressed mood in early adolescence , through experiences of problematic peer relationships, while friendship may function as a buffer (Rubin, Coplan, & Bowker, 2009). Our study examines the predictive relation between social withdrawal and depressive

  13. 20 CFR 410.232 - Withdrawal of a claim.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of a claim. 410.232 Section 410.232 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969... Claims and Evidence § 410.232 Withdrawal of a claim. (a) Before adjudication of claim. A claimant (or an...

  14. 20 CFR 410.690 - Withdrawal of charges.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Withdrawal of charges. 410.690 Section 410.690 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND SAFETY ACT OF 1969... Review, Finality of Decisions, and Representation of Parties § 410.690 Withdrawal of charges. If an...

  15. Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

    Science.gov (United States)

    Oh, Wonjung; Rubin, Kenneth H.; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

    2008-01-01

    Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in…

  16. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel alcohol...

  17. 75 FR 12804 - Withdrawal of Regulatory Guide 8.6

    Science.gov (United States)

    2010-03-17

    ... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

  18. Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

    Directory of Open Access Journals (Sweden)

    Vikas Seth

    2010-01-01

    Full Text Available The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K + ATP channel modulators were injected intraperitoneally (i.p. 30 minutes before the naloxone. It was found that a K + ATP channel opener, minoxidil (12.5–50 mg/kg i.p., suppressed the morphine withdrawal significantly. On the other hand, the K + ATP channel blocker glibenclamide (12.5–50 mg/kg i.p. caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K + ATP channels play an important role in the genesis of morphine withdrawal and K + ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K + ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K + currents.

  19. 40 CFR 180.8 - Withdrawal of petitions without prejudice.

    Science.gov (United States)

    2010-07-01

    ... prejudice. 180.8 Section 180.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 180.8 Withdrawal of petitions without prejudice. In some cases the Administrator will notify the... clarification or the obtaining of additional data. This withdrawal may be without prejudice to a future filing...

  20. Monitoring device for withdrawing control rods

    International Nuclear Information System (INIS)

    Higashigawa, Yuichi.

    1985-01-01

    Purpose: To improve the sensitivity and the responsivity to an equivalent extent to those in the case where local power range monitors are densely arranged near each of the control rods, with no actual but pseudo increase of the number of local power range monitors. Constitution: The monitor arrangement is patterned by utilizing the symmetricity of the reactor core and stored in a monitor designating device. The symmetricity of control rods to be selected and withdrawn by an operator is judged by a control rod symmetry monitoring device, while the symmetricity of the withdrawn control rods is judged by a control rod withdrawal state monitoring device. Then, only when both of the devices judge the symmetricity, the control rods are subjected to gang driving by the control rod drive mechanisms. In this way, monitoring at a high sensitivity and responsivity is enabled with no increase for the number of monitors. (Yoshino, Y.)

  1. 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.

  2. Bulimic symptoms and the social withdrawal syndrome.

    Science.gov (United States)

    Rotenberg, Ken J; Bharathi, Carla; Davies, Helen; Finch, Tom

    2013-08-01

    One hundred and thirty-seven undergraduates (81 females; mean age = 21 years-10 months) completed the Bulimic SEDS subscale and standardized measures of trust beliefs in close others (mother, father, and friend), disclosure to them, and loneliness. Structural Equation Modelling yielded: (1) a negative path between Bulimic Symptoms and trust beliefs, (2) a positive path between trust beliefs and disclosure, (3) a negative path between trust beliefs and loneliness, and (4) a negative path between disclosure and loneliness. As expected, trust beliefs statistically mediated the relations between Bulimic Symptoms and both disclosure and loneliness and disclosure statistically mediated the relation between trust beliefs and loneliness. The findings supported the conclusion that individuals with bulimia nervosa are prone to the social withdrawal syndrome comprising a coherent and integrated pattern of low trust beliefs in close others, low disclosure to close others, and high loneliness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Withdrawal of cerivastatin from the world market

    Directory of Open Access Journals (Sweden)

    Pitt Bertram

    2001-09-01

    Full Text Available Abstract Cerivastatin was recently withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure. The risk was found to be higher among patients who received the full dose (0.8 mg/day and those who received gemfibrozil concomitantly. Rhabdomyolysis was 10 times more common with cerivastatin than the other five approved statins. We address three important questions raised by this withdrawal. Should we continue to approve drugs on surrogate efficacy? Are all statins interchangeable? Do the benefits outweigh the risks of statins? We conclude that decisions regarding the use of drugs should be based on direct evidence from long-term clinical outcome trials.

  4. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

    Science.gov (United States)

    Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

    2016-09-01

    The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  5. Why withdrawal from the European Union is undemocratic

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents; Rostbøll, Christian F.

    2017-01-01

    The Lisbon Treaty from 2009 introduced the possibility for individual member states to withdraw from the European Union (EU) on the basis of a unilateral decision. In June 2016 the UK decided to leave the EU invoking article 50 of the treaty. But is withdrawal democratically legitimate? In fact......, the all affected principle suggests that it is undemocratic for subunits to leave larger political units when it adversely affects other citizens without including them in the decision. However, it is unclear what the currency of this affectedness is and, hence, why withdrawal would be undemocratic. We...... argue that it is the effect of withdrawal on the status of citizens as free and equal that is decisive and that explains why unilateral withdrawal of subunits from larger units is democratically illegitimate. Moreover, on the ‘all affected status principle’ that we develop, even multilaterally agreed...

  6. Demand-Withdraw Patterns in Marital Conflict in the Home.

    Science.gov (United States)

    Papp, Lauren M; Kouros, Chrystyna D; Cummings, E Mark

    2009-06-01

    The present study extended laboratory-based findings of demand-withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand-wife withdraw and wife demand-husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that concerned the marital relationship. For both patterns, conflict initiator was positively linked to the demander role. Accounting for marital satisfaction, both demand-withdraw patterns predicted negative emotions and tactics during marital interactions and lower levels of conflict resolution. Spousal depression was linked to increased likelihood of husband demand-wife withdraw.

  7. 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.

  8. Acute coronary ischemia during alcohol withdrawal: a case report

    Directory of Open Access Journals (Sweden)

    Sriram Ganeshalingam

    2011-08-01

    Full Text Available Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

  9. Neurobiology of opioid withdrawal: Role of the endothelin system.

    Science.gov (United States)

    Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

    2016-08-15

    Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as β-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and β-arrestin2), and the possible therapeutic implications of these findings are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    Science.gov (United States)

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

  11. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    Science.gov (United States)

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p nicotine dependence (p Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and

  12. Withdrawing to a Virtual World: Associations between Subtypes of Withdrawal, Media Use, and Maladjustment in Emerging Adults

    Science.gov (United States)

    Nelson, Larry J.; Coyne, Sarah M.; Howard, Emily; Clifford, Brandon N.

    2016-01-01

    An approach-avoidance model of social withdrawal (Asendorpf, 1990) identifies 3 types of social withdrawal including shyness, unsociability, and avoidance. Each appears to be uniquely associated with varying indicators of maladjustment in emerging adulthood (Nelson, 2013) but little, if any, work has been done to see how they might be linked to…

  13. Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

    Science.gov (United States)

    Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

    2008-10-01

    The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

  14. Cannabis Withdrawal in Adults With Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Chauchard, Emeline; Hartwell, Karen J; McRae-Clark, Aimee L; Sherman, Brian J; Gorelick, David A

    2018-02-22

    Cannabis withdrawal has not been studied in adults with attention-deficit/hyperactivity disorder (ADHD) who have high rates of cannabis use. We aimed to describe cannabis withdrawal, motivations to quit, and strategies to quit cannabis use in cannabis-dependent adults with ADHD. Twenty-three adults with ADHD enrolled in a controlled clinical trial of pharmacotherapy (atomoxetine) for cannabis dependence (DSM-IV criteria) completed the Marijuana Quit Questionnaire (MJQQ) to provide information on their "most serious" quit attempt made without formal treatment. The study was conducted between November 2005 and June 2008. Participants were predominantly male (82.6%, n = 19), with a mean (SD) age of 27.4 (8.5) years (range, 18-53) at the start of their index quit attempt. The most common motive for quitting cannabis was "to save money" (87%, n = 20); the most common strategy to maintain abstinence was "stopped associating with people who smoke marijuana" (43%, n = 10). Almost all (96%, n = 22) subjects reported ≥ 1 cannabis withdrawal symptom; 7 (30%) met DSM-5 diagnostic criteria for cannabis withdrawal syndrome. Participants with comorbid ADHD and cannabis dependence reported withdrawal symptoms similar to other samples of non-treatment-seeking cannabis-dependent adults with no psychiatric comorbidity. These findings suggest that ADHD does not influence cannabis withdrawal in the way that it does tobacco (nicotine) withdrawal. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT00360269. © Copyright 2018 Physicians Postgraduate Press, Inc.

  15. [The effect of palonosetron on rocuronium-induced withdrawal movement].

    Science.gov (United States)

    Park, Ki-Bum; Jeon, Younghoon; Yi, Junggu; Kim, Ji-Hyun; Chung, Seung-Yeon; Kwak, Kyung-Hwa

    Rocuronium causes pain and withdrawal movement during induction of anesthesia. In this study, palonosetron was investigated to have analgesic effect on the reduction of rocuronium-induced withdrawal movement. 120 patients were randomly assigned to one of three groups to receive either saline, lidocaine 20mg, or palonosetron 0.075mg with a tourniquet applied two minutes before thiopental sodium (5mg.kg -1 ) was given intravenously. After loss of consciousness, rocuronium (0.6mg.kg -1 ) was injected and the withdrawal movement was estimated by 4-point scale in a double-blind manner. The overall incidence of rocuronium withdrawal movement was 50% with lidocaine (p=0.038), 38% with palonosetron (p=0.006) compared with 75% for saline. The incidence of no pain to mild pain was significantly lower in the lidocaine and palonosetron groups (85% and 92% respectively) than in the saline group (58%). However, there was no significant difference in withdrawal movement between the lidocaine and palonosetron groups. There was no severe movement with palonosetron. Pretreatment of palonosetron with venous occlusion may attenuate rocuronium-induced withdrawal movement as effective as the use of lidocaine. It suggested that peripheral action of palonosetron was effective to reduce rocuronium-induced withdrawal movement. Copyright © 2016. Publicado por Elsevier Editora Ltda.

  16. Opioid withdrawal signs and symptoms in children: frequency and determinants.

    Science.gov (United States)

    Fisher, Deborah; Grap, Mary Jo; Younger, Janet B; Ameringer, Suzanne; Elswick, R K

    2013-01-01

    The purpose of this study was to, in a pediatric population, describe the frequency of opioid withdrawal signs and symptoms and to identify factors associated with these opioid withdrawal signs and symptoms. Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as 2-3 days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A prospective, descriptive study was conducted. The sample of 26 was drawn from all patients, ages 2 weeks to 21 years admitted to the Children's Hospital of Richmond pediatric intensive care unit (PICU) and who have received continuous infusion or scheduled opioids for at least 5 days. Data collected included: opioid withdrawal score (WAT-1), opioid taper rate (total dose of opioid per day in morphine equivalents per kilogram [MEK]), pretaper peak MEK, pretaper cumulative MEK, number of days of opioid exposure prior to taper, and age. Out of 26 enrolled participants, only 9 (45%) had opioid withdrawal on any given day. In addition, there was limited variability in WAT-1 scores. The most common symptoms notes were diarrhea, vomit, sweat, and fever. For optimal opioid withdrawal assessments, clinicians should use a validated instrument such as the WAT-1 to measure for signs and symptoms of opioid withdrawal. Further research is indicated to examine risk factors for opioid withdrawal in children. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Oxidative stress of crystalline lens in rat menopausal model

    OpenAIRE

    Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

    2016-01-01

    ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Gro...

  18. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    Science.gov (United States)

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

  19. The cannabis withdrawal syndrome: current insights

    Science.gov (United States)

    Bonnet, Udo; Preuss, Ulrich W

    2017-01-01

    The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition) and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to

  20. The cannabis withdrawal syndrome: current insights

    Directory of Open Access Journals (Sweden)

    Bonnet U

    2017-04-01

    Full Text Available Udo Bonnet,1,2 Ulrich W Preuss3,4 1Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Castrop-Rauxel, 2Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, 3Vitos-Klinik Psychiatrie und Psychotherapie Herborn, Herborn, 4Martin Luther University Halle-Wittenberg, Halle (Saale, Germany Abstract: The cannabis withdrawal syndrome (CWS is a criterion of cannabis use disorders (CUDs (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition and cannabis dependence (International Classification of Diseases [ICD]-10. Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1 receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox and

  1. Impact of recombinant TSH on quality of life in thyroid carcinoma patients undergoing remnant ablation or diagnostic whole body scanning

    International Nuclear Information System (INIS)

    Schroeder, Pamela R.; Ladenson, Paul W.; for the Members of the Thyrogen Trials

    2005-01-01

    Full text: Thyroid remnant ablation with 131 I is often necessary in the initial treatment of thyroid carcinoma. A recent study demonstrated that use of recombinant TSH (rh TSH) was equivalently effective to withdrawal from levothyroxine (L-T 4 ) for postoperative remnant ablation. Quality of life was also shown to be negatively impacted in patients withdrawn from L-T 4 , but not those maintained euthyroid and treated after rh TSH. In this study, we compare the impact of rh TSH on quality of life in patients undergoing remnant ablation versus those undergoing diagnostic whole body scanning (WBS) in a previous trial. Health-related quality of life was measured using the SF-36 survey, which consists of 8 domains describing the physical and mental functioning of patients and 2 physical and mental summary domains, in both trials at baseline on L-T 4 , after rh TSH while on L-T 4 and after L-T 4 withdrawal. Mean SF-36 scores declined from the rh TSH treatment versus L-T 4 withdrawal in both trials to a similar extent in all 8 domains and the 2 summary domains, as evidenced by overlapping 95% confidence intervals. Further SF-6D scores, which summarize all 8 domains in a single zero-to-one metric, were used to characterize the overall quality of life among patients in the two trials. The SF-6D scores for patients after rh TSH administration in the diagnostic and ablation trials were 0.803 and 0.714, respectively. In contrast, SF-6D scores for patients undergoing L-T 4 withdrawal in the diagnostic and ablation trials were 0.637 and 0.548, respectively (p 4 withdrawal both experience a comparable decrease in quality of life, which can be prevented by use of rh TSH in the euthyroid state. (author)

  2. USA Withdrawal from Paris Agreement – What Next?

    OpenAIRE

    Sergey Chestnoy; Dinara Gershinkova

    2017-01-01

    In June 2017, President Trump announced the USA’s withdrawal from the Paris Climate Accord, which had been ratified for less than a year, thanks in large part to the USA. That drastic shift followed the change in residency at the White House. Withdrawing from the Paris Accord presents an interesting topic for analysis. There’s the practical side of the withdrawal procedure as set out in Article 28 of the agreement, not to mention the consequences of US non-participation in address...

  3. The Treatment of Clozapine-Withdrawal Delirium with Electroconvulsive Therapy

    Directory of Open Access Journals (Sweden)

    Anish Modak

    2017-01-01

    Full Text Available Clozapine, a commonly used atypical antipsychotic, can precipitate a severe withdrawal syndrome. In this report, we describe a case of delirium with catatonic features emerging after the immediate cessation of clozapine subsequent to concerns of developing neuroleptic malignant syndrome. After multiple treatments were found to be inefficacious, electroconvulsive therapy (ECT was initiated, resulting in significant improvement. A literature search revealed six previous cases of clozapine-withdrawal syndromes of varied symptomatology treated with ECT. To our knowledge, the present case represents the first reported clozapine-withdrawal delirium treated successfully with ECT.

  4. Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.

    Science.gov (United States)

    Rebouças, Elce C C; Leal, Sandra; Silva, Susana M; Sá, Susana I

    2016-11-01

    Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Freshmen Program Withdrawal: Types and Recommendations

    Directory of Open Access Journals (Sweden)

    Ana Bernardo

    2017-09-01

    Full Text Available University program dropout is a problem that has important consequences not only for the student that leaves but also for the institution in which the withdrawal occurs. Therefore, higher education institutions must study the problem in greater depth to establish appropriate prevention measures in the future. However, most research papers currently focus primarily on the characteristics of students who leave university, rather than on those who choose to pursue alternative courses of study and therefore fail to take into account the different kinds of abandonment. The aim of this paper is to identify the different types of dropout to define their characteristics and propose some recommendations. Thus, an ex post facto study was carried out on a sample of 1,311 freshmen from a university in the north of Spain using data gathered using an ad-hoc designed questionnaire, applied by telephone or an online survey, and completed with data available in the university data warehouse. A descriptive analysis was performed to characterize the sample and identify five different groups, including 1. Students persisting in their initiated degree 2. Students who change of program (within the same university 3. Students transferring to a different university 4. Students enrolling in non-higher-education studies 5. Students that quit studying. Also, data mining techniques (decision trees were applied to classify the cases and generate predictive models to aid in the design of differentiated intervention strategies for each of the corresponding groups.

  6. Obesity and the Social Withdrawal Syndrome.

    Science.gov (United States)

    Rotenberg, Ken J; Bharathi, Carla; Davies, Helen; Finch, Tom

    2017-08-01

    The relation between obesity and Social Withdrawal Syndrome (SWS) was examined using the data gathered by Rotenberg, Bharathi, Davies, and Finch (2013). One hundred and 35 undergraduates (80 females; Mage=21years-10months) completed standardized scales that assessed the SWS (low emotional trust beliefs in close others, low disclosure to close others, and high loneliness). BMI was calculated from self-reported weight and height. As hypothesized, quadratic relations were found in which participants with BMI>30 (i.e., obese) demonstrated the SWS pattern of low emotional trust beliefs in close others, low disclosure to close others, and high loneliness. As further evidence, lower emotional trust in close others, lower disclosure to close others, and greater loneliness were found for obese participants (>30 BMI, n=27) than both normal weight (<25 BMI, n=67) and overweight participants (25 to 30 BMI, n=41). The findings confirmed the hypothesis that obesity was associated with the SWS. The findings suggested that the lack of trust in others by obese individuals contributes to their unwillingness to seek out help for health and psychosocial problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Freshmen Program Withdrawal: Types and Recommendations

    Science.gov (United States)

    Bernardo, Ana; Cervero, Antonio; Esteban, María; Tuero, Ellian; Casanova, Joana R.; Almeida, Leandro S.

    2017-01-01

    University program dropout is a problem that has important consequences not only for the student that leaves but also for the institution in which the withdrawal occurs. Therefore, higher education institutions must study the problem in greater depth to establish appropriate prevention measures in the future. However, most research papers currently focus primarily on the characteristics of students who leave university, rather than on those who choose to pursue alternative courses of study and therefore fail to take into account the different kinds of abandonment. The aim of this paper is to identify the different types of dropout to define their characteristics and propose some recommendations. Thus, an ex post facto study was carried out on a sample of 1,311 freshmen from a university in the north of Spain using data gathered using an ad-hoc designed questionnaire, applied by telephone or an online survey, and completed with data available in the university data warehouse. A descriptive analysis was performed to characterize the sample and identify five different groups, including 1. Students persisting in their initiated degree 2. Students who change of program (within the same university) 3. Students transferring to a different university 4. Students enrolling in non-higher-education studies 5. Students that quit studying. Also, data mining techniques (decision trees) were applied to classify the cases and generate predictive models to aid in the design of differentiated intervention strategies for each of the corresponding groups. PMID:28983263

  8. A Case Report of Acute Esotropia in a Young Woman following Heroin Withdrawal

    Directory of Open Access Journals (Sweden)

    Bethel Shiferaw

    2015-01-01

    Full Text Available Introduction. Esotropia is a form of strabismus that can give the affected individual a “cross-eyed” appearance. Acute onset of esotropia is an uncommon form; in the vast majority of cases, no underlying neurological etiology is found. Case Presentation. A 22-year-old female with a long history of opiate abuse presented with acute onset of diplopia. She noted her eyes were crossing and started seeing double. She stopped using heroin 11 days prior to presentation. There was large inward deviation of her left eye. Convergence was difficult and accompanied by horizontal nystagmus. Diplopia resolved by covering each eye. Further investigations including imaging studies were normal. Discussion. Acute onset esotropia is rare and must be investigated right away to exclude central nervous system pathologies, where no opiates use is reported. Diplopia in the form of acute esotropia may manifest in up to 30% of individuals undergoing heroin withdrawal. Evaluating acute esotropia requires detailed information of medical history with an emphasis on drug use. Conclusion. Acute onset esotropia with double vision can be caused by abrupt withdrawal of opiates. This case should serve to raise awareness among health care professionals, to avoid costly and unnecessary diagnostic evaluations and interventions.

