Sample records for enrichment affects opioid

  1. Dextromethorphan differentially affects opioid antinociception in rats (United States)

    Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh


    Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

  2. Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats. (United States)

    Hofford, Rebecca S; Chow, Jonathan J; Beckmann, Joshua S; Bardo, Michael T


    Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil. Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of age and were trained to lever press for 1 or 3 μg/kg/infusion remifentanil in young adulthood. Acquisition of self-administration and responding during increasing fixed ratio requirements were assessed, and a dose-response curve was generated. In all phases, Enr rats lever pressed significantly less than Std and Iso rats, with Enr rats pressing between 9 and 40% the amount of Iso rats. Enr rats did not acquire remifentanil self-administration when trained with 1 μg/kg/infusion, did not increase responding over increasing FR when trained at either dose, and their dose-response curves were flattened compared to Std and Iso rats. When expressed as economic demand curves, Enr rats displayed a decrease in both essential value (higher α) and reinforcer intensity (Q 0 ) compared to Std and Iso rats at the 1 μg/kg/infusion training dose. Environmental enrichment reduced remifentanil intake, suggesting that social and environmental novelty may protect against opioid abuse.

  3. The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways. (United States)

    Garland, Eric L; Froeliger, Brett; Zeidan, Fadel; Partin, Kaitlyn; Howard, Matthew O


    Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Maneckjee, R.; Minna, J.D.


    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for μ, δ, and κ opioid agonists and for nicotine and α-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas μ, δ, and κ opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (β-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer

  5. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Maneckjee, R.; Minna, J.D. (National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD (USA) Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))


    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.

  6. How is uranium supply affecting enrichment?

    International Nuclear Information System (INIS)

    Steve Kidd


    As a result of the enlivened uranium market, momentum has in turn picked up in the enrichment sector. What are the consequences of higher uranium prices? There is, of course, a link between uranium and enrichment supply to the extent that they are at least partial substitutes. On the enrichment supply side, the most obvious feature is the gradual replacement of the old gas diffusion facilities of Usec in the USA and EURODIF in France with more modern and economical centrifuge plants. Assuming Usec can overcome the financing and technical issues surrounding its plans, the last gas diffusion capacity should disappear around 2015 and the entire enrichment market should then be using centrifuges. On the commercial side, the key anticipated developments are mostly in Russia. Although there should still continue to be substantial quantities of surplus Russian HEU available for down blending in the period beyond 2013, it is now reasonable to expect that it will be mostly consumed by internal needs, to fuel Russian-origin reactors both at home and in export markets such as China and India. Finally, as a key sensitive area for the non-proliferation of nuclear weapons, the enrichment sector is likely to be a central point of the new international arrangements which must be developed to support a buoyant nuclear sector throughout this century.

  7. Does naltrexone affect craving in abstinent opioid-dependent patients?

    NARCIS (Netherlands)

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


    Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The

  8. Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    Full Text Available Dopamine D1 receptor (DRD1 modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD, the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD, subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0% reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0% felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR = 0.694; p = 0.001 and rs686 (HR = 0.681, p = 0.0003. Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR = 0.261 could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR = 0.535 and rs4532 (OR = 0.537 could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD≤30 days; OR = 0.603 or post-dependence euphoria (OR = 0.603 relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.

  9. Fresh pasta quality as affected by enrichment of nonstarch polysaccharides. (United States)

    Brennan, C S; Tudorica, C M


    Nonstarch polysaccharides (NSPs), both soluble and insoluble, were added to pasta doughs at levels of 2.5%, 5%, 7.5%, and 10% levels. The cooking and textural characteristics of the pastas were evaluated using a range of analytical techniques. Generally, NSP addition was found to increase the cooking losses, and reduce the protein and starch contents of the pasta. This effect was dependent on the level of NSP added and also the type (soluble or insoluble). Pasta firmness was generally reduced in relation to the level of NSP addition, although some gel-forming NSPs resulted in higher firmness values. Pasta stickiness, adhesiveness, and elasticity were also affected. The results indicate that careful selection of NSP addition is needed to ensure optimum textural and cooking characteristics in NSP enriched pasta products.

  10. Factors affecting radon removal from Rn-222 enriched water

    International Nuclear Information System (INIS)

    Abulfaraj, W.H.; Mamoon, A.


    Continued use of potable well water that has elevated levels of Rn-222 is harmful to human health. activated carbon, aeration and heating can remove radon from treated water. Water artificially enriched with Rn-222 using a pitchblende source was studied in a laboratory scale model under controlled conditions. (author), 3 figs., 3 refs

  11. What Factors Affect Physicians’ Decisions to Prescribe Opioids in Emergency Departments?

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    Lauren E. Sinnenberg BA


    Full Text Available Objective: With 42% of all emergency department visits in the United States related to pain, physicians who work in this setting are tasked with providing adequate pain management to patients with varying primary complaints and medical histories. Complicating this, the United States is in the midst of an opioid overdose epidemic. State governments and national organizations have developed guidelines and legislation to curtail opioid prescriptions in acute care settings, while also incentivizing providers for patient satisfaction and completeness of pain control. In order to inform future policies that focus on provider pain medication prescribing, we sought to characterize the factors physicians weigh when considering treating pain with opioids in the emergency department. Methods: We conducted and transcribed open-ended, semistructured qualitative interviews with 52 physicians at a national emergency medicine conference. Results: Participants reported a wide range of factors contributing to their opioid prescribing patterns related to three domains: 1 provider assessment of pain characteristics, 2 patient-based considerations, and 3 practice environment. Pain characteristics include the characteristics of various acute and chronic pain syndromes, including physicians’ empathy due to their own experiences with pain. Patient characteristics include “trustworthiness,” race and ethnicity, and the concern for risk of misuse. Factors related to the practice environment include hospital policy, legislation/regulation, and guidelines. Conclusion: The decision to prescribe opioids to patients in the emergency department is complex and nuanced. Physicians are interested in guidance and are concerned about the competing pressures placed on their opioid prescribing due to incentives related to patient satisfaction scores on one hand and inflexible policies that do not allow for individualized, patient-centered decisions on the other.

  12. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J


    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  13. Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study. (United States)

    Gimbel, Joseph; Spierings, Egilius L H; Katz, Nathaniel; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew


    A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was -0.98 (95% CI, -1.32 to -0.64; P opioid-experienced patients taking around-the-clock opioid treatment for chronic low back pain.

  14. Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials (United States)

    Kelly, Michael P.; Anderson, Paul A.; Sasso, Rick C.; Riew, K. Daniel


    Object The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery. Methods A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single-level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-ltem Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/ hydrocodone), and opioid-naïve groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively. Results Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naïve. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong –52.3, weak –50.6, naïve –54.0, p = 0.244; neck: strong –52.7, weak –50.8, naïve –44.6, p = 0.355); NDI scores (strong –36.0, weak –33.3, naïve –32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naïve 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naïve 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point. Conclusions Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient

  15. β-Arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but does not affect opioid-withdrawal-related adaptations in single PAG neurons. (United States)

    Connor, M; Bagley, E E; Chieng, B C; Christie, M J


    Tolerance to the behavioural effects of morphine is blunted in β-arrestin-2 knockout mice, but opioid withdrawal is largely unaffected. The cellular mechanisms of tolerance have been studied in some neurons from β-arrestin-2 knockouts, but tolerance and withdrawal mechanisms have not been examined at the cellular level in periaqueductal grey (PAG) neurons, which are crucial for central tolerance and withdrawal phenomena. μ-Opioid receptor (MOPr) inhibition of voltage-gated calcium channel currents (ICa ) was examined by patch-clamp recordings from acutely dissociated PAG neurons from wild-type and β-arrestin-2 knockout mice treated chronically with morphine (CMT) or vehicle. Opioid withdrawal-induced activation of GABA transporter type 1 (GAT-1) currents was determined using perforated patch recordings from PAG neurons in brain slices. MOPr inhibition of ICa in PAG neurons was unaffected by β-arrestin-2 deletion. CMT impaired coupling of MOPrs to ICa in PAG neurons from wild-type mice, but this cellular tolerance was not observed in neurons from CMT β-arrestin-2 knockouts. However, β-arrestin-2 knockouts displayed similar opioid-withdrawal-induced activation of GAT-1 currents as wild-type PAG neurons. In β-arrestin-2 knockout mice, the central neurons involved in the anti-nociceptive actions of opioids also fail to develop cellular tolerance to opioids following chronic morphine. The results also provide the first cellular physiological evidence that opioid withdrawal is not disrupted by β-arrestin-2 deletion. However, the unaffected basal sensitivity to opioids in PAG neurons provides further evidence that changes in basal MOPr sensitivity cannot account for the enhanced acute nociceptive response to morphine reported in β-arrestin-2 knockouts. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit © 2014 The British

  16. Opioid intoxication (United States)

    ... easily result in intoxication. The provider prescribes a sleep medicine (sedative) in addition to the opioid. The provider ... an opioid with certain other drugs, such as sleep medicines or alcohol Taking the opioid in ways not ...

  17. Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice. (United States)

    Maruoka, Takashi; Kodomari, Ikuko; Yamauchi, Rena; Wada, Etsuko; Wada, Keiji


    The maternal environment is thought to be important for fetal brain development. However, the effects of maternal environment are not fully understood. Here, we investigated whether enrichment of the maternal environment can influence prenatal brain development and postnatal behaviors in mice. An enriched environment is a housing condition with several objects such as a running wheel, tube and ladder, which are thought to increase sensory, cognitive and motor stimulation in rodents compared with standard housing conditions. First, we measured the number of BrdU-positive cells in the hippocampal dentate gyrus of fetuses from pregnant dams housed in an enriched environment. Our results revealed that maternal enrichment influences cell proliferation in the hippocampus of female, but not male, fetuses. Second, we used the open-field test to investigate postnatal behaviors in the offspring of dams housed in the enriched environment during pregnancy. We found that maternal enrichment significantly affects the locomotor activity and time spent in the center of the open-field in female, but not male, offspring. These results indicate that maternal enrichment influences prenatal brain development and postnatal behaviors in female offspring.

  18. The Exchange Relationship between Work-Family Enrichment and Affective Commitment: the Moderating Role of Gender. (United States)

    Marques, António Manuel; Chambel, Maria José; Pinto, Inês


    Workers' perception that their job experience enriches their family life has been considered a mechanism that explains their positive attitudes toward the organization where they work. However, because women and men live their work and family differently, gender may condition this relationship between the work-family enrichment and workers' attitudes. With a sample of 1885 workers from one Portuguese bank, with 802 women, the current study investigated the relationship between work-family enrichment and organizational affective commitment as well as the role of sex as a moderator of this relationship. The hypotheses were tested by using regression analysis. The results indicated that the perception held by workers that their work enriches their family is positively correlated with their affective commitment toward the organization. Furthermore, the data revealed that this relationship is stronger for women than for men. Study results have implications for management, particularly for human resource management, enhancing their knowledge about the relationship of work-family enrichment and workers' affective commitment toward organization.

  19. Nutrient enrichment differentially affects body sizes of primary consumers and predators in a detritus-based stream (United States)

    John M. Davis; Amy D. Rosemond; Sue L. Eggert; Wyatt F. Cross; J. Bruce. Wallace


    We assessed how a 5-yr nutrient enrichment affected the responses of different size classes of primary consumers and predators in a detritus-based headwater stream. We hypothesized that alterations in detritus availability because of enrichment would decrease the abundance and biomass of large-bodied consumers. In contrast, we found that 2 yr of enrichment increased...

  20. Work-family enrichment and job performance: a constructive replication of affective events theory. (United States)

    Carlson, Dawn; Kacmar, K Michele; Zivnuska, Suzanne; Ferguson, Merideth; Whitten, Dwayne


    Based on affective events theory (AET), we hypothesize a four-step model of the mediating mechanisms of positive mood and job satisfaction in the relationship between work-family enrichment and job performance. We test this model for both directions of enrichment (work-to-family and family-to-work). We used two samples to test the model using structural equation modeling. Results from Study 1, which included 240 full-time employees, were replicated in Study 2, which included 189 matched subordinate-supervisor dyads. For the work-to-family direction, results from both samples support our conceptual model and indicate mediation of the enrichment-performance relationship for the work-to-family direction of enrichment. For the family-to-work direction, results from the first sample support our conceptual model but results from the second sample do not. Our findings help elucidate mixed findings in the enrichment and job performance literatures and contribute to an understanding of the mechanisms linking these concepts. We conclude with a discussion of the practical and theoretical implications of our findings.

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

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    Shoaleh Shami


    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.

  2. Does trait affectivity predict work-to-family conflict and enrichment beyond job characteristics? (United States)

    Tement, Sara; Korunka, Christian


    The present study examines whether negative and positive affectivity (NA and PA, respectively) predict different forms of work-to-family conflict (WFC-time, WFC-strain, WFC-behavior) and enrichment (WFE-development, WFE-affect, WFE-capital) beyond job characteristics (workload, autonomy, variety, workplace support). Furthermore, interactions between job characteristics and trait affectivity while predicting WFC and WFE were examined. Using a large sample of Slovenian employees (N = 738), NA and PA were found to explain variance in WFC as well as in WFE above and beyond job characteristics. More precisely, NA significantly predicted WFC, whereas PA significantly predicted WFE. In addition, several interactive effects were found to predict forms of WFC and WFE. These results highlight the importance of trait affectivity in work-family research. They provide further support for the crucial impact of job characteristics as well.

  3. Enriched but not depleted uranium affects central nervous system in long-term exposed rat. (United States)

    Houpert, Pascale; Lestaevel, Philippe; Bussy, Cyrill; Paquet, François; Gourmelon, Patrick


    Uranium is well known to induce chemical toxicity in kidneys, but several other target organs, such as central nervous system, could be also affected. Thus in the present study, the effects on sleep-wake cycle and behavior were studied after chronic oral exposure to enriched or depleted uranium. Rats exposed to 4% enriched uranium for 1.5 months through drinking water, accumulated twice as much uranium in some key areas such as the hippocampus, hypothalamus and adrenals than did control rats. This accumulation was correlated with an increase of about 38% of the amount of paradoxical sleep, a reduction of their spatial working memory capacities and an increase in their anxiety. Exposure to depleted uranium for 1.5 months did not induce these effects, suggesting that the radiological activity induces the primary events of these effects of uranium.

  4. Opioid system and human emotions. (United States)

    Nummenmaa, Lauri; Tuominen, Lauri


    Emotions are states of vigilant readiness that guide human and animal behaviour during survival-salient situations. Categorical models of emotions posit neurally and physiologically distinct basic human emotions (anger, fear, disgust, happiness, sadness and surprise) that govern different survival functions. Opioid receptors are expressed abundantly in the mammalian emotion circuit, and the opioid system modulates a variety of functions related to arousal and motivation. Yet, its specific contribution to different basic emotions has remained poorly understood. Here, we review how the endogenous opioid system and particularly the μ receptor contribute to emotional processing in humans. Activation of the endogenous opioid system is consistently associated with both pleasant and unpleasant emotions. In general, exogenous opioid agonists facilitate approach-oriented emotions (anger, pleasure) and inhibit avoidance-oriented emotions (fear, sadness). Opioids also modulate social bonding and affiliative behaviour, and prolonged opioid abuse may render both social bonding and emotion recognition circuits dysfunctional. However, there is no clear evidence that the opioid system is able to affect the emotions associated with surprise and disgust. Taken together, the opioid systems contribute to a wide array of positive and negative emotions through their general ability to modulate the approach versus avoidance motivation associated with specific emotions. Because of the protective effects of opioid system-mediated prosociality and positive mood, the opioid system may constitute an important factor contributing to psychological and psychosomatic resilience. © 2017 The British Pharmacological Society.

  5. Factors Affecting Drug Use During Incarceration: A Cross-Sectional Study of Opioid-Dependent Persons from India. (United States)

    Rao, Ravindra; Mandal, Piyali; Gupta, Rishab; Ramshankar, Prashanth; Mishra, Ashwani; Ambekar, Atul; Jhanjee, Sonali; Dhawan, Anju


    Substance abuse and criminality share a complex relationship. The rates of substance use among the prisoners, and that of criminal acts among substance users in community setting are high. Data from South Asian countries, including from India are inadequate. This study aimed to assess the pattern of criminal acts among opioid-dependent subjects and their substance use pattern in the month before, during and after imprisonment. Using a cross-sectional study design and purposive sampling, opioid-dependent subjects (n=101) attending two community drug treatment clinics who have had any contact with the law were assessed using a specifically-designed tool to record criminal acts and substance use before, during and after last imprisonment. Most subjects (93%) had committed illegal acts in their lifetime. Physical assault was the most common illegal act, while 23% reported selling drugs and 9% reported committing serious crimes. About 95% were arrested and 92% had spent time in police lockups. About 29% were arrested for drugs possession or drug use, and 3% of injecting drug users arrested for carrying injection equipment. About 85% had been imprisoned at least once, of whom 88% used psychoactive substances in the 1-month period before their last imprisonment. Opioids were the most common substances used daily (68%), followed by cannabis (34%) and alcohol (22%). Ninety-seven percent reported the availability of substances in prisons, and 65% also used substances during their last imprisonment. Cannabis (35%) was the most common substances used in prison followed by opioids (19%). Seventy-six percent used substances soon after prison release, and 13% of opioid users experienced opioid overdose soon after prison release. Use of cannabis, injecting drugs, and opioid use before imprisonment were predictors of substance use in prison. Opioid-dependent people have various contacts with the law, including imprisonment. Many users are dependent on substances during prison

  6. Timing of Environmental Enrichment Affects Memory in the House Cricket, Acheta domesticus.

    Directory of Open Access Journals (Sweden)

    Heather S Mallory

    Full Text Available Learning appears to be ubiquitous among animals, as it plays a key role in many behaviors including foraging and reproduction. Although there is some genetic basis for differences in learning ability and memory retention, environment also plays an important role, as it does for any other trait. For example, adult animals maintained in enriched housing conditions learn faster and remember tasks for longer than animals maintained in impoverished conditions. Such plasticity in adult learning ability has often been linked to plasticity in the brain, and studies aimed at understanding the mechanisms, stimuli, and consequences of adult behavioral and brain plasticity are numerous. However, the role of experiences during post-embryonic development in shaping plasticity in adult learning ability and memory retention remain relatively unexplored. Using the house cricket (Acheta domesticus as a model organism, we developed a protocol to allow the odor preference of a large number of crickets to be tested in a short period of time. We then used this new protocol to examine how enrichment or impoverishment at two developmental stages (either the last nymphal instar or young adult affected adult memory. Our results show that regardless of nymphal rearing conditions, crickets that experienced an enriched rearing condition as young adults performed better on a memory task than individuals that experienced an impoverished condition. Older adult crickets (more than 1 week post adult molt did not demonstrate differences in memory of the odor task, regardless of rearing condition as a young adult. Our results suggest that environmentally-induced plasticity in memory may be restricted to the young adult stage.

  7. Enrichment, risk assessment, and statistical apportionment of heavy metals in tannery-affected areas

    International Nuclear Information System (INIS)

    Ali, Z.; Malik, R. N.; Shinwari, Z. K.; Qadir, A.


    Tannery-affected surface soils from 72 sampling sites from industrial area of Sialkot district, Pakistan, were collected and analyzed for nine physicochemical parameters, nine heavy metals, and four macro-nutrients. Most of the soils were poor in organic matter (0.11–2.98 %), basic in nature with p H (7.1–10.6) and electrical conductivity (1.2–17.9 mS/ cm). Mean concentration of total dissolved solids, Cl 1 -, alkalinity, NO 1 -N, salinity, and PO 4 3- was 3,093 mg/L, 6,587, 3,929, 301.3, 10.3, and 1.7 mg/kg. The results showed that concentration of macro-nutrients was in the order: Na[Mg[K[Ca whereas heavy metals followed the order: Cr>Fe>Ni>Mn>Cu>Zn>Co>Pb>Cd. Factor analysis based on principal component analysis, cluster analysis, and correlation analysis identified contribution of metals from tannery effluents, agrochemicals, automobiles exhaust, and natural weathering processes. Tannery-affected soils were enriched with Cd followed by Cr, Pb, Ni, Cu, Co, Zn, and Mn. Geo-accumulation index classified the soil samples in unpolluted tomoderately polluted categories. Metal pollution index provided better estimation of heavy metal pollution as compared to pollution load index. Ecological risk index showed high potential ecological risk associated with Cd and Cr with mean concentrations above respective average shale/ background values. The results are useful for heavy metals source identification, enrichment, risk assessment, and management of tannery-affected soils and can contribute to monitoring programs at regional levels.

  8. Enrichment with Wood Blocks Does Not Affect Toxicity Assessment in an Exploratory Toxicology Model Using Sprague–Dawley Rats (United States)

    Ditewig, Amy C; Bratcher, Natalie A; Davila, Donna R; Dayton, Brian D; Ebert, Paige; Lesuisse, Philippe; Liguori, Michael J; Wetter, Jill M; Yang, Hyuna; Buck, Wayne R


    Environmental enrichment in rodents may improve animal well-being but can affect neurologic development, immune system function, and aging. We tested the hypothesis that wood block enrichment affects the interpretation of traditional and transcriptomic endpoints in an exploratory toxicology testing model using a well-characterized reference compound, cyclophosphamide. ANOVA was performed to distinguish effects of wood block enrichment separate from effects of 40 mg/kg cyclophosphamide treatment. Biologically relevant and statistically significant effects of wood block enrichment occurred only for body weight gain. ANOVA demonstrated the expected effects of cyclophosphamide on food consumption, spleen weight, and hematology. According to transcriptomic endpoints, cyclophosphamide induced fewer changes in gene expression in liver than in spleen. Splenic transcriptomic pathways affected by cyclophosphamide included: iron hemostasis; vascular tissue angiotensin system; hepatic stellate cell activation and fibrosis; complement activation; TGFβ-induced hypertrophy and fibrosis; monocytes, macrophages, and atherosclerosis; and platelet activation. Changes in these pathways due to cyclophosphamide treatment were consistent with bone marrow toxicity regardless of enrichment. In a second study, neither enrichment nor type of cage flooring altered body weight or food consumption over a 28-d period after the first week. In conclusion, wood block enrichment did not interfere with a typical exploratory toxicology study; the effects of ingested wood on drug level kinetics may require further consideration. PMID:24827566

  9. Stability of flavoured phytosterol-enriched drinking yogurts during storage as affected by different packaging materials. (United States)

    Semeniuc, Cristina Anamaria; Cardenia, Vladimiro; Mandrioli, Mara; Muste, Sevastiţa; Borsari, Andrea; Rodriguez-Estrada, Maria Teresa


    The aim of this study was to investigate the influence of different packaging materials on storage stability of flavoured phytosterol-enriched drinking yogurts. White vanilla (WV) and blood orange (BO) phytosterol-enriched drinking yogurts conditioned in mono-layer and triple-layer co-extruded plastic bottles were stored at +6 ± 1 °C for 35 days (under alternating 12 h light and 12 h darkness) to simulate shelf-life conditions. Samples were collected at three different storage times and subjected to determination of total sterol content (TSC), peroxide value (PV) and thiobarbituric acid reactive substances (TBARs). TSC was not significantly affected by packaging material or storage time and met the quantity declared on the label. PV was significantly influenced by yogurt type × packaging material × storage time interaction and TBARs by packaging material × storage time interaction. Between the two packaging materials, the triple-layer plastic mini bottle with black coloured and completely opaque intermediate layer offered the best protection against lipid oxidation. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  10. Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism. (United States)

    Ostertag, Luisa M; Philo, Mark; Colquhoun, Ian J; Tapp, Henri S; Saha, Shikha; Duthie, Garry G; Kemsley, E Kate; de Roos, Baukje; Kroon, Paul A; Le Gall, Gwénaëlle


    Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. 1 H NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

  11. Prescription Opioids (United States)

    ... therapy in a primary care setting struggles with opioid addiction. 4,5,6 Once addicted, it can be ... of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction 2009;104(9):1541-8. Dunn KM, Saunders ...

  12. Exterior egg quality as affected by enrichment resources layout in furnished laying-hen cages. (United States)

    Li, Xiang; Chen, Donghua; Meng, Fanyu; Su, Yingying; Wang, Lisha; Zhang, Runxiang; Li, Jianhong; Bao, Jun


    This study aimed to investigate the effects of enrichment resources (a perch, dustbath, and nest) layout in furnished laying-hen cages (FC) on exterior quality of eggs. One hundred and sixty-eight (168) Hy-Line Brown laying hens at 16 weeks of age were randomly distributed to four treatments: small furnished cages (SFC), medium furnished cages type I (MFC-I), medium furnished cages type II (MFC-II), and medium furnished cages type III (MFC-III). Each treatment had 4 replicates or cages with 6 hens for SFC (24 birds for each SFC) and 12 hen/cage for MFC-I, -II, and -III (48 birds for each MFC-I, -II and -III). Following a 2-week acclimation, data collection started at 18 weeks of age and continued till 52 weeks of age. Dirtiness of egg surface or cracked shell as indicators of the exterior egg quality were recorded each week. The results showed that the proportion of cracked or dirty eggs was significantly affected by the FC type (p<0.01) in that the highest proportion of cracked or dirty eggs was found in MFC-I and the lowest proportion of dirty eggs in SFC. The results of this showed that furnished cage types affected both dirty eggs and cracked eggs (p<0.01). The results also indicated that not nest but dustbath lead to more dirty eggs. Only MFC-I had higher dirty eggs at nest than other FC (p< 0.01). The results of dirty eggs in MFC-I and MFC-II compared with SFC and MFC-III seemed suggest that a low position of dustbath led to more dirty eggs. SFC design affected exterior egg quality and the low position of dustbath in FC resulted in higher proportion of dirty eggs.

  13. A Three-wave Study of Antecedents of Work-Family Enrichment: The Roles of Social Resources and Affect. (United States)

    Siu, Oi Ling; Bakker, Arnold B; Brough, Paula; Lu, Chang-Qin; Wang, Haijiang; Kalliath, Thomas; O'Driscoll, Michael; Lu, Jiafang; Timms, Carolyn


    On the basis of conservation of resources theory (Hobfoll, ) and the resource-gain-development perspective (Wayne, Grzywacz, Carlson, & Kacmar, ), this paper examines the differential impact of specific social resources (supervisory support and family support) on specific types of affect (job satisfaction and family satisfaction, respectively), which, in turn, influence work-to-family enrichment and family-to-work enrichment, respectively. A sample of 276 Chinese workers completed questionnaires in a three-wave survey. The model was tested with structural equation modelling. Job satisfaction at time 2 partially mediated the relationship between time 1 supervisory support and time 3 work-to-family enrichment (capital), and the effect of supervisory support on work-to-family enrichment (affect) was fully mediated by job satisfaction. Family satisfaction at time 2 fully mediated the relationship between time 1 family support and time 3 family-to-work enrichment (affect, efficiency). Implications for theory, practice and future research are discussed. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Opioid Addiction (United States)

    ... breathing rate nausea, vomiting constipation physical agitation poor decision making abandoning responsibilities slurred speech sleeping more or less than normal mood swings euphoria (feeling high) irritability depression lowered motivation anxiety attacks. Symptoms of opioid overdose An overdose ...

  15. Opioid Overdose (United States)

    ... Updated: 03/10/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

  16. Does an onion-enriched diet beneficially affect the microbiotal composition in healthy human subjects?

    DEFF Research Database (Denmark)

    Bergström, Anders; Borg, Birgitte; Marin, Eduvigis Roldán

    enriched diet and one non-enriched supplemented diet in a double-blinded crossover design with a 25 days wash-out period in between. Six of the subjects delivered fecal samples on the last two days before starting on the diet and on the two last days of the 14 day diet. Total DNA was isolated from...

  17. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P


    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  18. NH4+ enrichment and UV radiation interact to affect the photosynthesis and nitrogen uptake of Gracilaria lemaneiformis (Rhodophyta)

    International Nuclear Information System (INIS)

    Xu Zhiguang; Gao Kunshan


    Highlights: ► Inhibition induced by UVR is alleviated with the enrichment of ammonia. ► Phycoerythrin plays a key protective role against UVR at higher level of ammonia. ► Effect of UVR on the uptakes of nitrate and ammonia is different. - Abstract: Solar ultraviolet radiation (UVR, 280–400 nm) is known to inhibit the photosynthesis of macroalgae, whereas nitrogen availability may alter the sensitivity of the algae to UVR. Here, we show that UV-B (280–315 nm) significantly reduced the net photosynthetic rate of Gracilaria lemaneiformis. This inhibition was alleviated by enrichment with ammonia, which also caused a decrease in dark respiration. The presence of both UV-A (315–400 nm) and UV-B stimulated the accumulation of UV-absorbing compounds. However, this stimulation was not affected by enrichment with ammonia. The content of phycoerythrin (PE) was increased by the enrichment of ammonia only in the absence of UVR. Ammonia uptake and the activity of nitrate reductase were repressed by UVR. However, exposure to UVR had an insignificant effect on the rate of nitrate uptake. In conclusion, increased PE content associated with ammonia enrichment played a protective role against UVR in this alga, and UVR differentially affected the uptake of nitrate and ammonia.

  19. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret (United States)

    Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.


    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

  20. Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

    Directory of Open Access Journals (Sweden)

    Carla Marchetti


    Full Text Available Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L., is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca2+ and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca2+ dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca2+ concentration (Ca2+i. Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca2+ channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca2+ channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca2+ channels and thereby dysregulating intracellular Ca2+ dynamics.

  1. How enrichment affects exploration trade-offs in rats: implications for welfare and well-being.

    Directory of Open Access Journals (Sweden)

    Becca Franks

    Full Text Available We propose that a comparative approach to well-being could be the key to understanding 'the good life.' Inspired by current theories of human well-being and animal welfare, we designed a novel test of exploration behavior. Environmentally and socially enriched Long-Evans female rats (N = 60 were trained in four simultaneously presented arms of an eight-arm radial-maze. They learned to expect successes in two arms and failures in the other two. After training, 20 animals remained in enriched housing (enrichment-maintenance while 40 animals were re-housed in standard, isolated conditions (enrichment-removal. Two weeks later, all animals were re-tested in the maze, initially with access to the four familiar arms only. In the final minute, they also had access to the unfamiliar ambiguous-arms. Though both groups showed significant interest in the ambiguous-arms (P.3. Thus, we show not only that rats will abandon known rewards and incur risk in order to explore, indicating that exploration is valuable in its own right, but also that individuals with (vs. without enriched housing conditions are more likely to engage in such exploratory behavior. This novel test contributes to the body of knowledge examining the importance of exploration in humans and other animals; implications for animal welfare and human well-being are discussed.

  2. NH4+ enrichment and UV radiation interact to affect the photosynthesis and nitrogen uptake of Gracilaria lemaneiformis (Rhodophyta). (United States)

    Xu, Zhiguang; Gao, Kunshan


    Solar ultraviolet radiation (UVR, 280-400 nm) is known to inhibit the photosynthesis of macroalgae, whereas nitrogen availability may alter the sensitivity of the algae to UVR. Here, we show that UV-B (280-315 nm) significantly reduced the net photosynthetic rate of Gracilaria lemaneiformis. This inhibition was alleviated by enrichment with ammonia, which also caused a decrease in dark respiration. The presence of both UV-A (315-400 nm) and UV-B stimulated the accumulation of UV-absorbing compounds. However, this stimulation was not affected by enrichment with ammonia. The content of phycoerythrin (PE) was increased by the enrichment of ammonia only in the absence of UVR. Ammonia uptake and the activity of nitrate reductase were repressed by UVR. However, exposure to UVR had an insignificant effect on the rate of nitrate uptake. In conclusion, increased PE content associated with ammonia enrichment played a protective role against UVR in this alga, and UVR differentially affected the uptake of nitrate and ammonia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Nitrogen enrichment in runoff sediments as affected by soil texture in Beijing mountain area. (United States)

    Yang, Yang; Ye, Zhihan; Liu, Baoyuan; Zeng, Xianqin; Fu, Suhua; Lu, Bingjun


    Enrichment ratio (ER) is widely used in nonpoint source pollution models to estimate the nutrient loss associated with soil erosion. The objective of this study was to determine the ER of total nitrogen (ERN) in the sediments eroded from the typical soils with varying soil textures in Beijing mountain area. Each of the four soils was packed into a 40 by 30 by 15 cm soil pan and received 40-min simulated rainfalls at the intensity of 90 mm h(-1) on five slopes. ERN for most sediments were above unity, indicating the common occurrence of nitrogen enrichment accompanied with soil erosion in Beijing mountain area. Soil texture was not the only factor that influenced N enrichment in this experiment since the ERN for the two fine-textured soils were not always lower. Soil properties such as soil structure might exert a more important influence in some circumstances. The selective erosion of clay particles was the main reason for N enrichment, as implied by the significant positive correlation between the ER of total nitrogen and clay fraction in eroded sediments. Significant regression equations between ERN and sediment yield were obtained for two pairs of soils, which were artificially categorized by soil texture. The one for fine-textured soils had greater intercept and more negative slope. Thus, the initially higher ERN would be lower than that for the other two soils with coarser texture once the sediment yield exceeded 629 kg ha(-1).

  4. CO2 enrichment affects eco-physiological growth of maize and alfalfa under different water stress regimes in the UAE. (United States)

    Ksiksi, Taoufik Saleh; Ppoyil, Shaijal Babu Thru; Palakkott, Abdul Rasheed


    Water stress has been reported to alter morphology and physiology of plants affecting chlorophyll content, stomatal size and density. In this study, drought stress mitigating effects of CO 2 enrichment was assessed in greenhouse conditions in the hot climate of UAE. Commercially purchased maize ( Zea mays L.) and alfalfa ( Medicago sativa L.) were seeded in three different custom-built cage structures, inside a greenhouse. One cage was kept at 1000 ppm CO 2 , the second at 700 ppm CO 2 , and the third at ambient greenhouse CO 2 environment (i.e. 435 ppm). Three water stress treatments HWS (200 ml per week), MWS (400 ml per week), and CWS (600 ml per week) were given to each cage so that five maize pots and five alfalfa pots in each cage received same water stress treatments. In maize, total chlorophyll content was similar or higher in water stress treatments compared to control for all CO 2 concentrations. Stomatal lengths were higher in enriched CO 2 environments under water stress. At 700 ppm CO 2 , stomatal widths decreased as water stress increased from MWS to HWS. At both enriched CO 2 environments, stomatal densities decreased compared to ambient CO 2 environment. In alfalfa, there was no significant increase in total chlorophyll content under enriched CO 2 environments, even though a slight increase was noticed.

  5. Selection based on indirect genetic effects for growth, environmental enrichment and coping style affect the immune status of pigs. (United States)

    Reimert, Inonge; Rodenburg, T Bas; Ursinus, Winanda W; Kemp, Bas; Bolhuis, J Elizabeth


    Pigs living in intensive husbandry systems may experience both acute and chronic stress through standard management procedures and limitations in their physical and social environment, which may have implications for their immune status. Here, the effect of a new breeding method where pigs were selected on their heritable influence on their pen mates' growth, and environmental enrichment on the immune status of pigs was investigated. Hereto, 240 pigs with a relatively positive genetic effect on the growth of their pen mates (+SBV) and 240 pigs with a relatively negative genetic effect on the growth of their pen mates (-SBV) were housed in barren or straw-enriched pens from 4 to 23 weeks of age (n  =  80 pens in total). A blood sample was taken from the pigs before, three days after a 24 h regrouping test, and at week 22. In addition, effects of coping style, as assessed in a backtest, and gender were also investigated. Mainly, +SBV were found to have lower leukocyte, lymphocyte and haptoglobin concentrations than -SBV pigs. Enriched housed pigs had a lower neutrophil to lymphocyte (N:L) ratio and lower haptoglobin concentrations, but had higher antibody titers specific for Keyhole Limpet Hemocyanin (KLH) than barren housed pigs. No interactions were found between SBV class and housing. Furthermore, pigs with a proactive coping style had higher alternative complement activity and, in the enriched pens, higher antibody titers specific for KLH than pigs with a reactive coping style. Lastly, females tended to have lower leukocyte, but higher haptoglobin concentrations than castrated males. Overall, these results suggest that +SBV pigs and enriched housed pigs were less affected by stress than -SBV and barren housed pigs, respectively. Moreover, immune activation might be differently organized in individuals with different coping styles and to a lesser extent in individuals of opposite genders.

  6. Selection based on indirect genetic effects for growth, environmental enrichment and coping style affect the immune status of pigs.

    Directory of Open Access Journals (Sweden)

    Inonge Reimert

    Full Text Available Pigs living in intensive husbandry systems may experience both acute and chronic stress through standard management procedures and limitations in their physical and social environment, which may have implications for their immune status. Here, the effect of a new breeding method where pigs were selected on their heritable influence on their pen mates' growth, and environmental enrichment on the immune status of pigs was investigated. Hereto, 240 pigs with a relatively positive genetic effect on the growth of their pen mates (+SBV and 240 pigs with a relatively negative genetic effect on the growth of their pen mates (-SBV were housed in barren or straw-enriched pens from 4 to 23 weeks of age (n  =  80 pens in total. A blood sample was taken from the pigs before, three days after a 24 h regrouping test, and at week 22. In addition, effects of coping style, as assessed in a backtest, and gender were also investigated. Mainly, +SBV were found to have lower leukocyte, lymphocyte and haptoglobin concentrations than -SBV pigs. Enriched housed pigs had a lower neutrophil to lymphocyte (N:L ratio and lower haptoglobin concentrations, but had higher antibody titers specific for Keyhole Limpet Hemocyanin (KLH than barren housed pigs. No interactions were found between SBV class and housing. Furthermore, pigs with a proactive coping style had higher alternative complement activity and, in the enriched pens, higher antibody titers specific for KLH than pigs with a reactive coping style. Lastly, females tended to have lower leukocyte, but higher haptoglobin concentrations than castrated males. Overall, these results suggest that +SBV pigs and enriched housed pigs were less affected by stress than -SBV and barren housed pigs, respectively. Moreover, immune activation might be differently organized in individuals with different coping styles and to a lesser extent in individuals of opposite genders.

  7. Emulsifier type, metal chelation and pH affect oxidative stability of n-3-enriched emulsions

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Jacobsen, Charlotte


    -enriched oil-in-water emulsion. The selected food emulsifiers were Tween 80, Citrem, sodium caseinate and lecithin. Lipid oxidation was evaluated by determination of peroxide values and secondary volatile oxidation products. Moreover, the zeta potential and the droplet sizes were determined. Twen resulted...... in the least oxidatively stable emulsions, followed by Citrem. When iron was present, caseinate-stabilized emulsions oxidized slower than lecithin emulsions at pH 3, whereas the opposite was the case at pH 7. Oxidation generally progressed faster at pH 3 than at pH 7, irrespective of the addition of iron. EDTA...

  8. Defensive behaviors and prosencephalic neurogenesis in pigeons (Columba livia) are affected by environmental enrichment in adulthood. (United States)

    Melleu, F F; Pinheiro, M V; Lino-de-Oliveira, C; Marino-Neto, J


    Neurogenesis in the adult brain appears to be phylogenetically conserved across the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons are observed in several prosencephalic areas, suggesting that neurogenesis may participate in the control of different behaviors. The mechanisms controlling neurogenesis and its relevance to defensive behaviors in non-oscine birds remain elusive. Herein, the contribution of the environment to behavior and neurogenesis of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed in standard (SE) or enriched environment (EE) for 42 days, were exposed to an unfamiliar environment (UE) followed by presentation to a novel object (NO). Video recordings of UE+NO tests were analyzed and scored for latency, duration and frequency of angular head movements, peeping, grooming, immobility and locomotion. Twenty-four hours later, pigeons were submitted to the tonic immobility test (TI) and number of trials for TI and TI duration were scored, followed by euthanasia 2 h later. Brains were immunohistochemically processed to reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed in SE, the pigeons housed in EE responded to a NO with more immobility. In addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum than those housed in SE. There was no correlation between the number of DCX-ir cells and the scores of immobility in behavioral tests. Together, these data suggest that enrichment favored behavioral inhibition and neurogenesis in the adult pigeons through different, parallel mechanisms.

  9. Heat stability and acid gelation properties of calcium-enriched reconstituted skim milk affected by ultrasonication. (United States)

    Chandrapala, Jayani; Bui, Don; Kentish, Sandra; Ashokkumar, Muthupandian


    The aggregation of proteins after heating of calcium-fortified milks has been an ongoing problem in the dairy industry. This undesirable effect restricts the manufacture of calcium rich dairy products. To overcome this problem, a completely new approach in controlling the heat stability of dairy protein solutions, developed in our lab, has been employed. In this approach, high intensity, low frequency ultrasound is applied for a very short duration after a pre-heating step at ⩾70 °C. The ultrasound breaks apart whey/whey and whey/casein aggregates through the process of acoustic cavitation. Protein aggregates do not reform on subsequent post-heating, thereby making the systems heat stable. In this paper, the acid gelation properties of ultrasonicated calcium-enriched skim milks have also been investigated. It is shown that ultrasonication alone does not change the gelation properties significantly whereas a sequence of preheating (72 °C/1 min) followed by ultrasonication leads to decreased gelation times, decreased gel syneresis and increased skim milk viscosity in comparison to heating alone. Overall, ultrasonication has the potential to provide calcium-fortified dairy products with increased heat stability. However, enhanced gelation properties can only be achieved when ultrasonication is completed in conjunction with heating.

  10. Healthy Adult Male Facial Skin Surface Lipid Pheromone p.o. to Treat Opioid Addiction (United States)


    Opioid Addiction; Opioid Abuse, Continuous Use; Opioid Use; Opioid-Related Disorders; Paternal Pheromone Deficiency; Opioid Dependence; Opioid Abuse; Opioid-use Disorder; Opioid Intoxication; Opioid Abuse, Episodic

  11. Opioid adjuvant strategy: improving opioid effectiveness. (United States)

    Bihel, Frédéric


    Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

  12. Neonatal opioid withdrawal syndrome. (United States)

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


    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.

  13. The opioid overdose epidemic: opportunities for pharmacists

    Directory of Open Access Journals (Sweden)

    Wu LT


    Full Text Available Li-Tzy Wu,1–4 Udi E Ghitza,5 Anne L Burns,6 Paolo Mannelli,1 1Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University School of Medicine, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, 5Center for Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, 6American Pharmacists Association, Washington, DC, USA The USA is experiencing an opioid overdose epidemic. It has been driven largely by prescription opioids and intensified by a surge of illicit opioids (e.g., heroin and fentanyl.1,2 Drug-involved overdose, mainly opioids (e.g., prescription opioids and heroin, is a leading cause of accidental death in the USA. The opioid overdose epidemic has been escalating consistently for over a decade.2 Every day, an estimated 91 Americans die from opioid-related overdose.3 Opioid overdose appears to have disproportionally affected men, adults aged 25–64 years, and non-Hispanic whites.2

  14. Radioreceptor opioid assay

    International Nuclear Information System (INIS)

    Miller, R.J.; Chang, K.-J.


    A radioreceptor assay is described for assaying opioid drugs in biological fluids. The method enables the assay of total opioid activity, being specific for opioids as a class but lacking specificity within the class. A radio-iodinated opioid and the liquid test sample are incubated with an opiate receptor material. The percentage inhibition of the binding of the radio-iodinated compound to the opiate receptor is calculated and the opioid activity of the test liquid determined from a standard curve. Examples of preparing radio-iodinated opioids and assaying opioid activity are given. A test kit for the assay is described. Compared to other methods, this assay is cheap, easy and rapid. (U.K.)

  15. Genetics Home Reference: opioid addiction (United States)

    ... Facebook Twitter Home Health Conditions Opioid addiction Opioid addiction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Opioid addiction is a long-lasting (chronic) disease that can ...

  16. The gut-brain interaction in opioid tolerance. (United States)

    Akbarali, Hamid I; Dewey, William L


    The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Ascorbyl palmitate, gamma-tocopherol, and EDTA affect lipid oxidation in fish oil enriched salad dressing differently

    DEFF Research Database (Denmark)

    Let, M.B.; Jacobsen, Charlotte; Meyer, Anne S.


    The aim of the study was to investigate the ability of γ-tocopherol, ethylenediaminetetraacetate (EDTA), and ascorbyl palmitate to protect fish oil enriched salad dressing against oxidation during a 6 week storage period at room temperature. The lipid-soluble γ-tocopherol (220 and 880 µg g-1...


    Directory of Open Access Journals (Sweden)

    Shihab Kattukulathil


    Full Text Available BACKGROUND Opioid dependence is a major public health problem in Kerala. Presence of psychiatric disorder among opioid dependent patients worsens the scenario. To date no attempts have been made to analyse the magnitude and pattern of comorbid psychiatric disorders in the state. MATERIALS AND METHODS We assessed 30 patients with ICD-10 diagnosis of opioid dependence syndrome for the presence of comorbid psychiatric disorders using structured clinical interview for DSM IV Axis 1 disorder (SCID-1. Patients with opioid withdrawal state, delirium and acute medical emergencies were excluded. RESULTS 56.7% of our subjects had a comorbid psychiatric disorder. Major depressive disorder was the most common one (n=7, 23.3%. Prevalence of other disorders were generalised anxiety disorder (n=6, 20%, bipolar affective disorder (n=3, 10% and schizophrenia (n=1, 3.3%. CONCLUSION Comorbid Psychiatric disorders are highly prevalent in opioid dependence. There is a need for further large sample studies in the areas of comorbidities and in the integrated strategies for the identification and management of both opioid dependence and comorbid psychiatric disorders.

  19. Differences between opioids

    DEFF Research Database (Denmark)

    Drewes, Asbjørn; Jensen, Rasmus D.; Nielsen, Lecia M.


    to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences......Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids...

  20. Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.

  1. Does attachment insecurity affect the outcomes of a multidisciplinary pain management program? The association between attachment insecurity, pain, disability, distress, and the use of opioids

    DEFF Research Database (Denmark)

    Andersen, T. E.


    Cognitive and behavioural treatments have been shown to be effective for the management of chronic pain. However, not all patients succeed at such a treatment. Attachment insecurity has recently been proposed as an individual vulnerability factor that may have a negative impact on pain, disability...... would be associated with anxiety and depression. Moreover, we hypothesised that attachment avoidance would be positively associated with the use of opioids. Finally, we predicted that patients with an insecure attachment orientation would profit less from a routine pain management program. Data were...... collected from 72 patients referred consecutively from December 2008 to August 2009 to a 13-week pain management program at a Danish multidisciplinary pain centre. Both attachment dimensions were positively associated with anxiety and depression. Moreover, the insecurely attached patients used significantly...

  2. Is this ?complicated? opioid withdrawal?


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


    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.

  3. Medications Development for Opioid Abuse (United States)

    Negus, S. Stevens; Banks, Matthew L.


    Here we describe methods for preclinical evaluation of candidate medications to treat opioid abuse and dependence. Our perspective is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effects, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) the states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and the effects of candidate medications. Effects of opioid medications on opioid choice in nondependent and opioid-dependent subjects are reviewed. Various nonopioid medications have also been examined, but none yet have been identified that safely and reliably reduce opioid choice. Future research will focus on (1) strategies for increasing safety and/or effectiveness of opioid medications, and (2) continued development of nonopioids such as inhibitors of endocannabinoid catabolic enzymes or inhibitors of opioid-induced glial activation. PMID:23125072

  4. Hiperalgesia Inducida por Opioides


    Jiménez Salazar, Andrés


    Los opioides producen analgesia a través de un efecto inhibitorio sobre el sistema nociceptivo principalmente. Hasta la fecha, los opioides siguen siendo los analgésicos más potentes para el manejo de dolor moderado a severo. La Asociación Internacional del Estudio del Dolor (IASP, en inglés) define hiperalgesia como "un aumento de la respuesta a un estímulo que normalmente es doloroso". En contraste, está bien establecido que la terapia crónica con opioides se asocia con el desarrollo de ...

  5. Managing Opioid Addiction Risk in Plastic Surgery during the Perioperative Period. (United States)

    Demsey, Daniel; Carr, Nicholas J; Clarke, Hance; Vipler, Sharon


    Opioid addiction is a public health crisis that affects all areas of medicine. Large numbers of the population across all racial and economic demographics misuse prescription opioids and use illicit opioids. The current understanding is that opioid misuse is a disease that requires treatment, and is not an issue of choice or character. Use of opioid medication is a necessary part of postoperative analgesia, but many physicians are unsure of how to do this safely given the risk of patients developing an opioid misuse disorder. This review gives an update of the current state of the opioid crisis, explains how current surgeons' prescribing practices are contributing to it, and gives recommendations on how to use opioid medication safely in the perioperative period.

  6. Benzodiazepines and Opioid (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  7. Opioid Summaries by State (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  8. Opioid Overdose Crisis (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  9. Opioid Prescribing PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the July 2017 CDC Vital Signs report. Higher opioid prescribing puts patients at risk for addiction and overdose. Learn what can be done about this serious problem.

  10. The opioid receptors of the rat periaqueductal gray

    Energy Technology Data Exchange (ETDEWEB)

    Fedynyshyn, J.P.


    The opioid binding characteristics of the rat (PAG) and the signal transduction mechanisms of the opioid receptors were examined with in vitro radioligand binding, GTPase, adenylyl cyclase, and inositol phosphate assays. The nonselective ligand {sup 3}H-ethylketocyclazocine (EKC), the {mu} and {delta} selective ligand {sup 3}H-(D-Ala{sup 2}, D-Leu{sup 5}) enkephalin (DADLE), the {mu} selective ligand {sup 3}H-(D-Ala{sup 2}, N-methyl Phe{sup 4}, Glyol{sup 5}) enkephalin (DAGO), and the {delta} selective ligand {sup 3}H-(D-Pen{sup 2}, D-Pen{sup 5}) enkephalin (DPDPE) were separately used as tracer ligands to label opioid binding sites in rat PAG enriched P{sub 2} membrane in competition with unlabeled DADLE, DAGO, DPDPE, or the {kappa} selective ligand trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzeneacetamide, methane sulfonate, hydrate (U50, 488H). Only {mu} selective high affinity opioid binding was observed. No high affinity {delta} or {kappa} selective binding was detected. {sup 3}H-DAGO was used as a tracer ligand to label {mu} selective high affinity opioid binding sites in PAG enriched P{sub 2} membrane in competition with unlabeled {beta}-endorphin, dynorphin A (1-17), BAM-18, methionine enkephalin, dynorphin A (1-8), and leucine enkephalin. Of these endogenous opioid peptides only those with previously reported high affinity {mu} type opioid binding activity competed with {sup 3}H-DAGO for binding sites in rat PAG enriched P{sub 2} membrane with affinities similar to that of unlabeled DAGO.