  9. [Social aspects of epilepsy: marriage, pregnancy, driving, antiepileptic drug withdrawal and against social stigma].

    Science.gov (United States)

    Tsuji, Sadatoshi

    2004-11-01

    Persons with epilepsy need adequate advice and effective counselling about issues such as marriage, pregnancy, risks of inheriting epilepsy, driving, employment and antiepileptic drug withdrawal, because these persons are not receiving important information and education about their condition and possible adverse effects of treatment. Furthermore, women with epilepsy have increased rates of pregnancy complications and poor fetal outcomes including congenital malformations and developmental delay related to both their epilepsy and antiepileptic drugs. However, approximately 90% of all women with epilepsy undergo normal pregnancy and give birth to children free of birth defects. Pregnancy is generally safe in women with epilepsy. The study of long-term prognosis of childhood-onset epilepsy in Japan shows that the majority of these patients have lower levels of educational background as well as employment and marital status compared with the general population (Wakamoto H. et al). Of patients with epilepsy, 60% to 70% achieve control with antiepileptic medication. However, several antiepileptic drug withdrawal studies show variable rates of success, with relapse rates ranging from 12% to 63% (Britton J.W.). Driving is listed as major problem in persons with epilepsy. However, the patients with seizure-free more than two years have been able to get the driver's license since June, 2002. Social attitudes towards epilepsy cause more distress to the patient than the disease itself. We should realize that persons with epilepsy are normal or near-normal. To ameliorate the social stigma against epilepsy, continuous and repetitive educational efforts would be needed.

  10. Predictors of long term opioid withdrawal outcome after short-term stabilization with buprenorphine.

    Science.gov (United States)

    Saleh, M I

    2014-01-01

    We aim to examine predictors of opiate abstinence status 3 months after the end of buprenorphine/naloxone treatment for opioid-dependent participants. Participants (n= 516, age > 15 years) received buprenorphine/ naloxone treatment for 4 weeks and then randomly assigned to undergo dose tapering over either 7 days or 28 days. Bivariate analysis was performed to identify possible predictors of successful opiate abstinence outome (p-value opioid and drug urine tests result at the end taper; employment status, family problems, and alcohol use domains of addiction severity index (ASI) score; and clinical opiate withdrawal scale (COWS) at the end of stabilization. Final predictor list identified by logistic regression include: ASI score for family and alcohol problems, COWS at the end of stabilization and opiate urine test at the end of taper. Participants presenting with a negative urine test for opiate, more severe alcohol, more severe family problems, or more symptoms of opiate withdrawal at the end of stabilization were more likely to have a successful opiate abstinence.

  11. TRACY transient experiment databook. 2) ramp withdrawal experiment

    International Nuclear Information System (INIS)

    Nakajima, Ken; Yamane, Yuichi; Ogawa, Kazuhiko; Aizawa, Eiju; Yanagisawa, Hiroshi; Miyoshi, Yoshinori

    2002-03-01

    This is a databook of TRACY ''ramp withdrawal'' experiments. TRACY is a reactor to perform supercritical experiments using low-enriched uranyl nitrate aqueous solution. The excess reactivity of TRACY is 3$ at maximum, and it is inserted by feeding the solution to a core tank or by withdrawing a control rod, which is called as the transient rod, from the core. In the ramp withdrawal experiment, the supercritical experiment is initiated by withdrawing the transient rod from the core in a constant speed using a motor drive system. The data in the present databook consist of datasheets and graphs. Experimental conditions and typical values of measured parameters are tabulated in the datasheet. In the graph, power and temperature profiles are plotted. Those data are useful for the investigation of criticality accidents with fissile solutions, and for validation of criticality accident analysis codes. (author)

  12. Prolonged social withdrawal disorder: a hikikomori case in Spain.

    Science.gov (United States)

    Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

    2014-09-01

    The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

  13. Ethical Analysis of Withdrawing Ventricular Assist Device Support

    OpenAIRE

    Mueller, Paul S.; Swetz, Keith M.; Freeman, Monica R.; Carter, Kari A.; Crowley, Mary Eliot; Severson, Cathy J. Anderson; Park, Soon J.; Sulmasy, Daniel P.

    2010-01-01

    OBJECTIVE: To describe a series of patients with heart failure supported with a ventricular assist device (VAD) who requested (or whose surrogates requested) withdrawal of VAD support and the legal and ethical aspects pertaining to these requests.

  14. 24 CFR 180.210 - Withdrawal or disqualification of ALJ.

    Science.gov (United States)

    2010-04-01

    ... EMPLOYMENT AND BUSINESS OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Administrative Law Judge § 180.210 Withdrawal or disqualification of ALJ. (a) Disqualification. If an ALJ finds...

  15. Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

    Science.gov (United States)

    Mitchell, S H; de Wit, H; Zacny, J P

    1995-08-01

    This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

  16. Steroid withdrawal in renal transplant patients: the Irish experience.

    LENUS (Irish Health Repository)

    Phelan, P J

    2012-02-01

    BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, <\\/= 5 mg\\/day, > 5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

  17. Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].

    Science.gov (United States)

    Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy

    2017-03-22

    Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].

  18. State National Pollutant Discharge Elimination System (NPDES) Program Withdrawal Petitions

    Data.gov (United States)

    U.S. Environmental Protection Agency — Search for pending and resolved NPDES withdrawal petitions by state, region, date, or keyword. "Pending" means EPA has received the petition and is working with the...

  19. Induction of synaptic long-term potentiation after opioid withdrawal.

    Science.gov (United States)

    Drdla, Ruth; Gassner, Matthias; Gingl, Ewald; Sandkühler, Jürgen

    2009-07-10

    mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.

  20. Consequences of a withdrawal from the use of nuclear energy

    International Nuclear Information System (INIS)

    Wagner, H.J.; Bundschuh, V.; Duering, K.; Martinsen, D.; Riemer, H.; Walbeck, M.

    1986-01-01

    First the consequences of an immediate withdrawal are considered, i.e. a replacement of electricity generation capacity can not be built up in time. Then assumptions and results for a withdrawal in stages are presented. This means, that a replacement of nuclear generation capacity is possible. The applied energy model allows statements about the future structure of energy supply, the mass balances, the costs, and the SO 2 , NO x and CO 2 emissions from increased coal combustion. (orig./HP) [de

  1. Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

    Science.gov (United States)

    Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

    2013-06-01

    Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

  2. A case of rhabdomyolysis associated with severe opioid withdrawal.

    Science.gov (United States)

    Gangahar, Deepali

    2015-08-01

    While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications. © American Academy of Addiction Psychiatry.

  3. Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS in Malay

    Directory of Open Access Journals (Sweden)

    Shafie Asrul A

    2010-05-01

    Full Text Available Abstract Background The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research. Methods A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization. Results Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured. Conclusions We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.

  4. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

    DEFF Research Database (Denmark)

    Jessen, L; Bjerrum, Ole Jannik; Christensen, Sten

    2007-01-01

    was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three...... water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes....

  5. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden)

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  6. Determinants of early withdrawal and of early withdrawal by reason of disability from the Irish labour force in the third age

    OpenAIRE

    Lawless, Martin

    2015-01-01

    III – Abstract: Determinants of early withdrawal and early withdrawal by reason of disability from the Irish labour force in the Third Age.Background. This study examines the relationship between early withdrawal and early withdrawal through disability from the Irish labour force in the Third Age. The relationship between unemployment or early retirement and ill health has been determined by a number of studies and, while unemployment through ill health or occupational disability may lead to ...

  7. To Withdraw Or Not To Withdraw? Evaluation of the Mandatory Right of Withdrawal in Consumer Distance Selling Contracts Taking Into Account Its Behavioural Effects on Consumers

    NARCIS (Netherlands)

    Luzak, J.A.

    2014-01-01

    The right of withdrawal was introduced to European consumer law as an exception to the general contractual principle of pacta sunt servanda. It has recently been upheld in the Consumer Rights Directive as a mandatory right for consumers concluding distance selling contracts. Among various

  8. Impacts of crop insurance on water withdrawals for irrigation

    Science.gov (United States)

    Deryugina, Tatyana; Konar, Megan

    2017-12-01

    Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, crop insurance may have unintended consequences for water resources sustainability, as the vast majority of freshwater withdrawals go to agriculture. The causal impact of crop insurance on water use in agriculture remains poorly understood. Here, we determine the empirical relationship between crop insurance and irrigation water withdrawals in the United States. Importantly, we use an instrumental variables approach to establish causality. Our methodology exploits a major policy change in the crop insurance system - the 1994 Federal Crop Insurance Reform Act - which imposed crop insurance requirements on farmers. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, with most coming from groundwater aquifers. We identify farmers growing more groundwater-fed cotton as an important mechanism contributing to increased withdrawals. A 1% increase in insured crop acreage leads to a 0.624% increase in cotton acreage, or 95,602 acres. These results demonstrate that crop insurance causally leads to more irrigation withdrawals. More broadly, this work underscores the importance of determining causality in the water-food nexus as we endeavor to achieve global food security and water resources sustainability.

  9. The acute tobacco withdrawal syndrome among black smokers.

    Science.gov (United States)

    Robinson, Cendrine D; Pickworth, Wallace B; Heishman, Stephen J; Waters, Andrew J

    2014-03-01

    Black smokers have greater difficulty quitting tobacco than White smokers, but the mechanisms underlying between-race differences in smoking cessation are not clear. One possibility is that Black smokers experience greater acute withdrawal than Whites. We investigated whether Black (n = 104) and White smokers (n = 99) differed in abstinence-induced changes in self-report, physiological, and cognitive performance measures. Smokers not wishing to quit completed two counterbalanced experimental sessions. Before one session, they abstained from smoking for at least 12 hr. They smoked normally before the other session. Black smokers reported smaller abstinence-induced changes on a number of subjective measures including the total score of the 10-item Questionnaire for Smoking Urges (QSU) and the total score of the Wisconsin Smoking Withdrawal Scale (WSWS). However, on most subjective measures, and on all objective measures, there were no between-race differences in abstinence-induced change scores. Moreover, Black participants did not report lower QSU and WSWS ratings at the abstinent session, but they did experience significantly higher QSU and WSWS ratings at the nonabstinent session. Abstinence-induced changes in subjective, physiological, and cognitive measures in White smokers were similar for smokers of nonflavored and menthol-flavored cigarettes. There was no evidence that Black smokers experienced greater acute tobacco withdrawal than Whites. To the contrary, Black participants experienced smaller abstinence-induced changes in self-reported craving and withdrawal on some measures. Racial differences in smoking cessation are unlikely to be explained by acute withdrawal.

  10. Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets.

    Science.gov (United States)

    Rehni, Ashish K; Jaggi, Amteshwar S; Singh, Nirmal

    2013-02-01

    Opioid withdrawal syndrome is a debilitating manifestation of opioid dependence and responds poorly to the available clinical therapies. Studies from various in vivo and in vitro animal models of opioid withdrawal syndrome have led to understanding of its pathobiology which includes complex interrelated pathways leading to adenylyl cyclase superactivation based central excitation. Advancements in the elucidation of opioid withdrawal syndrome mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the neurobiology of opioid withdrawal syndrome and its therapeutic target recptors like calcitonin gene related peptide receptors (CGRP), N-methyl-D-aspartate (NMDA) receptors, gamma aminobutyric acid receptors (GABA), G-proteingated inwardly rectifying potassium (GIRK) channels and calcium channels. The present review further details the potential role of second messengers like calcium (Ca2+) / calmodulin-dependent protein kinase (CaMKII), nitric oxide synthase, cytokines, arachidonic acid metabolites, corticotropin releasing factor, fos and src kinases in causing opioid withdrawal syndrome. The exploitation of these targets may provide effective therapeutic agents for the management of opioid dependence-induced abstinence syndrome.

  11. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

    Science.gov (United States)

    Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

    2018-05-01

    Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  12. 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.

  13. Histological changes of the adult albino rats entorhinal cortex under ...

    African Journals Online (AJOL)

    Ibrahim K. Ragab

    2016-06-03

    Jun 3, 2016 ... Treated group received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks. All ani- ... withdrawal reactions include restlessness, agitation, anxiety, ... (in particular, selective serotonin reuptake inhibitors and ... out in rats, dogs and rabbits. ... tionally accepted principles for laboratory animal use and care.

  14. The mechanism of thioacetamide-induced apoptosis in the L37 albumin-SV40 T-antigen transgenic rat hepatocyte-derived cell line occurs without DNA fragmentation.

    Science.gov (United States)

    Bulera, S J; Sattler, C A; Gast, W L; Heath, S; Festerling, T A; Pitot, H C

    1998-10-01

    The hepatotoxicant thioacetamide (TH) has classically been used as a model to study hepatic necrosis; however, recent studies have shown that TH can also induce apoptosis. In this report we demonstrate that 2.68+/-0.54% of the albumin-SV40 T-antigen transgenic rat hepatocytes undergo TH-induced apoptosis, a level comparable to other in vivo models of liver apoptosis. In addition, TH could induce apoptosis and necrosis in the L37 albumin-SV40 T-antigen transgenic rat liver-derived cell line. Examination of dying L37 cells treated with 100 mM TH by electron microscopy revealed distinct morphological characteristics that could be attributed to apoptosis. Quantitation of apoptosis by FACS analysis 24 h after treatment with 100 mM TH revealed that 81.3+/-1.6% of the cells were undergoing apoptosis. In contrast, when L37 cells were treated with 250 mM TH, cells exhibited characteristics consistent with necrotic cell death. DNA fragmentation ladders were produced by growth factor withdrawal-induced apoptosis; however, in 100 mM TH-induced apoptosis, DNA fragmentation ladders were not observed. Analysis of endonuclease activity in L37 cells revealed that the enzymes were not inactivated in the presence of 100 mM TH. The data presented in this report indicate that the L37 cell line could be used to study the mechanism of TH-induced apoptosis that was not mediated through a mechanism requiring DNA fragmentation.

  15. Drug withdrawal symptoms in children after continuous infusions of fentanyl.

    Science.gov (United States)

    French, J P; Nocera, M

    1994-04-01

    The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p observation protocol and a possible weaning regimen after fentanyl is discontinued.

  16. Emplotting Hikikomori: Japanese Parents' Narratives of Social Withdrawal.

    Science.gov (United States)

    Rubinstein, Ellen

    2016-12-01

    Hikikomori, often glossed as "social withdrawal," emerged as a sociomedical condition among Japanese youth at the end of the twentieth century, and it continues to fascinate and concern the public. Explanatory frameworks for hikikomori abound, with different stakeholders attributing it to individual psychopathology, poor parenting, and/or a lack of social support structures. This article takes an interpretive approach to hikikomori by exploring parents' narrative constructions of hikikomori children in support group meetings and in-depth interviews. I argue that some parents were able to find hope in hikikomori by 'emplotting' their children's experiences into a larger narrative about onset, withdrawal, and recovery, which helped them remain invested in the present by maintaining a sense of possibility about the future. Contrary to literature that examines hikikomori as an epidemic of isolated individuals, I demonstrate how parents play a key role in hikikomori through meaning-making activities that have the potential to shape their children's experiences of withdrawal.

  17. Withdrawal of immunosuppresive agents in the treatment of disseminated coccidioidomycosis.

    Science.gov (United States)

    Kaplan, J E; Zoschke, D; Kisch, A L

    1980-04-01

    Disseminated coccidioidomycosis is a systemic fungal infection that causes high mortality in the renal transplatn patient. Cell-mediated immunity, which appears to be the relevant host defense mechanism, is impaired by the immunosupressive agents used to prevent allograft rejection. In the case presented, immunosuppressive therapy was stopped as an adjunct to treatment of this infection. The patient has shown evidence of improvement, and his allograft has continued to function nine months after the withdrawal of immunosuppressive therapy and 18 months after the diagnosis. In vitro lymphocyte function studies indicate that the impairment in cell-mediated immunity detected prior to withdrawal of immunosuppressive therapy has persisted, probably accounting for allograft survival. Withdrawal of immunosuppressive therapy may prolong survival in renal transplant patients with disseminated coccidioidomycosis. Additionally, depression in cell-mediated immunity associated with the fungal infection itself may be sufficient to prevent allograft rejection in these patients.

  18. Takotsubo Cardiomyopathy and Catatonia in the Setting of Benzodiazepine Withdrawal

    Directory of Open Access Journals (Sweden)

    Teng J. Peng

    2016-01-01

    Full Text Available We report two serious and unusual complications of benzodiazepine withdrawal in a single patient: takotsubo cardiomyopathy and catatonia. This 61-year-old female patient was brought to the emergency department with lethargy and within hours had declined into a state of catatonia. Although there was never a complaint of chest pain, ECG showed deep anterior T-wave inversions and cardiac enzymes were elevated. An echocardiogram was consistent with takotsubo cardiomyopathy. She later received 1 mg of midazolam and within minutes had resolution of catatonic symptoms. Careful history revealed that she had omitted her daily dose of lorazepam for 3 days prior to admission. To our knowledge, the case presented herein is the first report of simultaneous catatonia and takotsubo cardiomyopathy in the setting of benzodiazepine withdrawal. The pathogenesis of both conditions is poorly understood but may be indirectly related to the sudden decrease in γ-aminobutyric acid (GABA signaling during benzodiazepine withdrawal.

  19. Deadly pressure pneumothorax after withdrawal of misplaced feeding tube

    DEFF Research Database (Denmark)

    Andresen, Erik Nygaard; Frydland, Martin; Usinger, Lotte

    2016-01-01

    BACKGROUND: Many patients have a nasogastric feeding tube inserted during admission; however, misplacement is not uncommon. In this case report we present, to the best of our knowledge, the first documented fatality from pressure pneumothorax following nasogastric tube withdrawal. CASE PRESENTATION......, but our patient died less than an hour after withdrawal. The autopsy report stated that cause of death was tension pneumothorax, which developed following withdrawal of the misplaced feeding tube. CONCLUSIONS: The indications for insertion of nasogastric feeding tubes are many and the procedure...... is considered harmless; however, if the tube is misplaced there is good reason to be cautious on removal as this can unmask puncture of the pleura eliciting pneumothorax and, as this case report shows, result in an ultimately deadly tension pneumothorax....

  20. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    DEFF Research Database (Denmark)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders

    2016-01-01

    BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total...

  1. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    Science.gov (United States)

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats.

  2. Water withdrawals, use, and trends in Florida, 2010

    Science.gov (United States)

    Marella, Richard L.