  11. Root dynamics in an artificially constructed regenerating longleaf pine ecosystem are affected by atmospheric CO(2) enrichment. (United States)

    Pritchard, S G.; Davis, M A.; Mitchell, R J.; Prior, S A.; Boykin, D L.; Rogers, H H.; Runion, G B.


    Differential responses to elevated atmospheric CO(2) concentration exhibited by different plant functional types may alter competition for above- and belowground resources in a higher CO(2) world. Because C allocation to roots is often favored over C allocation to shoots in plants grown with CO(2) enrichment, belowground function of forest ecosystems may change significantly. We established an outdoor facility to examine the effects of elevated CO(2) on root dynamics in artificially constructed communities of five early successional forest species: (1) a C(3) evergreen conifer (longleaf pine, Pinus palustris Mill.); (2) a C(4) monocotyledonous bunch grass (wiregrass, Aristida stricta Michx.); (3) a C(3) broadleaf tree (sand post oak, Quercus margaretta); (4) a C(3) perennial herbaceous legume (rattlebox, Crotalaria rotundifolia Walt. ex Gemel); and (5) an herbaceous C(3) dicotyledonous perennial (butterfly weed, Asclepias tuberosa L.). These species are common associates in early successional longleaf pine savannahs throughout the southeastern USA and represent species that differ in life-form, growth habit, physiology, and symbiotic relationships. A combination of minirhizotrons and soil coring was used to examine temporal and spatial rooting dynamics from October 1998 to October 1999. CO(2)-enriched plots exhibited 35% higher standing root crop length, 37% greater root length production per day, and 47% greater root length mortality per day. These variables, however, were enhanced by CO(2) enrichment only at the 10-30 cm depth. Relative root turnover (flux/standing crop) was unchanged by elevated CO(2). Sixteen months after planting, root biomass of pine was 62% higher in elevated compared to ambient CO(2) plots. Conversely, the combined biomass of rattlebox, wiregrass, and butterfly weed was 28% greater in ambient compared to high CO(2) plots. There was no difference in root biomass of oaks after 16 months of exposure to elevated CO(2). Using root and shoot

  12. Psychiatric disorders in opioid dependants. (United States)

    Ahmadi, Jamshid; Toobaee, Shahin; Kharras, Mohammad; Radmehr, Mohammad


    Psychiatric disorders are common among substance dependants. The objectives of this study were to assess the rate of neurotic disorders among opioid addicts, and reassess the rate of those neurotic disorders two weeks after complete detoxification of the patients. Data were gathered from 500 (496 men and 4 women) opioid dependants, using DSM-IV criteria. The Middlesex Hospital Questionnaire (MHQ) was used to measure free-floating anxiety, depression, phobia, obsession, hysteria and somatization. Four hundred and ninety-six (99.2%) of the subjects were men of whom the majority (65.2%) were married, 26.4% single and the others were divorced or separated. Three hundred and thirty-four (66.8%) were in age range of 20 to 39 years. Of the subjects 154 (30.8) were self-employed, 116 (23.2%) were factory workers, 100 (20%) unemployed, 64 (12.8%) employees and 32 (6.4%) retailers. The majority, 322 (64.4%), reported elementary and high school as their level of education and only 20 (4%) were illiterate. The means for neurotic disorders (using the MHQ) before and two weeks after detoxification were 10.12 and 9.98 for anxiety, 7.54 and 7.41 for phobia, 10.10 and 9.76 for depression, 11.11 and 11.05 for obsession, 8.47 and 8.49 for hysteria and 9.82 and 9.46 for somatization, respectively. The mean difference was significant only for depression. Present findings indicated that the rate of neurotic disorders in opioid dependants is high and (except for depression) was not significantly different before detoxification and two weeks after detoxification. Opium was found to be the most prevalent form of opioid used. Also it can be concluded that during the last years some demographic characteristics of Iranian opioid addicts in this sample have changed. Cultural attitudes toward substance use quite likely affect the pattern of substance use. These findings can be considered when planning preventive and therapeutic programs.

  13. Analysis of the energy efficiency of short rotation woody crops biomass as affected by different methods of soil enrichment

    International Nuclear Information System (INIS)

    Stolarski, Mariusz J.; Krzyżaniak, Michał; Tworkowski, Józef; Szczukowski, Stefan; Niksa, Dariusz


    The aim of this study was to determine the energy input and energy efficiency of the production of willow, poplar and black locust chips in four-year harvest rotation. The highest energy input was made in poplar production when soil was enriched with lignin and by mineral fertilisation (33.02 GJ ha −1 ). For willow production it was 30.76 GJ ha −1 when lignin, mycorrhiza and mineral fertilisation were used. The energy input in the production of black locust was much lower. The largest energy gain was obtained in the production of poplar when soil was enriched with lignin and mineral fertilisation (673.7 GJ ha −1 ). A similar level of this parameter (669.7 GJ ha −1 ) was achieved in the production of willow when lignin, mycorrhiza and mineral fertilisation was used. In general, a higher energy gain was obtained in the production of willow and poplar than in the production of black locust. On the other hand, the best energy efficiency ratio was achieved for willow (28.9) in the option with lignin. The ratio for poplar production ranged from 19.7 to 25.9. On the other hand, the energy efficiency ratio for black locust ranged from 10.6 to 21.7. - Highlights: • The energy input ranged from 6.69 GJ ha −1 to 33.02 GJ ha −1 . • The largest energy gain was obtained for poplar (673.7 GJ ha −1 ). • The best energy efficiency ratio was achieved for willow (28.9). • The energy efficiency ratio for poplar ranged from 19.7 to 25.9. • The energy efficiency ratio for black locust ranged from 10.6 to 21.7.

  14. Uranium enrichment. Enrichment processes

    International Nuclear Information System (INIS)

    Alexandre, M.; Quaegebeur, J.P.


    Despite the remarkable progresses made in the diversity and the efficiency of the different uranium enrichment processes, only two industrial processes remain today which satisfy all of enriched uranium needs: the gaseous diffusion and the centrifugation. This article describes both processes and some others still at the demonstration or at the laboratory stage of development: 1 - general considerations; 2 - gaseous diffusion: physical principles, implementation, utilisation in the world; 3 - centrifugation: principles, elementary separation factor, flows inside a centrifuge, modeling of separation efficiencies, mechanical design, types of industrial centrifuges, realisation of cascades, main characteristics of the centrifugation process; 4 - aerodynamic processes: vortex process, nozzle process; 5 - chemical exchange separation processes: Japanese ASAHI process, French CHEMEX process; 6 - laser-based processes: SILVA process, SILMO process; 7 - electromagnetic and ionic processes: mass spectrometer and calutron, ion cyclotron resonance, rotating plasmas; 8 - thermal diffusion; 9 - conclusion. (J.S.)

  15. Are Prescription Opioids Driving the Opioid Crisis? Assumptions vs Facts. (United States)

    Rose, Mark Edmund


    Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.

  16. The influence of propoxyphene withdrawal on opioid use in veterans. (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


    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.

  17. The effects of blue-enriched light treatment compared to standard light treatment in seasonal affective disorder

    NARCIS (Netherlands)

    Gordijn, M. C. M.; 't Mannetje, D.; Meesters, Y.

    Background: One of the most frequently investigated hypotheses of the pathophysiology underlying Seasonal Affective Disorder (SAD) is a disturbance of circadian rhythms. Since the circadian system as well as other non-visual effects is especially sensitive to blue light, a new light therapy device

  18. Hypothalamic kappa opioid receptor mediates both diet- and MCH-induced liver damage through inflammation and ER stress

    NARCIS (Netherlands)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Romero-Picó, Amparo; Kalló, Imre; Chee, Melissa J; Porteiro, Begoña; Al-Massadi, Omar; Contreras, Cristina; Fernø, Johan; Senra, Ana; Gallego, Rosalia; Folgueira, Cintia; Seoane, Luisa M; van Gestel, Margriet; Adan, Roger A; Liposits, Zsolt; Dieguez, Carlos; Lopez, Miguel; Nogueiras, Ruben


    The opioid system is widely known to modulate the brain reward system and thus affect human and animal behaviour, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and

  19. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri


    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  20. Probiotic-enriched foods and dietary supplement containing SYNBIO positively affects bowel habits in healthy adults: an assessment using standard statistical analysis and Support Vector Machines. (United States)

    Silvi, Stefania; Verdenelli, M Cristina; Cecchini, Cinzia; Coman, M Magdalena; Bernabei, M Simonetta; Rosati, Jessica; De Leone, Renato; Orpianesi, Carla; Cresci, Alberto


    A randomised, double-blind, placebo-controlled, parallel group study assessed in healthy adults how daily consumption of the probiotic combination SYNBIO®, administered in probiotic-enriched foods or in a dietary supplement, affected bowel habits. Primary and secondary outcomes gave the overall assessment of bowel well-being, while a Psychological General Well-Being Index compiled by participants estimated the health-related quality of life as well as the gastrointestinal tolerance determined with the Gastrointestinal Symptom Rating Scale. Support Vector Machine models for classification problems were used to validate the total outcomes on bowel well-being. SYNBIO® consumption improved bowel habits of volunteers consuming the probiotic foods or capsules, while the same effects were not registered in the control groups. The recovery of probiotic bacteria from the faeces of a cohort of 100 subjects for each supplemented group showed the persistence of strains in the gastrointestinal tract.

  1. Opioid Prescribing PSA (:60)

    Centers for Disease Control (CDC) Podcasts


    This 60 second public service announcement is based on the July 2017 CDC Vital Signs report. Higher opioid prescribing puts patients at risk for addiction and overdose. Learn what can be done about this serious problem.  Created: 7/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/6/2017.

  2. Reading Touch Screen Storybooks with Mothers Negatively Affects 7-Year-Old Readers’ Comprehension but Enriches Emotional Engagement (United States)

    Ross, Kirsty M.; Pye, Rachel E.; Randell, Jordan


    Touch screen storybooks turn reading into an interactive multimedia experience, with hotspot-activated animations, sound effects, and games. Positive and negative effects of reading multimedia stories have been reported, but the underlying mechanisms which explain how children’s learning is affected remain uncertain. The present study examined the effect of storybook format (touch screen and print) on story comprehension, and considered how level of touch screen interactivity (high and low) and shared reading behaviors (cognitive and emotional scaffolding, emotional engagement) might contribute to comprehension. Seven-year-olds (n = 22) were observed reading one touch screen storybook and one print storybook with their mothers. Story comprehension was inferior for the touch screen storybooks compared to the print formats. Touch screen interactivity level had no significant effect on comprehension but did affect shared reading behaviors. The mother–child dyads spent less time talking about the story in the highly interactive touch screen condition, despite longer shared reading sessions because of touch screen interactions. Positive emotional engagement was greater for children and mothers in the highly interactive touch screen condition, due to additional positive emotions expressed during touch screen interactions. Negative emotional engagement was greater for children when reading and talking about the story in the highly interactive condition, and some mothers demonstrated negative emotional engagement with the touch screen activities. The less interactive touch screen storybook had little effect on shared reading behaviors, but mothers controlling behaviors were more frequent. Storybook format had no effect on the frequency of mothers’ cognitive scaffolding behaviors (comprehension questions, word help). Relationships between comprehension and shared reading behaviors were examined for each storybook, and although length of the shared reading session and

  3. Reading touch screen storybooks with mothers negatively affects seven-year-old readers’ comprehension but enriches emotional engagement

    Directory of Open Access Journals (Sweden)

    Kirsty Mhairi Ross


    Full Text Available Touch screen storybooks turn reading into an interactive multimedia experience, with hotspot-activated animations, sound effects, and games. Positive and negative effects of reading multimedia stories have been reported, but the underlying mechanisms which explain how children’s learning is affected remain uncertain. The present study examined the effect of storybook format (touch screen and print on story comprehension, and considered how level of touch screen interactivity (high and low and shared reading behaviors (cognitive and emotional scaffolding, emotional engagement might contribute to comprehension. Seven-year-olds (n = 22 were observed reading one touch screen storybook and one print storybook with their mothers. Story comprehension was inferior for the touch screen storybooks compared to the print versions. Touch screen interactivity had no significant effect on comprehension but did affect shared reading behaviors. The mother-child dyads spent less time talking about the story in the highly interactive touch screen condition, despite longer shared reading sessions because of touch screen interactions. Positive emotional engagement was greater for children and mothers in the highly interactive touch screen condition, due to additional positive emotions expressed during touch screen interactions. Negative emotional engagement was greater for children when reading and talking about the story in the highly interactive condition, and some mothers demonstrated negative emotional engagement with the touch screen activities. The less interactive touch screen storybook had little effect on shared reading behaviors, but mothers controlling behaviors were more frequent. Storybook format had no effect on the frequency of mothers’ cognitive scaffolding behaviors (comprehension questions, word help. Relationships between comprehension and shared reading behaviors were examined for each storybook, and length of the shared reading session and

  4. Opioid dependence - management in general practice. (United States)

    Frei, Matthew


    Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

  5. Opioid Abuse and Addiction - Multiple Languages (United States)

    ... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... español (Spanish) PDF Pain - Opioids, part 2 - English MP3 Pain - Opioids, part 2 - español (Spanish) MP3 Pain - ...

  6. Chimeric opioid peptides: tools for identifying opioid receptor types.


    Xie, G X; Miyajima, A; Yokota, T; Arai, K; Goldstein, A


    We synthesized several chimeric peptides in which the N-terminal nine residues of dynorphin-32, a peptide selective for the kappa opioid receptor, were replaced by opioid peptides selective for other opioid receptor types. Each chimeric peptide retained the high affinity and type selectivity characteristic of its N-terminal sequence. The common C-terminal two-thirds of the chimeric peptides served as an epitope recognized by the same monoclonal antibody. When bound to receptors on a cell surf...

  7. CDC Vital Signs: Opioid Painkiller Prescribing (United States)

    ... Mental Health Services Administration Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends Opioid Overdose Prevention ... Abuse Drugs, Brains, and Behavior: The Science of Addiction Opioid and Pain Management CMEs/CEs Prescription Drugs U.S. ...

  8. Changing patterns in opioid addiction (United States)

    Sproule, Beth; Brands, Bruna; Li, Selina; Catz-Biro, Laura


    ABSTRACT OBJECTIVE To evaluate the clinical observation that the number of individuals seeking opioid detoxification from oxycodone was increasing at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ont; and to identify the characteristics of individuals seeking opioid detoxification at CAMH. DESIGN Retrospective analysis of patient health records. SETTING Medical Withdrawal Management Service at CAMH. PARTICIPANTS All patients admitted for opioid detoxification between January 2000 and December 2004. MAIN OUTCOME MEASURES Number of opioid detoxification admissions each year; type, dose, and source of opioids; comorbid problems and symptoms. RESULTS There were 571 opioid detoxification admissions during the 5-year study period. The number of admissions increased steadily over the 5 years; in particular, the number of admissions related to controlled-release oxycodone increased substantially (3.8%, 8.3%, 20.8%, 30.6%, and 55.4% of the total opioid admissions in 2000 to 2004, respectively; χ42= 105.5, P < .001). The rates of admissions involving heroin remained low and stable. Use of controlled-release oxycodone was associated with considerably higher doses than use of other prescription opioids was. Physician prescriptions were the source of the prescription opioids for a large percentage of patients, particularly for older patients. Prescription opioid users reported considerable comorbid substance use problems, pain, and psychiatric symptoms. CONCLUSION This study has demonstrated a significant rise in the number of individuals seeking treatment at CAMH for controlled-release oxycodone addiction. The substantial comorbid pain, psychiatric symptoms, and other psychoactive substance use problems in these patients, coupled with the finding that prescriptions were an important source of opioids, highlight the clinical complexities encountered in the treatment of these individuals. Further research examining these complexities and the many possible

  9. Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms. (United States)

    Schindler, Abigail G; Li, Shuang; Chavkin, Charles


    Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

  10. Isotope enrichment

    International Nuclear Information System (INIS)

    Lydtin, H-J.; Wilden, R.J.; Severin, P.J.W.


    The isotope enrichment method described is based on the recognition that, owing to mass diffusion and thermal diffusion in the conversion of substances at a heated substrate while depositing an element or compound onto the substrate, enrichment of the element, or a compound of the element, with a lighter isotope will occur. The cycle is repeated for as many times as is necessary to obtain the degree of enrichment required

  11. Uranium enrichment

    International Nuclear Information System (INIS)


    This report looks at the following issues: How much Soviet uranium ore and enriched uranium are imported into the United States and what is the extent to which utilities flag swap to disguise these purchases? What are the U.S.S.R.'s enriched uranium trading practices? To what extent are utilities required to return used fuel to the Soviet Union as part of the enriched uranium sales agreement? Why have U.S. utilities ended their contracts to buy enrichment services from DOE?

  12. Mu Opioid Receptor Gene: New Point Mutations in Opioid Addicts

    Directory of Open Access Journals (Sweden)

    Amin Dinarvand


    Full Text Available Introduction: Association between single-nucleotide polymorphisms (SNPs in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction.  Methods: 79 opioid-dependent subjects (55 males, 24 females and 134 non-addict or control individuals (74 males, 60 females participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR whose products were then sequenced.  Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant.  Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population.

  13. Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness. (United States)

    Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar


    Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  14. Chimeric opioid peptides: Tools for identifying opioid receptor types

    International Nuclear Information System (INIS)

    Xie, G.; Miyajima, A.; Yokota, T.; Arai, K.; Goldstein, A.


    The authors synthesized several chimeric [125J-labelled] peptides in which the N-terminal nine residues of dynorphin-32, a peptide selective for the κ opioid receptor, were replaced by opioid peptides selective for other opioid receptor types. Each chimeric peptide retained the high affinity and type selectivity characteristic of its N-terminal sequence. The common C-terminal two-thirds of the chimeric peptides served as an epitope recognized by the same monoclonal antibody. When bound to receptors on a cell surface or membrane preparation, these peptides could still bind specifically to the monoclonal antibody. These chimeric peptides should be useful for isolating μ, δ, and κ opioid receptors and for identifying opioid receptors on transfected cells in expression cloning procedures. The general approach using chimeric peptides should be applicable to other peptide receptors

  15. Uranium enrichment

    International Nuclear Information System (INIS)


    GAO was asked to address several questions concerning a number of proposed uranium enrichment bills introduced during the 100th Congress. The bill would have restructured the Department of Energy's uranium enrichment program as a government corporation to allow it to compete more effectively in the domestic and international markets. Some of GAO's findings discussed are: uranium market experts believe and existing market models show that the proposed DOE purchase of a $750 million of uranium from domestic producers may not significantly increase production because of large producer-held inventories; excess uranium enrichment production capacity exists throughout the world; therefore, foreign producers are expected to compete heavily in the United States throughout the 1990s as utilities' contracts with DOE expire; and according to a 1988 agreement between DOE's Offices of Nuclear Energy and Defense Programs, enrichment decommissioning costs, estimated to total $3.6 billion for planning purposes, will be shared by the commercial enrichment program and the government

  16. Free atmospheric CO2 enrichment increased above ground biomass but did not affect symbiotic N2-fixation and soil carbon dynamics in a mixed deciduous stand in Wales

    Directory of Open Access Journals (Sweden)

    A. R. Smith


    Full Text Available Through increases in net primary production (NPP, elevated CO2 is hypothesized to increase the amount of plant litter entering the soil. The fate of this extra carbon on the forest floor or in mineral soil is currently not clear. Moreover, increased rates of NPP can be maintained only if forests can escape nitrogen limitation. In a Free atmospheric CO2 Enrichment (FACE experiment near Bangor, Wales, 4 ambient and 4 elevated [CO2] plots were planted with patches of Betula pendula, Alnus glutinosa and Fagus sylvatica on a former arable field. After 4 years, biomass averaged for the 3 species was 5497 (se 270 g m−2 in ambient and 6450 (se 130 g m−2 in elevated [CO2] plots, a significant increase of 17% (P = 0.018. During that time, only a shallow L forest floor litter layer had formed due to intensive bioturbation. Total soil C and N contents increased irrespective of treatment and species as a result of afforestation. We could not detect an additional C sink in the soil, nor were soil C stabilization processes affected by elevated [CO2]. We observed a decrease of leaf N content in Betula and Alnus under elevated [CO2], while the soil C/N ratio decreased regardless of CO2 treatment. The ratio of N taken up from the soil and by N2-fixation in Alnus was not affected by elevated [CO2]. We infer that increased nitrogen use efficiency is the mechanism by which increased NPP is sustained under elevated [CO2] at this site.

  17. Preventing Opioid Use Disorders among Fishing Industry Workers

    Directory of Open Access Journals (Sweden)

    Angela Wangari Walter


    Full Text Available Fishing industry workers are at high risk for work-related musculoskeletal disorders (MSDs and injuries. Prescription opioids used to treat pain injuries may put these workers at increased risk for developing substance disorders. Using a Community-Based Participatory Research approach, formative research was conducted to inform the eventual development of relevant interventions to prevent and reduce opioid use disorders among fishing industry workers. Qualitative interviews (n = 21 were conducted to assess: knowledge and attitudes about opioid use disorders; features of fishing work that might affect use and/or access to treatment; and community and organizational capacity for prevention and treatment. Participants reported numerous pathways connecting commercial fishing with opioid use. The combination of high stress and physically tasking job duties requires comprehensive workplace interventions to prevent chronic pain and MSDs, in addition to tailored and culturally responsive treatment options to address opioid use disorders in this population. Public health programs must integrate workplace health and safety protection along with evidence-based primary, secondary, and tertiary interventions in order to address opioid use disorders, particularly among workers in strenuous jobs.

  18. Pavlovian conditioning of multiple opioid-like responses in mice. (United States)

    Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S


    Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

  19. Macroeconomic conditions and opioid abuse. (United States)

    Hollingsworth, Alex; Ruhm, Christopher J; Simon, Kosali


    We examine how deaths and emergency department (ED) visits related to use of opioid analgesics (opioids) and other drugs vary with macroeconomic conditions. As the county unemployment rate increases by one percentage point, the opioid death rate per 100,000 rises by 0.19 (3.6%) and the opioid overdose ED visit rate per 100,000 increases by 0.95 (7.0%). Macroeconomic shocks also increase the overall drug death rate, but this increase is driven by rising opioid deaths. Our findings hold when performing a state-level analysis, rather than county-level; are primarily driven by adverse events among whites; and are stable across time periods. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Uranium enrichment

    International Nuclear Information System (INIS)

    Rae, H.K.; Melvin, J.G.


    Canada is the world's largest producer and exporter of uranium, most of which is enriched elsewhere for use as fuel in LWRs. The feasibility of a Canadian uranium-enrichment enterprise is therefore a perennial question. Recent developments in uranium-enrichment technology, and their likely impacts on separative work supply and demand, suggest an opportunity window for Canadian entry into this international market. The Canadian opportunity results from three particular impacts of the new technologies: 1) the bulk of the world's uranium-enrichment capacity is in gaseous diffusion plants which, because of their large requirements for electricity (more than 2000 kW·h per SWU), are vulnerable to competition from the new processes; 2) the decline in enrichment costs increases the economic incentive for the use of slightly-enriched uranium (SEU) fuel in CANDU reactors, thus creating a potential Canadian market; and 3) the new processes allow economic operation on a much smaller scale, which drastically reduces the investment required for market entry and is comparable with the potential Canadian SEU requirement. The opportunity is not open-ended. By the end of the century the enrichment supply industry will have adapted to the new processes and long-term customer/supplier relationships will have been established. In order to seize the opportunity, Canada must become a credible supplier during this century

  1. Uranium enrichment

    International Nuclear Information System (INIS)

    Mohrhauer, H.


    The separation of uranium isotopes in order to enrich the fuel for light water reactors with the light isotope U-235 is an important part of the nuclear fuel cycle. After the basic principals of isotope separation the gaseous diffusion and the centrifuge process are explained. Both these techniques are employed on an industrial scale. In addition a short review is given on other enrichment techniques which have been demonstrated at least on a laboratory scale. After some remarks on the present situation on the enrichment market the progress in the development and the industrial exploitation of the gas centrifuge process by the trinational Urenco-Centec organisation is presented. (orig.)

  2. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals. (United States)

    Guest, Charlotte; Sobotka, Fabian; Karavasopoulou, Athina; Ward, Stephen; Bantel, Carsten


    Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses' mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses' mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses' mental models: "conscious decision-making"; "medication-related fears"; "practice-based observations"; and "risk assessment". They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Nurses in both countries employ analytical and affective mental models when administering the opioids and seem to learn from experience

  3. Medication-assisted therapy for opioid addiction


    Tai, Betty; Saxon, Andrew J.; Ling, Walter


    The “Medication-Assisted Therapy for Opioid Addiction” session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).

  4. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice


    Navani, Dipesh M.; Sirohi, Sunil; Madia, Priyanka A.; Yoburn, Byron C.


    On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, ...

  5. Nicotine and endogenous opioids: neurochemical and pharmacological evidence. (United States)

    Hadjiconstantinou, Maria; Neff, Norton H


    Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

  6. Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis. (United States)

    Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L


    Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

  7. Spatiotemporal expression of endogenous opioid processing enzymes in mouse uterus at peri-implantation. (United States)

    Wu, Weiwei; Kong, Shuangbo; Wang, Bingyan; Chen, Yongjie; Wang, Haibin


    Successful implantation requires intimate interactions between a competent blastocyst and a receptive uterus. We recently demonstrated that the aberrant activation of opioid signaling by exogenous ligands adversely affects preimplantation embryonic development and subsequent implantation in mice. However, the underlying machinery governing the dynamic homeostasis of the endogenous opioid system in the uterus during early pregnancy remains elusive. We now show that all three major endogenous opioid precursors are spatiotemporally expressed in the uterus during early pregnancy. Moreover, we observe the well-coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3) at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type 1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend to reduce the uterine levels of opioid ligand precursors in the ovariectomized mouse model. This tight regulation of the endogenous opioid system by PC1/3, Pcsk1n and MME has been further confirmed in physiologically related pseudopregnancy and delayed implantation mouse models. The coordinated regulation of opioid precursor biosynthesis and metabolism helps to create appropriate opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous uterine opioid levels are primarily determined by the coordinated expressions of PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our findings raise an additional cautionary note regarding the effects of opioid abuse on early pregnancy events.

  8. Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients. (United States)

    Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J


    Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.

  9. Creating opioid dependence in the emergency department. (United States)

    Upadhye, Suneel


    Clinical question What is the risk of creating opioid dependence from an ED opioid prescription? Article chosen Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376:663-73, doi:10.1056/NEJMsa1610524. This study examined the risk of creating long-term opioid dependence from a prescription written in an opioid-naive patient in the ED.

  10. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.


    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  11. A Trigger for Opioid Misuse: Chronic Pain and Stress Dysregulate the Mesolimbic Pathway and Kappa Opioid System. (United States)

    Massaly, Nicolas; Morón, Jose A; Al-Hasani, Ream


    Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor (KOR) system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.

  12. A trigger for opioid misuse: Chronic pain and stress dysregulate the mesolimbic pathway and kappa opioid system

    Directory of Open Access Journals (Sweden)

    Nicolas Massaly


    Full Text Available Pain and stress are protective mechanisms essential in avoiding harmful or threatening stimuli and ensuring survival. Despite these beneficial roles, chronic exposure to either pain or stress can lead to maladaptive hormonal and neuronal modulations that can result in chronic pain and a wide spectrum of stress-related disorders including anxiety and depression. By inducing allostatic changes in the mesolimbic dopaminergic pathway, both chronic pain and stress disorders affect the rewarding values of both natural reinforcers, such as food or social interaction, and drugs of abuse. Despite opioids representing the best therapeutic strategy in acute pain conditions, they are often misused as a result of these allostatic changes induced by chronic pain and stress. The kappa opioid receptor system is critically involved in these neuronal adaptations in part through its control of dopamine release in the nucleus accumbens. Therefore, it is likely that changes in the kappa opioid system following chronic exposure to pain and stress play a key role in increasing the misuse liability observed in pain patients treated with opioids. In this review, we will discuss how chronic pain and stress-induced pathologies can affect mesolimbic dopaminergic transmission, leading to increased abuse liability. We will also assess how the kappa opioid system may underlie these pathological changes.

  13. Isotope enrichment

    International Nuclear Information System (INIS)

    Garbuny, M.


    The invention discloses a method for deriving, from a starting material including an element having a plurality of isotopes, derived material enriched in one isotope of the element. The starting material is deposited on a substrate at less than a critical submonatomic surface density, typically less than 10 16 atoms per square centimeter. The deposit is then selectively irradiated by a laser (maser or electronic oscillator) beam with monochromatic coherent radiation resonant with the one isotope causing the material including the one istope to escape from the substrate. The escaping enriched material is then collected. Where the element has two isotopes, one of which is to be collected, the deposit may be irradiated with radiation resonant with the other isotope and the residual material enriched in the one isotope may be evaporated from the substrate and collected

  14. Lipid oxidation in fish oil enriched oil-in-water emulsions and cream cheese with pre-emulsified fish oil is affected differently by the emulsifier used

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Andersen, Ulf

    It is well-documented that a high intake of long chain omega-3 polyunsaturated fatty acids has several health beneficial effects in humans. Consequently, the interest in food products enriched with marine oils has increased during recent years. However, addition of these highly unsaturated fatty...... will include results from studies on lipid oxidation in simple oil-in-water emulsions prepared with milk proteins alone or combinations of milk proteins and phospholipids. In addition, a study on fish oil enriched cream cheese will be presented. In this study, the cream cheese was enriched with either neat...... acids to foods invariably increases the risk of lipid oxidation. A possible strategy to avoid lipid oxidation and the consecutive development of unpleasant off-flavours is to protect the oil in a delivery emulsion in which the oil droplets are shielded from its possible pro-oxidative surroundings...

  15. Newer approaches to opioid detoxification

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar


    Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

  16. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R


    The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

  17. Gene Variants Reduce Opioid Risks (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  18. A Conceptual Framework for Understanding Unintended Prolonged Opioid Use. (United States)

    Hooten, W Michael; Brummett, Chad M; Sullivan, Mark D; Goesling, Jenna; Tilburt, Jon C; Merlin, Jessica S; St Sauver, Jennifer L; Wasan, Ajay D; Clauw, Daniel J; Warner, David O


    An urgent need exists to better understand the transition from short-term opioid use to unintended prolonged opioid use (UPOU). The purpose of this work is to propose a conceptual framework for understanding UPOU that posits the influence of 3 principal domains that include the characteristics of (1) individual patients, (2) the practice environment, and (3) opioid prescribers. Although no standardized method exists for developing a conceptual framework, the process often involves identifying corroborative evidence, leveraging expert opinion to identify factors for inclusion in the framework, and developing a graphic depiction of the relationships between the various factors and the clinical problem of interest. Key patient characteristics potentially associated with UPOU include (1) medical and mental health conditions; (2) pain etiology; (3) individual affective, behavioral, and neurophysiologic reactions to pain and opioids; and (4) sociodemographic factors. Also, UPOU could be influenced by structural and health care policy factors: (1) the practice environment, including the roles of prescribing clinicians, adoption of relevant practice guidelines, and clinician incentives or disincentives, and (2) the regulatory environment. Finally, characteristics inherent to clinicians that could influence prescribing practices include (1) training in pain management and opioid use; (2) personal attitudes, knowledge, and beliefs regarding the risks and benefits of opioids; and (3) professionalism. As the gatekeeper to opioid access, the behavior of prescribing clinicians directly mediates UPOU, with the 3 domains interacting to determine this behavior. This proposed conceptual framework could guide future research on the topic and allow plausible hypothesis-based interventions to reduce UPOU. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  19. Resisting Prescribed Opioids: A Qualitative Study of Decision Making in Patients Taking Opioids for Chronic Noncancer Pain. (United States)

    Paterson, Charlotte; Ledgerwood, Kay; Arnold, Carolyn; Hogg, Malcolm; Xue, Charlie; Zheng, Zhen


    Opioids are increasingly prescribed for chronic noncancer pain across the developed world. Clinical guidelines for management of these patients focus on over-use. However, research into other types of long-term medication indicates that many patients minimize drug use whenever possible. To identify the varying influences on patients' decisions about their use of prescribed opioids and explore whether concepts of resistance and minimization of intake apply to these patients. A multiprofessional team performed a qualitative interview study using the constant-comparative method. Patient's decision making was explored in depth and with a thematic analysis utilizing a published "Model of medicine-taking." A purposive sample of 20 participants drawn from two pain clinics in Melbourne, Australia. The sample was biased toward patients interested in nonmedication pain management options. Patients' needs to obtain relief from severe pain, maintain function, and minimize side effects could lead to under-use as well as over-use of prescribed opioids. In keeping with the published Model of medicine-taking, resistance to taking opioids was a common and important influence on behavior. In the face of severe chronic pain, many participants used a variety of strategies to evaluate, avoid, reduce, self-regulate, and replace opioids. Furthermore, participants perceived a resistance to opioids within the system and among some healthcare professionals. This sometimes adversely affected their adherence. Both patients and doctors exhibit aspects of resistance to the use of prescribed opioids for chronic noncancer pain, suggesting that this shared concern could be the basis of a productive therapeutic alliance to improve communication and shared decision making. Clinical guidelines for opioids use for chronic noncancer pain focus on over-use. Our qualitative interview study found that many patients resisted and minimized the use of opioids. Using a published "Model of medicine-taking," we

  20. Uranium enrichment in the United States

    International Nuclear Information System (INIS)

    Hill, J.H.; Parks, J.W.


    History, improvement programs, status of electrical power availability, demands for uranium enrichment, operating plan for the U. S. enriching facilities, working inventory of enriched uranium, possible factors affecting deviations in the operating plan, status of gaseous diffusion technology, status of U. S. gas centrifuge advances, transfer of enrichment technology, gaseous diffusion--gas centrifuge comparison, new enrichment capacity, U. S. separative work pricing, and investment in nuclear energy are discussed. (LK)

  1. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM


    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  2. How resistant to tampering are codeine containing analgesics on the market? Assessing the potential for opioid extraction


    Kimergård, Andreas; Deluca, Paolo; Hindersson, Peter; Breindahl, Torben


    IntroductionMisuse of opioid analgesics, in combination with diversion, dependence, and fatal overdoses, presents a serious problem for public health, which affects many countries worldwide. Within this context, tampering with opioids has been associated with serious harm. The aim of the present study was to assess the tampering potential of codeine combination analgesics on the market (containing codeine/non-opioid analgesics) by the extraction of codeine.MethodsCodeine was extracted from th...

  3. Illicit Opioid Intoxication: Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    A. Fareed


    Full Text Available Opioid intoxications and overdose are associated with high rates of morbidity and mortality. Opioid overdose may occur in the setting of intravenous or intranasal heroin use, illicit use of diverted opioid medications, intentional or accidental misuse of prescription pain medications, or iatrogenic overdose. In this review, we focused on the epidemiology of illict opioid use in the United States and on the mechanism of action of opioid drugs. We also described the signs and symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose.

  4. Targinact--opioid pain relief without constipation? (United States)


    Targinact (Napp Pharmaceuticals Ltd) is a modified-release combination product containing the strong opioid oxycodone plus the opioid antagonist naloxone. It is licensed for "severe pain, which can be adequately managed only with opioid analgesics".1 The summary of product characteristics (SPC) states that "naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut". Advertising for the product claims "better pain relief", "superior GI [gastrointestinal] tolerability" and "improved quality of life" "compared to previous treatment in a clinical practice study (n=7836)". Here we consider whether Targinact offers advantages over using strong opioids plus laxatives where required.

  5. Low efficacy of non-opioid drugs in opioid withdrawal symptoms. (United States)

    Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard


    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.

  6. Pharmacist's role in dispensing opioids for acute and chronic pain. (United States)

    Marlowe, Karen F; Geiler, Richard


    Pain continues to be a serious health care concern in the United States. Patients with chronic pain experience the impact of the disease throughout their lives including their social interactions, family relationships, and in many cases economic productivity. Multiple surveys have found that many pharmacists hold misconceptions regarding opioids, pain disease states, and their understandings of current regulations. Multiple barriers affect the ability of pharmacists to deliver care to patients' prescribed opioid therapy. Inadequate communication between health care professionals and patients is one of the hurdles, which prevents quality care. Increased communication between health care providers including access to health information is one step, which is crucial to improving provision of pharmacotherapy. Finally, the quality of educational opportunities relative to opioids and pain management specifically for pharmacists needs to be increased, and consideration needs to be given for making appropriate pain management education mandatory.

  7. 42 CFR 8.11 - Opioid treatment program certification. (United States)


    ... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP... opioid addiction. (2) To obtain certification from SAMHSA, an OTP must meet the Federal opioid treatment... governmental entities to regulate the use of opioid drugs in the treatment of opioid addiction. The provisions...

  8. Novel approaches for the treatment of psychostimulant and opioid abuse - focus on opioid receptor-based therapies. (United States)

    Bailey, Chris P; Husbands, Stephen M


    Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making 'anti-relapse' therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. First, there are three key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all three stimuli. Second, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would, therefore, be effective against all classes of drugs of abuse. In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into two categories: 'memory-based' and 'receptor-based' and the authors discuss the key targets here within. Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel 'anti-relapse' medication targets, research suggests that a 'non-selective' approach to targeting opioid receptors will be the most effective.

  9. Functional characteristics of the naked mole rat μ-opioid receptor.

    Directory of Open Access Journals (Sweden)

    Melanie Busch-Dienstfertig

    Full Text Available While humans and most animals respond to µ-opioid receptor (MOR agonists with analgesia and decreased aggression, in the naked mole rat (NMR opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1 can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.

  10. Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain. (United States)

    Navratilova, Edita; Xie, Jennifer Yanhua; Meske, Diana; Qu, Chaoling; Morimura, Kozo; Okun, Alec; Arakawa, Naohisa; Ossipov, Michael; Fields, Howard L; Porreca, Frank


    Pain is aversive, and its relief elicits reward mediated by dopaminergic signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward motivation pathway. How the reward pathway is engaged by pain-relieving treatments is not known. Endogenous opioid signaling in the anterior cingulate cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation. We examined whether endogenous ACC opioid neurotransmission is required for relief of pain and subsequent downstream activation of NAc dopamine signaling. Conditioned place preference (CPP) and in vivo microdialysis were used to assess negative reinforcement and NAc dopaminergic transmission. In rats with postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain-relieving treatments, including peripheral nerve block or spinal clonidine, an α2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid receptors of injured, but not pain-free, animals was sufficient to stimulate dopamine release in the NAc and produce CPP. In neuropathic, but not sham-operated, rats, systemic doses of morphine that did not affect withdrawal thresholds elicited CPP and NAc dopamine release, effects that were prevented by blockade of ACC opioid receptors. The data provide a neural explanation for the preferential effects of opioids on pain affect and demonstrate that engagement of NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to be both necessary and sufficient for relief of pain aversiveness. Copyright © 2015 the authors 0270-6474/15/357264-08$15.00/0.

  11. Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain. (United States)

    Wachholtz, Amy; Gonzalez, Gerardo


    Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's opioid maintenance compared to active methadone patients (p opioid naïve control group participants (p's opioid abstinence increased (R = .37; p opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Opioid tapering in patients with prescription opioid use disorder : A retrospective study

    NARCIS (Netherlands)

    Zhou, Kehua; Jia, Peng; Bhargava, Swati; Zhang, Yong; Reza, Taslima; Peng, Yuan Bo; Wang, Gary G.


    Background and aims: Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use

  13. Uranium enrichment

    International Nuclear Information System (INIS)


    This paper reports that in 1990 the Department of Energy began a two-year project to illustrate the technical and economic feasibility of a new uranium enrichment technology-the atomic vapor laser isotope separation (AVLIS) process. GAO believes that completing the AVLIS demonstration project will provide valuable information about the technical viability and cost of building an AVLIS plant and will keep future plant construction options open. However, Congress should be aware that DOE still needs to adequately demonstrate AVLIS with full-scale equipment and develop convincing cost projects. Program activities, such as the plant-licensing process, that must be completed before a plant is built, could take many years. Further, an updated and expanded uranium enrichment analysis will be needed before any decision is made about building an AVLIS plant. GAO, which has long supported legislation that would restructure DOE's uranium enrichment program as a government corporation, encourages DOE's goal of transferring AVLIS to the corporation. This could reduce the government's financial risk and help ensure that the decision to build an AVLIS plant is based on commercial concerns. DOE, however, has no alternative plans should the government corporation not be formed. Further, by curtailing a planned public access program, which would have given private firms an opportunity to learn about the technology during the demonstration project, DOE may limit its ability to transfer AVLIS to the private sector

  14. Help, Resources and Information: National Opioids Crisis (United States)

    ... Search Search Help, Resources and Information National Opioids Crisis Search Search Need Help? Call the National Helpline ... HHS 5-POINT STRATEGY TO COMBAT THE OPIOIDS CRISIS BETTER ADDICTION PREVENTION, TREATMENT, AND RECOVERY SERVICES BETTER ...

  15. Enrichment: Dealing with overcapacity

    International Nuclear Information System (INIS)

    Peterson, C.H.


    Today's surplus of enrichment capacity will continue until at least the end of this century. This will challenge the ingenuity of the separative work unit (SWU) suppliers as they attempt to keep market share and remain profitable in a very competitive marketplace. The utilities will be faced with attractive choices, but making the best choice will require careful analysis and increased attention to market factors. Current demand projections will probably prove too high to the extent that more reactors are canceled or delayed. The DOE has the vast majority of the unused capacity, so it will feel the most immediate impact of this large surplus in productive capacity. The DOE has responded to these market challenges by planning another reorganization of its enriching operations. Without a major agreement among the governments affected by the current surplus in enrichment capacity, the future will see lower prices, more competitive terms, and the gradual substitution of centrifuge or laser enrichment for the gaseous diffusion plants. The competition that is forcing the gaseous diffusion prices down to marginal cost will provide the long-term price basis for the enrichment industry

  16. Buprenorphine for managing opioid withdrawal. (United States)

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


    outcome. Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion.Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine.It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research.Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual.

  17. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals

    Directory of Open Access Journals (Sweden)

    Guest C


    % did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41% than German (28% nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38% when using opioids. Four latent variables were identified which likely influence nurses’ mental models: “conscious decision-making”; “medication-related fears”; “practice-based observations”; and “risk assessment”. They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Conclusion: Nurses in both countries employ analytical and affective mental models when administering the opioids and seem to learn from experience rather than from formal teaching. Additionally, some attitudes and emotions towards opioids are likely the result of nurses’ cultural background. Keywords: nurses, opioids, mental models, decision-making

  18. Role and psychological dependenci arrangement of opioid by type of reseptor opioid


    Arif Nurrochmad, Arif Nurrochmad


    Opioid receptor can be classified as p., 8, and K-opioid receptor that widely expressed in the CNS. The development of selective receptor agonist and cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. This review focuses on the functional interaction among these opioid receptor types that contribute to opioid dependence especially in psychological dependence. Several lines of evidence provide argument...

  19. In-hospital resuscitation: opioids and other factors influencing survival

    Directory of Open Access Journals (Sweden)

    Karamarie Fecho


    Full Text Available Karamarie Fecho1, Freeman Jackson1, Frances Smith1, Frank J Overdyk21Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina, USA; 2Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USAPurpose: “Code Blue” is a standard term used to alertt hospital staff that a patient requires resuscitation. This study determined rates of survival from Code Blue events and the role of opioids and other factors on survival.Methods: Data derived from medical records and the Code Blue and Pharmacy databases were analyzed for factors affecting survival.Results: During 2006, rates of survival from the code only and to discharge were 25.9% and 26.4%, respectively, for Code Blue events involving cardiopulmonary resuscitation (CPR; N = 216. Survival rates for events not ultimately requiring CPR (N = 77 were higher, with 32.5% surviving the code only and 62.3% surviving to discharge. For CPR events, rates of survival to discharge correlated inversely with time to chest compressions and defibrillation, precipitating event, need for airway management, location and age. Time of week, witnessing, postoperative status, gender and opioid use did not influence survival rates. For non-CPR events, opioid use was associated with decreased survival. Survival rates were lowest for patients receiving continuous infusions (P < 0.01 or iv boluses of opioids (P < 0.05.Conclusions: One-quarter of patients survive to discharge after a CPR Code Blue event and two-thirds survive to discharge after a non-CPR event. Opioids may influence survival from non-CPR events.Keywords: code blue, survival, opioids, cardiopulmonary resuscitation, cardiac arrest, patient safety

  20. Medical encounters for opioid-related intoxications in Southern Nevada: sociodemographic and clinical correlates. (United States)

    Feng, Jing; Iser, Joseph P; Yang, Wei


    Despite today's heightened concern over opioid overdose, the lack of population-based data examining clinical and contextual factors associated with opioid use represents a knowledge gap with relevance to prevention and treatment interventions. We sought to quantify rates of emergency department (ED) visits and inpatient hospitalizations for harmful opioid effects and their sociodemographic differentials as well as clinical correlates in Southern Nevada, using ED visit and hospital inpatient discharge records from 2011 to 2013. Cases were identified by ICD-9-CM diagnosis codes for opioid poisoning and opioid-type drug dependence and abuse as well as poisoning and adverse effect E-codes. Comorbid conditions, including pain-related diagnoses, major chronic diseases, affective disorders, sleep disorders, sexually transmitted infections and viral hepatitis were assessed from all available diagnosis fields. Counts by age-race per zip code were modeled by negative binomial regression. Opioid injuries were further examined as a function both of neighborhood income and individual characteristics, with mixed-effects logistic regression to estimate the likelihood for an adverse outcome. Opioid intoxications and comorbidities were more common in low-income communities. The multivariable-adjusted rate for opioid-related healthcare utilization was 42 % higher in the poorest vs. richest quartile during the study period. The inter-quartile (quartile 1 vs. 4) rate increases for chronic bodily pains (44 %), hypertension (89 %), renal failure/diabetes (2.6 times), chronic lower respiratory disease (2.2 times), and affective disorders (57 %) were statistically significant. Chronic disease comorbidity was greater among non-Hispanic blacks, whereas abuse/dependence related disorders, alcohol or benzodiazepine co-use, chronic bodily pains, and affective disorders were more prevalent among non-Hispanic whites than nonwhites. There were consistent patterns of disparities in healthcare

  1. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.


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

  2. A brain-targeted ampakine compound protects against opioid-induced respiratory depression. (United States)

    Dai, Wei; Xiao, Dian; Gao, Xiang; Zhou, Xin-Bo; Fang, Tong-Yu; Yong, Zheng; Su, Rui-Bin


    The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression. XD-8-17C was intravenously administered before or after TH-030418. The effect of XD-8-17C on opioid-induced respiratory depression was evaluated in terms of the opioid-induced acute death rate, arterial blood gas analysis and pulmonary function tests. In addition, the hot-plate test was conducted to investigate whether XD-8-17C influenced opioid-induced analgesia. Pre-treatment with XD-8-17C significantly reduced opioid-induced acute death, and increased the median lethal dose of TH-030418 by 4.7-fold. Blood gas analysis and pulmonary function tests demonstrated that post-treatment with XD-8-17C alleviated respiratory depression, as indicated by restoration of arterial blood gas (pO 2 , sO 2 , cK + ) and lung function parameters (respiratory frequency, minute ventilation) to the normal range. The hot-plate test showed that XD-8-17C had no impact on the antinociceptive efficacy of morphine. The ability of XD-8-17C to reverse opioid-induced respiratory depression has the potential to increase the safety and convenience of opioid treatment. These findings contribute to the discovery of novel therapeutic agents that protect against opioid-induced respiratory depression without loss of analgesia. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Site-directed alkylation of multiple opioid receptors. I. Binding selectivity

    International Nuclear Information System (INIS)

    James, I.F.; Goldstein, A.


    A method for measuring and expressing the binding selectivity of ligands for mu, delta, and kappa opioid binding sites is reported. Radioligands are used that are partially selective for these sites in combination with membrane preparations enriched in each site. Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands. After enrichment for mu receptors, [ 3 H] dihydromorphine bound to a single type of site as judged by the slope of competition binding curves. After enrichment for delta or kappa receptors, binding sites for [ 3 H] [D-Ala2, D-Leu5]enkephalin and [3H]ethylketocyclazocine, respectively, were still not homogeneous. There were residual mu sites in delta-enriched membranes but no evidence for residual mu or delta sites in kappa-enriched membranes were found. This method was used to identify ligands that are highly selective for each of the three types of sites

  4. Opioid antagonists with minimal sedation for opioid withdrawal. (United States)

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


    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

  5. Association Between Human Pain-Related Genotypes and Variability in Opioid Analgesia

    DEFF Research Database (Denmark)

    Nielsen, Lecia M; Olesen, Anne E; Branford, Ruth


    On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and...... as opioid consumption or changes in pain scores. Studies have shown promising results regarding pharmacogenetics as a diagnostic tool for predicting the individual response to a given opioid in the experimental settings; however, in the clinic, it is a more complicated task to accomplish....

  6. Dependence and addiction during chronic opioid therapy. (United States)

    Juurlink, David N; Dhalla, Irfan A


    The use of opioids for chronic noncancer pain has increased dramatically over the past 25 years in North America and has been accompanied by a major increase in opioid addiction and overdose deaths. The increase in opioid prescribing is multifactorial and partly reflects concerns about the effectiveness and safety of alternative medications, particularly the nonsteroidal anti-inflammatory drugs. However, much of the rise in opioid prescribing reflects the assertion, widely communicated to physicians in the 1990s, that the risks of dependence and addiction during chronic opioid therapy were low, predictable, and could be minimized by the use of controlled-release opioid formulations. In this narrative review, we offer a critical appraisal of the publications most frequently cited as evidence that the risk of addiction during chronic opioid therapy is low. We conclude that very few well-designed studies support the notion that opioid addiction is rare during chronic opioid therapy and that none can be readily generalized to present-day practice. Despite serious methodological limitations, these studies have been repeatedly mischaracterized as showing that the risk of addiction during chronic opioid therapy is rare. These studies are countered by a larger, more rigorous and contemporary body of evidence demonstrating that dependence and addiction are relatively common consequences of chronic opioid therapy, occurring in up to one-third of patients in some series.