    2014-01-01

    In 2010, the total amount of water withdrawn in Florida was estimated to be 14,988 million gallons per day (Mgal/d). Saline water accounted for 8,589 Mgal/d (57 percent) and freshwater accounted for 6,399 Mgal/d (43 percent). Groundwater accounted for 4,166 Mgal/d (65 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,233 Mgal/d (35 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. An additional 659 Mgal/d of reclaimed wastewater was used in Florida during 2010. Freshwater withdrawals were greatest in Palm Beach County (707 Mgal/d), and saline-water withdrawals were greatest in Hillsborough County (1,715 Mgal/d). Fresh groundwater provided drinking water (public supplied and self-supplied) for 17.33 million people (92 percent of Florida’s population), and fresh surface water provided drinking water for 1.47 million people (8 percent). The statewide public-supply gross per capita use for 2010 was 134 gallons per day, whereas the statewide public-supply domestic per capita use was 85 gallons per day. The majority of groundwater withdrawals (almost 62 percent) in 2010 were obtained from the Floridan aquifer system, which is present throughout most of the State. The majority of fresh surface-water withdrawals (56 percent) came from the southern Florida hydrologic unit subregion and is associated with Lake Okeechobee and the canals in the Everglades Agricultural Area of Glades, Hendry, and Palm Beach Counties, as well as the Caloosahatchee River and its tributaries in the agricultural areas of Collier, Glades, Hendry, and Lee Counties. Overall, agricultural irrigation accounted for 40 percent of the total freshwater withdrawals (ground and surface), followed by public supply with 35 percent. Public supply accounted for 48 percent of groundwater withdrawals, followed by agricultural self-supplied (34 percent), commercial-industrial-mining self-supplied (7 percent), recreational

  3. Water Withdrawals, Use, and Trends in Florida, 2005

    Science.gov (United States)

    Marella, Richard L.

    2009-01-01

    In 2005, the total amount of water withdrawals in Florida was estimated at 18,359 million gallons per day (Mgal/d). Saline water accounted for 11,486 Mgal/d (63 percent), and freshwater accounted for 6,873 Mgal/d (37 percent). Groundwater accounted for 4,247 Mgal/d (62 percent) of freshwater withdrawals, and surface water accounted for the remaining 2,626 Mgal/d (38 percent). Surface water accounted for nearly all (99.9 percent) saline-water withdrawals. An additional 660 Mgal/d of reclaimed wastewater was used in Florida during 2005. The largest amount of freshwater was withdrawn from Palm Beach County, and the largest amount of saline water was withdrawn from Pasco County. Fresh groundwater provided drinking water (public supplied and self-supplied) for 16.19 million people (90 percent of Florida's population), and fresh surface water provided drinking water for 1.73 million people (10 percent). The majority of groundwater withdrawals (nearly 60 percent) in 2005 was obtained from the Floridan aquifer system which is present throughout the entire State. The majority of fresh surface-water withdrawals (59 percent) came from the southern Florida hydrologic unit subregion and is associated with Lake Okeechobee and the canals in the Everglades Agricultural Area of Glades, Hendry, and Palm Beach Counties, as well as the Caloosahatchee River and its tributaries in the agricultural areas of Collier, Glades, Hendry, and Lee Counties. Overall, agricultural irrigation accounted for 40 percent of the total freshwater withdrawals (ground and surface), followed by public supply with 37 percent. Public supply accounted for 52 percent of groundwater withdrawals, followed by agricultural self-supplied (31 percent), ommercial-industrial-mining self-supplied (8.5 percent), recreational irrigation and domestic self-supplied (4 percent each), and power generation (0.5 percent). Agricultural self-supplied accounted for 56 percent of fresh surface-water withdrawals, followed by power

  4. Sports Participation and Withdrawal: A Developmental Motivational Commentary.

    Science.gov (United States)

    Hom, Larry L.

    1996-01-01

    Examines the nature of adolescents' sports involvement as reflected in reasons for participation and withdrawal. Claims that the degree of fun, the motivation to attain competence, and the capacity to distinguish ability from effort are important. Concludes that if the goal of sports is to foster a healthy lifestyle, the issue of maximizing…

  5. Opiate withdrawal syndrome in buprenorphine abusers admitted to ...

    African Journals Online (AJOL)

    The sex v time interaction and the mode of consumption of buprenorphine had significant ... and cancer patients. .... The anal- ysis of the main simple effects revealed a significant ef- fect of time on withdrawal scores for both men (F=65.4,.

  6. Study of possible reduction or withdrawal of vitamin premix during ...

    African Journals Online (AJOL)

    Jane

    2011-07-06

    Jul 6, 2011 ... The effect of dietary vitamin premix withdrawal or reduction between 29 and 35, 36 and 42, and 29 and. 42 days of age on broiler chicken performance and immunocompetence was evaluated. The diets were formulated based on wheat and barley, and the experiment was conducted in floor pens ...

  7. 29 CFR 1956.24 - Procedures for withdrawal of approval.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Procedures for withdrawal of approval. 1956.24 Section 1956.24 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... do so, at least developmentally), no industrial or occupational issues may be considered a separable...

  8. Nontraditional Student Withdrawal from Undergraduate Accounting Programmes: A Holistic Perspective

    Science.gov (United States)

    Fortin, Anne; Sauvé, Louise; Viger, Chantal; Landry, France

    2016-01-01

    A collaborative project of several Quebec universities, this study investigates nontraditional student withdrawal from undergraduate accounting programmes. A nontraditional student is older than 24, or is a commuter or a part-time student, or combines some of these characteristics. Univariate and multivariate analyses of student dropout factors…

  9. 37 CFR 2.19 - Revocation or withdrawal of attorney.

    Science.gov (United States)

    2010-07-01

    ...., a corporate officer or general partner of a partnership). In the case of joint applicants or joint... a trademark case may withdraw upon application to and approval by the Director or, when applicable..., DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Representation by Attorneys Or Other Authorized...

  10. Should Colleges Withdraw Students Who Threaten or Attempt Suicide?

    Science.gov (United States)

    Pavela, Gary

    2005-01-01

    This article discusses the pros and cons of "involuntary withdrawals" in cases of students who are at risk of suicide. A June, 2005, Massachusetts Superior Court summary judgment ruling in the case of "Shin v. Massachusetts Institute of Technology (MIT)" concluded that MIT administrators owed a duty of care to suicide victim,…

  11. Study of possible reduction or withdrawal of vitamin premix during ...

    African Journals Online (AJOL)

    The effect of dietary vitamin premix withdrawal or reduction between 29 and 35, 36 and 42, and 29 and 42 days of age on broiler chicken performance and immunocompetence was evaluated. The diets were formulated based on wheat and barley, and the experiment was conducted in floor pens (experiment 1) and battery ...

  12. It's self defense: how perceived discrimination promotes employee withdrawal.

    Science.gov (United States)

    Volpone, Sabrina D; Avery, Derek R

    2013-10-01

    Integrating theory on stress, stigma, and coping, the present study sheds light on how employees react to perceived discrimination (PD) in the workplace. Using three national samples, we found that PD based on race, sex, age, family obligation, and sexual orientation related to physical withdrawal (i.e., lateness, absenteeism,and intent to quit) indirectly through psychological withdrawal (i.e., burnout and engagement) such that PD corresponded in less engagement and more burnout, which related to increased lateness, absenteeism, and intent to quit [corrected].Further, these indirect relationships were moderated by employees' coping mechanisms with those who were more apt to change the situation or to avoid the stressor exhibiting weaker relationships between PD and psychological withdrawal. Though each of these studies is cross-sectional in nature and therefore cannot provide strong evidence of causal ordering of the variables in our model, the replication and extension of results over three databases and multiple forms of discrimination, coping, psychological, and physical withdrawal demonstrates that understanding the relationships explored in these studies can aid researchers and practitioners in enhancing employee quality of life and productivity.

  13. 46 CFR 391.7 - Tax treatment of nonqualified withdrawals.

    Science.gov (United States)

    2010-10-01

    ... the Code. In lieu of the interest and additions to tax under such sections, simple interest on the... income, and the payment of interest with respect to such amounts. (b) Nonqualified withdrawals defined... in the fund), see § 391.4(e). (e) Interest. (1) For the period on or before the last date prescribed...

  14. 26 CFR 3.7 - Tax treatment of nonqualified withdrawals.

    Science.gov (United States)

    2010-04-01

    ... and additions to tax under such sections, simple interest on the amount of the tax attributable to any... payment of interest with respect to such amounts. (b) Nonqualified withdrawals defined. Except as provided...(e). (e) Interest. (1) For the period on or before the last date prescribed by law, including...

  15. Occupational Asthma after Withdrawal from the Occupational Allergen Exposure

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Pelclová, D.; Lebedová, J.; Marečková, H.; Brabec, Marek

    2006-01-01

    Roč. 44, č. 4 (2006), s. 629-638 ISSN 0019-8366 Source of funding: V - iné verejné zdroje Keywords : occupational asthma * allergen exposure withdrawal Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.911, year: 2006 http://www.jniosh.go.jp/en/indu_hel/pdf/indhealth_44_4_629.pdf

  16. Social Withdrawal Subtypes during Early Adolescence in India

    Science.gov (United States)

    Bowker, Julie C.; Raja, Radhi

    2011-01-01

    The overarching goal of this study was to examine the associations between three social withdrawal subtypes (shyness, unsociability, avoidance), peer isolation, peer difficulties (victimization, rejection, exclusion, low acceptance), and loneliness in India during early adolescence. Participants were 194 adolescents in Surat, India (M age=13.35…

  17. Social Anxiety and Adolescents' Friendships: The Role of Social Withdrawal

    Science.gov (United States)

    Biggs, Bridget K.; Vernberg, Eric M.; Wu, Yelena P.

    2012-01-01

    Research indicates social anxiety is associated with lower friendship quality, but little is known about the underlying mechanisms. This 2-month longitudinal study examined social withdrawal as a mediator of the social anxiety-friendship quality link in a sample of 214 adolescents (M[subscript age] = 13.1 years, SD = 0.73) that included an…

  18. Young Children's Perceptions of Social Withdrawal in China and Canada

    Science.gov (United States)

    Coplan, Robert J.; Zheng, Shujie; Weeks, Murray; Chen, Xinyin

    2012-01-01

    The goal of the present study was to explore attitudes and responses to different forms of social withdrawal in China and Canada. Participants in this study were children in early elementary school in the People's Republic of China (n = 213; 113 boys, 100 girls, M[subscript age] = 6.11 years) and Canada (n = 162; 60 boys, 102 girls, M[subscript…

  19. The social side of shame : approach versus withdrawal

    NARCIS (Netherlands)

    de Hooge, Ilona E.; Breugelmans, Seger M.; Wagemans, Fieke M.A.; Zeelenberg, Marcel

    2018-01-01

    At present, the consequences and functions of experiences of shame are not yet well understood. Whereas psychology literature typically portrays shame as being bad for social relations, motivating social avoidance and withdrawal, there are recent indications that shame can be reinterpreted as having

  20. The social side of shame: approach versus withdrawal

    NARCIS (Netherlands)

    Hooge, De Ilona E.; Breugelmans, Seger M.; Wagemans, Fieke M.A.; Zeelenberg, Marcel

    2018-01-01

    At present, the consequences and functions of experiences of shame are not yet well understood. Whereas psychology literature typically portrays shame as being bad for social relations, motivating social avoidance and withdrawal, there are recent indications that shame can be reinterpreted as having

  1. Evolution of Metabolic Abnormalities in Alcoholic Patients during Withdrawal

    Directory of Open Access Journals (Sweden)

    X. Vandemergel

    2015-01-01

    Full Text Available Chronic alcohol intoxication is accompanied by metabolic abnormalities. Evolution during the early withdrawal period has been poorly investigated. The aim of this study was to determine the evolution of metabolic parameters during alcohol withdrawal. Patients and Methods. Thirty-three patients admitted in our department for alcohol withdrawal were prospectively included. Results. Baseline hypophosphatemia was found in 24% of cases. FEPO4 was reduced from 14.2 ± 9% at baseline to 7.3 ± 4.2% at day 3 (Pnl, respectively. No correlation was found between the sodium and CPK levels (P=0.75 nor between the CPK level and the amount of alcohol ingested (rs = 0.084, P=0.097. Baseline urate level was elevated and returned to normal after three days. Baseline magnesium concentration was normal and stable over time. Conclusion. Chronic alcohol intoxication was accompanied by phosphaturia, rapidly reversible after alcohol withdrawal and inversely correlated with albuminemia, slight hyponatremia, low levels of 25 hydroxy vitamin D, elevated CPK level in about 30% of women, and hyperuricemia with rapid normalization.

  2. Parents, Peers, and Social Withdrawal in Childhood: A Relationship Perspective

    Science.gov (United States)

    Rubin, Kenneth H.; Root, Amy Kennedy; Bowker, Julie

    2010-01-01

    In this chapter, the authors review the history of the Waterloo Longitudinal Project (WLP), the first longitudinal study (1980-1992) dedicated to the study of social withdrawal, its correlates, and consequences. Theories underlying the WLP are described, as are its empirical findings. Recent research from other labs that has extended the findings…

  3. The impact of withdrawal rofecoxib on NSAIDs utilization

    NARCIS (Netherlands)

    Atthobari, J.; Boersma, C.; Visser, S.T.; Postma, M.J.; De Jong-Van Den Berg, L.T.W.

    2010-01-01

    Background: Pharmacovigilance is an important tool to gather real-life information on effectiveness and adverse effects of drugs. Therefore, post-marketing study can lead to new therapeutic insights or even market withdrawal. In September 2004, rofecoxib was withdrawn from the market for reasons of

  4. 18 CFR 801.3 - Allocations, diversions, withdrawals and release.

    Science.gov (United States)

    2010-04-01

    ... wherein the demands upon supply made by water users have developed or threaten to develop to such a degree..., or withdrawals of water be based on the common law principles of riparian rights which entitles... actual and immediate shortage of available and usable water supply, determine and delineate the area of...

  5. 17 CFR 41.47 - Withdrawal of margin.

    Science.gov (United States)

    2010-04-01

    ... PRODUCTS Customer Accounts and Margin Requirements § 41.47 Withdrawal of margin. (a) By the customer... positions in the account under this Regulation (Subpart E, §§ 41.42 through 41.49). (b) By the security...) Interest charged on credit maintained in the account; (3) Communication or shipping charges with respect to...

  6. 75 FR 2894 - Withdrawal of Regulatory Guide 1.148

    Science.gov (United States)

    2010-01-19

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0013] Withdrawal of Regulatory Guide 1.148 AGENCY: Nuclear...

  7. 75 FR 70044 - Withdrawal of Regulatory Guide 1.39

    Science.gov (United States)

    2010-11-16

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doollectionsc-c . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0354] Withdrawal of Regulatory Guide 1.39 AGENCY: Nuclear...

  8. 9 CFR 355.38 - Withdrawal of service.

    Science.gov (United States)

    2010-01-01

    ... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Withdrawal of service. 355.38 Section 355.38 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE...

  9. Polymerization catalysts containing electron-withdrawing amide ligands

    Science.gov (United States)

    Watkin, John G.; Click, Damon R.

    2002-01-01

    The present invention describes methods of making a series of amine-containing organic compounds which are used as ligands for group 3-10 and lanthanide metal compounds. The ligands have electron-withdrawing groups bonded to them. The metal compounds, when combined with a cocatalyst, are catalysts for the polymerization of olefins.

  10. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

    Science.gov (United States)

    Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

    2017-06-01

    Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. 47 CFR 76.917 - Notification of certification withdrawal.

    Science.gov (United States)

    2010-10-01

    ... certification withdrawal. A franchising authority that has been certified to regulate rates may, at any time... include the franchising authority's determination that rate regulation no longer serves the interests of cable subscribers served by the cable system within the franchising authority's jurisdiction, and that...

  12. Temporal Withdrawal Behaviors in an Educational Policy Context

    Science.gov (United States)

    Rosenblatt, Zehava; Shapira-Lishchinsky, Orly

    2017-01-01

    Purpose: The purpose of this paper is to investigate the differential relations between two teacher withdrawal behaviors: work absence and lateness, and two types of school ethics: organizational justice (distributive, procedural) and ethical climate (formal, caring), all in the context of school turbulent environment. Design/methodology/approach:…

  13. Withdrawal cognition among workers in distressed banks: Roles of ...

    African Journals Online (AJOL)

    Results indicated that employees who perceived low organisational support and high inequality had high level of withdrawal cognition. Based on these findings, the researchers recommended that bank managers should provide adequate social supports for their employees and treat them equally or make sure that rewards ...

  14. 46 CFR 391.6 - Tax treatment of qualified withdrawals.

    Science.gov (United States)

    2010-10-01

    ... accounting whereby (1) payments shall reduce the basis of the property on the day such payments are actually... 46 Shipping 8 2010-10-01 2010-10-01 false Tax treatment of qualified withdrawals. 391.6 Section...-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.6 Tax treatment of qualified...

  15. Withdrawal from the International Criminal Court: Does Africa have ...

    African Journals Online (AJOL)

    After a century in the making, the International Criminal Court (ICC) came into existence in 2002 with an overwhelming number of states ratifying the Rome Statute. With 34 signatories, Africa is the largest contributor in the Assembly of State Parties, yet Africa has become its severest critic. As threats of withdrawal become a ...

  16. Steroid withdrawal in renal transplant patients: the Irish experience.

    LENUS (Irish Health Repository)

    Phelan, P J

    2010-10-29

    BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, ≤5 mg\\/day, >5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

  17. 9 CFR 362.4 - Denial or withdrawal of service.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Denial or withdrawal of service. 362.4 Section 362.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE..., assaults, abuse, or any other improper means; (iv) has knowingly falsely made, issued, altered, forged, or...

  18. Withdrawal Strength and Bending Yield Strength of Stainless Steel Nails

    Science.gov (United States)

    Douglas R. Rammer; Samuel L. Zelinka

    2015-01-01

    It has been well established that stainless steel nails have superior corrosion performance compared to carbon steel or galvanized nails in treated wood; however, their mechanical fastening behavior is unknown. In this paper, the performance of stainless steel nails is examined with respect to two important properties used in wood connection design: withdrawal strength...

  19. A Case Report of Severe Delirium after Amantadine Withdrawal

    Directory of Open Access Journals (Sweden)

    Franz Marxreiter

    2017-03-01

    Full Text Available Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD. However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors. Also, amantadine had been part of his long-term medication for more than 2 years. The severity of his psychotic symptoms required a L-Dopa monotherapy. After changing his medication, the patient developed severe delirium that resolved rapidly after i.v. amantadine infusion, suggesting an amantadine withdrawal syndrome. Amantadine withdrawal syndrome is a rare adverse event that may present even in PD patients without cognitive impairment. This case report highlights the need for a gradual withdrawal of amantadine even if acute and severe psychotic symptoms are present. Moreover, this is the first report of a cognitively unimpaired patient developing an amantadine withdrawal syndrome.

  20. The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

    Science.gov (United States)

    Kristensen, B O; Steiness, E; Weeke, J

    1979-12-01

    1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

  1. 18 CFR 806.23 - Standards for water withdrawals.

    Science.gov (United States)

    2010-04-01

    ...) Investigate additional sources or storage options to meet the demand of the project. (ii) Submit a water... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Standards for water withdrawals. 806.23 Section 806.23 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN...

  2. 29 CFR 4281.18 - Outstanding claims for withdrawal liability.

    Science.gov (United States)

    2010-07-01

    ... INSOLVENCY, REORGANIZATION, TERMINATION, AND OTHER RULES APPLICABLE TO MULTIEMPLOYER PLANS DUTIES OF PLAN... in insolvency proceedings. The plan sponsor shall value an outstanding claim for withdrawal liability... title 11, United States Code, or any case or proceeding under similar provisions of state insolvency...

  3. 76 FR 12992 - Notice of Public Meeting for Proposed Withdrawal

    Science.gov (United States)

    2011-03-09

    ... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLCAC09000 L14300000.ET0000; CACA 51408] Notice of Public Meeting for Proposed Withdrawal AGENCY: Bureau of Land Management, Interior. ACTION: Notice of public meeting. SUMMARY: A Notice was published in the Federal Register on August 3, 2010...