  7. [The endogenous opioid system and drug addiction]. (United States)

    Maldonado, R


    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  8. Opioid-free anaesthesia in three dogs

    Directory of Open Access Journals (Sweden)

    Donna M. White


    Full Text Available Opioid-free anaesthesia (OFA is a relatively new and growing field in human medicine. There are multiple motivations behind this emerging practice with the recognition of several serious potential opioid-related adverse effects including opioid induced hyperalgesia, opioid tolerance and immunomodulatory effects of opioids. Opioids have long been the mainstay of veterinary anaesthesia and pain management practice. The feasibility of OFA in veterinary patients is presented here. A case series of three dogs that underwent OFA for canine ovariohysterectomy is reported. The authors conclude OFA is possible in veterinary medicine; however the move away from the familiar effects of opioids perioperatively is challenging. Gaining experience with these types of protocols for standard procedures in healthy animals, such as neutering, will provide the anaesthetist with the building blocks for more invasive surgeries.

  9. Non-analgesic effects of opioids: opioids and the endocrine system. (United States)

    Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E


    Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

  10. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S


    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  11. Uranium enrichment

    International Nuclear Information System (INIS)


    This paper analyzes under four different scenarios the adequacy of a $500 million annual deposit into a fund to pay for the cost of cleaning up the Department of Energy's (DOE) three aging uranium enrichment plants. These plants are located in Oak Ridge, Tennessee; Paducah, Kentucky; and Portsmouth, Ohio. In summary the following was found: A fixed annual $500 million deposit made into a cleanup fund would not be adequate to cover total expected cleanup costs, nor would it be adequate to cover expected decontamination and decommissioning (D and D) costs. A $500 million annual deposit indexed to an inflation rate would likely be adequate to pay for all expected cleanup costs, including D and D costs, remedial action, and depleted uranium costs

  12. Opioid use in palliative care

    African Journals Online (AJOL)


    care. The confident and safe use of opioids in palliative care is an essential skill required by all. d o c t o r s . ... patient for ongoing clinical review. Start the elderly and frail .... (24 hour subcutaneous infusion ... (nursing or medical), pain special-.

  13. Feeding Releases Endogenous Opioids in Humans. (United States)

    Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri


    The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

  14. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte


    The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during...... storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...

  15. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status. (United States)

    van der Merwe, Johanna Debora; de Beer, Dalene; Joubert, Elizabeth; Gelderblom, Wentzel C A


    An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction.

  16. Opioid modulation of immunocompetence: Receptor characterization and second messenger involvement

    International Nuclear Information System (INIS)

    Hemmick, L.M.


    The purpose of this thesis was to examine the effects of opioids on several indices of immunocompetence, determined the receptor specificity of these effects, and ascertain whether the actions of opioids on lymphocytes could be correlated with activation of second messenger systems. By measuring 45 Ca 2+ uptake into lymphocytes, it was demonstrated that β-endorphin 1-31 (β-END 1-31) enhanced rat thymocyte Ca 2+ uptake in response to concanavalin A (Con A) but not phytohemagglutinin (PHA). Related opioid peptides and alkaloids were unable to mimic the effect, and naloxone did not block it, suggesting that β-END 1-31 acted by binding to specific, non-opioid receptors on the thymocytes. Rat splenocyte Con A-stimulated Ca 2+ uptake was not affected by β-END 1-31. β-END 1-31 did not affect basal Ca 2+ uptake by either cell type. Using [ 3 H]thymidine uptake as an index of lymphocyte proliferation, β-END 1-31 and several related opioid peptides reversed prostaglandin E 1 (PGE 1 ) suppression of rat lymph node cell Con A- and PHA-stimulated proliferation. Naloxone did not block the reversal. β-END 1-31 was unable to reverse forskolin and cholera toxin suppression of proliferation, indicating that the lowering of cyclic AMP levels was not the mechanism involved. Verapamil inhibition of proliferation was also not reversed by β-END 1-31, suggesting that promotion of Ca 2+ influx was not a major mechanism involved

  17. Opioid modulation of immunocompetence: Receptor characterization and second messenger involvement

    Energy Technology Data Exchange (ETDEWEB)

    Hemmick, L.M.


    The purpose of this thesis was to examine the effects of opioids on several indices of immunocompetence, determined the receptor specificity of these effects, and ascertain whether the actions of opioids on lymphocytes could be correlated with activation of second messenger systems. By measuring {sup 45}Ca{sup 2+} uptake into lymphocytes, it was demonstrated that {beta}-endorphin 1-31 ({beta}-END 1-31) enhanced rat thymocyte Ca{sup 2+} uptake in response to concanavalin A (Con A) but not phytohemagglutinin (PHA). Related opioid peptides and alkaloids were unable to mimic the effect, and naloxone did not block it, suggesting that {beta}-END 1-31 acted by binding to specific, non-opioid receptors on the thymocytes. Rat splenocyte Con A-stimulated Ca{sup 2+} uptake was not affected by {beta}-END 1-31. {beta}-END 1-31 did not affect basal Ca{sup 2+} uptake by either cell type. Using ({sup 3}H)thymidine uptake as an index of lymphocyte proliferation, {beta}-END 1-31 and several related opioid peptides reversed prostaglandin E{sub 1} (PGE{sub 1}) suppression of rat lymph node cell Con A- and PHA-stimulated proliferation. Naloxone did not block the reversal. {beta}-END 1-31 was unable to reverse forskolin and cholera toxin suppression of proliferation, indicating that the lowering of cyclic AMP levels was not the mechanism involved. Verapamil inhibition of proliferation was also not reversed by {beta}-END 1-31, suggesting that promotion of Ca{sup 2+} influx was not a major mechanism involved.

  18. Assessment and Treatment of Abuse Risk in Opioid Prescribing for Chronic Pain

    Directory of Open Access Journals (Sweden)

    Robert N. Jamison


    Full Text Available Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic back pain and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. In this review, we discuss opioid abuse and misuse issues that often arise in the treatment of patients with chronic back pain and present an overview of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain. Many persons with chronic back pain have significant medical, psychiatric and substance use comorbidities that affect treatment decisions and a comprehensive evaluation that includes a detailed history, physical, and mental health evaluation is essential. Although there is no “gold standard” for opioid misuse risk assessment, several validated measures have been shown to be useful. Controlled substance agreements, regular urine drug screens, and interventions such as motivational counseling have been shown to help improve patient compliance with opioids and to minimize aberrant drug-related behavior. Finally, we discuss the future of abuse-deterrent opioids and other potential strategies for back pain management.

  19. Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study. (United States)

    Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John


    To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  20. Availability and utilization of opioids for pain management: global issues. (United States)

    Manjiani, Deepak; Paul, D Baby; Kunnumpurath, Sreekumar; Kaye, Alan David; Vadivelu, Nalini


    Pain can significantly influence an individual's health status and can have serious negative consequences: poor nutrition, decreased appetite, abnormal sleep patterns, fatigue, and impairment of daily living activities. Pain can cause psychological impairment and decrease healing and recovery from injuries and illness. A hallmark of many chronic conditions, pain affects more patients' lives than diabetes mellitus, heart disease, and cancer combined. However, many chronic sufferers do not have access to effective pain management for a variety of reasons, including limited access, restrictions, and personal and cultural biases. This review summarizes issues of access, distribution, and cultural bias with regard to opioid agents and seeks to clarify the challenges related to opioid delivery. The considerable negative physical and mental consequences of chronic pain are discussed for the general and palliative care population. Opioids are an effective treatment for various intractable painful conditions, but problems in global opioid access for safe and rational use in pain management contribute to unnecessary suffering. These problems persist despite increased understanding in recent years of the pathophysiology of pain. Comprehensive guidelines for goal-directed and patient-friendly chronic opiate therapy will potentially enhance the outlook for future chronic pain management. The improvement of pain education in undergraduate and postgraduate training will benefit patients and clinicians. The promise of new medications, along with the utilization of multimodal approaches, has the potential to provide effective pain relief to future generations of sufferers.

  1. Criminal justice continuum for opioid users at risk of overdose. (United States)

    Brinkley-Rubinstein, Lauren; Zaller, Nickolas; Martino, Sarah; Cloud, David H; McCauley, Erin; Heise, Andrew; Seal, David


    The United States (US) is in the midst of an epidemic of opioid use; however, overdose mortality disproportionately affects certain subgroups. For example, more than half of state prisoners and approximately two-thirds of county jail detainees report issues with substance use. Overdose is one of the leading causes of mortality among individuals released from correctional settings. Even though the criminal justice (CJ) system interacts with a disproportionately high number of individuals at risk of opioid use and overdose, few CJ agencies screen for opioid use disorder (OUD). Even less provide access to medication assisted treatment (e.g. methadone, buprenorphine, and depot naltrexone), which is one of the most effective tools to combat addiction and lower overdose risk. However, there is an opportunity to implement programs across the CJ continuum in collaboration with law enforcement, courts, correctional facilities, community service providers, and probation and parole. In the current paper, we introduce the concept of a "CJ Continuum of Care for Opioid Users at Risk of Overdose", grounded by the Sequential Intercept Model. We present each step on the CJ Continuum and include a general overview and highlight opportunities for: 1) screening for OUD and overdose risk, 2) treatment and/or diversion, and 3) overdose prevention and naloxone provision. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Using behavioral economics to predict opioid use during prescription opioid dependence treatment. (United States)

    Worley, Matthew J; Shoptaw, Steven J; Bickel, Warren K; Ling, Walter


    Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, peconomic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Transcriptome and Gene Ontology (GO) Enrichment Analysis Reveals Genes Involved in Biotin Metabolism That Affect L-Lysine Production in Corynebacterium glutamicum. (United States)

    Kim, Hong-Il; Kim, Jong-Hyeon; Park, Young-Jin


    Corynebacterium glutamicum is widely used for amino acid production. In the present study, 543 genes showed a significant change in their mRNA expression levels in L-lysine-producing C. glutamicum ATCC21300 than that in the wild-type C. glutamicum ATCC13032. Among these 543 differentially expressed genes (DEGs), 28 genes were up- or downregulated. In addition, 454 DEGs were functionally enriched and categorized based on BLAST sequence homologies and gene ontology (GO) annotations using the Blast2GO software. Interestingly, NCgl0071 (bioB, encoding biotin synthase) was expressed at levels ~20-fold higher in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain. Five other genes involved in biotin metabolism or transport--NCgl2515 (bioA, encoding adenosylmethionine-8-amino-7-oxononanoate aminotransferase), NCgl2516 (bioD, encoding dithiobiotin synthetase), NCgl1883, NCgl1884, and NCgl1885--were also expressed at significantly higher levels in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain, which we determined using both next-generation RNA sequencing and quantitative real-time PCR analysis. When we disrupted the bioB gene in C. glutamicum ATCC21300, L-lysine production decreased by approximately 76%, and the three genes involved in biotin transport (NCgl1883, NCgl1884, and NCgl1885) were significantly downregulated. These results will be helpful to improve our understanding of C. glutamicum for industrial amino acid production.

  4. Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain. (United States)

    Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; McHugh, R Kathryn; Haller, Deborah; Jacobs, Petra; Gardin, John; Fischer, Dan; Rosen, Kristen D


    The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K


    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

  6. A mixed methods study of patient-provider communication about opioid analgesics. (United States)

    Hughes, Helen Kinsman; Korthuis, Philip Todd; Saha, Somnath; Eggly, Susan; Sharp, Victoria; Cohn, Jonathan; Moore, Richard; Beach, Mary Catherine


    To describe patient-provider communication about opioid pain medicine and explore how these discussions affect provider attitudes toward patients. We audio-recorded 45 HIV providers and 423 patients in routine outpatient encounters at four sites across the country. Providers completed post-visit questionnaires assessing their attitudes toward patients. We identified discussions about opioid pain management and analyzed them qualitatively. We used logistic regression to assess the association between opioid discussion and providers' attitudes toward patients. 48 encounters (11% of the total sample) contained substantive discussion of opioid-related pain management. Most conversations were initiated by patients (n=28, 58%) and ended by the providers (n=36, 75%). Twelve encounters (25%) contained dialog suggesting a difference of opinion or conflict. Providers more often agreed than disagreed to give the prescription (50% vs. 23%), sometimes reluctantly; in 27% (n=13) of encounters, no decision was made. Fewer than half of providers (n=20, 42%) acknowledged the patient's experience of pain. Providers had a lower odds of positive regard for the patient (adjusted OR=0.51, 95% CI: 0.27-0.95) when opioids were discussed. Pain management discussions are common in routine outpatient HIV encounters and providers may regard patients less favorably if opioids are discussed during visits. The sometimes-adversarial nature of these discussions may negatively affect provider attitudes toward patients. Empathy and pain acknowledgment are tools that clinicians can use to facilitate productive discussions of pain management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.


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


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

  8. Opioid Therapy for Chronic Nonmalignant Pain

    Directory of Open Access Journals (Sweden)

    Russell K Portenoy


    Full Text Available Long term administration of an opioid drug for chronic nonmalignant pain continues to be controversial, but is no longer uniformly rejected by pain specialists. This is true despite concerns that the regulatory agencies that oversee physician prescribing of opioid drugs continue to stigmatize the practice. The changing clinical perspective has been driven, in part, by widespread acknowledgement of the remarkably favourable outcomes achieved during opioid treatment of cancer pain. These outcomes contrast starkly with popular teaching about chronic opioid therapy and affirm the potential for prolonged efficacy, tolerable side effects, enhanced function associated with improved comfort and minimal risk of aberrant drug-related behaviours consistent with addiction. A large anecdotal experience in populations with nonmalignant pain suggests that these patients are more heterogeneous and that opioid therapy will greatly benefit some and will contribute to negative outcomes for others. The few controlled clinical trials that have been performed support the safety and efficacy of opioid therapy, but have been too limited to ensure generalization to the clinical setting. A critical review of the medical literature pertaining to chronic pain, opioid pharmacology and addiction medicine can clarify misconceptions about opioid therapy and provide a foundation for patient selection and drug administration. The available data support the view that opioids are no panacea for chronic pain, but should be considered in carefully selected patients using clinically derived guidelines that stress a structured approach and ongoing monitoring of efficacy, adverse effects, functional outcomes and the occurrence of aberrant drug-related behaviours.

  9. America's Opioid Epidemic: Supply and Demand Considerations. (United States)

    Clark, David J; Schumacher, Mark A


    America is in the midst of an opioid epidemic characterized by aggressive prescribing practices, highly prevalent opioid misuse, and rising rates of prescription and illicit opioid overdose-related deaths. Medical and lay public sentiment have become more cautious with respect to prescription opioid use in the past few years, but a comprehensive strategy to reduce our reliance on prescription opioids is lacking. Addressing this epidemic through reductions in unnecessary access to these drugs while implementing measures to reduce demand will be important components of any comprehensive solution. Key supply-side measures include avoiding overprescribing, reducing diversion, and discouraging misuse through changes in drug formulations. Important demand-side measures center around educating patients and clinicians regarding the pitfalls of opioid overuse and methods to avoid unnecessary exposure to these drugs. Anesthesiologists, by virtue of their expertise in the use of these drugs and their position in guiding opioid use around the time of surgery, have important roles to play in reducing patient exposure to opioids and providing education about appropriate use. Aside from the many immediate steps that can be taken, clinical and basic research directed at understanding the interaction between pain and opioid misuse is critical to identifying the optimal use of these powerful pain relievers in clinical practice.

  10. Elevated CO{sub 2} in a prototype free-air CO{sub 2} enrichment facility affects photosynthetic nitrogen relations in a maturing pine forest

    Energy Technology Data Exchange (ETDEWEB)

    Ellsworth, D.S.; LaRoche, J.; Hendrey, G.R.


    A maturing loblolly pine (Pinus taeda L.) forest was exposed to elevated CO{sub 2} in the natural environment in a perturbation study conducted over three seasons using the free-air CO{sub 2} enrichment (FACE) technique. At the time measurements were begun in this study, the pine canopy was comprised entirely of foliage which had developed under elevated CO{sub 2} conditions (atmospheric CO{sub 2} {approx} 550 {micro}mol/mol{sup {minus}1}). Measurements of leaf photosynthetic responses to CO{sub 2} were taken to examine the effects of elevated CO{sub 2} on photosynthetic N nutrition in a pine canopy under elevated CO{sub 2}. Photosynthetic CO{sub 2} response curves (A-c{sub i} curves) were similar in FACE trees under elevated CO{sub 2} compared with counterpart trees in ambient plots for the first foliage cohort produced in the second season of CO{sub 2} exposure, with changes in curve form detected in the foliage cohorts subsequently produced under elevated CO{sub 2}. Differences in the functional relationship between carboxylation rate and N{sub a} suggest that for a given N{sub a} allocated among successive cohorts of foliage in the upper canopy, V{sub c max} was 17% lower in FACE versus Ambient trees. The authors also found that foliar Rubisco content per unit total protein derived from Western blot analysis was lower in late-season foliage in FACE foliage compared with ambient-grown foliage. The results illustrate a potentially important mode of physiological adjustment to growth conditions that may operate in forest canopies. Findings suggest that mature loblolly pine trees growing in the field may have the capacity for shifts in intrinsic nitrogen utilization for photosynthesis under elevated CO{sub 2} that are not dependent on changes in leaf N. Findings suggest a need for continued examination of internal feedbacks at the whole-tree and ecosystem level in forests that may influence long-term photosynthetic responses to elevated CO{sub 2}.


    Energy Technology Data Exchange (ETDEWEB)



    A maturing loblolly pine (Pinus taeda L.) forest was exposed to elevated CO{sub 2} in the natural environment in a perturbation study conducted over three seasons using the free-air CO{sub 2} enrichment (FACE) technique. At the time measurements were begun in this study, the pine canopy was comprised entirely of foliage which had developed under elevated CO{sub 2} conditions (atmospheric [CO{sub 2}] {approx} 550 {micro}mol mol{sup {minus}1}). Measurements of leaf photosynthetic responses to CO{sub 2} were taken to examine the effects of elevated CO{sub 2} on photosynthetic N nutrition in a pine canopy under elevated CO{sub 2}. Photosynthetic CO{sub 2} response curves (A-c{sub i} curves) were similar in FACE trees under elevated CO{sub 2} compared with counterpart trees in ambient plots for the first foliage cohort produced in the second season of CO{sub 2} exposure, with changes in curve form detected in the foliage cohorts subsequently produced under elevated CO{sub 2}. Differences in the functional relationship between carboxylation rate and N{sub a} suggest that for a given N{sub a} allocated among successive cohorts of foliage in the upper canopy, V{sub c max} was 17% lower in FACE versus Ambient trees. The authors also found that foliar Rubisco content per unit total protein derived from Western blot analysis was lower in late-season foliage in FACE foliage compared with ambient-grown foliage. The results illustrate a potentially important mode of physiological adjustment to growth conditions that may operate in forest canopies. Their findings suggest that mature loblolly pine trees growing in the field may have the capacity for shifts in intrinsic nitrogen utilization for photosynthesis under elevated CO{sub 2} that are not dependent on changes in leaf N. While carboxylation efficiency per unit N apparently decreased under elevated CO{sub 2}, photosynthetic rates in trees at elevated CO{sub 2} concentrations {approx} 550 pmol mol{sub {minus}1} are still

  12. An enriched, cereal-based bread affects appetite ratings and glycemic, insulinemic, and gastrointestinal hormone responses in healthy adults in a randomized, controlled trial. (United States)

    Gonzalez-Anton, Carolina; Lopez-Millan, Belen; Rico, Maria C; Sanchez-Rodriguez, Estefania; Ruiz-Lopez, Maria D; Gil, Angel; Mesa, Maria D


    Bread can contribute to the regulation of appetite. The objective of this study was to investigate the appetite ratings and postprandial glucose, insulin, and gastrointestinal hormone responses related to hunger and satiety after the intake of a cereal-based bread. A randomized, controlled crossover trial was conducted in 30 healthy adults (17 men and 13 women) aged 19-32 y with body mass index of 19.2-28.5. Each volunteer consumed the cereal-based bread and the control bread 2 times, with a 1-wk wash-out period, over a total of 4 sessions. The cereal-based bread contained a variety of cereal flours (wheat, oat, and spelt) and consisted of 22% dried fruits (figs, apricots, raisins, and prunes). It was also enriched with both fiber (7% from wheat cross-linked maltodextrins and pea) and protein (10-11% from wheat gluten and hydrolyzed wheat proteins). The control bread consisted of white bread with margarine and jam to control for energy density, fat, and sugar content. We measured appetite ratings using standardized visual analogue scales and glucose, insulin, and gastrointestinal hormone responses over a postprandial time of 4 h after the ingestion of each bread. Linear mixed-effects models were used to compare the areas under the curve (AUCs) for different variables. Consuming the cereal-based bread decreased prospective consumption more than consumption of the control bread (-5.3 ± 0.6 m · min and -4.4 ± 0.6 m · min, respectively; P = 0.02) and increased satiety more (6.2 ± 0.7 m · min and 5.2 ± 0.6 m · min, respectively; P = 0.04), although subsequent ad libitum energy intake 4 h later did not differ. Postprandial blood glucose, insulin, ghrelin, glucagon-like peptide 1 and gastric inhibitory polypeptide AUCs were lower after the ingestion of the cereal-based bread, whereas the pancreatic polypeptide AUC was higher than with the control bread (P < 0.05). Consumption of the cereal-based bread contributed to appetite control by reducing hunger and

  13. Juvenile psittacine environmental enrichment. (United States)

    Simone-Freilicher, Elisabeth; Rupley, Agnes E


    Environmental enrichment is of great import to the emotional, intellectual, and physical development of the juvenile psittacine and their success in the human home environment. Five major types of enrichment include social, occupational, physical, sensory, and nutritional. Occupational enrichment includes exercise and psychological enrichment. Physical enrichment includes the cage and accessories and the external home environment. Sensory enrichment may be visual, auditory, tactile, olfactory, or taste oriented. Nutritional enrichment includes variations in appearance, type, and frequency of diet, and treats, novelty, and foraging. Two phases of the preadult period deserve special enrichment considerations: the development of autonomy and puberty. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Opioids and immunosupression in oncological postoperative patients

    Directory of Open Access Journals (Sweden)

    José Luis Bonilla-García

    Full Text Available Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068. Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

  15. Stress-evoked opioid release inhibits pain in major depressive disorder. (United States)

    Frew, Ashley K; Drummond, Peter D


    To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

  16. Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine (United States)

    Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.


    Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

  17. Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors (United States)


    Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators. PMID:24010861

  18. Ethanol, Neurodevelopment, Infant and Child Health (ENRICH prospective cohort: Study design considerations

    Directory of Open Access Journals (Sweden)

    Ludmila N. Bakhireva


    Full Text Available Background: While intervention is the leading factor in reducing long-term disabilities in children with fetal alcohol spectrum disorder (FASD, early identification of children affected by prenatal alcohol exposure (PAE remains challenging. Deficits in higher-order cognitive domains (e.g. executive function might be more specific to FASD than global neurodevelopmental tests, yet these functions are not developed in very young children. Measures of early sensorimotor development may provide early indications of atypical brain development during the first two years of life. Methods: This paper describes the novel methodology of the Ethanol, Neurodevelopment, Infant and Child Health (ENRICH prospective cohort study of 120 maternal-infant pairs with a goal to identify early indices of functional brain impairment associated with PAE. The cohort is established by recruiting women early in pregnancy and classifying them into one of three study groups: patients on opioid-maintenance therapy who consume alcohol during pregnancy (Group 1, patients on opioid-maintenance therapy who abstain from alcohol during pregnancy (Group 2, and healthy controls (Group 3. After the initial prenatal assessment (Visit 1, patients are followed to Visit 2 occurring at delivery, and two comprehensive assessments of children at six (Visit 3 and 20 months (Visit 4 of age. ENRICH recruitment started in November 2013 and 87 women were recruited during the first year. During Year 1, the biospecimen (maternal whole blood, serum, urine, dry blood spots of a newborn collection rate was 100% at Visit 1, and 97.6% for those who completed Visit 2. Discussion: The tiered screening approach, evaluation of confounders, neurocognitive and magneto-/electro-encephalography (MEG/EEG outcomes, and ethical considerations are discussed.