  4. Withdrawal of valproic acid treatment during pregnancy and seizure outcome

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2016-01-01

    Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesi...

  5. 78 FR 15009 - Consideration of Withdrawal From Commercial Production and Distribution of the Radioisotope...

    Science.gov (United States)

    2013-03-08

    ... DEPARTMENT OF ENERGY Consideration of Withdrawal From Commercial Production and Distribution of... its consideration of DOE withdrawal from the commercial production and distribution of germanium-68... Statement of Policy, referenced above. In summary, DOE's evaluation will include consideration of: a...

  6. Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

    DEFF Research Database (Denmark)

    Hesse, Morten; Thylstrup, Birgitte

    2013-01-01

    Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco...... the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results...... With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams...

  7. 8 CFR 1292.2 - Organizations qualified for recognition; requests for recognition; withdrawal of recognition...

    Science.gov (United States)

    2010-01-01

    ...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. 1292.2...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. (a) Qualifications of organizations. A non-profit religious, charitable, social service, or similar organization...

  8. 8 CFR 292.2 - Organizations qualified for recognition; requests for recognition; withdrawal of recognition...

    Science.gov (United States)

    2010-01-01

    ...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. 292.2...; withdrawal of recognition; accreditation of representatives; roster. (a) Qualifications of organizations. A non-profit religious, charitable, social service, or similar organization established in the United...

  9. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    Science.gov (United States)

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

  10. Flumazenil in treatment benzodiazepine withdrawal syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Ramah Aleksandar J.

    2015-01-01

    Full Text Available Background: Today in the world and in Serbia is growing number of people who are addicted to benzodiazepine. A particular problem is the process of detoxification and treatment of benzodiazepine withdrawal syndrome due to a recurrence of symptoms of anxiety disorder, availability of benzodiazepines, falling motivation. Standard procedures have often proved unsuccessful and the last decade, and the search for new protocols, including the flumazenil, benzodiazepine receptor antagonist, is actualized. Case report: The patient aged 48 years was admitted to the specialist psychiatric clinic, for treatment of benzodiazepine addiction. Anxiety disorder was diagnosed since adolescence perennial addiction on benzodiazepines and the initial withdrawal syndrome. Former motivated topical treatments for detoxification were unsuccessful. The presence of dual diagnosis, persistence of both disorders in perennial cycle, treatment resistance and actual motivation contributed to the decision to opt rapid detoxification from benzodiazepines by flumazenil application protocol, for hospital treatment by adjuvant therapy with lamotrigine. After discharge from hospital in stable condition it was with no signs of withdrawal syndrome and a rebound of anxiety symptoms. Lamotrigine medication continued including CBT, held during the one-year abstinence monitoring, with sufficient social functionality. Discussion: The efficacy and safety of flumazenil in the treatment of benzodiazepine withdrawal syndrome was investigated in numerous clinical trials, and the mechanism of action is complex, from the benzodiazepine antagonist to inverse agonist in certain circumstances, as well as 'up-regulation' receptors, which together leads to a reduction in symptoms of abstinence syndrome and anxiety in the longer term after treatment, thereby acting favorably to the adherence and remission. Conclusions: Flumazenil protocol is an efficient method in the treatment of the benzodiazepine

  11. Safety of oral dronabinol during opioid withdrawal in humans.

    Science.gov (United States)

    Jicha, Crystal J; Lofwall, Michelle R; Nuzzo, Paul A; Babalonis, Shanna; Elayi, Samy Claude; Walsh, Sharon L

    2015-12-01

    Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (popioid agonist effects (e.g., miosis). Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. U.S. withdrawal from the Paris Agreement: Reasons, impacts, and China's response

    OpenAIRE

    Hai-Bin Zhang; Han-Cheng Dai; Hua-Xia Lai; Wen-Tao Wang

    2017-01-01

    Applying qualitative and quantitative methods, this article explains the driving forces behind U.S. President Donald Trump's decision to withdraw from the Paris Agreement, assesses the impacts of this withdrawal on the compliance prospects of the agreement, and proposes how China should respond. The withdrawal undercuts the foundation of global climate governance and upsets the process of climate cooperation, and the impacts are manifold. The withdrawal undermines the universality of the Pari...

  13. Alcohol withdrawal delirium manifested by manic symptoms in an elderly patient.

    Science.gov (United States)

    Chan, Hung-Yu; Lee, Kuan-I

    2015-03-01

    Alcohol withdrawal syndrome is a commonly seen problem in psychiatric practice. Alcohol withdrawal delirium is associated with significant morbidity and mortality. Withdrawal symptoms usually include tremulousness, psychotic and perceptual symptoms, seizures, and consciousness disturbance. Herein, we report a case involving a 63-year-old man who had alcohol withdrawal delirium that was manifested mainly by manic symptoms. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

  14. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.

    Science.gov (United States)

    Peters, James H; Gallaher, Zachary R; Ryu, Vitaly; Czaja, Krzysztof

    2013-10-15

    Vagotomy, a severing of the peripheral axons of the vagus nerve, has been extensively utilized to determine the role of vagal afferents in viscerosensory signaling. Vagotomy is also an unavoidable component of some bariatric surgeries. Although it is known that peripheral axons of the vagus nerve degenerate and then regenerate to a limited extent following vagotomy, very little is known about the response of central vagal afferents in the dorsal vagal complex to this type of damage. We tested the hypothesis that vagotomy results in the transient withdrawal of central vagal afferent terminals from their primary central target, the nucleus of the solitary tract (NTS). Sprague-Dawley rats underwent bilateral subdiaphragmatic vagotomy and were sacrificed 10, 30, or 60 days later. Plastic changes in vagal afferent fibers and synapses were investigated at the morphological and functional levels by using a combination of an anterograde tracer, synapse-specific markers, and patch-clamp electrophysiology in horizontal brain sections. Morphological data revealed that numbers of vagal afferent fibers and synapses in the NTS were significantly reduced 10 days following vagotomy and were restored to control levels by 30 days and 60 days, respectively. Electrophysiology revealed transient decreases in spontaneous glutamate release, glutamate release probability, and the number of primary afferent inputs. Our results demonstrate that subdiaphragmatic vagotomy triggers transient withdrawal and remodeling of central vagal afferent terminals in the NTS. The observed vagotomy-induced plasticity within this key feeding center of the brain may be partially responsible for the response of bariatric patients following gastric bypass surgery. Copyright © 2013 Wiley Periodicals, Inc.

  15. Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

    Science.gov (United States)

    Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

    2015-01-15

    Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (Pmorphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (Pmorphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (Pmorphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. 34 CFR 472.34 - Under what circumstances may a project continue if a partner withdraws?

    Science.gov (United States)

    2010-07-01

    ... project continue if a partner withdraws? (a) A project may continue despite the withdrawal of a partner... the grant agreement by the partner that is withdrawing without a change in the project's scope or... 34 Education 3 2010-07-01 2010-07-01 false Under what circumstances may a project continue if a...

  17. 40 CFR 97.86 - Withdrawal from NOX Budget Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.86 Withdrawal from NOX Budget Trading Program. (a) Requesting withdrawal. To...

  18. Social Withdrawal and Maladjustment in a Very Group-Oriented Society

    Science.gov (United States)

    Valdivia, Ibis Alvarez; Schneider, Barry H.; Chavez, Kenia Lorenzo; Chen, Xinyin

    2005-01-01

    Elementary-school children in Cuba and Canada participated in measures of loneliness, sociometric status, friendship, aggression, and social withdrawal. Withdrawal was associated with loneliness in the Cuban data from both cohorts, Grade 4 and Grade 6. In the Canadian data, withdrawal was only linked to loneliness in Grade 6. In contrast with…

  19. 29 CFR 4211.35 - Direct attribution method for withdrawals after the initial plan year.

    Science.gov (United States)

    2010-07-01

    ... WITHDRAWING EMPLOYERS Allocation Methods for Merged Multiemployer Plans § 4211.35 Direct attribution method for withdrawals after the initial plan year. The allocation method under this section is the... 29 Labor 9 2010-07-01 2010-07-01 false Direct attribution method for withdrawals after the initial...

  20. 42 CFR 8.6 - Withdrawal of approval of accreditation bodies.

    Science.gov (United States)

    2010-10-01

    ... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Accreditation § 8.6 Withdrawal of approval of... 42 Public Health 1 2010-10-01 2010-10-01 false Withdrawal of approval of accreditation bodies. 8.6... to establish that the problems that were grounds for withdrawal of approval have been resolved. (2...

  1. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Science.gov (United States)

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in wine...

  2. Opioid antagonists with minimal sedation for opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M

    2017-05-29

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies. We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants. We used standard methodological procedures expected by Cochrane. Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha 2 -adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient

  3. Complex motivated behaviors for natural rewards following a binge-like regimen of morphine administration: mixed phenotypes of anhedonia and craving after short-term withdrawal

    Directory of Open Access Journals (Sweden)

    Yunjing eBai

    2014-02-01

    Full Text Available The anhedonia-like behaviors following about one-week withdrawal from morphine were examined in the present study. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. Three types of natural reward were used, food reward (2.5%, 4%, 15%, 30%, 40% and 60% sucrose solutions, social reward (male rat and sexual reward (estrous female rat. For each type of natural stimulus, consummatory behavior and motivational behaviors under varied testing conditions were investigated. The results showed that the morphine-treated rats significantly reduced their consumption of 2.5% sucrose solution during the 1-hour consumption testing and their operant responding for 15%, 30% and 40% sucrose solutions under a fixed ratio 1 (FR1 schedule. However, performance under a progressive ratio (PR schedule increased in morphine-treated rats reinforced with 60% sucrose solution, but not in those reinforced with sucrose concentrations lower than 60%. Pretreatment with morphine significantly decreased the male rats’ ejaculation frequency during the 1-hour copulation testing, and impaired the maintenance of appetitive motivations to sexual and social stimuli under a free-approach condition. Moreover, the morphine-treated rats demonstrated a diminished motivation to approach social stimulus in the effort-based appetitive behavior test but showed a remarkable increase in motivation to approach sexual stimulus in the risky appetitive behavior test. These results demonstrated some complex motivated behaviors following about one week of morphine withdrawal: (1 The anhedonia-like behavior was consistently found in animals withdrawn from morphine. However, for a given reward, there was often a dissociation of the consummatory behaviors from the motivational behaviors, and whether the consummatory or the motivational anhedonia-like behaviors could be discovered heavily depended on the type and magnitude of the reward and the type

  4. A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.

    Science.gov (United States)

    Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

    2014-02-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

  5. Repercussões cardíacas após infarto do miocárdio em ratas submetidas previamente a exercício físico Cardiac implications after myocardial infarction in rats previously undergoing physical exercise

    Directory of Open Access Journals (Sweden)

    Eduardo Carvalho de Arruda Veiga

    2013-01-01

    Full Text Available FUNDAMENTO: Poucos estudos analisaram os efeitos cardíacos do exercício físico prévio à oclusão coronariana. OBJETIVO: Avaliar, em ratas submetidas a exercício físico, as repercussões do infarto do miocárdio. MÉTODOS: Ratas foram submetidas à natação ou permaneceram sedentárias por oito semanas e foram randomizadas para oclusão coronariana ou cirurgia simulada, compondo quatro grupos: Sedentário (S, Exercício (E, Sedentário infarto (SIM e Exercício infarto (EIM. Após seis semanas, foram analisados biometria, ecodopplercardiograma, hemodinâmica e mecânica miocárdica. RESULTADOS: Não foram observados cardioproteção nos animais EIM e diferença no tamanho do infarto (%VE entre EIM (38,50 ± 4,60% e SIM (36,58 ± 4,11%. Os teores de água pulmonar (% de SIM (80 ± 0,59 e EIM (80 ± 0,57 foram maiores do que em S (78 ± 0,15 e E (78 ± 0,57. A pressão sistólica (mmHg do ventrículo esquerdo (S: 130 ± 5; E: 118 ± 8; SIM: 91 ± 3; EIM: 98 ± 3 e a primeira derivada temporal (mmHg/s positiva da pressão (S: 8.216 ± 385; E: 8.437 ± 572; SIM: 4.674 ± 455; EIM: 5.080 ± 412 de S e E foram maiores do que em SIM e EIM. As frações de encurtamento da área transversa (% de SIM (27 ± 2 e EIM (25 ± 2 foram similares e menores do que E (65 ± 2 e S (69 ± 2. A relação E/A foi maior em SIM (5,14 ± 0,61 e EIM (4,73 ± 0,57 em relação a S (2,96 ± 0,24 e E (2,83 ± 0,21. Em estudos de músculos papilares isolados foi verificada depressão da capacidade contrátil semelhante em SIM e EIM, e não houve alteração da rigidez miocárdica. CONCLUSÃO: O treinamento prévio por natação não atenuou as repercussões cardíacas em virtude do infarto do miocárdio.BACKGROUND: Few studies have analyzed the cardiac effects of exercise prior to coronary occlusion. OBJECTIVE: To evaluate the effects of myocardial infarction in rats undergoing physical exercise. METHODS: Female rats underwent swimming exercise or were kept sedentary

  6. Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha,5beta-THP: a possible model of premenstrual dysphoric disorder.

    Science.gov (United States)

    Smith, Sheryl S; Ruderman, Yevgeniy; Frye, Cheryl; Homanics, Gregg; Yuan, Maoli

    2006-06-01

    3alpha-OH-5alpha[beta]-pregnan-20-one (THP) is a positive modulator of the GABAA receptor (GABAR), which underlies its reported anxiolytic effect. However, there are conditions such as premenstrual dysphoric disorder (PMDD) where increases in THP levels can be associated with adverse mood. In order to test for conditions where THP might be anxiogenic, we developed a mouse model of THP withdrawal. Because delta-containing GABAR are highly sensitive to THP modulation, results were compared in wild-type and delta knockout mice. Finasteride, a 5alpha-reductase blocker, was administered for 3 days to female wild-type or delta knockout mice. Then, animals were tested in the elevated plus maze, following acute administration of THP, lorazepam, flumazenil, or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), and results compared to vehicle-injected controls. CA1 hippocampal GABAR alpha4 subunit levels were assessed by Western blot. After THP withdrawal, THP produced anxiogenic effects, decreasing open arm entries on the elevated plus maze, following a brief shock, in contrast to its expected anxiolytic effects. As we have shown in rats, THP withdrawal also resulted in increased expression of the alpha4 subunit in mouse CA1 hippocampus. As expected for increases in alpha4-containing GABAR, THP withdrawn mice were relatively insensitive to the benzodiazepine (BDZ) lorazepam and had atypical responses to the BDZ antagonist flumazenil when tested on the plus maze. In contrast, they showed a greater anxiolytic response to THIP, which has greater efficacy at alpha4betadelta than other GABAR. Although THP withdrawal in delta knockout mice also increased the alpha4 GABAR subunit, the anxiogenic effects of THP and the anxiolytic effects of THIP were not observed, implicating alpha4betadelta GABAR in these effects. Based on these behavioral and pharmacological findings, we suggest that THP withdrawal in the mouse may serve as a rodent model of PMDD.

  7. Estimated water withdrawals and use in Pennsylvania, 1995

    Science.gov (United States)

    Ludlow, Russell A.; Gast, William A.

    2000-01-01

    In practical terms, water use is divided into two basic types: instream use and offstream use. Instream use is water used in its natural channel, basin, or behind a dam and includes activities such as fishing, boating, and other recreational activities. Instream use also includes hydroelectric power generation. Off-stream use is water pumped or diverted from its natural channel, basin, or aquifer. Off-stream uses are divided into the following categories: public supply, domestic, commercial, industrial, thermoelectric power, mining, livestock, and irrigation. This fact sheet provides an overview of offstream and hydroelectric power water use in Pennsylvania. It describes water withdrawals by source, water withdrawals and deliveries by category, changes in water use over time, and water-management responsibilities in the State.

  8. USA Withdrawal from Paris Agreement – What Next?

    Directory of Open Access Journals (Sweden)

    Sergey Chestnoy

    2017-12-01

    Full Text Available In June 2017, President Trump announced the USA’s withdrawal from the Paris Climate Accord, which had been ratified for less than a year, thanks in large part to the USA. That drastic shift followed the change in residency at the White House. Withdrawing from the Paris Accord presents an interesting topic for analysis. There’s the practical side of the withdrawal procedure as set out in Article 28 of the agreement, not to mention the consequences of US non-participation in addressing international climate issues. There are other international forums (Such as G8 and G20, which also have an interest in climate related topics. The Article analyses the U.S. position in negotiations and its commitments assumed the moment the United Nations Framework Convention on Climate Change (UNFCCC came into effect until now: the reduction of greenhouse gas emissions, financial aid and reporting. It also provides general analysis of national legal obligations under the Paris Accord, ratification of that agreement in general and in particularly another that took place in the USA, it focuses on the specifics of withdrawal. The specified three-year period from the Agreement becoming active, after which any party may withdraw from it (2019, is a noteworthy detail. It is well-known that the Paris Agreement provides a framework that does not impose individual national commitments or a commitment to a compliance system. In essence, and from a legal point of view, it is nonbinding. This was what allowed the USA to accept the terms of the accord relatively quickly and to use the simplified procedure, which by-passed Congress. In the opinion of the authors, President Trump’s resolution to withdraw should, possibly, be considered as a simple continuation of his election discourse and the fulfilment of a campaign promise. Additionally, President Trump’s declared intent to review the Paris Accord has legal grounds on which to launch further international negotiations

  9. International Companies Withdrawal from Lithuania: Problematics and Alternative Solutions

    Directory of Open Access Journals (Sweden)

    Viktorija Tauraitė

    2017-06-01

    Full Text Available The main attention in this article is focused on the problematic of international companies’ withdrawal from Lithuania and presentation of alternative solutions of this problem. The macro(Sweden, Austria, Latvia, Lithuania, Estonia, Poland level analysis and micro (“Coca-Cola”, “Nordea” and DNB, “Orkla” level analysis showed that competitiveness, business conditions, employment relations, institutional environment and innovation should be improved and the corruption should be reduced in Lithuania. It is advisable that current Lithuanian Labour Code should be revised in order to increase the efficiency of labour relations. It is found out that the significance of “Coca-Cola”company is the highest in the context of the withdrawing companies from Lithuania. It is assumed that the most rational solution for each company is to move from Lithuania to another country.

  10. Intractable nausea caused by zolpidem withdrawal: a case report.

    Science.gov (United States)

    Baruch, Edward; Vernon, Leonard F; Hasbun, Rafael J

    2007-03-01

    First launched in France in 1988, zolpidem (Ambien®) is a short-acting hypnotic agent. Early studies reported that that the development of physical dependence and tolerance to sedative-hypnotic drugs, such as the depressant and anticonvulsant effects evidenced with benzodiazepines, is not found with zolpidem. Direct to consumer advertising by the manufacturer continues to state that the risk for dependency is low; however, recent publications seem to contradict this. Additionally, adverse drug reactions affecting the central nervous system, gastrointestinal tract, and respiratory system have been reported. Other studies have examined the interactions of selective serotonin reuptake inhibitors and zolpidem as a possible cause of hallucinations. With continued physician marketing efforts touting the safety and efficacy of zolpidem, there is a high likelihood to overlook the risk of dependency and the symptoms related to zolpidem withdrawal. We report a case of a 41-year-old female who developed a dependency to zolpidem, who on her own decided to decrease her dosage, resulting in intractable nausea requiring hospitalization. Reported cases of zolpidem withdrawal have occurred with doses in excess of 160 mg per day, none of these have reported with intractable nausea as the sole symptom. In our reported case, although exceeding recommended dosage withdrawal phenomenon seemed to be severe after withdrawal from a comparatively low dose of zolpidem. Before zolpidem is prescribed, patient education should include warnings about the potential problems associated with dependency and abrupt discontinuation. Education about this common and likely underrecognized clinical phenomenon will help prevent future episodes and minimize the risk of misdiagnosis.

  11. On the ethics of withholding and withdrawing medical treatment.

    Science.gov (United States)

    Reichlin, Massimo

    2014-01-01

    A general rationale is presented for withholding and withdrawing medical treatment in end-of-life situations, and an argument is offered for the moral irrelevance of the distinction, both in the context of pharmaceutical treatments, such as chemotherapy in cancer, and in the context of life-sustaining treatments, such as the artificial ventilator in lateral amyotrophic sclerosis. It is argued that this practice is not equivalent to sanctioning voluntary active euthanasia and that it is not likely to favour it.

  12. The social side of shame: approach versus withdrawal

    OpenAIRE

    Hooge, De, Ilona E.; Breugelmans, Seger M.; Wagemans, Fieke M.A.; Zeelenberg, Marcel

    2018-01-01

    At present, the consequences and functions of experiences of shame are not yet well understood. Whereas psychology literature typically portrays shame as being bad for social relations, motivating social avoidance and withdrawal, there are recent indications that shame can be reinterpreted as having clear social tendencies in the form of motivating approach and social affiliation. Yet, until now, no research has ever put these alternative interpretations of shame-motivated behaviours directly...

  13. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

  14. Caffeine withdrawal and high-intensity endurance cycling performance.

    Science.gov (United States)

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users.

  15. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

  16. A 12-month study of the hikikomori syndrome of social withdrawal: Clinical characterization and different subtypes proposal.

    Science.gov (United States)

    Malagón-Amor, Ángeles; Martín-López, Luis Miguel; Córcoles, David; González, Anna; Bellsolà, Magda; Teo, Alan R; Pérez, Víctor; Bulbena, Antoni; Bergé, Daniel

    2018-03-23

    Social withdrawal is a new mental health problem increasingly common, present in different cultures, whose psychopathology and treatment is not yet established. This study aims to determine the socio-demographic and clinical features and possible clinical subtypes that predict the 12-month outcomes of cases with hikikomori syndrome, a severe form of social withdrawal. Socio-demographic and clinical data at baseline were analysed as well as data obtained for 12 months after at-home treatment in 190 cases. The inclusion criteria were: spending all time at home, avoiding social situations and relationships, significant deterioration due to social isolation, with a minimum duration of 6 months. Six major diagnostic groups were identified: affective, anxiety, psychotic, drug use, personality and other Axis I disorders. The anxiety-affective subgroup demonstrated lower clinical severity, but worse evolution. Less than half of the cases were available for medical follow-up at 12-months. Subjects undergoing intensive treatment had a higher medical follow-up rate and better social networks at 12-months. Therefore, our findings provide data to reach consensus on the specific characteristics of social isolation hikikomori syndrome. The analysis demonstrated the fragility and tendency to relapse and have disengagement, particularly relevant in the anxiety-affective subgroup, suggesting that intensive treatments are more effective. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Ethical Decision Making With End-of-Life Care: Palliative Sedation and Withholding or Withdrawing Life-Sustaining Treatments

    Science.gov (United States)

    Olsen, Molly L.; Swetz, Keith M.; Mueller, Paul S.

    2010-01-01

    Palliative sedation (PS) is the use of medications to induce decreased or absent awareness in order to relieve otherwise intractable suffering at the end of life. Although uncommon, some patients undergoing aggressive symptom control measures still have severe suffering from underlying disease or therapy-related adverse effects. In these circumstances, use of PS is considered. Although the goal is to provide relief in an ethically acceptable way to the patient, family, and health care team, health care professionals often voice concerns whether such treatment is necessary or whether such treatment equates to physician-assisted suicide or euthanasia. In this review, we frame clinical scenarios in which PS may be considered, summarize the ethical underpinnings of the practice, and further differentiate PS from other forms of end-of-life care, including withholding and/or withdrawing life-sustaining therapy and physician-assisted suicide and euthanasia. PMID:20805544

  18. APR1400 CEA Withdrawal at Power Accident Analysis using KNAP

    International Nuclear Information System (INIS)

    Lee, Dong-Hyuk; Yang, Chang-Keun; Kim, Yo-Han; Sung, Chang-Kyung

    2006-01-01

    KEPRI (Korea Electric Power Research Institute) has been developing safety analysis methodology for non- LOCA (Loss Of Coolant Accident) analysis of OPR1000 (Optimized Power Reactor 1000, formerly KSNP). The new methodology, named KNAP (Korea Non-LOCA Analysis Package), uses RETRAN as the main system analysis code. RETRAN code is a non- LOCA safety analysis code developed by EPRI. The new methodology will replace existing CE (Combustion Engineering) supplied codes and methodologies currently used in non-LOCA analysis of OPR1000. In this paper, we apply KNAP methodology to APR1400 (Advanced Power Reactor 1400). The CEA (Control Element Assembly) withdrawal at power accident is one of the 'reactivity and power distribution anomalies' events and the results are typically described in the chapter 15.4.2 of SAR (Safety Analysis Report). The APR1400 has been designed to generate 1,400MWe of electricity with advanced features for greatly enhanced safety and economic goals. The CEA withdrawal at power analysis in APR1400 SSAR (Standard Safety Analysis Report) is analyzed with CESEC-III computer code. In this study, to confirm the applicability of the KNAP methodology and code system to APR1400, CEA withdrawal at power accident is analyzed using RETRAN code and it is compared with results from APR1400 SSAR

  19. Control device for the withdrawal of control rod

    International Nuclear Information System (INIS)

    Ando, Masaki.

    1985-01-01

    Purpose: To significantly suppress the maximum value of the control-rod worth upon control rod withdrawal. Constitution: At first, a signal for designating the first class is sent from a class-control section to the group-control section. In the group-control section, the peripheral group among the first class is designated by which the withdrawal of the control rods other than the peripheral group is inhibited and the control-rods in the peripheral group are withdrawn one by one. When all of them have been withdrawn, the group-control section designates the central group of the first class. All the control rods of the central group have been withdrawn, then the group-control section designates the peripheral group of the second class. Thereafter, the central group in the second class is designated. The control rods are thus withdrawn in the same manner hereinafter. The maximum value for the control-rod worth can be decreased by such a withdrawing sequence for the control rods. (Horiuchi, T.)

  20. Spanish adaptation of social withdrawal motivation and frequency scales.

    Science.gov (United States)

    Indias García, Sílvia; De Paúl Ochotorena, Joaquín

    2016-11-01

    To adapt into Spanish three scales measuring frequency (SWFS) and motivation for social withdrawal (CSPS and SWMS) and to develop a scale capable of assessing the five motivations for social withdrawal. Participants were 1,112 Spanish adolescents, aged 12-17 years. The sample was randomly split into two groups in which exploratory and confirmatory (CFA) factor analyses were performed separately. A sample of adolescents in residential care (n = 128) was also used to perform discriminant validity analyses. SWFS was reduced to eight items that account for 40% of explained variance (PVE), and its reliability is high. SWMS worked adequately in the original version, according to CFA. Some items from the CSPS were removed from the final Spanish version. The newly developed scale (SWMS-5D) is composed of 20 items including five subscales: Peer Isolation, Unsociability, Shyness, Low Mood and Avoidance. Analyses reveal adequate convergent and discriminant validities. The resulting SWFS-8 and SWMS-5D could be considered useful instruments to assess frequency and motivation for social withdrawal in Spanish samples.

  1. The social side of shame: approach versus withdrawal.

    Science.gov (United States)

    de Hooge, Ilona E; Breugelmans, Seger M; Wagemans, Fieke M A; Zeelenberg, Marcel

    2018-01-05

    At present, the consequences and functions of experiences of shame are not yet well understood. Whereas psychology literature typically portrays shame as being bad for social relations, motivating social avoidance and withdrawal, there are recent indications that shame can be reinterpreted as having clear social tendencies in the form of motivating approach and social affiliation. Yet, until now, no research has ever put these alternative interpretations of shame-motivated behaviours directly to the test. The present paper presents such a test by studying the extent to which shame motivates a preference for social withdrawal versus a preference for social approach. Two studies (N = 148 and N = 133) using different shame inductions both showed people experiencing shame to prefer to be together with others (social approach) over being alone (social withdrawal). In addition, the preference for a social situation was found to be unique for shame; it was not found for the closely related emotion of guilt. Taken together, these findings provide direct empirical support for the idea that shame can have positive interpersonal consequences.

  2. Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

    Science.gov (United States)

    Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

    2018-05-08

    Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p trend toward a shorter hospitalization.

  3. Neural effects of positive and negative incentives during marijuana withdrawal.

    Directory of Open Access Journals (Sweden)

    Francesca M Filbey

    Full Text Available In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms.

  4. 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.

  5. Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

    Science.gov (United States)

    Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

    2017-01-01

    Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

  6. Tobacco Withdrawal Amongst African American, Hispanic, and White Smokers.

    Science.gov (United States)

    Bello, Mariel S; Pang, Raina D; Cropsey, Karen L; Zvolensky, Michael J; Reitzel, Lorraine R; Huh, Jimi; Leventhal, Adam M

    2016-06-01

    Persistent tobacco use among racial and ethnic minority populations in the United States is a critical public health concern. Yet, potential sources of racial/ethnic disparities in tobacco use remain unclear. The present study examined racial/ethnic differences in tobacco withdrawal-a clinically-relevant underpinning of tobacco use that has received sparse attention in the disparities literature-utilizing a controlled laboratory design. Daily smokers (non-Hispanic African American [n = 178], non-Hispanic white [n = 118], and Hispanic [n = 28]) attended two counterbalanced sessions (non-abstinent vs. 16-hour abstinent). At both sessions, self-report measures of urge, nicotine withdrawal, and affect were administered and performance on an objective behavioral task that assessed motivation to reinstate smoking was recorded. Abstinence-induced changes (abstinent scores vs. non-abstinent scores) were analyzed as a function of race/ethnicity. Non-Hispanic African American smokers reported greater abstinence-induced declines in several positive affect states in comparison to other racial/ethnic groups. Relative to Hispanic smokers, non-Hispanic African American and non-Hispanic white smokers displayed larger abstinence-provoked increases in urges to smoke. No racial/ethnic differences were detected for a composite measure of nicotine withdrawal symptomatology, negative affect states, and motivation to reinstate smoking behavior. These results suggest qualitative differences in the expression of some components of tobacco withdrawal across three racial/ethnic groups. This research helps shed light on bio-behavioral sources of tobacco-related health disparities, informs the application of smoking cessation interventions across racial/ethnic groups, and may ultimately aid the overall effort towards reducing the public health burden of tobacco addiction in minority populations. The current study provides some initial evidence that there may be qualitative differences in the

  7. Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

    Science.gov (United States)

    Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

    2016-11-01

    Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

  8. Tachykinin NK₁ receptor antagonist co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation.

    Science.gov (United States)

    Tumati, Suneeta; Largent-Milnes, Tally M; Keresztes, Attila I; Yamamoto, Takashi; Vanderah, Todd W; Roeske, William R; Hruby, Victor J; Varga, Eva V

    2012-06-05

    Prolonged morphine treatment increases pain sensitivity in many patients. Enhanced spinal Substance P release is one of the adaptive changes associated with sustained opioid exposure. In addition to pain transmitting second order neurons, spinal microglia and astrocytes also express functionally active Tachykinin NK₁ (Substance P) receptors. In the present work we investigated the role of glial Tachykinin NK₁ receptors in morphine withdrawal-mediated spinal microglia and astrocyte activation. Our data indicate that intrathecal co-administration (6 days, twice daily) of a selective Tachykinin NK₁ receptor antagonist (N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138; 20 μg/injection)) attenuates spinal microglia and astrocyte marker and pro-inflammatory mediator immunoreactivity as well as hyperalgesia in withdrawn rats. Furthermore, covalent linkage of the opioid agonist with a Tachykinin NK₁ antagonist pharmacophore yielded a bivalent compound that did not augment spinal microglia or astrocyte marker or pro-inflammatory mediator immunoreactivity and did not cause paradoxical pain sensitization upon drug withdrawal. Thus, bivalent opioid/Tachykinin NK₁ receptor antagonists may provide a novel paradigm for long-term pain management.

  9. Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

    Science.gov (United States)

    Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

    2014-11-01

    Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores

  10. Specialised care in patients undergoing pancreatoduodenectomy

    NARCIS (Netherlands)

    Tol, J.A.M.G.

    2014-01-01

    This thesis studies the controversies in the management of patients with pancreatic cancer undergoing pancreatoduodenectomy and determines different factors that will improve this management and thereby the postoperative outcomes. The studies were performed in both the pre-, peri- and postoperative

  11. Antibiotic prophylaxis for patients undergoing elective endoscopic ...

    African Journals Online (AJOL)

    Antibiotic prophylaxis for patients undergoing elective endoscopic retrograde cholangiopancreatography. M Brand, D Bisoz. Abstract. Background. Antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is controversial. We set out to assess the current antibiotic prescribing practice among ...

  12. Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

    Science.gov (United States)

    Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

    2016-07-19

    Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

  13. Enhanced striatial 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

    International Nuclear Information System (INIS)

    Bhargava, H.N.

    1984-01-01

    Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for 3 H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH 2 or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of 3 H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures

  14. Perioperative Endocrine Therapy for Patients with Cushing's Syndrome Undergoing Retroperitoneal Laparoscopic Adrenalectomy

    Directory of Open Access Journals (Sweden)

    Xiaobo Cui

    2012-01-01

    Full Text Available Objectives. To investigate the efficacy and safety of perioperative endocrine therapy (PET for patients with Cushing’s syndrome (CS undergoing retroperitoneal laparoscopic adrenalectomy (RLA. Methods. The novel, simplified PET modality of 82 patients who underwent RLA procedures for CS were studied. Clinical manifestations were observed for all patients on days 1 and 5 postoperatively, and clinical data, such as blood pressure (BP, levels of serum cortisol, adrenocorticotropin (ACTH, blood glucose, and electrolytes, were acquired and analyzed. Results. Supraphysiological doses of glucocorticoid were administered during the perioperative period, and the dosage was reduced gradually. In all 82 cases, the RLAs were performed successfully without any perioperative complication, such as steroid withdrawal symptoms. The patient’s symptoms and signs were improved quickly and safely during the hospital days. The serum cortisol and potassium levels were rather stable on days 1 and 5 postoperatively, and most were within the normal range. The clinical manifestations, serum levels of cortisol, ACTH, and potassium in most patients restored to normal gradually after several months (mean, 6.7 ± 1.2 months, except for one patient undergoing bilateral adrenalectomy. Conclusions. This perioperative endocrine therapy for patients with Cushing’s syndrome (mainly for adrenocortical adenoma undergoing retro-laparoscopic adrenalectomy is both effective and safe.

  15. Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction.

    Science.gov (United States)

    Scott, Daniel; Hiroi, Noboru

    2010-10-15

    Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood. The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared. A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence. A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Infants in Drug Withdrawal: A National Description of Nurse Workload, Infant Acuity, and Parental Needs.

    Science.gov (United States)

    Smith, Jessica G; Rogowski, Jeannette A; Schoenauer, Kathryn M; Lake, Eileen T

    Infants in drug withdrawal have complex physiological and behavioral states, requiring intensive nursing care. The study objectives were to describe acuity, parental needs, and nurse workload of infants in drug withdrawal compared with other infants. The design was cross-sectional and involved secondary nurse survey data from 6045 staff nurses from a national sample of 104 neonatal intensive care units. Nurses reported the care of 15 233 infants, 361 (2.4%) of whom were in drug withdrawal. Three-fourths of hospitals had at least 1 infant in drug withdrawal. In these hospitals, the mean number of infants in drug withdrawal was 4.7. Infant acuity was significantly higher among infants in drug withdrawal. Parents of infants in drug withdrawal required significantly more care to address complex social situations (51% vs 12%). The number of infants assigned to nurses with at least 1 infant in withdrawal (mean = 2.69) was significantly higher than typical (mean = 2.51). Given infant acuity and parental needs, policies legislating patient-to-nurse ratios should permit professional discretion on the number of patients to assign nurses caring for infants in drug withdrawal. Managers and charge nurses should consider the demands of caring for infants in drug withdrawal in assignment decisions and provide support and education.

  17. Adenoma detection in patients undergoing a comprehensive colonoscopy screening

    International Nuclear Information System (INIS)

    Raju, Gottumukkala S; Vadyala, Vikram; Slack, Rebecca; Krishna, Somashekar G; Ross, William A; Lynch, Patrick M; Bresalier, Robert S; Hawk, Ernest; Stroehlein, John R

    2013-01-01

    Measures shown to improve the adenoma detection during colonoscopy (excellent bowel preparation, cecal intubation, cap fitted colonoscope to examine behind folds, patient position change to optimize colon distention, trained endoscopy team focusing on detection of subtle flat lesions, and incorporation of optimum endoscopic examination with adequate withdrawal time) are applicable to clinical practice and, if incorporated are projected to facilitate comprehensive colonoscopy screening program for colon cancer prevention. To determine adenoma and serrated polyp detection rate under conditions designed to optimize quality parameters for comprehensive screening colonoscopy. Retrospective analysis of data obtained from a comprehensive colon cancer screening program designed to optimize quality parameters. Academic medical center. Three hundred and forty-three patients between the ages of 50 years and 75 years who underwent first screening colonoscopy between 2009 and 2011 among 535 consecutive patients undergoing colonoscopy. Comprehensive colonoscopy screening program was utilized to screen all patients. Cecal intubation was successful in 98.8% of patients. The Boston Bowel Preparation Scale for quality of colonoscopy was 8.97 (95% confidence interval [CI]; 8.94, 9.00). The rate of adenoma detection was 60% and serrated lesion (defined as serrated adenomas or hyperplastic polyps proximal to the splenic flexure) detection was 23%. The rate of precancerous lesion detection (adenomas and serrated lesions) was 66%. The mean number of adenomas per screening procedure was 1.4 (1.2, 1.6) and the mean number of precancerous lesions (adenomas or serrated lesions) per screening procedure was 1.6 (1.4, 1.8). Retrospective study and single endoscopist experience. A comprehensive colonoscopy screening program results in high-quality screening with high detection of adenomas, advanced adenomas, serrated adenomas, and multiple adenomas

  18. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

  19. Youth social withdrawal behavior (hikikomori): A systematic review of qualitative and quantitative studies.

    Science.gov (United States)

    Li, Tim M H; Wong, Paul W C

    2015-07-01

    Acute and/or severe social withdrawal behavior among youth was seen as a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal cases in different countries have been discovered recently. However, due to the lack of a formal definition and diagnostic tool for youth social withdrawal, cross-cultural observational and intervention studies are limited. We aimed to consolidate existing knowledge in order to understand youth social withdrawal from diverse perspectives and suggest different interventions for different trajectories of youth social withdrawal. This review examined the current available scientific information on youth social withdrawal in the academic databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included quantitative and qualitative studies of socially withdrawn youths published in English and academic peer-reviewed journals. We synthesized the information into the following categories: (1) definitions of youth social withdrawal, (2) developmental theories, (3) factors associated with youth social withdrawal and (4) interventions for socially withdrawn youths. Accordingly, there are diverse and controversial definitions for youth social withdrawal. Studies of youth social withdrawal are based on models that lead to quite different conclusions. Researchers with an attachment perspective view youth social withdrawal as a negative phenomenon, whereas those who adopt Erikson's developmental theory view it more positively as a process of seeking self-knowledge. Different interventions for socially withdrawn youths have been developed, mainly in Japan, but evidence-based practice is almost non-existent. We propose a theoretical framework that views youth social withdrawal as resulting from the interplay between psychological, social and behavioral factors. Future validation of the framework will help drive forward advances in theory and interventions for youth social withdrawal as an emerging issue in developed

  20. A genetic perspective on the proposed inclusion of cannabis withdrawal in the DSM-5

    Science.gov (United States)

    Verweij, K.J.H.; Agrawal, A.; Nat, N.O.; Creemers, H.E.; Huizink, A.C.; Martin, N.G.; Lynskey, M.T.