  19. Opioid addiction and misuse in adult and adolescent patients with cancer. (United States)

    Pinkerton, Ross; Hardy, Janet R


    In the context of a therapeutic opioid epidemic, particularly in the USA, where increasingly stringent screening for 'at risk' individuals and close monitoring of opioid prescription and use is strongly recommended, the issue of misuse within the cancer population must be addressed. Most patients with advanced cancer will have pain requiring opioid therapy at some stage during their disease course. In the majority, this will provide good pain relief with no short- or longer-term adverse sequelae. A subset will present with substance misuse issues that will influence management and prescribing practice. The potential ethical issues of limiting effective analgesia on the basis of addiction risk or history must be acknowledged. Both a judgemental or 'relaxed' approach to such patients is problematic. Ignoring the situation will not be in the patient's best interest, but an undue focus on this aspect may damage therapeutic relationships with clinicians and adversely affect a holistic approach to care. Clinical practitioners must be aware of the risk factors for opioid misuse and in patients who are not under palliative care consider screening prior to commencing opioids. Clinicians must be able to manage and monitor those identified as having an opioid misuse problem. © 2017 Royal Australasian College of Physicians.

  20. Neurobiology of opioid dependence in creating addiction vulnerability [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Christopher J. Evans


    Full Text Available Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality — the “drug-dependent” state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to

  1. Fish oil, but not soy bean or olive oil enriched infusion decreases histopathological severity of acute pancreatitis in rats without affecting eicosanoid synthesis. (United States)

    Kilian, Maik; Heukamp, Ina; Gregor, Ja Ilja; Schimke, Ingolf; Kristiansen, Glen; Wenger, Frank Axel


    Different dietary fatty acids affect eicosanoid metabolism in different ways, thus influencing the pro- and anti-inflammatory balance of prostaglandins and leukotrienes. Therefore, we analyzed the impact of [n-3], [n-6], and [n-9] fatty acids on eicosanoid metabolism and histopathology in acute pancreatitis in rats. Seventy-five male Sprague-Dawley rats were randomized into five groups (n = 15). Group 1 underwent only laparotomy, while in groups, 2-5 pancreatitis was induced. Groups 1 and 2 were then given saline infusion, groups 3-5 received fat emulsion (group 3: rich in [n-6], group 4: rich in [n-9], group 5: rich in [n-3] fatty acids) for another 18 h. Infusion rich in [n-3] fatty acids significantly decreased histopathological severity of pancreatitis, compared to all other groups. There was no difference concerning the concentrations of prostaglandins and leukotrienes between all groups. Parenteral infusion rich in [n-3] fatty acids reduced histopathological severity of acute pancreatitis in rats without changing eicosanoid metabolism at the endpoint.

  2. Postharvest stilbenes and flavonoids enrichment of table grape cv Redglobe (Vitis vinifera L.) as affected by interactive UV-C exposure and storage conditions. (United States)

    Crupi, Pasquale; Pichierri, Arianna; Basile, Teodora; Antonacci, Donato


    Flavonoids and stilbenes are secondary metabolites produced in plants that can play an important health-promoting role. The biosynthesis of these compounds generally increases as a response to biotic or abiotic stress; therefore, in order to achieve as high phenolic accumulation as possible, the interactive effects of storage conditions (temperature and time) and UV-C radiation on polyphenols content in postharvest Redglobe table grape variety were investigated. During a storage time longer than 48h, both cold storage (4°C) and UV-C exposure of almost 3min (2.4kJm(-2)) positively enhanced the content of cis- and trans-piceid (34 and 90μgg(-1) of skin, respectively) together with quercetin-3-O-galactoside and quercetin-3-O-glucoside (15 and 140μgg(-1) of skin, respectively) up to three fold respect to control grape samples. Conversely, catechin was not significantly affected by irradiation and storage treatments. With regard anthocyanins, the highest concentrations of cyanidin-3-O-glucoside and peonidin-3-Oglucoside were observed in Redglobe, stored at both room temperature and 4°C, after 5min (4.1kJm(-2)) of UV-C treatment and 24h of storage. Gathered findings showed that combined postharvest treatments can lead to possible "functional" grapes, within normal conditions of market commercialization, responding to the rising consumers demand to have foods that support and promote health. Copyright © 2013. Published by Elsevier Ltd.

  3. Can we predict addiction to opioid analgesics? A possible tool to estimate the risk of opioid addiction in patients with pain. (United States)

    Skala, Katrin; Reichl, Lukas; Ilias, Wilfried; Likar, Rudolf; Grogl-Aringer, Gabriele; Wallner, Christina; Schlaff, Golda; Herrmann, Peter; Lesch, Otto; Walter, Henriette


    The use of opioid analgesics in the treatment of chronic pain conditions has long been controversial. They have been reported to be relatively safe when prescribed with caution, but a brief and valid instrument to estimate a person's risk of addiction is still missing. The aim of this study was to investigate a self-rating questionnaire allowing an estimation of a person's risk of addiction to opioid analgesics. Retrospective review. Four Austrian hospitals. Seven hundred forty-one patients were interviewed. Of these, 634 patients were affected with chronic pain while 107 patients had a history of opioid addiction. Patients were interviewed about alcohol and nicotine consumption and family history of psychiatric disorders. Attitudes towards medication and the origin of pain were examined. We asked patients with an opioid addiction and patients suffering from chronic pain to complete a short questionnaire intended to help screen for addiction potential. Compared to the patients suffering from chronic pain, patients with an opioid addiction significantly more often had alcohol- and nicotine-related pathologies and psychiatric comorbidity. A family history of mental illness and developmental problems were significantly more frequent in this group. Compared to those not addicted, those with an opioid addiction had significantly higher expectations concerning the potential of medication to change one's mental state; they thought that psychological  factors might contribute to the pain they feel. The main limitation of this study is the use of a self-rating instrument which reduces objectivity and introduces the possibility of misreporting. Also, the 2 groups differ in number and are not homogenous. We found differences in questionnaire responses between patients with an opioid addiction and patients suffering from chronic pain to be dependent upon the prevalence of current or former addiction, psychiatric history, attitudes towards medication, and ideas about the

  4. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization (United States)

    Chen, Wenling; Marvizón, Juan Carlos G.


    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

  5. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization. (United States)

    Chen, W; Marvizón, J C G


    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

  6. Gut Homeostasis, Microbial Dysbiosis, and Opioids. (United States)

    Wang, Fuyuan; Roy, Sabita


    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  7. Management of opioid addiction with buprenorphine: French history and current management

    Directory of Open Access Journals (Sweden)

    Poloméni P


    Full Text Available Pierre Poloméni,1 Raymund Schwan2,3 1Department of Addictology, Paris Seine Saint Denis University Hospital, AP-HP, Site René Muret Sevran, France; 2Care Center for the Treatment and Prevention of Addictions (CSAPA, Nancy University Hospital, 3General Psychiatric Division for the Greater Nancy Urban Community, Psychotherapeutic Center of Nancy, Laxou, France Abstract: The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000–360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the

  8. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain. (United States)

    Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina


    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

  9. Other enrichment related contracts

    International Nuclear Information System (INIS)

    Hall, J.C.


    In addition to long-term enrichment contracts, DOE has other types of contracts: (1) short-term, fixed-commitment enrichment contract; (2) emergency sales agreement for enriched uranium; (3) feed material lease agreement; (4) enriched uranium storage agreement; and (5) feed material usage agreement

  10. A prospective, longitudinal study to evaluate the clinical utility of a predictive algorithm that detects risk of opioid use disorder (United States)

    Brenton, Ashley; Lee, Chee; Lewis, Katrina; Sharma, Maneesh; Kantorovich, Svetlana; Smith, Gregory A; Meshkin, Brian


    Purpose The purpose of this study was to determine the clinical utility of an algorithm-based decision tool designed to assess risk associated with opioid use. Specifically, we sought to assess how physicians were using the profile in patient care and how its use affected patient outcomes. Patients and methods A prospective, longitudinal study was conducted to assess the utility of precision medicine testing in 5,397 patients across 100 clinics in the USA. Using a patent-protected, validated algorithm combining specific genetic risk factors with phenotypic traits, patients were categorized into low-, moderate-, and high-risk patients for opioid abuse. Physicians who ordered precision medicine testing were asked to complete patient evaluations and document their actions, decisions, and perceptions regarding the utility of the precision medicine tests. The patient outcomes associated with each treatment action were carefully documented. Results Physicians used the profile to guide treatment decisions for over half of the patients. Of those, guided treatment decisions for 24.5% of the patients were opioid related, including changing the opioid prescribed, starting an opioid, or titrating a patient off the opioid. Treatment guidance was strongly influenced by profile-predicted opioid use disorder (OUD) risk. Most importantly, patients whose physicians used the profile to guide opioid-related treatment decisions had improved clinical outcomes, including better pain management by medication adjustments, with an average pain decrease of 3.4 points on a scale of 1–10. Conclusion Patients whose physicians used the profile to guide opioid-related treatment decisions had improved clinical outcomes, as measured by decreased pain levels resulting from better pain management with prescribed medications. The clinical utility of the profile is twofold. It provides clinically actionable recommendations that can be used to 1) prevent OUD through limiting initial opioid

  11. Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test. (United States)

    Filho, Carlos B; Del Fabbro, Lucian; de Gomes, Marcelo G; Goes, André T R; Souza, Leandro C; Boeira, Silvana P; Jesse, Cristiano R


    The opioid system has been implicated as a contributing factor for major depression and is thought to play a role in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of hesperidin in the mouse forced swimming test. Our results demonstrate that hesperidin (0.1, 0.3 and 1 mg/kg; intraperitoneal) decreased the immobility time in the forced swimming test without affecting locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) in the forced swimming test was prevented by pretreating mice with naloxone (1 mg/kg, a nonselective opioid receptor antagonist) and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl] acetamide (DIPPA (1 mg/kg), a selective κ-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective δ-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective μ-opioid receptor antagonist) or caffeine (3 mg/kg, a nonselective adenosine receptor antagonist). In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg). The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders. Published by Elsevier B.V.

  12. Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens. (United States)

    Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R


    Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety

  13. Stereotype threat and social function in opioid substitution therapy patients. (United States)

    von Hippel, Courtney; Henry, Julie D; Terrett, Gill; Mercuri, Kimberly; McAlear, Karen; Rendell, Peter G


    People with a history of substance abuse are subject to widespread stigmatization. It seems likely that this societal disapproval will result in feelings of stereotype threat, or the belief that one is the target of demeaning stereotypes. If so, stereotype threat has the potential to contribute to functional difficulties including poor social outcomes. Eighty drug users on opioid substitution therapy and 84 demographically matched controls completed measures of mental health and social function. The opioid substitution therapy group were additionally asked to complete a measure that focused on their feelings of stereotype threat in relation to their drug use history. Bivariate correlations and hierarchical regression analyses were conducted to establish the magnitude and specificity of the relationship between stereotype threat and social functioning. Relative to controls, the opioid substitution therapy group reported higher levels of negative affect and schizotypy, and poorer social functioning, with all three of these indices significantly correlated with their feelings of stereotype threat. The results also showed that stereotype threat contributed significant unique variance to social functioning in the opioid substitution therapy group, even after taking into account other background, clinical, and mental health variables. Social functioning is an important aspect of recovery, yet these data indicate that people with a history of drug abuse who believe they are the target of stereotypical attitudes have poorer social functioning. This relationship holds after controlling for the impact of other variables on social functioning, including mental health. The theoretical and practical implications of these findings are discussed. Concerns about being stereotyped can shape the social experiences of opioid substitution therapy patients. Opioid substitution therapy patients who feel negatively stereotyped experience greater social function deficits, and this

  14. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. (United States)

    Hah, Jennifer M; Bateman, Brian T; Ratliff, John; Curtin, Catherine; Sun, Eric


    Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

  15. Physician Introduction to Opioids for Pain Among Patients with Opioid Dependence and Depressive Symptoms (United States)

    Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.


    This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704

  16. Distance traveled and frequency of interstate opioid dispensing in opioid shoppers and nonshoppers. (United States)

    Cepeda, M Soledad; Fife, Daniel; Yuan, Yingli; Mastrogiovanni, Greg


    Little is known about how far opioid shoppers travel or how often they cross state lines to fill their opioid prescriptions. This retrospective cohort study evaluated these measures for opioid shoppers and nonshoppers using a large U.S. prescription database. Patients with ≥3 opioid dispensings were followed for 18 months. A subject was considered a shopper when he or she filled overlapping opioid prescriptions written by >1 prescriber at ≥3 pharmacies. A heavy shopper had ≥5 shopping episodes. Outcomes assessed were distance traveled among pharmacies and number of states visited to fill opioid prescriptions. A total of 10,910,451 subjects were included; .7% developed any shopping behavior and their prescriptions accounted for 8.6% of all opioid dispensings. Shoppers and heavy shoppers were younger than the nonshoppers. Shoppers traveled a median of 83.8 miles, heavy shoppers 199.5 miles, and nonshoppers 0 miles. Almost 20% of shoppers or heavy shoppers, but only 4% of nonshoppers, visited >1 state. Shoppers traveled greater distances and more often crossed state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. Sharing of data among prescription-monitoring programs will likely strengthen those programs and may decrease shopping behavior. This study shows that opioid shoppers travel greater distances and more often cross state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. The findings support the need for data sharing among prescription-monitoring programs to deter opioid shopping behavior. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  17. Does the kappa opioid receptor system contribute to pain aversion?

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill


    Full Text Available The kappa opioid receptor (KOR and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.

  18. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

    Directory of Open Access Journals (Sweden)

    Kimberly Fernandes

    Full Text Available To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.Interventional time-series analysis.Ontario, Canada, from 2003 to 2014.Ontario Drug Benefit (ODB beneficiaries aged 15 to 64 years from 2003 to 2014.Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010 and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011.Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03 which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43. Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7% over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68 or enactment of the NSAA (p-value = .59.Although the Canadian clinical practice guidelines for use of opioids in chronic non

  19. Biotinylated human. beta. -endorphins as probes for the opioid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Hochhaus, G.; Gibson, B.W.; Sadee, W.


    The reaction of human ..beta..-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH/sup +/), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human ..beta..-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Try-1. Three HPLC fractions were isolated for receptor binding studies monobiotinylation of Lys-9, Lys-19, and a mixture of Lys-24, Lys-28, and Lys-29 derivatives. IC/sub 50/ values for binding to and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human ..beta..-endorphin. Association with avidin decreased opioid receptor affinities for the C/sub 6/ spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to and delta sites for derivatives biotinylated at the ..cap alpha..-helical part of the molecule (Lys-19, -24, -28, and -29). Biotinylated human ..beta..-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human ..beta..-endorphin to cross-link the and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.

  20. Characterizing the Interrelationships of Prescription Opioid and Benzodiazepine Drugs With Worker Health and Workplace Hazards. (United States)

    Kowalski-McGraw, Michele; Green-McKenzie, Judith; Pandalai, Sudha P; Schulte, Paul A


    Prescription opioid and benzodiazepine drug use, which has risen significantly, can affect worker health. Exploration of the scientific literature assessed (1) interrelationships of such drug use, occupational risk factors, and illness and injury, and (2) occupational and personal risk factor combinations that can affect their use. The scientific literature from 2000 to 2015 was searched to determine any interrelationships. Evidence for eight conceptual models emerged based on the search yield of 133 articles. These models summarize interrelationships among prescription opioid and benzodiazepine use with occupational injury and illness. Factors associated with the use of these drugs included fatigue, impaired cognition, falls, motor vehicle crashes, and the use of multiple providers. Prescription opioid and benzodiazepine drugs may be both a personal risk factor for work-related injury and a consequence of workplace exposures.

  1. Long-term course of opioid addiction. (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas


    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  2. Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain

    Directory of Open Access Journals (Sweden)

    Webster LR


    Full Text Available Lynn R Webster,1 Darren M Brenner,2 Andrew C Barrett,3 Craig Paterson,3 Enoch Bortey,3 William P Forbes3 1PRA Health Sciences, Salt Lake City, UT, 2Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 3Salix, a Division of Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA Background: Subcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC but may theoretically disrupt opioid-mediated analgesia. Methods: Opioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores were reported in a randomized, double-blind trial with an open-label extension (RCT and an open-label trial (OLT evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methylnaltrexone 12 mg once daily (n=150, every other day (n=148, or placebo (n=162 for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364 for 8 weeks. In the OLT, patients (n=1,034 on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks. Results: Minimal fluctuations of median morphine equivalent dose from baseline (BL were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d, RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0 and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d. No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1 of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, —0.2 to 0.1. Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all. Conclusion: Methylnaltrexone did not affect

  3. Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology.

    Directory of Open Access Journals (Sweden)

    Jarred W Younger

    Full Text Available The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

  4. Hiperalgesia asociada al tratamiento con opioides


    A. Gil Martín; M. Moreno García; J. Sánchez-Rubio Ferrández; T. Molina García


    La hiperalgesia inducida por opioides es una reacción paradójica caracterizada por una percepción intensificada de dolor relacionada con el uso de estos medicamentos en ausencia de progresión de la enfermedad o de síndrome de retirada. A diferencia de los casos de tolerancia, definida como pérdida de potencia analgésica durante el uso prolongado de opioides, no se produce mejoría con el escalado de dosis. La hiperalgesia inducida por opioides se ha manifestado en pacientes con dosis de manten...

  5. Neuraxial opioid-induced pruritus: a review.

    LENUS (Irish Health Repository)

    Szarvas, Szilvia


    When intrathecal and epidural opioids are administered, pruritus occurs as an unwanted and troublesome side effect. The reported incidence varies between 30% and 100%. The exact mechanisms of neuraxial opioid-induced pruritus remain unclear. Postulated mechanisms include the presence of an "itch center" in the central nervous system, medullary dorsal horn activation, and antagonism of inhibitory transmitters. The treatment of intrathecal opioid-induced pruritus remains a challenge. Many pharmacological therapies, including antihistamines, 5-HT(3)-receptor antagonists, opiate-antagonists, propofol, nonsteroid antiinflammatory drugs, and droperidol, have been studied. In this review, we will summarize pathophysiological and pharmacological advances that will improve understanding and ultimately the management of this troublesome problem.

  6. Opioid tapering in patients with prescription opioid use disorder: A retrospective study. (United States)

    Zhou, Kehua; Jia, Peng; Bhargava, Swati; Zhang, Yong; Reza, Taslima; Peng, Yuan Bo; Wang, Gary G


    Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use disorder. An evidence-based management for people who are already addicted to opioids has been identified as the national priority in the US; however, options are limited in clinical practices. In this study, we aimed to explore the success rate and important adjuvant medications in the medication assisted treatment with temporary use of methadone for opioid discontinuation in patients with prescription OUD. This is a retrospective chart review performed at a private physician office for physical medicine and rehabilitation. We reviewed all medical records dated between December 1st, 2011 and August 30th, 2016. The initial evaluation of the included patients (N=140) was completed between December 1st, 2011 and December 31st, 2014. They all have concumittant prescription OUD and chronic non-cancer pain. The patients (87 female and 53 male) were 46.7±12.7 years old, and had a history of opioid use of 7.7±6.1 years. All patients received the comprehensive opioid taper treatments (including interventional pain management techniques, psychotherapy, acupuncture, physical modalities and exercises, and adjuvant medications) on top of the medication assisted treatment using methadone (transient use). Opioid tapering was considered successful when no opioid medication was used in the last patient visit. The 140 patients had pain of 9.6±8.4 years with 8/10 intensity before treatment which decreased after treatment in all comparisons (pOUD. For patients with OUD, indefinite opioid maintenance treatment may not be necessary. Considering the ethical values of autonomy, nonmaleficence, and beneficence, clinicians should provide patients with OUD the option of opioid tapering. Copyright © 2017

  7. Increased Burden of Healthcare Utilization and Cost Associated with Opioid-Related Constipation Among Patients with Noncancer Pain (United States)

    Fernandes, Ancilla W.; Kern, David M.; Datto, Catherine; Chen, Yen-Wen; McLeskey, Charles; Tunceli, Ozgur


    Background Opioids are widely accepted as treatment for moderate to severe pain, and opioid-induced constipation is one of the most common side effects of opioids. This side effect negatively affects pain management and patients’ quality of life, which could result in increased healthcare utilization and costs. Objective To assess healthcare utilization and costs (all-cause, constipation-related, and pain-related) for individuals with and without opioid-induced constipation during the 12 months after initiation of opioid therapy for noncancer pain. Methods This retrospective cohort study was conducted using administrative claims data from HealthCore Integrated Research Environment between January 1, 2006, and June 30, 2014. The analysis was limited to patients aged ≥18 years who filled a prescription for continuous opioid treatment (≥28 days) for noncancer pain. Propensity scores were used to match opioid users with constipation (cohort 1) and opioid users without constipation (cohort 2), using a 1:1 ratio. Generalized linear models were used to estimate all-cause, constipation-related, and pain-related healthcare utilization and costs during the 12 months after the initiation of opioid therapy. Results After matching and balancing for all prespecified variables, 17,384 patients were retained in each cohort (mean age, 56 years; 63% female). Opioid users with constipation were twice as likely as those without constipation to have ≥1 inpatient hospitalizations (odds ratio, 2.28; 95% confidence interval [CI], 2.17–2.39) during the 12 months. The total mean adjusted overall costs per patient during the study period were $12,413 higher for patients with constipation versus those without it (95% CI, $11,726–$13,116). The total mean adjusted overall pain-related costs per patient were $6778 (95% CI, $6293–$7279) higher for the patients with constipation than those without. Among patients using opioids for noncancer pain, the annual mean constipation

  8. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

    Directory of Open Access Journals (Sweden)

    Mark R. Hutchinson


    Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

  9. Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain. (United States)

    Shurman, Joseph; Koob, George F; Gutstein, Howard B


    Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

  10. Opioid Overdose Reversal with Naloxone (Narcan, Evzio) (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  11. Teens Mix Prescription Opioids with Other Substances (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  12. Endogenous opioids encode relative taste preference. (United States)

    Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L


    Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

  13. Medicare Part D Opioid Drug Mapping Tool (United States)

    U.S. Department of Health & Human Services — The Medicare Part D opioid prescribing mapping tool is an interactive tool that shows geographic comparisons, at the state, county, and ZIP code levels, of...

  14. Derived enriched uranium market

    International Nuclear Information System (INIS)

    Rutkowski, E.


    The potential impact on the uranium market of highly enriched uranium from nuclear weapons dismantling in the Russian Federation and the USA is analyzed. Uranium supply, conversion, and enrichment factors are outlined for each country; inventories are also listed. The enrichment component and conversion components are expected to cause little disruption to uranium markets. The uranium component of Russian derived enriched uranium hexafluoride is unresolved; US legislation places constraints on its introduction into the US market

  15. Uranium enrichment plans

    International Nuclear Information System (INIS)

    Thomas, D.C.; Gagne, R.W.


    The following topics are covered: the status of the Government's existing uranium enrichment services contracts, natural uranium requirements based on the latest contract information, uncertainty in predicting natural uranium requirements based on uranium enrichment contracts, and domestic and foreign demand assumed in enrichment planning

  16. Opioid withdrawal signs and symptoms in children: frequency and determinants. (United States)

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


    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. State Emergency Department Opioid Guidelines: Current Status. (United States)

    Broida, Robert I; Gronowski, Tanner; Kalnow, Andrew F; Little, Andrew G; Lloyd, Christopher M


    The purpose of this study was to evaluate and categorize current state-sponsored opioid guidelines for the practice of emergency medicine (EM). We conducted a comprehensive search of EM-specific opioid prescribing guidelines and/or policies in each state to determine current state involvement in EM opioid prescribing, as well as to evaluate some of the specifics of each guideline or policy. The search was conducted using an online query and a follow-up email request to each state chapter of ACEP. We found that 17 states had emergency department-specific guidelines. We further organized the guidelines into four categories: limiting prescriptions for opioids with 67 total recommendations; preventing/diverting abuse with 56 total recommendations; addiction-related guidelines with 29 total recommendations; and a community resources section with 24 total recommendations. Our results showed that current state guidelines focus on providers limiting opioid pain prescriptions and vetting patients for possible abuse/diversion. This study highlights the 17 states that have addressed opioid prescribing guidelines and categorizes their efforts to date. It is hoped that this study will provide the basis for similar efforts in other states.

  18. Drug interactions: volatile anesthetics and opioids. (United States)

    Glass, P S; Gan, T J; Howell, S; Ginsberg, B


    Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

  19. The opioid manager: a point-of-care tool to facilitate the use of the Canadian Opioid Guideline. (United States)

    Furlan, Andrea D; Reardon, Rhoda; Salach, Lena


    The Opioid Manager is designed to be used as a point-of-care tool for providers prescribing opioids for chronic noncancer pain. It condenses the key elements from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid Manager has been validated and is available for download from the Guideline's Web site The Opioid Manager is divided into the following four parts: A) before you write the first script, B) initiation trial, C) maintenance and monitoring, and D) when is it time to decrease the dose or stop the opioid completely? The Opioid Manager has been downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists, 13 percent other physicians, and 22 percent miscellaneous. To show how to use the Opioid Manager, the authors created a 10-minute video that is available on the Internet. The Opioid Manager is being translated to French, Spanish, Portuguese, and Farsi.

  20. FMRFamide: low affinity inhibition of opioid binding to rabbit brain membranes

    International Nuclear Information System (INIS)

    Zhu, X.Z.; Raffa, R.B.