    2013-01-01

    Background Various studies support the inclusion of cannabis withdrawal to the diagnosis of cannabis use disorders in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (Criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal, and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV defined abuse/dependence. Methods The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with Criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, as well as its covariation with abuse/dependence. Results Of all cannabis users 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence. Conclusions We showed that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those influencing abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 cannabis use disorders. PMID:23194657

  1. Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic.

    Science.gov (United States)

    Chakrabarti, Sumita; Liu, Nai-Jiang; Zadina, James E; Sharma, Tarak; Gintzler, Alan R

    2012-01-01

    We studied adaptations to acute precipitated opioid withdrawal of spinal μ-opioid receptor (MOR)-coupled regulation of the release of endomorphin 2 (EM2). The release of this highly MOR-selective endogenous opioid from opioid-naive spinal tissue of male rats is subjected to MOR-coupled positive as well as negative modulation via cholera toxin-sensitive G(s) and pertussis toxin-sensitive G(i)/G(o), respectively. The net effect of this concomitant bidirectional modulation is inhibitory. MOR-coupled pleiotropic regulation of EM2 release is retained in opioid-withdrawn spinal tissue of male rats, but the balance of MOR-coupled inhibitory and facilitatory regulation shifted such that facilitatory regulation predominates. Augmented coupling of MOR to G(s) is causally associated with this change. Strikingly, pleiotropic characteristics of MOR-coupled regulation of spinal EM2 release and adaptations thereof to opioid withdrawal are male-specific. In females, MOR-coupled regulation of EM2 release from opioid-naive and -withdrawn spinal tissue does not have a significant G(s)-coupled facilitatory component, and MOR-coupled inhibition of EM2 release persists unabated in withdrawn preparations. The male-specific adaptations to chronic morphine that shift the relative predominance of opposing dual G protein-coupled MOR pathways provides a mechanism for mitigating inhibitory MOR signaling without losing MOR-coupled feedback regulation. These adaptations enable using endogenous EM2 as a substitute for morphine that had been precipitously removed. The sexually dimorphic functionality and regulation of spinal EM2/MOR-coupled signaling suggest the clinical utility of using sex-specific treatments for addiction that harness the activity of endogenous opioids.

  2. The influence of propoxyphene withdrawal on opioid use in veterans.

    Science.gov (United States)

    Hayes, Corey J; Hudson, Teresa J; Phillips, Martha M; Bursac, Zoran; Williams, James S; Austin, Mark A; Edlund, Mark J; Martin, Bradley C

    2015-11-01

    Our aim is to determine if propoxyphene withdrawal from the US market was associated with opioid continuation, continued chronic opioid use, and secondary propoxyphene-related adverse events (emergency department visits, opioid-related events, and acetaminophen toxicity). Medical service use and pharmacy data from 19/11/08 to 19/11/11 were collected from the national Veterans Healthcare Administration healthcare databases. A quasi-experimental pre-post retrospective cohort design utilizing a historical comparison group provided the study framework. Logistic regression controlling for baseline covariates was used to estimate the effect of propoxyphene withdrawal. There were 24,328 subjects (policy affected n = 10,747; comparison n = 13,581) meeting inclusion criteria. In the policy-affected cohort, 10.6% of users ceased using opioids, and 26.6% stopped chronic opioid use compared with 3.8% and 13.5% in the historical comparison cohort, respectively. Those in the policy-affected cohort were 2.7 (95%CI: 2.5-2.8) and 3.2 (95%CI: 2.9-3.6) times more likely than those in the historical comparison cohort to discontinue chronic opioid and any opioid use, respectively. Changes in adverse events and Emergency Department (ED) visits were not different between policy-affected and historical comparison cohorts (p > 0.05). The withdrawal of propoxyphene-containing products resulted in rapid and virtually complete elimination in propoxyphene prescribing in the veterans population; however, nearly 90% of regular users of propoxyphene switched to an alternate opioid, and three quarters continued to use opioids chronically. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Why do care workers withdraw from elderly care?

    DEFF Research Database (Denmark)

    Liveng, Anne

    2012-01-01

    . The article illustrates how working consciously with the researcher's subjectivity makes it possible to understand apparently irrational patterns. The insights thus gained may be used to prevent withdrawals in care work as an argument for care workers' need for emotional supervision....... relations, independently of whether we are in the role of care providers or care receivers. Through collusion theory, the interpretation accepts both the anxiety which the helpless elderly people arouse in the care workers and their motivation for care work as two sides of a subjectively important theme...

  4. Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

    Directory of Open Access Journals (Sweden)

    Marianna E. Jung

    2010-07-01

    Full Text Available Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2, interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors. The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17

  5. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

  6. Radiohippuran renography in chronic alcoholics with acute alcohol withdrawal syndromes

    International Nuclear Information System (INIS)

    Dobrzanski, T.

    1975-01-01

    Functional changes found in radiohippuran renography in chronic alcoholics with acute alcohol withdrawal syndromes (n=82; AAWS) regressed to normal values with recovery from AAWS (during 4 days on the average) with the exception of the secretory value which increased to a maximum on the 7th day of observation, remaining approximately unchanged for the following 3 days and decreasing more gradually to a normal value on the 23rd day of observation. In various forms of AAWS the same functional changes in the radiohippuran renogram were observed. (author)

  7. Withdrawal and consumption of water by thermoelectric power plants in the United States, 2010

    Science.gov (United States)

    Diehl, Timothy H.; Harris, Melissa A.

    2014-01-01

    Estimates of water use at thermoelectric plants were developed by the U.S. Geological Survey based on linked heat and water budgets, and complement reported thermoelectric water withdrawals and consumption. The heat- and water-budget models produced withdrawal and consumption estimates, including thermodynamically plausible ranges of minimum and maximum withdrawal and consumption, for 1,290 water-using plants in the United States for 2010. Total estimated withdrawal for 2010 was about 129 billion gallons per day (Bgal/d), and total estimated consumption was about 3.5 Bgal/d. In contrast, total withdrawal reported by the U.S. Department of Energy, Energy Information Administration (EIA), was about 24 percent higher than the modeled estimates, and total EIA-reported consumption was about 8 percent lower. Most thermoelectric generation in 2010 was not associated with thermodynamically plausible EIA-reported values of both withdrawal and consumption.

  8. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

    Directory of Open Access Journals (Sweden)

    Darin J. Knapp

    2016-07-01

    Full Text Available Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif ligand 2 (CCL2, interleukin-1-beta (IL-1β, tumor necrosis factor alpha (TNFα and toll-like receptor 4 (TLR4 mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1 receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals

  9. A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour.

    Science.gov (United States)

    Dunham, James P; Hulse, Richard P; Donaldson, Lucy F

    2015-07-15

    Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: -11.3 °C to -11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain. Copyright © 2015. Published by Elsevier B.V.

  10. Stories of Hell and Healing: Internet Users’ Construction of Benzodiazepine Distress and Withdrawal

    OpenAIRE

    Fixsen, Alison; Ridge, Damien T.

    2017-01-01

    Abstract Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recov...

  11. Response to CPAP Withdrawal in Patients with Mild Versus Severe Obstructive Sleep Apnea/Hypopnea Syndrome

    Science.gov (United States)

    Young, Laura R.; Taxin, Zachary H.; Norman, Robert G.; Walsleben, Joyce A.; Rapoport, David M.; Ayappa, Indu

    2013-01-01

    Background: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Study Objective: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Patients and Interventions: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% 30/h, n = 20) SDB. Results: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Conclusions: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Citation: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013

  12. A rare case of complicated opioid withdrawal in delirium without convulsions

    OpenAIRE

    B Neeraj Raj; N Manamohan; Divya Hegde; Chandrashekar B Huded; Johnson Pradeep

    2017-01-01

    Opioids are one of the commonly abused substances in India. Opioid withdrawal symptoms classically include severe muscle cramps, bone aches, autonomic symptoms, anxiety, restlessness, insomnia, and temperature dysregulation. However, reports of cases with delirium during withdrawal are few. A 25-year-old male with severe opioid withdrawal symptoms developed delirium. Investigations were normal. There were no comorbidities, no significant past history and family history. Patient treated for op...

  13. Swimming exercise attenuates psychological dependence and voluntary methamphetamine consumption in methamphet- amine withdrawn rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Damghani

    2016-06-01

    Conclusion: This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH.

  14. Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics

    DEFF Research Database (Denmark)

    Madsbad, S; Gluud, C; Bennett, Patrick

    1986-01-01

    Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal......, testosterone and dihydrotestosterone concentrations were lower in the diabetics after 4 h of insulin withdrawal and remained so throughout the study. The concentrations of androstenedione were not significantly different between diabetics and normal subjects except after 4 h of insulin withdrawal. Despite...

  15. Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

    Science.gov (United States)

    Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

    2018-01-01

    This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  16. Phenibut (β-Phenyl-γ-aminobutyric Acid Dependence and Management of Withdrawal: Emerging Nootropics of Abuse

    Directory of Open Access Journals (Sweden)

    Tania Ahuja

    2018-01-01

    Full Text Available This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  17. Residents' perceptions about surrogate decision makers' financial conflicts of interest in ventilator withdrawal.

    Science.gov (United States)

    Wastila, Lisa J; Farber, Neil J

    2014-05-01

    There have been no studies to date that examine physicians' decisions to withdraw life-sustaining treatment for patients based on their surrogates' financial gain. The authors' objective was to ascertain physician attitudes about withdrawing life-sustaining treatment when financial considerations are involved. A survey was developed and pretested containing eight scenarios in which a terminally ill patient's spouse had a decision to make regarding withdrawal of the ventilator, which was deemed medically futile. Nested variables included agreement or disagreement between the spouse and patient, decision to withdraw or continue the ventilator, and financial gain or no financial gain for the spouse. The authors surveyed all internal medicine residents at the University of California, San Diego in the autumn of 2011 and winter of 2012. The responses on each of the three variables for which respondents were likely to withdraw the ventilator were analyzed via student's t-tests. Residents were more likely to withdraw the ventilator when requested to do so than when it was requested to be continued. They were also more likely to withdraw the ventilator when there was agreement in the decision between the spouse and the patient. Residents were more likely to withdraw the ventilator when the spouse would not benefit financially. Internal medicine residents make some decisions about whether to withdraw life-sustaining treatment based on financial considerations. There needs to be ongoing communication with residents about end-of-life decisions where conflicts may exist between the surrogate decision makers and patients or physicians.

  18. Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal.

    Science.gov (United States)

    Çoban, Dilek; Kurtoğlu, Selim; Akın, Mustafa Ali; Akçakuş, Mustafa; Güneş, Tamer

    2010-01-01

    The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50-100 μg/ml) and 6.37 μg/dl (10-20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.

  19. Gene expression in the neuropeptide Y system during ethanol withdrawal kindling in rats

    DEFF Research Database (Denmark)

    Olling, Janne D; Ulrichsen, Jakob; Correll, Mette

    2010-01-01

    ), and an isocalorically fed control group. Gene expression of NPY and its receptors Y1, Y2, and Y5 was studied in the hippocampal dentate gyrus (DG) and CA3/CA1, as well as piriform cortex (PirCx), and neocortex (NeoCx). RESULTS: MW+/- as well as SW groups showed decreased NPY gene expression in all hippocampal areas...

  20. Similar precipitated withdrawal effects on intracranial self-stimulation during chronic infusion of an e-cigarette liquid or nicotine alone.

    Science.gov (United States)

    Harris, A C; Muelken, P; Smethells, J R; Krueger, M; LeSage, M G

    2017-10-01

    The FDA recently extended their regulatory authority to electronic cigarettes (ECs). Because the abuse liability of ECs is a leading concern of the FDA, animal models are urgently needed to identify factors that influence the relative abuse liability of these products. The ability of tobacco products to induce nicotine dependence, defined by the emergence of anhedonia and other symptoms of nicotine withdrawal following cessation of their use, contributes to tobacco abuse liability. The present study compared the severity of precipitated withdrawal during chronic infusion of nicotine alone or nicotine-dose equivalent concentrations of three different EC refill liquids in rats, as indicated by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Because these EC liquids contain constituents that may enhance their abuse liability (e.g., minor alkaloids), we hypothesized that they would be associated with greater withdrawal effects than nicotine alone. Results indicated that the nicotinic acetylcholine receptor antagonist mecamylamine precipitated elevations in ICSS thresholds in rats receiving a chronic infusion of nicotine alone or EC liquids (3.2mg/kg/day, via osmotic pump). Magnitude of this effect did not differ between formulations. Our findings indicate that nicotine alone is the primary CNS determinant of the ability of ECs to engender dependence. Combined with our previous findings that nicotine alone and these EC liquids do not differ in other preclinical addiction models, these data suggest that product standards set by the FDA to reduce EC abuse liability should primarily target nicotine, other constituents with peripheral sensory effects (e.g. flavorants), and factors that influence product appeal (e.g., marketing). Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The environmental cost of a reference withdrawal from surface waters: Definition and geography

    Science.gov (United States)

    Soligno, Irene; Ridolfi, Luca; Laio, Francesco

    2017-12-01

    World freshwater ecosystems are significantly deteriorating at a faster rate than other ecosystems. Water withdrawals are recognized as one of the main drivers of growing water stress in river basins worldwide. Over the years, much effort has been devoted to quantify water withdrawals at a global scale; however, comparisons are not simple because the uneven spatiotemporal distribution of surface water resources entails that the same amount of consumed water does not have the same environmental cost in different times or places. In order to account for this spatiotemporal heterogeneity, this work proposes a novel index to assess the environmental cost of a withdrawal from a generic river section. The index depends on (i) the environmental relevance of the impacted fluvial ecosystem (e.g., bed-load transport capacity, width of the riparian belt, biodiversity richness) and (ii) the downstream river network affected by the water withdrawal. The environmental cost has been estimated in each and every river section worldwide considering a reference withdrawal. Being referred to a unitary reference withdrawal that can occur in any river section worldwide, our results can be suitably arranged for describing any scenario of surface water consumption (i.e., as the superposition of the actual pattern of withdrawals). The index aims to support the interpretation of the volumetric measure of surface water withdrawal with a perspective that takes into account the fluvial system where the withdrawal actually occurs. The application of the index highlights the river regions where withdrawals can cause higher environmental costs, with the challenge of weighting each water withdrawal considering the responsibilities that it has on downstream freshwater ecosystems.

  2. Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass.

    Science.gov (United States)

    Flom-Halvorsen, Hanne I; Øvrum, Eivind; Øystese, Rolf; Brosstad, Frank

    2003-09-01

    Intraoperative autologous blood withdrawal protects the pooled blood from the deleterious effects of cardiopulmonary bypass. Following reinfusion after cardiopulmonary bypass, the fresh autologous blood contributes to less coagulation abnormalities and reduces postoperative bleeding and the need for allogeneic blood products. However, few data have been available concerning the quality and potential activation of fresh blood stored at room temperature in the operating room. Forty coronary artery bypass grafting patients undergoing a consistent intraoperative and postoperative autotransfusion protocol had a median of 1,000 mL of autologous blood withdrawn before cardiopulmonary bypass. After heparinization the blood was drained from the venous catheter via venous cannula into standard blood bags and stored in the operating room until termination of cardiopulmonary bypass. Samples for hemostatic and inflammatory markers were taken from the pooled blood immediately before it was returned to the patient. There was some activation of platelets in the stored autologous blood, as measured by an increase of beta-thromboglobulin. Indications of thrombin formation, as assessed by plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 were not seen, and there was no fibrinolytic activity. The red blood cells remained intact, indicated by the absence of plasma free hemoglobin. As for the inflammatory response, the levels of the terminal complement complex remained stable, and the cytokines tumor necrosis factor-alpha and interleukin 6 levels were not increased during storage. The complement activation products increased minimally, but remained within normal ranges. Except for slight activation of platelets, there was no indication of coagulation, hemolysis, fibrinolysis, or immunologic activity in the autologous blood after approximately 1 hour of operating room storage. The autologous blood was preserved in a condition of high quality, and retransfusion

  3. Optimizing withdrawal from drinking water reservoirs to reduce downstream temperature pollution and reservoir hypoxia.

    Science.gov (United States)

    Weber, M; Rinke, K; Hipsey, M R; Boehrer, B

    2017-07-15

    Sustainable management of drinking water reservoirs requires balancing the demands of water supply whilst minimizing environmental impact. This study numerically simulates the effect of an improved withdrawal scheme designed to alleviate the temperature pollution downstream of a reservoir. The aim was to identify an optimal withdrawal strategy such that water of a desirable discharge temperature can be supplied downstream without leading to unacceptably low oxygen concentrations within the reservoir. First, we calibrated a one-dimensional numerical model for hydrodynamics and oxygen dynamics (GLM-AED2), verifying that the model reproduced water temperatures and hypolimnetic dissolved oxygen concentrations accurately over a 5 year period. Second, the model was extended to include an adaptive withdrawal functionality, allowing for a prescribed withdrawal temperature to be found, with the potential constraint of hypolimnetic oxygen concentration. Scenario simulations on epi-/metalimnetic withdrawal demonstrate that the model is able to autonomously determine the best withdrawal height depending on the thermal structure and the hypolimnetic oxygen concentration thereby optimizing the ability to supply a desirable discharge temperature to the downstream river during summer. This new withdrawal strategy also increased the hypolimnetic raw water volume to be used for drinking water supply, but reduced the dissolved oxygen concentrations in the deep and cold water layers (hypolimnion). Implications of the results for reservoir management are discussed and the numerical model is provided for operators as a simple and efficient tool for optimizing the withdrawal strategy within different reservoir contexts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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

  5. 25 CFR 1200.13 - How does a tribe apply to withdraw funds?

    Science.gov (United States)

    2010-04-01

    ... contain the items listed below. (a) Proof that the tribe has notified its members of its intent to remove... proof that the tribe has notified its members of intent to transfer the funds. The resolution must... governing body has the legal authority to withdraw funds from trust status and that the withdrawal does not...

  6. 46 CFR 159.005-15 - Approval of equipment or material: Suspensions, withdrawals, and terminations.

    Science.gov (United States)

    2010-10-01

    ..., withdrawals, and terminations. 159.005-15 Section 159.005-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL APPROVAL OF..., withdrawals, and terminations. (a) The Commandant suspends an approval issued under this subchapter in...

  7. Internalizing Behaviors among Kindergarten Children: Measuring Dimensions of Social Withdrawal with a Checklist

    Science.gov (United States)

    Thijs, Jochem T.; Koomen, Helma M. Y.; de Jong, Peter F.; van der Leij, Aryan; van Leeuwen, Mirella G. P.

    2004-01-01

    Three studies examined whether different types of withdrawal among young children could be assessed with a short checklist. In Study 1, kindergarten teachers rated 487 children on a modified version of the Behavior Questionnaire for Two- to Six-Year-Olds (BQTSYO). Exploratory factor analyses yielded 2 withdrawal factors, Social Inhibition and…

  8. Effect of inclusion levels and withdrawal periods of Tetracin® on ...

    African Journals Online (AJOL)

    ... when withdrawal time was not observed. The study showed that strict adherence to label dosage and withdrawal time should be followed to mitigate the presence of feed grade antibiotic residues in broiler meat among the consuming public. Keywords: Tetracin®; Growth; Carcass; Primal cuts; Organs; Residue; Broiler ...

  9. 40 CFR 96.286 - Withdrawal from CAIR SO2 Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from CAIR SO2 Trading... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR SO2 Opt-in Units § 96.286 Withdrawal from CAIR SO2 Trading Program. Except as provided...

  10. 40 CFR 96.86 - Withdrawal from NOX Budget Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.86 Withdrawal from NOX Budget Trading Program. (a) Requesting...

  11. 40 CFR 97.286 - Withdrawal from CAIR SO2 Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from CAIR SO2 Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR SO2 Opt-in Units § 97.286 Withdrawal from CAIR SO2 Trading Program. Except as provided under paragraph (g) of...

  12. 39 CFR 955.23 - Copies of papers, withdrawal of exhibits.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Copies of papers, withdrawal of exhibits. 955.23... SERVICE BOARD OF CONTRACT APPEALS § 955.23 Copies of papers, withdrawal of exhibits. (a) When books, records, papers, or documents have been received in evidence, a true copy thereof or of such part thereof...

  13. Paying Attention to and Not Neglecting Social Withdrawal and Social Isolation

    Science.gov (United States)

    Rubin, Kenneth H.; Coplan, Robert J.

    2004-01-01

    This commentary outlines the origins, history, and current status of research related to children's social withdrawal and social isolation. Early research related to children's peer relationships is first explored, followed by a discussion of the relative "neglect" of social withdrawal prior to the 1980s. Increased research attention since that…

  14. 20 CFR 408.360 - Can you cancel your request to withdraw your application?

    Science.gov (United States)

    2010-04-01

    ... application? 408.360 Section 408.360 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.360 Can you cancel your... (c) A cancellation request received after we have approved your withdrawal must be filed no later...

  15. 20 CFR 410.233 - Cancellation of a request for withdrawal.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Cancellation of a request for withdrawal. 410.233 Section 410.233 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL COAL MINE HEALTH AND... Entitlement; Filing of Claims and Evidence § 410.233 Cancellation of a request for withdrawal. Before or after...

  16. Trajectories of Social Withdrawal from Grades 1 to 6: Prediction from Early Parenting, Attachment, and Temperament

    Science.gov (United States)

    Booth-LaForce, Cathryn; Oxford, Monica L.

    2008-01-01

    From 1,092 children in the NICHD Study of Early Child Care and Youth Development, the authors identified 3 trajectory patterns of social withdrawal from teacher reports in Grades 1-6: a normative consistently low group (86%), a decreasing group (5%) with initially high withdrawal that decreased, and an increasing group (9%) with initially low…

  17. 20 CFR 416.360 - Cancellation of a request to withdraw.

    Science.gov (United States)

    2010-04-01

    ....360 Section 416.360 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Filing of Applications Withdrawal of Application § 416.360... received after we have approved the withdrawal, the cancellation request is filed no later than 60 days...

  18. Going It Alone: Comparing Subtypes of Withdrawal on Indices of Adjustment and Maladjustment in Emerging Adulthood

    Science.gov (United States)

    Nelson, Larry J.

    2013-01-01

    Scholars have distinguished conceptually between multiple forms of social withdrawal among children and adolescents, but this distinction has yet to be investigated fully during emerging adulthood. Therefore, the overarching goal of this study was to employ a person-oriented approach to examine differences between subtypes of withdrawal on…

  19. Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

    Science.gov (United States)

    Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najmanm, Jake M.

    2011-01-01

    Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and…

  20. 20 CFR 404.641 - Cancellation of a request to withdraw.

    Science.gov (United States)

    2010-04-01

    ....641 Section 404.641 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Filing of Applications and Other Forms Withdrawal of Application § 404.641... received after we have approved the withdrawal, the request is filed no later than 60 days after the date...

  1. The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations

    NARCIS (Netherlands)

    Velthorst, Eva; Meijer, Carin; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

    2012-01-01

    Background: Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a

  2. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients

    NARCIS (Netherlands)

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W.; Pols, Huibert A. P.; van der Cammen, Tischa J. M.

    2008-01-01

    BACKGROUND: Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. METHOD: Within a common geriatric outpatient

  3. 10 CFR 95.21 - Withdrawal of requests for facility security clearance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Withdrawal of requests for facility security clearance. 95.21 Section 95.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.21 Withdrawal of...

  4. 19 CFR 19.18 - Smelting and refining; allowance for wastage; withdrawal for consumption.

    Science.gov (United States)

    2010-04-01

    ...; withdrawal for consumption. 19.18 Section 19.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT... wastage; withdrawal for consumption. (a) Except where absolute deductions have been allowed in the... entered for consumption or for warehouse, during a 12-month period beginning on the first day of the month...

  5. 19 CFR 144.42 - Combined entry for rewarehouse and withdrawal for consumption.

    Science.gov (United States)

    2010-04-01

    ... consumption. 144.42 Section 144.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Rewarehouse Entries § 144.42 Combined entry for rewarehouse and withdrawal for consumption. (a) Applicability... rewarehouse and withdrawal for consumption. (b) Procedure for entry. The procedures set forth in § 144.41 are...

  6. 8 CFR 246.4 - Immigration judge's authority; withdrawal and substitution.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judge's authority; withdrawal... IMMIGRATION REGULATIONS RESCISSION OF ADJUSTMENT OF STATUS § 246.4 Immigration judge's authority; withdrawal and substitution. In any proceeding conducted under this part, the immigration judge shall have...

  7. 76 FR 14351 - Proposed Withdrawal of Certain Federal Aquatic Life Water Quality Criteria Applicable to Wisconsin

    Science.gov (United States)

    2011-03-16

    ... Proposed Withdrawal of Certain Federal Aquatic Life Water Quality Criteria Applicable to Wisconsin AGENCY... aquatic life water quality criteria for chronic and acute copper and nickel, and chronic endrin and...., Washington, DC 20460 or Francine Norling, Proposed Withdrawal of Certain Federal Aquatic Life Water Quality...

  8. 76 FR 57646 - Final Withdrawal of Certain Federal Aquatic Life Water Quality Criteria Applicable to Wisconsin

    Science.gov (United States)

    2011-09-16

    ... Final Withdrawal of Certain Federal Aquatic Life Water Quality Criteria Applicable to Wisconsin AGENCY... aquatic life water quality criteria applicable to Wisconsin? C. Why is the EPA not withdrawing Wisconsin's chronic endrin aquatic life use criterion for waters designated as Warm Water Sportfish and Warm Water...

  9. Complementing the Numbers: A Text Mining Analysis of College Course Withdrawals

    Science.gov (United States)

    Michalski, Greg V.

    2011-01-01

    Excessive college course withdrawals are costly to the student and the institution in terms of time to degree completion, available classroom space, and other resources. Although generally well quantified, detailed analysis of the reasons given by students for course withdrawal is less common. To address this, a text mining analysis was performed…

  10. 25 CFR 1200.34 - Can a tribe withdraw redeposited funds?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Can a tribe withdraw redeposited funds? 1200.34 Section 1200.34 Indians OFFICE OF THE SPECIAL TRUSTEE FOR AMERICAN INDIANS, DEPARTMENT OF THE INTERIOR AMERICAN INDIAN TRUST FUND MANAGEMENT REFORM ACT Returning Tribal Funds to Trust § 1200.34 Can a tribe withdraw...

  11. Withdrawal of fall-risk-increasing drugs in older persons: Effect on mobility test outcomes

    NARCIS (Netherlands)

    N. van der Velde (Nathalie); B.H.Ch. Stricker (Bruno); H.A.P. Pols (Huib); T.J.M. van der Cammen (Tischa)

    2007-01-01

    textabstractBackground: Previously, we have shown that withdrawal of fall-risk-increasing drugs (FRIDs) as a single intervention reduces falls incidence. Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal.

  12. Withdrawal of fall-risk-increasing drugs in older persons: effect on mobility test outcomes

    NARCIS (Netherlands)

    van der Velde, Nathalie; Stricker, Bruno H. Ch; Pols, Huibert A. P.; van der Cammen, Tischa J. M.

    2007-01-01

    BACKGROUND: Previously, we have shown that withdrawal of fall-risk-increasing drugs (FRIDs) as a single intervention reduces falls incidence. Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal. METHODS: In

  13. 77 FR 15378 - Agency Information Collection Activities: Application for Withdrawal of Bonded Stores for Fishing...

    Science.gov (United States)

    2012-03-15

    ... Activities: Application for Withdrawal of Bonded Stores for Fishing Vessels and Certificate of Use AGENCY: U... information collection request to the Office of Management and Budget (OMB) for review and approval in accordance with the Paperwork Reduction Act: Application for Withdrawal of Bonded Stores for Fishing Vessels...

  14. 75 FR 71559 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Withdrawal of...

    Science.gov (United States)

    2010-11-24

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 261 [EPA-R06-RCRA-2010-0066; SW FRL-9231-4] Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Withdrawal of Direct Final Exclusion AGENCY: Environmental Protection Agency (EPA). ACTION: Withdrawal of direct final exclusion...

  15. A comparison of three federal datasets for thermoelectric water withdrawals in the United States for 2010

    Science.gov (United States)

    Harris, Melissa A.; Diehl, Timothy H.

    2017-01-01

    Historically, thermoelectric water withdrawal has been estimated by the Energy Information Administration (EIA) and the U.S. Geological Survey's (USGS) water-use compilations. Recently, the USGS developed models for estimating withdrawal at thermoelectric plants to provide estimates independent from plant operator-reported withdrawal data. This article compares three federal datasets of thermoelectric withdrawals for the United States in 2010: one based on the USGS water-use compilation, another based on EIA data, and the third based on USGS model-estimated data. The withdrawal data varied widely. Many plants had three different withdrawal values, and for approximately 54% of the plants the largest withdrawal value was twice the smallest, or larger. The causes of discrepancies among withdrawal estimates included definitional differences, definitional noise, and various nondefinitional causes. The uncertainty in national totals can be characterized by the range among the three datasets, from 5,640 m3/s (129 billion gallons per day [bgd]) to 6,954 m3/s (158 bgd), or by the aggregate difference between the smallest and largest values at each plant, from 4,014 m3/s (92 bgd) to 8,590 m3/s (196 bgd). When used to assess the accuracy of reported values, the USGS model estimates identify plants that need to be reviewed.

  16. 75 FR 80061 - Abbott Laboratories, Inc.; Withdrawal of Approval of a New Drug Application for MERIDIA

    Science.gov (United States)

    2010-12-21

    ... withdrawing approval of a new drug application (NDA) for MERIDIA (sibutramine hydrochloride (HCl)) oral... requested that Abbott voluntarily withdraw MERIDIA (sibutramine HCl) oral capsules from the market, based on FDA's recent analysis of clinical trial data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT...

  17. Adaptation to Work: An Analysis of Employee Health, Withdrawal and Change. Working Paper 82-19.

    Science.gov (United States)

    Rosse, Joseph G.

    According to an employee withdrawal model suggested by Miller and Rosse (1982), workers engage in a variety of integrated behaviors that are intended to place physical and psychological distance between themselves and a noxious work environment. To investigate the relationship of job satisfaction and employee withdrawal behaviors, 48 newly hired,…

  18. Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics

    DEFF Research Database (Denmark)

    Madsbad, S; Gluud, C; Bennett, Patrick

    1986-01-01

    Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal no sig...

  19. 77 FR 67666 - Notice of Proposed Renewal of Information Collection: Application To Withdraw Tribal Funds From...

    Science.gov (United States)

    2012-11-13

    ... Renewal of Information Collection: Application To Withdraw Tribal Funds From Trust Status AGENCY: Office... request renewal approval for the collection of information for Application to Withdraw Tribal Funds from... nature of the information collection and the expected burden and cost. DATES: OMB has up to 60 days to...

  20. 78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

    Science.gov (United States)

    2013-08-23

    ... 558 [Docket No. FDA-2013-N-0839] New Animal Drugs; Withdrawal of Approval of New Animal Drug...: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the withdrawal of approval of three new animal drug applications (NADAs) at the sponsors' request...

  1. Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management.

    Science.gov (United States)

    Chiu, Ada W; Contreras, Sofia; Mehta, Sangeeta; Korman, Jennifer; Perreault, Marc M; Williamson, David R; Burry, Lisa D

    2017-12-01

    To (1) provide an overview of the epidemiology, clinical presentation, and risk factors of iatrogenic opioid withdrawal in critically ill patients and (2) conduct a literature review of assessment and management of iatrogenic opioid withdrawal in critically ill patients. We searched MEDLINE (1946-June 2017), EMBASE (1974-June 2017), and CINAHL (1982-June 2017) with the terms opioid withdrawal, opioid, opiate, critical care, critically ill, assessment tool, scale, taper, weaning, and management. Reference list of identified literature was searched for additional references as well as www.clinicaltrials.gov . We restricted articles to those in English and dealing with humans. We identified 2 validated pediatric critically ill opioid withdrawal assessment tools: (1) Withdrawal Assessment Tool-Version 1 (WAT-1) and (2) Sophia Observation Withdrawal Symptoms Scale (SOS). Neither tool differentiated between opioid and benzodiazepine withdrawal. WAT-1 was evaluated in critically ill adults but not found to be valid. No other adult tool was identified. For management, we identified 5 randomized controlled trials, 2 prospective studies, and 2 systematic reviews. Most studies were small and only 2 studies utilized a validated assessment tool. Enteral methadone, α-2 agonists, and protocolized weaning were studied. We identified 2 validated assessment tools for pediatric intensive care unit patients; no valid tool for adults. Management strategies tested in small trials included methadone, α-2 agonists, and protocolized sedation/weaning. We challenge researchers to create validated tools assessing specifically for opioid withdrawal in critically ill children and adults to direct management.

  2. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as provided...

  3. Nebraska withdraws its intent to deny site license

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The state of Nebraska has withdrawn its notice of intent to deny the US Ecology (USE) license application for the proposed low-level radioactive waste disposal site in Boyd County, near Butte, Neb. On October 4, after review of USE's August 27 submittal of a revision to the boundaries of the proposed site, a letter from the state's Department of Health (DOH) and Department of Environmental Quality (DEQ) to John. H. DeOld, the USE project manager for the Central Interstate Compact's proposed LLW site, noted that open-quotes...we are hereby withdrawing the Notice of Intent to Deny License as a moot, and will conduct a substantive review of the reconfigured site for compliance with the applicable regulations.close quotes

  4. Renouncement of renal replacement therapy: withdrawal and refusal

    Directory of Open Access Journals (Sweden)

    José Andrade Moura Neto

    Full Text Available Abstract Renouncement of renal replacement therapy (RRT is a medical dilemma. This review covers the concept, the magnitude, the prognosis, and discusses strategies and management approaches about this subject in patients with CKD and AKI. Evidence suggests that refusal is more frequent and carries a more guarded prognosis than withdrawal of RRT. When RRT is not expected to be beneficial in terms of survival or quality of life, conservative treatment and palliative care are alternatives. We review the historical evolution of guidelines about renouncement of RRT and palliative care, and highlight the absence of specific recommendations in Brazil. However renouncement of RRT may be ethically and legally accepted in Brazil, as the right to a dignified death. Longer life expectancy, economic pressures, and greater awareness will require a more detailed discussion about indications and sustainable use of RRT, and possibly the elaboration of national guidelines.

  5. The Director General withdraws its proposal to Council

    CERN Multimedia

    Staff Association

    2015-01-01

    Dear Colleagues, The Staff Association and the CERN-ESO Pensioners’ Association want to let you know that they are deeply worried. Decisions taken by CERN Council at its latest closed sessions attracted our attention.  Since these sessions took place behind closed doors, without the presence of the Association, we had to investigate, crossing several sources of information. Result: The attitude of some delegations shocked us and fills us with indignation. Let us recall the facts: the Management's action plan to compensate for the soaring Swiss franc against the euro, did not reach a consensus among the Member States, forcing Management to withdraw it. Strange, when one considers that CERN was the only international organization based in Switzerland to come forward with such an initiative. On the contrary, Council is once again using the Pension Fund as a “scape goat”. It should be recalled here, that past decisions by CERN Council on the Fund's manag...

  6. Ecuador to withdraw from OPEC; group to maintain present flow

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that the Organization of Petroleum Exporting Countries, which has agreed to maintain its present combined production of 24.2 million b/d of oil in the fourth quarter, will soon see the first pullout of a member. The 13 member group will shrink to 12, probably in November, when Ecuador withdraws. Ecuador President Sixto Duran Ballen issued notice of the pullout Sept. 17, a little more than 1 month after he took office. Ecuador, strapped for cash, wants to save OPEC membership dues reported to be $2-3 million/year. It plans to remain an associate member, although it wasn't immediately clear what that means. No other countries are regarded as associate members

  7. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

    OpenAIRE

    Zhu, Hong; Ho, Ing K.; Kramer, Robert E.; Baker, Rodney C.; Rockhold, Robin W.

    2002-01-01

    Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP), an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl/h) for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, d...

  8. The Relationship between Trail Running Withdrawals and Race Topography

    Directory of Open Access Journals (Sweden)

    Antonini Philippe Roberta

    2017-12-01

    Full Text Available Context: A growing amount of recent research in sport psychology has focused on trying to understand withdrawals from ultra-races. However, according to the Four E approach, the studies underestimated the embedded components of these experiences and particularly how they were linked to the specific environmental conditions in which the experiences occurred. Objective: This study aimed to characterize trail running withdrawals in relationship to race topography. Design: Qualitative design, involving self-confrontation interviews and use of a race map. Setting: Use of the race map for description of the race activity and self-confrontation interviews took place 1–3 days after the races. Participants: Ten runners who withdrew during an ultra-trail race. Data Collection and Analysis: Data on past activity traces and experiences were elicited from self-confrontation interviews. Data were coded and compared to identify common sequences and then each type of sequence was counted with regard to race topography. Results: Results showed that each sequence was related to runners’ particular possibilities for acting, feeling, and thinking, which were in turn embedded in the race topography. These sequences allowed the unfolding of the activity and increased its overall effectiveness in relation to the constraints of this specific sport. Conclusion: This study allowed us to highlight important information on how ultra-trail runners manage their races in relationship to the race environment and more specifically to its topography. The result will also help us to recommend potential adjustments to ultra-trail runners’ performance-oriented training and preparation.

  9. What influences parents' decisions to limit or withdraw life support?

    Science.gov (United States)

    Sharman, Mahesh; Meert, Kathleen L; Sarnaik, Ashok P

    2005-09-01

    Decisions to forgo life support from critically ill children are commonly faced by parents and physicians. Previous research regarding parents' perspectives on the decision-making process has been limited by retrospective methods and the use of closed-ended questionnaires. We prospectively identified and described parents' self-reported influences on decisions to forgo life support from their children. Deeper understanding of parents' views will allow physicians to focus end-of-life discussions on factors important to parents and help resolve conflicts. Prospective, qualitative pilot study. Pediatric intensive care unit of a university-affiliated children's hospital. A total of 14 parents of ten children whose pediatric intensive care unit physician had made a recommendation to limit or withdraw life support. : In-depth, semistructured interviews were conducted with parents during their decision-making process. Factors influencing the parents in this study in their decision to forgo life support included their previous experience with death and end-of-life decision making for others, their personal observations of their child's suffering, their perceptions of their child's will to survive, their need to protect and advocate for their child, and the family's financial resources and concerns regarding life-long care. Parents in this study expressed the desire to do what is best for their child but struggled with feelings of selfishness, guilt, and the need to avoid agony and sorrow. Physician recommendations, review of options, and joint formulation of a plan helped parents gain a sense of control over their situation. Parents of eight children agreed to forgo life support and parents of two did not. Prospective interviews with open-ended questions identified factors influencing parents' decision making not previously described in the critical care literature such as parents' past experiences with end-of-life decisions and their anticipated emotional adjustments and

  10. Gender Differences in Child and Adolescent Social Withdrawal: A Commentary.

    Science.gov (United States)

    Rubin, Kenneth H; Barstead, Matthew G

    2014-04-01

    In a manuscript entitled, "Bashful boys and coy girls: A review of gender differences in childhood shyness" Doey et al. (2013) suggest that shyness and its related constructs pose a greater developmental risk for boys compared to girls. They support this claim by citing empirical evidence suggesting that shy and anxiously withdrawn boys are responded to more negatively by important others (i.e., parents, peers, and teachers) and that the relationship between internalizing problems and anxious withdrawal is stronger for boys compared to girls. The principal aim of our commentary is to provide a critical examination of Doey et al.'s conclusions vis-à-vis gender differences in child and adolescent shyness. In this response, we begin by providing important theoretical background regarding shyness and its related constructs. Next, we critically examine the two main arguments the authors use in support of their conclusion through a review of existing empirical and theoretical work as well as the presentation of data from The Friendship Project . These data were analyzed with the specific purpose of providing an empirical test of the hypotheses implicit in Doey et al.'s primary arguments: 1) shy and anxiously withdrawn boys are responded to more negatively than girls and 2) the association between anxious withdrawal and internalizing problems is stronger for boys compared to girls. Our results indicate mixed support for these two claims. Finally, we conclude by suggesting new directions for future researchers interested in clarifying the relationship between gender and both the correlates and outcomes of childhood shyness.