    FMRFamide (Phe-Met-Arg-Phe-NH 2 ) was first isolated from the ganglia of molluscs by Price and Greenberg in 1977. The peptide was subsequently shown to have diverse actions on various types of molluscan and mammalian tissues. The presence of immunoreactive FMRFamide-like material (irFMRF) in multiple areas of rat brain, spinal cord, and gastrointestinal tract suggests that irFMRF may have a physiological role in mammals. Tang, Yang and Costa recently demonstrated that FMRFamide attenuates morphine antinociception in rats and postulated, based on this and several other lines of evidence, that irFMRF might be an endogenous opioid antagonist. In the present study, they tested the ability of FMRFamide to inhibit the binding of opioid receptor ligands to rabbit membrane preparations. FMRFamide inhibited the specific binding of both 3 [H]-dihydromorphine and 3 [H]-ethylketocyclazocine (IC 50 = 14 μM and 320 μM, respectively) in a dose-related manner, suggesting that FMRFamide may affect binding to at least two types of opioid receptors (mu and kappa). These data are consistent with the concept that irFMRF might act as an endogenous opioid antagonist. However, the low affinity of FMRFamide leaves open the possibility of another mechanism of opioid antagonism, such as neuromodulation

  1. FMRFamide: low affinity inhibition of opioid binding to rabbit brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Z.; Raffa, R.B.


    FMRFamide (Phe-Met-Arg-Phe-NH/sub 2/) was first isolated from the ganglia of molluscs by Price and Greenberg in 1977. The peptide was subsequently shown to have diverse actions on various types of molluscan and mammalian tissues. The presence of immunoreactive FMRFamide-like material (irFMRF) in multiple areas of rat brain, spinal cord, and gastrointestinal tract suggests that irFMRF may have a physiological role in mammals. Tang, Yang and Costa recently demonstrated that FMRFamide attenuates morphine antinociception in rats and postulated, based on this and several other lines of evidence, that irFMRF might be an endogenous opioid antagonist. In the present study, they tested the ability of FMRFamide to inhibit the binding of opioid receptor ligands to rabbit membrane preparations. FMRFamide inhibited the specific binding of both /sup 3/(H)-dihydromorphine and /sup 3/(H)-ethylketocyclazocine (IC/sub 50/ = 14 and 320, respectively) in a dose-related manner, suggesting that FMRFamide may affect binding to at least two types of opioid receptors (mu and kappa). These data are consistent with the concept that irFMRF might act as an endogenous opioid antagonist. However, the low affinity of FMRFamide leaves open the possibility of another mechanism of opioid antagonism, such as neuromodulation.

  2. Amygdala mu-opioid receptors mediate the motivating influence of cue-triggered reward expectations. (United States)

    Lichtenberg, Nina T; Wassum, Kate M


    Environmental reward-predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue-directed action using the outcome-specific Pavlovian-to-instrumental transfer (PIT) test in rats. Inactivation of BLA mu-, but not delta-opioid receptors was found to dose-dependently attenuate the ability of a reward-predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i.e. to express outcome-specific PIT). BLA mu-opioid receptor inactivation did not affect the ability of a reward itself to similarly motivate action (outcome-specific reinstatement), suggesting a more selective role for the BLA mu-opioid receptor in the motivating influence of currently unobservable rewarding events. These data reveal a new role for BLA mu-opioid receptor activation in the cued recall of precise reward memories and the use of this information to motivate specific action plans. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Sex versus sweet: opposite effects of opioid drugs on the reward of sucrose and sexual pheromones. (United States)

    Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique


    Endogenous opioids mediate some reward processes involving both natural (food, sweet taste) and artificial (morphine, heroin) rewards. In contrast, sexual behavior (which is also reinforcing) is generally inhibited by opioids. To establish the role of endogenous opioids for a newly described natural reinforcer, namely male sexual pheromones for female mice, we checked the effects of systemic injections of the general opioid antagonist naloxone (1-10 mg/kg) and the agonist fentanyl (0.1- 0.5 mg/kg) in a number of behavioral tests. Naloxone affected neither the innate preference for male-soiled bedding (vs. female-soiled bedding) in 2-choice tests nor the induction of place conditioning using male pheromones as rewarding stimuli, although it effectively blocked the preference for consuming a sucrose solution. In contrast, fentanyl inhibited the preference for male chemosignals without altering sucrose preference. These results suggest that, in macrosmatic animals such as rodents, opioidergic inhibition of sexual behavior might be due, at least partially, to an impaired processing of pheromonal cues and that the hedonic value of sweet-tasting solutions and sexual pheromones are under different opioid modulation.

  4. Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents. (United States)

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


    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.

  5. Non-analgesic effects of opioids: management of opioid-induced constipation by peripheral opioid receptor antagonists: prevention or withdrawal? (United States)

    Holzer, Peter


    The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.

  6. Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats. (United States)

    Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi


    The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Uranium Enrichment, an overview

    International Nuclear Information System (INIS)

    Coates, J.H.


    This general presentation on uranium enrichment will be followed by lectures on more specific topics including descriptions of enrichment processes and assessments of the prevailing commercial and industrial situations. I shall therefore avoid as much as possible duplications with these other lectures, and rather dwell on: some theoretical aspects of enrichment in general, underlying the differences between statistical and selective processes, a review and comparison between enrichment processes, remarks of general order regarding applications, the proliferation potential of enrichment. It is noteworthy that enrichment: may occur twice in the LWR fuel cycle: first by enriching natural uranium, second by reenriching uranium recovered from reprocessing, must meet LWR requirements, and in particular higher assays required by high burn up fuel elements, bears on the structure of the entire front part of the fuel cycle, namely in the conversion/reconversion steps only involving UF 6 for the moment. (author). tabs., figs., 4 refs

  8. Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

    NARCIS (Netherlands)

    Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne


    BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.

  9. Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

    NARCIS (Netherlands)

    Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R.; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M.; Kreek, Mary Jeanne


    Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic

  10. Behavioral and electrographic effects of opioids on kindled seizures in rats. (United States)

    Caldecott-Hazard, S; Shavit, Y; Ackermann, R F; Engel, J; Frederickson, R C; Liebeskind, J C


    Our laboratory previously suggested that opioid peptides are released by an amygdaloid kindled seizure and may affect the elicitation of a subsequent seizure. The present study examined the effects of morphine, naloxone, enkephalin analogues, and conditions of morphine tolerance and withdrawal on the severity and duration of a series of amygdaloid kindled seizures. The results suggest two distinct opiate/opioid actions on seizures. The first is an anticonvulsant effect on the behavioral manifestations of seizures. This effect is seen following a high dose (50 mg/kg) of morphine or a low dose (6 mg/kg) of enkephalin analogue (LY146104), and is reversed by naloxone. The second is a naloxone-reversible prolonging effect of the high dose of morphine on the electrographic components of the seizures. Receptor affinities of these various opiate/opioid drugs suggest that these two actions are mediated by different receptors which appear not to include high affinity mu receptors.

  11. Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors. (United States)

    Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J


    Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

  12. The prescription opioid epidemic: an overview for anesthesiologists. (United States)

    Alam, Asim; Juurlink, David N


    The objectives for preparing this article were to review the historical context and epidemiology surrounding the North American prescription opioid crisis, to summarize the evidence regarding the benefits and harms of long-term opioid therapy for non-cancer pain, and to outline ways in which anesthesiologists may help ameliorate the problem. We searched PubMed, Google Scholar, and EMBASE™ for relevant articles using various search terms, including pain, opioid epidemic, history of opioid use, perioperative care, and addiction. Related citations were further explored and searched depending on the specific subtopic of interest. In the 1980s and early 1990s, opioids were infrequently used for the treatment of chronic pain. Thereafter, however, physicians were gradually inculcated with the message that long-term opioid therapy was a safe and effective treatment option for patients with chronic non-cancer pain. Pharmaceutical companies supported this growing movement and employed aggressive and sometimes misleading marketing strategies for new opioid formulations. As a result, the practice of prescribing opioids flourished in the late 1990s. The surge in prescribing opioids was accompanied by a marked increase in opioid-related morbidity and mortality. This change in practice transpired despite the absence of randomized trials showing clinically significant benefit from the long-term use of opioids. Subsequently, however, a large and growing body of evidence has emerged quantifying the harms associated with long-term opioid therapy. Anesthesiologists widely prescribe opioids for acute and chronic pain; yet, as a group, they may be largely unaware of the current state of this growing epidemic and what role they can play to rectify this problem. Anesthesiologists are well positioned to take a leadership role in the management of postoperative discharge opioid therapy in an effort to curb the overutilization of opioids. Furthermore, anesthesiologists who regularly

  13. The impact of opioids on the endocrine system. (United States)

    Katz, Nathaniel; Mazer, Norman A


    Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

  14. Possible Opioid Shopping and its Correlates. (United States)

    Walker, Alexander M; Weatherby, Lisa B; Cepeda, M Soledad; Bradford, Daniel; Yuan, Yingli


    We created an operational definition of possible opioid shopping in US commercial health insurance data and examined its correlates. The population consisted of 264,204 treatment courses in persons with a fill for an opioid or diuretic prescription in 2012 and a second within 18 months. We examined counts of prescribers and pharmacies and the numbers of fills and overlaps for ability to discriminate courses of opioids from diuretics, which were a negative control. The most discriminatory measure, indicating possible shopping behavior, was cross-tabulated against other prescriptions filled and diagnoses as found in insurance claims. The associations between claims characteristics and shopping behavior were assessed in a logistic regression. A definition that classified possible "moderate" or "extensive" shopping when a person obtained drug through at least 3 practices and at least 3 pharmacies over 18 months was highly discriminatory between opioid and diuretic treatment. Overlaps between fills and number of fills did not improve the discrimination. Data from insurance claims strongly predicted moderate-to-extensive levels of possible shopping (c=0.82). Prominent among 20 significant predictors were: state of residence; amount of opioid dispensed; self-payment; use of nonspecialist prescribers; high use of anxiolytics, hypnotics, psychostimulants, and antipsychotics; and use of both immediate release and extended-release or long-acting opioids. The use of ≥3 prescribing practices and ≥3 dispensing pharmacies over 18 months sharply discriminated courses of opioid treatment from courses of diuretics. This pattern of fills was additionally associated with the numbers of nonspecialist and self-paid fills, the total morphine milligram equivalents dispensed, and heavier use of drugs for anxiety, sleep, attention, and psychosis.

  15. Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Poulsen JL


    Full Text Available Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential

  16. The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents. (United States)

    Häuser, Winfried; Schug, Stephan; Furlan, Andrea D


    A marked rise in opioid prescriptions for patients with chronic noncancer pain (CNCP) with a parallel increase in opioid abuse/misuse, and resulting deaths was noted in the Unites states in the past decade (opioid epidemic). In response, the US Center of Diseases Control (CDC) developed a guideline for prescribing of opioids for patients with CNCP. To assess (1) if there is an opioid epidemic in Australia, Canada, and Germany (2) to compare Australian, Canadian, German, and Center of Diseases Control guidelines recommendations for long-term opioid therapy for CNCP. National evidence-based guidelines and PubMed were searched for recommendations for opioid prescriptions for CNCP. There are signs of an opioid epidemic in Australia and Canada, but not in Germany. Guidelines in all 4 countries provide similar recommendations: opioids are not the first-line therapy for patients with CNCP; regular clinical assessments of benefits and harms are necessary; excessive doses should be avoided (recommended morphine equivalent daily doses range from 50 to 200 mg/d); stopping rules should be followed. All guidelines do not recommend the use of opioids in chronic pain conditions without an established nociceptive or neuropathic cause such as fibromyalgia and primary headache. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

  17. Opioid Overdoses Treated in Emergency Departments PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.

  18. Opioids and Chronic Pain | NIH MedlinePlus the Magazine (United States)

    ... Long-term daily use of opioids leads to physical dependence, which is not to be confused with addiction ... be screened and closely monitored. When people have physical dependence and the opioid use is stopped, withdrawal symptoms ...

  19. Pain Management in the Opioid-Dependent Pregnant Woman. (United States)

    Safley, Rebecca R; Swietlikowski, Jamie

    Opioid dependence is an epidemic in the United States, and the percentage of pregnant women who are opioid dependent has increased dramatically in the last decade. Pain management, already a concern for intrapartum and postpartum care, is complicated in the context of opioid dependence. This clinical review surveys the literature on pain management in opioid-dependent pregnant women to summarize current consensus and evidence to guide clinical practice. Points of consensus for pain management in opioid-dependent pregnant women include continual opioid maintenance therapy throughout the pregnancy and the postpartum period; adequate management of acute pain; the contraindication of opioid agonist-antagonists for pain management; and the need for interdisciplinary teams using a multimodal approach to provide optimal care to opioid-dependent pregnant women.

  20. Recovering from Opioid Overdose: Resources for Overdose Survivors & Family Members (United States)

    ... and gratitude, all accompanied by the discomfort of opioid withdrawal. Most need the support of family and friends to take the next steps toward recovery. While many factors can contribute to opioid overdose, it is al most always an accident. ...

  1. Advanced enrichment techniques

    International Nuclear Information System (INIS)

    Johnson, A.


    BNFL is in a unique position in that it has commercial experience of diffusion enrichment, and of centrifuge enrichment through its associate company Urenco. In addition BNFL is developing laser enrichment techniques as part of a UK development programme in this area. The paper describes the development programme which led to the introduction of competitive centrifuge enrichment technology by Urenco and discusses the areas where improvements have and will continue to be made in the centrifuge process. It also describes the laser development programme currently being undertaken in the UK. The paper concludes by discussing the relative merits of the various methods of uranium enrichment, with particular reference to the enrichment market likely to obtain over the rest of the century

  2. Advanced enrichment techniques

    International Nuclear Information System (INIS)

    Johnson, A.


    BNFL is in a unique position in that it has commercial experience of diffusion enrichment, and of centrifuge enrichment through its associate company Urenco. In addition BNFL is developing laser enrichment techniques as part of a UK development programme in this area. The paper describes the development programme which led to the introduction of competitive centrifuge enrichment technology by Urenco and discusses the areas where improvements have and will continue to be made in the centrifuge process. It also describes the laser development programme currently being undertaken in the UK. The paper concludes by discussing the relative merits of the various methods of uranium enrichment, with particular reference to the enrichment market likely to obtain over the rest of the century. (author)

  3. Past-year Prescription Drug Monitoring Program Opioid Prescriptions and Self-reported Opioid Use in an Emergency Department Population With Opioid Use Disorder. (United States)

    Hawk, Kathryn; D'Onofrio, Gail; Fiellin, David A; Chawarski, Marek C; O'Connor, Patrick G; Owens, Patricia H; Pantalon, Michael V; Bernstein, Steven L


    Despite increasing reliance on prescription drug monitoring programs (PDMPs) as a response to the opioid epidemic, the relationship between aberrant drug-related behaviors captured by the PDMP and opioid use disorder is incompletely understood. How PDMP data should guide emergency department (ED) assessment has not been studied. The objective was to evaluate a relationship between PDMP opioid prescription records and self-reported nonmedical opioid use of prescription opioids in a cohort of opioid-dependent ED patients enrolled in a treatment trial. PDMP opioid prescription records during 1 year prior to study enrollment on 329 adults meeting Diagnostic and Statistical Manual IV criteria for opioid dependence entering a randomized clinical trial in a large, urban ED were cross-tabulated with data on 30-day nonmedical prescription opioid use self-report. The association among these two types of data was assessed by the Goodman and Kruskal's gamma; a logistic regression was used to explore characteristics of participants who had PDMP record of opioid prescriptions. During 1 year prior to study enrollment, 118 of 329 (36%) patients had at least one opioid prescription (range = 1-51) in our states' PDMP. Patients who reported ≥15 of 30 days of nonmedical prescription opioid use were more likely to have at least four PDMP opioid prescriptions (20/38; 53%) than patients reporting 1 to 14 days (14/38, 37%) or zero days of nonmedical prescription opioid use (4/38, 11%; p = 0.002). Female sex and having health insurance were significantly more represented in the PDMP (p Medicine.

  4. Uranium enrichment: an overview

    International Nuclear Information System (INIS)

    Cazalet, J.


    This paper is a general presentation of uranium enrichment processes and assessments of the prevailing commercial and industrial situations. It gives first some theoretical aspects of enrichment in general and explains the differences between statistical and selective processes in particular. Then a review of the different processes is made with a comparison between them. Finally, some general remarks concerning applications are given and the risks of proliferation related to enrichment are mentioned. (J.S.). 4 refs., 5 figs., 8 tabs

  5. The enrichment secondary market

    International Nuclear Information System (INIS)

    Einbund, D.R.


    This paper will addresses two topics: the background to the present status of the enrichment secondary market and the future outlook of the secondary market in enrichment services, and the viability of the nuclear fuel brokerage industry. These two topics are inevitably connected, as most secondary market activity, not only in enrichment but also in natural uranium, has traditionally been conducted with the participation of brokers. Therefore, the author interrelates these topics

  6. Review of environmental enrichment for broiler chickens

    DEFF Research Database (Denmark)

    Riber, Anja Brinch; Van de Weerd, H.A.; de Jong, I.C.


    to improvements of the biological function. This definition has been broadened to include practical and economic aspects, as any enrichment strategy that adversely affects the health of animals or that has too many economic or practical constraints will never be implemented on commercial farms and thus never...... benefit animals. Environmental enrichment for broilers often has the purpose of satisfying behavioral needs and/or stimulating the broilers to an increased level of activity, which among others will reduce the occurrence of leg problems. Potentially successful environmental enrichments for broiler...... chickens are elevated resting-places, panels, barriers, and bales of straw (“point-source enrichment”), as well as covered verandas and outdoor ranges (“complex enriched environments”). Many of the ideas for environmental enrichment for broilers need to be further developed and studied, preferably...

  7. The evolution of chronic opioid therapy and recognizing addiction. (United States)

    Daum, Akiva M; Berkowitz, Oren; Renner, John A


    Chronic pain is one of the most common complaints in the United States. Opioids have become a frequently prescribed treatment for patients with chronic nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic levels. Studies investigating iatrogenic opioid addiction have been of limited quality. Aberrant drug-related behaviors may be warning signs of impending addiction. Proper screening and close monitoring are essential for managing patients on opioids for chronic nonmalignant pain.

  8. Endogenous Opioid Inhibition of Chronic Low Back Pain Influences Degree of Back Pain Relief Following Morphine Administration (United States)

    Bruehl, Stephen; Burns, John W.; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Schuster, Erik; France, Christopher R.


    Background and Objectives Factors underlying differential responsiveness to opioid analgesic medications used in chronic pain management are poorly understood. We tested whether individual differences in endogenous opioid inhibition of chronic low back pain were associated with magnitude of acute reductions in back pain ratings following morphine administration. Methods In randomized, counterbalanced order over three sessions, 50 chronic low back pain patients received intravenous naloxone (8mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated pre-drug and again after peak drug activity was achieved using the McGill Pain Questionnaire-Short Form (Sensory and Affective subscales, VAS intensity measure). Opioid blockade effect measures to index degree of endogenous opioid inhibition of back pain intensity were derived as the difference between pre-to post-drug changes in pain intensity across placebo and naloxone conditions, with similar morphine responsiveness measures derived across placebo and morphine conditions. Results Morphine significantly reduced back pain compared to placebo (MPQ-Sensory, VAS; P effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with degree of acute morphine-related reductions in back pain on all measures, even after controlling for effects of age, sex, and chronic pain duration (P morphine. Conclusions Morphine appears to provide better acute relief of chronic back pain in individuals with lower natural opioidergic inhibition of chronic pain intensity. Possible implications for personalized medicine are discussed. PMID:24553304

  9. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates. (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A


    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

  10. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans. (United States)

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


    The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Access to opioids: a global pain management crisis. (United States)

    Buitrago, Rosa


    The lack of availability of opioids in many countries has created a pain management crisis. Because the Single Convention on Narcotic Drugs requires governments to report annual opioid statistics, there is a need for methods to calculate individual nations' opioid needs. Ways to address this need are discussed.

  12. Global Supply and Demand of Opioids for Pain Management. (United States)

    Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini


    The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

  13. Opioid Analgesics and Nicotine: More Than Blowing Smoke. (United States)

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F


    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

  14. The opioid ketobemidone has a NMDA blocking effect

    DEFF Research Database (Denmark)

    Andersen, S; Dickenson, A H; Kohn, M


    There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effect...

  15. Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena


    Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

  16. Chronic intermittent hypoxia is independently associated with reduced postoperative opioid consumption in bariatric patients suffering from sleep-disordered breathing.

    Directory of Open Access Journals (Sweden)

    Alparslan Turan

    Full Text Available Evidence suggests that recurrent nocturnal hypoxemia may affect pain response and/or the sensitivity to opioid analgesia. We tested the hypothesis that nocturnal hypoxemia, quantified by sleep time spent at an arterial saturation (SaO2 < 90% and minimum nocturnal SaO2 on polysomnography, are associated with decreased pain and reduced opioid consumption during the initial 72 postoperative hours in patients having laparoscopic bariatric surgery.With Institutional Review Board approval, we examined the records of all patients who underwent laparoscopic bariatric surgery between 2004 and 2010 and had an available nocturnal polysomnography study. We assessed the relationships between the time-weighted average of pain score and total opioid consumption during the initial 72 postoperative hours, and: (a the percentage of total sleep time spent at SaO2 < 90%, (b the minimum nocturnal SaO2, and (c the number of apnea/hypopnea episodes per hour of sleep. We used multivariable regression models to adjust for both clinical and sleep-related confounders.Two hundred eighteen patients were included in the analysis. Percentage of total sleep time spent at SaO2 < 90% was inversely associated with total postoperative opioid consumption; a 5-%- absolute increase in the former would relatively decrease median opioid consumption by 16% (98.75% CI: 2% to 28%, P = 0.006. However, the percentage of total sleep time spent at SaO2 < 90% was not associated with pain. The minimum nocturnal SaO2 was associated neither with total postoperative opioid consumption nor with pain. In addition, neither pain nor total opioid consumption was significantly associated with the number of apnea/hypopnea episodes per hour of sleep.Preoperative nocturnal intermittent hypoxia may enhance sensitivity to opioids.

  17. Postoperative opioid analgesia: time for a reconsideration?

    DEFF Research Database (Denmark)

    Kehlet, H; Rung, G W; Callesen, T


    Postoperative pain relief has improved in recent years with the development of new analgesics, additional routes of administration and the appearance of the hypothesis of preemptive as well as balanced analgesia (Kehlet H; Postoperative pain relief-what is the issue? Br J Anaesth 1994;72:375-8). ......Postoperative pain relief has improved in recent years with the development of new analgesics, additional routes of administration and the appearance of the hypothesis of preemptive as well as balanced analgesia (Kehlet H; Postoperative pain relief-what is the issue? Br J Anaesth 1994......;72:375-8). Many initial improvements simply involved the administration of opioid analgesics in new ways, such as continuous or on demand intravenous (i.v.) or epidural infusion. These methods allow lower total opioid dosages, provide a more stable concentration of opioid at the receptor and correspondingly...

  18. Emergency Department Patient Perspectives on the Risk of Addiction to Prescription Opioids. (United States)

    Conrardy, Michael; Lank, Patrick; Cameron, Kenzie A; McConnell, Ryan; Chevrier, Alison; Sears, Jill; Ahlstrom, Eric; Wolf, Michael S; Courtney, D Mark; McCarthy, Danielle M


    To characterize emergency department (ED) patients' knowledge and beliefs about the addictive potential of opioids. Mixed methods analysis of data from a randomized controlled trial. Urban academic ED (>88,000 visits). One hundred and seventy four discharged ED patients prescribed hydrocodone-acetaminophen for acute pain. The study analyzed data collected from a randomized controlled trial investigating patients' knowledge of opioids. ED patients discharged with hydrocodone-acetaminophen completed an audio-recorded phone interview 4–7 days later. This analysis focuses on responses about addiction. Responses were categorized using content analysis; thematic analysis identified broad themes common across different categories. Participants' mean age was 45.5 years (SD, 14.8), 58.6% female, 50.6% white, and the majority had an orthopedic diagnosis (24.1% back pain, 52.3% other injuries). Responses were categorized first based on whether the patient believed that opioids could be addictive (categorized as: yes, 58.7%; no, 19.5%; depends, 17.2%; or do not know, 4.6%), and second based on whether or not the patient discussed his/her own experience with the medication (categorized as: personalized, 35.6%; or not personalized, 64.4%). Cohen's Kappa was 0.84 for all categories. Three themes emerged in the thematic analysis: theme 1) patients expect to “feel” addicted if they are addicted, theme 2) patients fear addiction, and theme 3) side effects affected patient views of addiction. In this sample, patients had misconceptions about opioid addiction. Some patients did not know opioids could be addictive, others underestimated their personal risk of addiction, and others overtly feared addiction and, therefore, risked inadequate pain management. Despite limited data, we recommend providers discuss opioid addiction with their patients. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government

  19. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems. (United States)

    Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo


    All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted

  20. Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review. (United States)

    Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M


    Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Primary care for opioid use disorder

    Directory of Open Access Journals (Sweden)

    Mannelli P


    Full Text Available Paolo Mannelli,1 Li-Tzy Wu1–41Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University Medical Center, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, USARecent reports on prescription opioid misuse and abuse have described unprecedented peaks of a national crisis and the only answer is to expand prevention and treatment, including different levels of care.1 Nonetheless, concerns remain about the ability of busy primary care settings to manage problem opioid users along with other patients. In particular, proposed extensions of buprenorphine treatment, a critically effective intervention for opioid use disorder (OUD, are cautiously considered due to the potential risk of misuse or abuse.2 General practitioners are already facing this burden daily in the treatment of chronic pain, and expert supervision and treatment model adjustment are needed to help improve outcomes. Approximately 20% of patients in primary care have noncancer pain symptoms, with most of them receiving opioid prescriptions by their physicians, and their number is increasing.3 Pain diagnoses are comparable in severity to those of tertiary centers and are complicated by significant psychiatric comorbidity, with a measurable lifetime risk of developing OUD.4,5 Some primary care physicians report frustration about opioid abuse and diversion by their patients; support from pain specialists would improve their competence, the quality f their performance, and the ability to identify patients at risk of opioid misuse.6 Thus, buprenorphine treatment should not be adding to a complex clinical scenario. To this end, the promising models of care emphasize the integration of medical with psychological and pharmacological expertise for the management of OUD. 