  11. Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease.

    Science.gov (United States)

    Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel Fm; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter Ma

    2016-01-01

    The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland-Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of -0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis.

  12. The role of spiritual intelligence in employees’ withdrawal behaviors in physical education organization

    Directory of Open Access Journals (Sweden)

    Davoud Noroozi

    2015-03-01

    Full Text Available Spiritual intelligence is the mind’s capacity to handle substantial and spiritual aspects of life. According to previous studies, spiritual intelligence can be effective in reducing the withdrawal behavior of employees. This study investigated the effect of spiritual intelligence on employees’ withdrawal behavior in Ardabil Physical Education organization. The statistical population of this study included all the employees of Physical Education organization of Ardabil (N=60. Descriptive Statistics, Pearson Correlation, and Linear Regression Analyses were used to assess the association between spiritual intelligence and withdrawal behaviors. The results of the study revealed that spiritual intelligence had positive and significant effect on reducing employees’ withdrawal behavior. The findings supported that spiritual intelligence training as a new psychological and religious construction may reduce psychological and physical withdrawal behaviors and improve the employees’ perception of themselves.

  13. Attention biases to threat and behavioral inhibition in early childhood shape adolescent social withdrawal.

    Science.gov (United States)

    Pérez-Edgar, Koraly; Bar-Haim, Yair; McDermott, Jennifer Martin; Chronis-Tuscano, Andrea; Pine, Daniel S; Fox, Nathan A

    2010-06-01

    Behavioral inhibition (BI) is a temperament characterized in young children by a heightened sensitivity to novelty, social withdrawal, and anxious behaviors. For many children, these social difficulties dissipate over time. For others, patterns of social withdrawal continue into adolescence. Over time, attention biases to threat may influence the stability of BI and its association with social withdrawal, ultimately modulating the risk for anxiety disorders in BI children. However, we know relatively little about the cognitive processes that accompany BI and shape later socio-emotional functioning. We examined the relations among BI in childhood, attention biases to threat in adolescence, and adolescent social withdrawal in a longitudinal study (N = 126, Mean age = 15 years). As has been reported in anxious adults, adolescents who were behaviorally inhibited as toddlers and young children showed heightened attention bias to threat. In addition, attention bias to threat moderated the relation between childhood BI and adolescent social withdrawal.

  14. Object relations, reality testing, and social withdrawal in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Hansen, Charlotte Fredslund; Torgalsbøen, Anne-Kari; Røssberg, Jan Ivar; Romm, Kristin Lie; Andreassen, Ole Andreas; Bell, Morris D; Melle, Ingrid

    2013-03-01

    In this study, we investigated the relationships between observed social withdrawal (Positive and Negative Syndrome Scale [PANSS] Passive Social Withdrawal and PANSS Active Social Avoidance), subjectively experienced social withdrawal (Social Functioning Scale [SFS] Withdrawal and SFS Interpersonal Behavior), and their associations to the underlying psychological patterns of Object Relations and Reality Testing. Patients with schizophrenia (n = 55) and bipolar disorder (n = 51) from the ongoing Thematically Organized Psychosis project, Oslo University Hospital, Norway, were evaluated using the Bell Object Relations and Reality Testing Inventory, the PANSS, and the SFS. Object relations and reality testing subscales related differentially to PANSS Passive Social Withdrawal and PANSS Active Social Avoidance. These two measures, together with the level of alienation, explained a significant amount of variance in self-experienced social dysfunction. Findings reveal the multidimensional nature of social dysfunction in severe mental disorders.

  15. Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

    Science.gov (United States)

    Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

    2005-06-01

    Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

  16. Effect of intensive epilimnetic withdrawal on phytoplankton community in a (subtropical deep reservoir

    Directory of Open Access Journals (Sweden)

    Man Zhang

    2013-10-01

    Full Text Available Withdrawal is an important process in reservoir hydrodynamics, removing phytoplankton with flushed water. Zooplankton,the grazers of phytoplankton, having longer generation times, are even more susceptible than phytoplankton to flushing loss. Therefore phytoplankton are affected not only by abiotic conditions linked to hydrodynamics but also by zooplankton due to weakened grazing pressure. During the Asian Games (November 12-27, 2010 in Guangzhou, China, two intensive epilimnetic withdrawals were conducted in Liuxihe, a deep canyon-shaped reservoir. To examine the influence of the intensive epilimnetic withdrawals on the phytoplankton community, a seven-week field observation and a hydrodynamic simulation were carried out. The observation was divided in two stages: stage 1 represented partial surface vertical mixing period, and stage 2 represented intensive epilimnetic withdrawal period. It was found that phytoplankton abundance and biomass declined with water temperature and partial surface vertical mixing in stage 1. However, the intensive epilimnetic withdrawal reversed this decreasing trend and increased phytoplankton biomass and abundance in stage 2. Phytoplankton showed a higher rate of composition change in stage 2. A numerical model (DYRESM-CAEDYM simulated scenarios with and without epilimnetic withdrawal to test their effects on abiotic factors (water temperature, suspended sediment and soluble reactive phosphorus for phytoplankton. The results showed no obvious difference in the abiotic factors between the two scenarios during stage 2. We therefore suggested that the abiotic factors in the water column were probably driven by a seasonal pattern, not by epilimnetic withdrawal. It is likely that the intensive epilimnetic withdrawal could remove large crustaceans. The reduced grazing pressure probably explained the increase of phytoplankton biomass and abundance after the withdrawal. Thus, we suggest that reservoir operation should pay

  17. Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey

    NARCIS (Netherlands)

    van Biesen, Wim; van de Luijtgaarden, Moniek W. M.; Brown, Edwina A.; Michel, Jean-Pierre; van Munster, Barbara C.; Jager, Kitty J.; van der Veer, Sabine N.

    2015-01-01

    Background. There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these

  18. Aspirin in patients undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Devereaux, P J; Mrkobrada, Marko; Sessler, Daniel I

    2014-01-01

    BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10......,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before...... the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum...

  19. Platelet activation in outpatients undergoing esophagogastroduodenoscopy

    International Nuclear Information System (INIS)

    Sagripanti, A.; Polloni, A.; Materazzi, F.; Ferdeghini, M.; Pinori, E.; Bianchi, R.

    1989-01-01

    To evaluate the influence of emotional stress on platelet function mesured by radioimmunoassay in plasma two platelet factor 4, in a series of outpatients undergoing esophagogastroduodenoscopy for upper digestive complaints has been measured. The plasma levels of β-thromboglobulin and platelet factor 4, determined just before the instrumental examination, were significantly more elevated as compared to basal values, checked a week later. These results provide evidence of enhanced in vivo platelet release reaction during emotional stress

  20. Reconstruction of global gridded monthly sectoral water withdrawals for 1971-2010 and analysis of their spatiotemporal patterns

    Science.gov (United States)

    Huang, Zhongwei; Hejazi, Mohamad; Li, Xinya; Tang, Qiuhong; Vernon, Chris; Leng, Guoyong; Liu, Yaling; Döll, Petra; Eisner, Stephanie; Gerten, Dieter; Hanasaki, Naota; Wada, Yoshihide

    2018-04-01

    Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scales, due to a lack of observations at seasonal and local scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5°) sectoral water withdrawal dataset for the period 1971-2010, which distinguishes six water use sectors, i.e., irrigation, domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that total global water withdrawal has increased significantly during 1971-2010, mainly driven by the increase in irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of total annual irrigation water withdrawal in mid- and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual

  1. Coagulation management in patients undergoing neurosurgical procedures.

    Science.gov (United States)

    Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

    2017-10-01

    Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

  2. Non-Competitive NMDA Receptor Antagonist Hemantane Reduces Ethanol Consumption in Long-Term Alcohol Experienced Rats.

    Science.gov (United States)

    Kolik, L G; Nadorova, A V; Seredenin, S B

    2017-12-01

    Activity of hemantane, an amino adamantane derivative, exhibiting the properties of lowaffinity non-competitive NMDA receptor antagonist, was evaluated in experimental in vivo models of alcoholism. Hemantane had no effects on the formation and manifestation of behavioral sensitization to ethanol in DBA/2 mice. Under conditions of free choice between 10% ethanol and water, hemantane (20 mg/kg/day for 14 days, intraperitoneally) significantly reduced the daily ethanol intake in random-bred male rats with formed alcohol motivation (>4 g/kg of ethanol). During modelling of withdrawal syndrome, hemantane administered intraperitoneally in doses of 5-20 mg/kg dose-dependently attenuated alcohol-deprivation effect after acute withdrawal with no effects on protracted abstinence. It was found that hemantane suppressed alcohol drinking behavior in long-term ethanol experienced rats and attenuated alcohol-seeking behavior after acute withdrawal.

  3. 48 CFR 52.214-23 - Late submissions, modifications, revisions, and withdrawals of technical proposals under two-step...

    Science.gov (United States)

    2010-10-01

    ..., modifications, revisions, and withdrawals of technical proposals under two-step sealed bidding. 52.214-23... Late submissions, modifications, revisions, and withdrawals of technical proposals under two-step..., Modifications, Revisions, and Withdrawals of Technical Proposals Under Two-Step Sealed Bidding (NOV 1999) (a...

  4. Kindergarten Social Withdrawal and Reading Achievement: A Cross-Lagged Path Model for At-Risk Learners

    Science.gov (United States)

    Hall, Cristin M.; Welsh, Janet A.; Bierman, Karen L.; Nix, Robert

    2016-01-01

    The association between social withdrawal, school adjustment, and academic functioning in preschool and school entry is well-established. Children who experience social withdrawal in primary grades are at risk for decreased academic performance. The bidirectional relationships among early literacy and social withdrawal in primary grades have not…

  5. 21 CFR 170.103 - Withdrawal without prejudice of a premarket notification for a food contact substance (FCN).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Withdrawal without prejudice of a premarket... ADDITIVES Premarket Notifications § 170.103 Withdrawal without prejudice of a premarket notification for a food contact substance (FCN). A manufacturer or supplier may withdraw an FCN without prejudice to a...

  6. The application of a non-linear analysis technique to the monitoring of anesthetic effects in the rat

    NARCIS (Netherlands)

    Broek, P.L.C. van den; Egmond, J. van; Rijn, C.M. van; Dirksen, R.; Coenen, A.M.L.; Booij, L.H.D.J.; Lehnertz, K.; Elger, C.E.; Arnhold, J.; Grassberger, P.

    2000-01-01

    To find a new measure from the EEG that quantifies the effects of anesthetics during surgery, the correlation dimension (CD) of the EEG of eight rats was estimated. To get informed about the anesthetic state, the noxious induced withdrawal reflex (NIWR) was measured, i.e. the force elicited by

  7. Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system

    Science.gov (United States)

    Aricioglu, Feyza; Means, Andrea; Regunathan, Soundar

    2010-01-01

    Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure. PMID:15541421

  8. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Antje Brand

    Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  9. Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

    Science.gov (United States)

    Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

    2010-12-21

    Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

  10. Feed withdrawal and transportation effects on Salmonella enterica levels in market-weight pigs.

    Science.gov (United States)

    Eicher, S D; Rostagno, M H; Lay, D C

    2017-07-01

    Feed withdrawal and transport commonly occur together in pigs. Objectives of this study were to determine if these preslaughter stressors, feed withdrawal and transportation, affect the levels of , stress hormone concentrations, and immune functions in infected market pigs. A 2 × 2 factorial analysis of a randomized complete block design with feed withdrawal and transport as fixed effects was used. Sixty market-weight pigs were individually inoculated with serovar Typhimurium. The experiment was replicated 3 times (blocking factor) with 20 pigs per replicate. Three days after inoculation, the pigs were randomly assigned to 1 of 4 treatments (5 pigs per treatment in each/replicate), including 1) control (Control; or no stress), 2) feed withdrawal for 12 h (FW), 3) transportation for 2 h (T), and 4) feed withdrawal for 12 h followed by transportation for 2 h (FWT). Feed withdrawal by itself or followed by transportation caused an increase of levels in ileal contents ( 0.10). Cortisol increased in pigs from all 3 stress treatments ( 0.03). Each granulocyte percentage (neutrophil, eosinophils, and basophils) increased ( transport but was attenuated ( > 0.05) by feed withdrawal with transport. Lymphocytes were suppressed ( transported (T and FWT). However, monocytes were suppressed ( transportation, lead to greater intestinal levels and gut-associated lymphoid tissue markers of inflammation in market pigs and, consequently, to an increased food safety risk.

  11. Neuroticism and Conscientiousness as Moderators of the Relation Between Social Withdrawal and Internalizing Problems in Adolescence.

    Science.gov (United States)

    Smith, Kelly A; Barstead, Matthew G; Rubin, Kenneth H

    2017-04-01

    Social withdrawal, or refraining from social interaction in the presence of peers, places adolescents at risk of developing emotional problems like anxiety and depression. The personality traits of neuroticism and conscientiousness also relate to emotional difficulties. For example, high conscientiousness predicts lower incidence of anxiety disorders and depression, while high neuroticism relates to greater likelihood of these problems. Based on these associations, socially withdrawn adolescents high in conscientiousness or low in neuroticism were expected to have lower levels of anxiety and depressive symptoms. Participants included 103 adolescents (59 % female) who reported on their personality traits in 8th grade and their anxiety and depressive symptoms in 9th grade. Peer ratings of social withdrawal were collected within schools in 8th grade. A structural equation model revealed that 8th grade withdrawal positively predicted 9th grade anxiety and depressive symptoms controlling for 8th grade anxiety and depressive symptoms, but neuroticism did not. Conscientiousness moderated the relation of withdrawal with depressive symptoms but not anxiety, such that high levels of conscientiousness attenuated the association between withdrawal and depressive symptoms. This buffering effect may stem from the conceptual relation between conscientiousness and self-regulation. Conscientiousness did not, however, moderate the association between withdrawal and anxiety, which may be partly due to the role anxiety plays in driving withdrawal. Thus, a conscientious, well-regulated personality partially protects withdrawn adolescents from the increased risk of emotional difficulties.

  12. Socially anxious smokers experience greater negative affect and withdrawal during self-quit attempts.

    Science.gov (United States)

    Buckner, Julia D; Langdon, Kirsten J; Jeffries, Emily R; Zvolensky, Michael J

    2016-04-01

    Despite evidence of a strong and consistent relation between smoking and elevated social anxiety, strikingly little empirical work has identified mechanisms underlying the smoking-social anxiety link. Persons with elevated social anxiety may rely on smoking to cope with more severe nicotine withdrawal and post-quit negative mood states; yet, no known studies have investigated the relation of social anxiety to withdrawal severity. The current study examined the relation of social anxiety to post-quit nicotine withdrawal severity among 51 (33.3% female, Mage = 34.6) community-recruited smokers during the first two weeks following an unaided (i.e., no treatment) cessation attempt. Ecological momentary assessment was used to collect multiple daily ratings of withdrawal and negative mood states. Baseline social anxiety was related to increases in negative affect during the monitoring period and remained significantly related to post-quit withdrawal after controlling for negative affect, gender, lapses, and substance use. Persons with elevated social anxiety experience more severe post-quit withdrawal symptoms and increases in negative affect during a cessation attempt and may therefore benefit from intervention and treatment strategies geared toward helping them learn to cope with withdrawal and negative affect to improve cessation rates among these vulnerable smokers.

  13. Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay

    2011-01-01

    Full Text Available Many patients are admitted to the intensive care unit (ICU for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α2 agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.

  14. Acute pregabalin withdrawal: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Barrett JA

    2015-05-01

    Full Text Available Objective: Pregabalin is a commonly prescribed GABA analog most commonly used for the treatment of neuralgia. Recently, case reports on pregabalin have been published describing episodes that may be associated with withdrawal-like symptoms after extended or aggressive therapy. This report describes a case in which long term exposure of high dose pregabalin may have resulted in acute withdrawal, and outlines the subsequent medical management of these symptoms. Case Summary: A 61-year-old male presenting with severe agitation presumed to be withdrawal from long term and high dose exposure to pregabalin. Medical management included the use of haloperidol, diphenhydramine, lorazepam and the addition of clonidine over the course of several days for the pharmacological management of withdrawal symptoms. Discussion: Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed. Conclusion: Caution must be practiced when prescribing and educating patients on the use of pregabalin to prevent associated withdrawal-like symptoms. In addition, documentation by the medical community on methods utilized to treat pregabalin withdrawal syndromes remains crucial for the advancement of patient care. Benzodiazepines and clonidine are the current therapies that have been documented as potentially effective treatment modalities at this time.

  15. Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

    Science.gov (United States)

    Kotlyar, Michael; Lindgren, Bruce R; Vuchetich, John P; Le, Chap; Mills, Anne M; Amiot, Elizabeth; Hatsukami, Dorothy K

    2017-08-01

    Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (pnicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Tolerance and withdrawal from prolonged opioid use in critically ill children.

    Science.gov (United States)

    Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

    2010-05-01

    After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

  17. Determination of Screw and Nail Withdrawal Resistance of Some Important Wood Species

    Directory of Open Access Journals (Sweden)

    Alper Aytekin

    2008-04-01

    Full Text Available In this study, screw and nail withdrawal resistance of fir (Abies nordmanniana, oak (Quercus robur L. black pine (Pinus nigra Arnold and Stone pine (Pinus pinea L. wood were determined and compared. The data represent the testing of withdrawal resistance of three types of screws as smart, serrated and conventional and common nails. The specimens were prepared according to TS 6094 standards. The dimensions of the specimens were 5x5x15cm and for all of the directions. Moreover, the specimens were conditioned at ambient room temperature and 65±2% relative humidity. The screws and nails were installed according to ASTM-D 1761 standards. Nail dimensions were 2.5mm diameter and 50 mm length, conventional screws were 4x50mm, serrated screws were 4x45mm and smart screws were 4x50mm. Results show that the maximum screw withdrawal resistance value was found in Stone pine for the serrated screw. There were no significant differences between Stone pine and oak regarding screw withdrawal resistance values. Conventional screw yielded the maximum screw withdrawal resistance value in oak, followed by Stone pine, black pine and fir. Oak wood showed the maximum screw withdrawal resistance value for the smart screw, followed by Stone pine, black pine, and fir. Oak wood showed higher nail withdrawal resistances than softwood species. It was also determined that oak shows the maximum nail withdrawal resistance in all types. The nail withdrawal resistances at the longitudinal direction are lower with respect to radial and tangential directions.

  18. Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.

    Science.gov (United States)

    Park, Min Jung; Guest, Christopher B; Barnes, Meredith B; Martin, Jonathan; Ahmad, Uzma; York, Jason M; Freund, Gregory G

    2008-11-01

    Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal. Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines. Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal. These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.

  19. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    Science.gov (United States)

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-05

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.