  2. Protocol: mixed-methods study to evaluate implementation, enforcement, and outcomes of U.S. state laws intended to curb high-risk opioid prescribing. (United States)

    McGinty, Emma E; Stuart, Elizabeth A; Caleb Alexander, G; Barry, Colleen L; Bicket, Mark C; Rutkow, Lainie


    The U.S. opioid epidemic has been driven by the high volume of opioids prescribed by healthcare providers. U.S. states have recently enacted four types of laws designed to curb high-risk prescribing practices, such as high-dose and long-term opioid prescribing, associated with opioid-related mortality: (1) mandatory Prescription Drug Monitoring Program (PDMP) enrollment laws, which require prescribers to enroll in their state's PDMP, an electronic database of patients' controlled substance prescriptions, (2) mandatory PDMP query laws, which require prescribers to query the PDMP prior to prescribing an opioid, (3) opioid prescribing cap laws, which limit the dose and/or duration of opioid prescriptions, and (4) pill mill laws, which strictly regulate pain clinics to prevent nonmedical opioid prescribing. Some pain experts have expressed concern that these laws could negatively affect pain management among patients with chronic non-cancer pain. This paper describes the protocol for a mixed-methods study analyzing the independent effects of these four types of laws on opioid prescribing patterns and chronic non-cancer pain treatment, accounting for variation in implementation and enforcement of laws across states. Many states have enacted multiple opioid prescribing laws at or around the same time. To overcome this issue, our study focuses on 18 treatment states that each enacted a single law of interest, and no other potentially confounding laws, over a 4-year period (2 years pre-/post-law). Qualitative interviews with key leaders in each of the 18 treatment states will characterize the timing, scope, and strength of each state law's implementation and enforcement. This information will inform the design and interpretation of synthetic control models analyzing the effects of each of the two types of laws on two sets of outcomes: measures of (1) high-risk opioid prescribing and (2) non-opioid treatments for chronic non-cancer pain. Study of mandatory PDMP enrollment

  3. Effect of Tramadol (μ-opioid receptor agonist on orthodontic tooth movements in a rat model

    Directory of Open Access Journals (Sweden)

    E. Javadi


    Full Text Available Objective: Tramadol is a synthetic analgesic of opioids which has more flexible mechanisms of action than typical opioids. Since it has been reported in previous study that typical opioids like morphine can affect the bone homeostasis, it is worthwhile to examine the effects of tramadol on tooth movement. In this study we investigated effects of tramadol on orthodontic tooth movement in rats.Materials and Methods: 30 male wistar rats were selected and received orthodontic appliance. 3 groups were designed based on the substance that they received daily injections of during a 2-week orthodontic treatment. 1. Control group with no injection.2.Control group with normal saline injection.3. the tramadol group. After the two-week treatment period the amount of tooth movement were measured in all the groups. Also the histological analysis was performed assessing the root resorption, osteoclasts numbers and bone resorption.Results: The amount of tooth movement was not significantl in the tramadol group comparing to the other groups (P>0.05.The results of 3 histological parameters (amount of root resorption, osteoclastic numbers and bone resorption were statistically insignificant (P>0.05.Conclusion: Tramadol as an atypical opioid does not interfere with the process of bone remodeling and tooth movement in rat. Tramadol does not affect osteoclastic activity and bone resorption and it does not cause to change the resulted root resorption either.

  4. Opioid receptor mediated anticonvulsant effect of pentazocine. (United States)

    Khanna, N; Khosla, R; Kohli, J


    Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

  5. Non-analgesic effects of opioids

    DEFF Research Database (Denmark)

    Højsted, Jette; Kurita, Geana Paula; Kendall, Sally


    Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher...

  6. Opioids in Cancer Pain: Right or Privilege? (United States)

    Jackson, Leanne K; Imam, Syed N; Braun, Ursula K


    Opioid analgesia is a mainstay of the treatment of cancer pain. Treatment of pain in patients with cancer with an ongoing substance abuse disorder can be difficult. We report the ethical challenges of treating a patient with cancer with a concomitant substance abuse disorder in an outpatient palliative care setting. We present an analysis of ethical considerations for the palliative care physician and strategies to aid in the successful treatment of such patients. We argue that there are select patients with cancer for whom exclusion from treatment with opioid therapy is warranted if their health is endangered by prescription of these medications.

  7. Uranium enrichment plans

    International Nuclear Information System (INIS)

    Gagne, R.W.; Thomas, D.C.


    The status of existing uranium enrichment contracts in the US is reviewed and expected natural uranium requirements for existing domestic uranium enrichment contracts are evaluated. Uncertainty in natural uranium requirements associated with requirements-type and fixed-commitment type contracts is discussed along with implementation of variable tails assay

  8. The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents

    Directory of Open Access Journals (Sweden)

    Winfried Häuser


    Conclusion:. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

  9. Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain. (United States)

    Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D


    Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p opioid overdose risk factors (12.1 versus 13.5, p opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

  10. Prescription opioid abuse, pain and addiction: clinical issues and implications. (United States)

    Ling, Walter; Mooney, Larissa; Hillhouse, Maureen


    Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  11. Development and preliminary validation of the Opioid Abuse Risk Screener

    Directory of Open Access Journals (Sweden)

    Patricia Henrie-Barrus


    Full Text Available Prescription opioid drug abuse has reached epidemic proportions. Individuals with chronic pain represent a large population at considerable risk of abusing opioids. The Opioid Abuse Risk Screener was developed as a comprehensive self-administered measure of potential risk that includes a wide range of critical elements noted in the literature to be relevant to opioid risk. The creation, refinement, and preliminary modeling of the item pool, establishment of preliminary concurrent validity, and the determination of the factor structure are presented. The initial development and validation of the Opioid Abuse Risk Screener shows promise for effective risk stratification.

  12. Psychological and drug abuse symptoms associated with nonmedical use of opioid analgesics among adolescents. (United States)

    Boyd, Carol J; Young, Amy; McCabe, Sean E


    Approximately 18% of US adolescents engaged in prescription opioid abuse in 2013. However, this estimate may be misleading because it includes both medical misusers and nonmedical users, and there is evidence that these are 2 groups that differ relative to substance abuse and criminal risk. Thus, this study does not combine medical and nonmedical users; rather, it seeks to better understand the characteristics of nonmedical users. This was a school-based, cross-sectional study that was conducted during 2009-2010 in southeastern Michigan with a sample of 2627 adolescents using a Web-based survey. Three mutually exclusive groups were created based on responses regarding medical and nonmedical use of opioid analgesics. Group 1 had never used an opioid analgesic, Group 2 used an opioid analgesic only as prescribed, and Group 3 nonmedically used an opioid analgesic. In addition, Group 3 was divided into 2 mutually exclusive subgroups (self-treaters and sensation-seekers) based on reasons for nonmedical use. A series of multinomial logistic regressions were conducted to determine if the groups differed on the presence of pain, psychological symptoms (e.g., affective disorder, conduct disorder, attention-deficit/hyperactivity disorder [ADHD]), and drug abuse. Sixty-five percent (65.0%) of the sample was white/Caucasian and 29.5% was African American. The average age was 14.8 years (SD = 1.9). Seventy percent (70.4%; n = 1850) reported no lifetime opioid use, 24.5% (n = 644) were medical users, 3.5% (n = 92) were nonmedical users who used for pain relief only, and 1.6% (n = 41) were classified as nonmedical users for reasons other than for pain relief (e.g., to get high). Both medical users and nonmedical users reported more pain and substance abuse symptoms compared with never users. Those nonmedical users who used opioids for sensation-seeking motivations had greater odds of having psychological symptoms. These data support the need to further consider subgroups of

  13. The Relative Potency of Inverse Opioid Agonists and a Neutral Opioid Antagonist in Precipitated Withdrawal and Antagonism of Analgesia and Toxicity


    Sirohi, Sunil; Dighe, Shveta V.; Madia, Priyanka A.; Yoburn, Byron C.


    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was exa...

  14. Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor. (United States)

    Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell


    Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Sucrose ingestion causes opioid analgesia

    Directory of Open Access Journals (Sweden)

    F.N. Segato


    Full Text Available The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12 for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47 = 9.521, P<0.001 and the Tukey multiple comparison test (P<0.05 showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7 receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7 had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03. This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

  16. Computational opioid prescribing: a novel application of clinical pharmacokinetics. (United States)

    Linares, Oscar A; Linares, Annemarie L


    We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

  17. Developments in uranium enrichment

    International Nuclear Information System (INIS)

    Mohrhauer, H.


    The enrichment services market is still characterized by overcapacities. While consumption worldwide will rise by some 15% to 39,000 t SWU/a over the next ten years, capacities amount to nearly 50,000 t SWU/a. The price for enrichment services probably has reached its all time low. Prices below U.S. $ 100/kg SWU are not likely to cover costs even of the economically most advanced enrichment processes. Urenco has prepared for the difficult enrichment business in the years to come by streamlining and cost cutting measures. The company intends to hold and increase its share of more than 10% in the world market. The uranium enrichment plant of Gronau will be expanded further. Expansion beyond 1000 t is subject to another permit being granted under the Atomic Energy Act, an application for which was filed in December 1994. Centrifuge technology is the superior enrichment technology, i.e., there is still considerable potential for further development. Construction of enrichment plants employing the centrifuge technology in the United States and in France is being pursued in various phases, from feasibility studies to licensing procedures. Before these plants could be implemented, however, considerable problems of organization would have to be solved, and the market would have to change greatly, respectively. The laser process, at the present time, does not seem to be able to develop into a major industrial competitor. (orig.) [de

  18. Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

    Directory of Open Access Journals (Sweden)

    Azita Chehri


    Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

  19. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk

    Directory of Open Access Journals (Sweden)

    Elizabeth Huber


    Full Text Available Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, “Who is at risk of opioid misuse?” should evolve to, “Who may benefit from COT?” in light of the current evidence.

  20. TRIGA low enrichment fuel

    International Nuclear Information System (INIS)

    Gietzen, A.


    Sixty TRIGA reactors have been sold and the earliest of these are now passing twenty years of operation. All of these reactors use the uranium zirconium hydride fuel (UZrH) which provides certain unique advantages arising out of its large prompt negative temperature coefficient, very low fission product release, and high temperature capability. Eleven of these Sixty reactors are conversions from plate fuel to TRIGA fuel which were made as a result of these advantages. With only a few exceptions, TRIGA reactors have always used low-enriched uranium (LEU) fuel with an enrichment of 19.9%. The exceptions have either been converted from the standard low-enriched fuel to the 70% enriched FLIP fuel in order to achieve extended lifetime, or are higher powered reactors which were designed for long life using 93%-enriched uranium during the time when the use and export of highly enriched uranium (HEU) was not restricted. The advent of international policies focusing attention on nonproliferation and safeguards made the HEU fuels obsolete. General Atomic immediately undertook a development effort (nearly two years ago) in order to be in a position to comply with these policies for all future export sales and also to provide a low-enriched alternative to fully enriched plate-type fuels. This important work was subsequently partially supported by the U.S. Department of Energy. The laboratory and production tests have shown that higher uranium densities can be achieved to compensate for reducing the enrichment to 20%, and that the fuels maintain the characteristics of the very thoroughly proven standard TRIGA fuels. In May of 1978, General Atomic announced that these fuels were available for TRIGA reactors and for plate-type reactors with power levels up to 15 MW with General Atomic's standard commercial warranty

  1. TRIGA low enrichment fuel

    International Nuclear Information System (INIS)

    Gietzen, A.


    Sixty TRIGA reactors have been sold and the earliest of these are now passing twenty years of operation. All of these reactors use the uranium-zirconium hydride fuel (UZrH) which provides certain unique advantages arising out of its large prompt negative temperature coefficient, very low fission product release, and high temperature capability. Eleven of these Sixty reactors are conversions from plate fuel to TRIGA fuel which were made as a result of these advantages. With only a few exceptions, TRIGA reactors have always used low-enriched-uranium (LEU) fuel with an enrichment of 19.9%. The exceptions have either been converted from the standard low-enriched fuel to the 70% enriched FLIP fuel in order to achieve extended lifetime, or are higher powered reactors which were designed for long life using 93%-enriched uranium during the time when the use and export of highly enriched uranium (HEU) was not restricted. The advent of international policies focusing attention on nonproliferation and safeguards made the HEU fuels obsolete. General Atomic immediately undertook a development effort (nearly two years ago) in order to be in a position to comply with these policies for all future export sales and also to provide a low-enriched alternative to fully enriched plate-type fuels. This important work was subsequently partially supported by the U.S. Department of Energy. The laboratory and production tests have shown that higher uranium densities can be achieved to compensate for reducing the enrichment to 20%, and that the fuels maintain the characteristics of the very thoroughly proven standard TRIGA fuels. In May of 1978, General Atomic announced that these fuels were available for TRIGA reactors and for plate-type reactors with power levels up to 15 MW with GA's standard commercial warranty

  2. Prescription opioid abuse: pharmacists’ perspective and response

    Directory of Open Access Journals (Sweden)

    Cochran G


    Full Text Available Gerald Cochran,1,2 Valerie Hruschak,2 Brooke DeFosse,3 Kenneth C Hohmeier3 1Department of Psychiatry, School of Medicine, 2School of Social Work, University of Pittsburgh, Pittsburgh, PA, 3Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis, TN, USA Abstract: Opioid medication abuse and overdose are major concerns for public health, and a number of responses to address these issues have taken place across the US. Pharmacists and the pharmacy profession have made important contributions as a part of the response to this national crisis. This article provides a brief review of the antecedents, driving forces, and health status of patients involved in the opioid medication and overdose epidemic. This review further discusses pharmacy-based actions that have been undertaken to address this issue, including prescription drug monitoring, take-back, and naloxone training/distribution programs. This review likewise examines current efforts underway in the field to educate practitioners and needed future steps that must be taken by pharmacists in order to continue the profession’s pivotal role in working toward resolving this national public health problem. In particular, evidence and arguments are presented for proactively identifying and intervening with patients who abuse and/or are at risk for overdose. Continued and active engagement by pharmacists in these efforts has the potential to result in important reductions in opioid medication abuse and overdose and improvements for patient’s health. Keywords: opioid pain medication, addiction, pharmacy practice

  3. 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


    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

  4. The Prescription Opioid Pain Medication Overdose Epidemic

    Centers for Disease Control (CDC) Podcasts


    Overdose related to prescription opioids has become an epidemic. This podcast discusses the risks of this type of drug sometimes used to treat pain, and how to protect yourself. .  Created: 4/19/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/19/2016.

  5. Most drug overdose deaths from nonprescription opioids

    Directory of Open Access Journals (Sweden)

    Robbins RA


    Full Text Available No abstract available. Article truncated at 150 words. The Centers for Disease Control (CDC is reporting in Morbidity and Mortality Weekly that the number of people dying from an opioid overdose rose 15.5% from 2014 to 2015, but the increase had little to do with prescription painkillers such as oxycodone or hydrocodone (1. Roughly 52,000 people died from drug overdoses in 2015 and of those deaths 33,091 involved an opioid. The increases in “death rates were driven by synthetic opioids other than methadone (72.2%, most likely illicitly-manufactured fentanyl, and heroin (20.6%”. Deaths from methadone, which is usually prescribed by physicians, decreased 9.1%. The largest increase in deaths occurred in the South and Northeast with 3% and 24% increases in deaths from synthetic opioids from 2014 to 2015. In the Midwest and West, there were more modest 17% and 9% increases during the same period. States in the Southwest with “good” to “excellent” reporting included Colorado, Nevada, and New …

  6. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B


    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chr...

  7. 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


    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

  8. Parasite and nutrient enrichment effects on Daphnia interspecific competition

    NARCIS (Netherlands)

    Decaestecker, Ellen; Verreydt, Dino; De Meester, Luc; Declerck, Steven A.J.


    Increased productivity due to nutrient enrichment is hypothesized to affect density-dependent processes, such as transmission success of horizontally transmitting parasites. Changes in nutrient availability can also modify the stoichiometry and condition of individual hosts, which may affect their

  9. Linking nutrient enrichment, sediment erodibility and biofilms (United States)

    Conrad, B.; Mahon, R.; Sojka, S. L.


    Sediment movement in coastal lagoons affects nutrient flux and primary producer growth. Previous research has shown that sediment erodibility is affected by biofilm concentration and that growth of benthic organisms, which produce biofilm, is affected by nutrient enrichment. However, researchers have not examined possible links between nutrient addition and sediment erodibility. We manipulated nutrient levels in the water column of 16 microcosms filled with homogenized sediment from a shallow coastal lagoon and artificial seawater to determine the effects on biofilm growth, measured through chlorophyll a and colloidal carbohydrate concentrations. Erosion tests using a Gust microcosm were conducted to determine the relationship between sediment erodibility and biofilm concentration. Results show that carbohydrate levels decreased with increasing nutrient enrichment and were unrelated to chlorophyll concentrations and erodibility. The nutrient levels did not predictably affect the chlorophyll levels, with lower chlorophyll concentrations in the control and medium enrichment treatments than the low and high enrichment treatments. Controls on biofilm growth are still unclear and the assumed relationship between carbohydrates and erodibility may be invalid. Understanding how biofilms respond to nutrient enrichment and subsequent effects on sediment erodibility is essential for protecting and restoring shallow coastal systems.

  10. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans


    Schalling Martin; Lonsdorf Tina B; Jensen Karin B; Kosek Eva; Ingvar Martin


    Abstract Background There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expressio...

  11. Women who abuse prescription opioids: findings from the Addiction Severity Index-Multimedia Version Connect prescription opioid database. (United States)

    Green, Traci C; Grimes Serrano, Jill M; Licari, Andrea; Budman, Simon H; Butler, Stephen F


    Evidence suggests gender differences in abuse of prescription opioids. This study aimed to describe characteristics of women who abuse prescription opioids in a treatment-seeking sample and to contrast gender differences among prescription opioid abusers. Data collected November 2005 to April 2008 derived from the Addiction Severity Index Multimedia Version Connect (ASI-MV Connect) database. Bivariate and multivariable logistic regression examined correlates of prescription opioid abuse stratified by gender. 29,906 assessments from 220 treatment centers were included, of which 12.8% (N=3821) reported past month prescription opioid abuse. Women were more likely than men to report use of any prescription opioid (29.8% females vs. 21.1% males, phistory of drug overdose. Men-specific correlates were age screen and identify those at highest risk of prescription opioid abuse. Prevention and intervention efforts with a gender-specific approach are warranted.

  12. Thallium exists in opioid poisoned patients. (United States)

    Ghaderi, Amir; Vahdati-Mashhadian, Naser; Oghabian, Zohreh; Moradi, Valiallah; Afshari, Reza; Mehrpour, Omid


    Thallium (Tl) is a toxic heavy metal that exists in nature. Tl poisoning (thallotoxicosis) may occur in opioid addicts. This study was designed to evaluate the frequency and level of urinary Tl in opioid abusers. In addition, clinical findings were evaluated. A total of 150 subjects were examined. Cases with a history of at least 3 years of abuse were admitted in the Imam Reza Hospital as the case group; 50 non-opioid abusers from the target population were included as the control group. Twenty-four hour urinary qualitative and quantitative Tl analyses were performed on both groups. Out of the 150 subjects, 128 (85 %) were negative for qualitative urinary Tl, followed by 5 % (trace), 7 % (1+), 2 % (2+), and 1 % (3+). Mean (standard error (SE), Min-Max) quantitative urinary Tl level was 14 μg/L (3.5 μg/L, 0-346 μg/L). Mean urinary Tl level in the case group was 21 μg/L (5 μg/L, 0-346 μg/L) and that in the controls was 1 μg/L (0.14 μg/L, 0-26 μg/L), which were significantly different (P = 0.001). The most frequent clinical findings were ataxia (86 %), sweating (81 %), and constipation (54 %). In all cases (n = 150), the mean (SE) value for cases with positive qualitative urinary Tl was 26.8 μg/L (0.9 μg/L) and that in the negative cases was 2.3 μg/L (0.2 μg/L), which were significantly different (P = 0.002). This study showed that long-term opioid abuse may lead to Tl exposure. In opioid abusers with the clinical manifestation of thallotoxicosis, urinary Tl should be determined.

  13. Assessment of prescription opioid intentional exposures across the rural-urban continuum in the United States using both population and drug availability rates. (United States)

    Le Lait, Marie-Claire; Martinez, Erin M; Severtson, Stevan G; Lavery, Sarah A; Bucher-Bartelson, Becki; Dart, Richard C


    Prescription opioid abuse and misuse are a serious problem in the U.S. today. Several studies have shown that the epidemic disproportionately affects rural areas. This paper uses three different rates to gain a more complete picture of opioid abuse in rural areas. This study examines prescription opioid intentional exposures using opioid classes tracked in the RADARS(®) System Poison Center Program. Intentional exposure rates were calculated adjusting for population and unique recipients of dispensed drug (URDD). These rates were analyzed using time (quarter) and the proportion of a three-digit zip code residing in a rural area as covariates. Additionally, the URDD per population rate was calculated to examine the proportion of the population filling prescriptions for opioids. After adjusting for population, intentional exposure cases significantly increased as the proportion of the population residing in a rural area increased. However, when adjusting for URDD, intentional exposure cases decreased with increasing rural population. The URDD per population increased as the proportion of people residing in a rural area increased. Using both population and URDD adjusted intentional exposure rates gives a more complete picture of opioid abuse in rural areas. Considering product availability can be used to develop opioid abuse prevention strategies and further the education of physicians serving rural areas about this epidemic. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction. (United States)

    Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C


    Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  15. Effects of Competing Narratives on Public Perceptions of Opioid Pain Reliever Addiction during Pregnancy. (United States)

    Kennedy-Hendricks, Alene; McGinty, Emma E; Barry, Colleen L


    Opioid pain reliever addiction has increased among women of reproductive age over the last fifteen years. News media and public attention have focused on the implications of this trend for infants exposed to opioids prenatally, with state policy responses varying in the extent to which they are punitive or public health oriented. We fielded a six-group randomized experiment among a nationally representative sample of US adults to test the effects of narratives portraying a woman with opioid pain reliever addiction during pregnancy on beliefs about people addicted to opioid pain relievers, perceptions of treatment effectiveness, policy attitudes, and emotional responses. Portraying a high socioeconomic status (SES) woman in the narrative lowered perceptions of individual blame for addiction and reduced public support for punitive policies. Depicting the barriers to treatment faced by a low SES woman lowered support for punitive policies and increased support for expanded insurance coverage for treatment. The extent to which narratives portraying successfully treated addiction affected public attitudes depended on the SES of the woman portrayed. These findings can inform the development of communication strategies to reduce stigma toward this population, reduce support for punitive policies, and increase support for more public health-oriented approaches to addressing this problem. Copyright © 2016 by Duke University Press.

  16. Experiences of burnout among drug counselors in a large opioid treatment program: A qualitative investigation. (United States)

    Beitel, Mark; Oberleitner, Lindsay; Muthulingam, Dharushana; Oberleitner, David; Madden, Lynn M; Marcus, Ruthanne; Eller, Anthony; Bono, Madeline H; Barry, Declan T


    Little is known about possible experiences of burnout among drug counselors in opioid treatment programs that are scaling up capacity to address the current opioid treatment gap. Participants in this quality improvement study were 31 drug counselors employed by large opioid treatment programs whose treatment capacities were expanding. Experiences of burnout and approaches for managing and/or preventing burnout were examined using individual semi-structured interviews, which were audiotaped, transcribed, and systematically coded by a multidisciplinary team using grounded theory. Rates of reported burnout (in response to an open-ended question) were lower than expected, with approximately 26% of participants reporting burnout. Counselor descriptions of burnout included cognitive, affective, behavioral, and physiological symptoms; and job-related demands were identified as a frequent cause. Participants described both self-initiated (e.g., engaging in pleasurable activities, exercising, taking breaks during workday) and system-supported strategies for managing or preventing burnout (e.g., availing of supervision and paid time off). Counselors provided recommendations for system-level changes to attenuate counselor risk of burnout (e.g., increased staff-wide encounters, improved communication, accessible paid time off, and increased clinical supervision). Findings suggest that drug counselor burnout is not inevitable, even in opioid treatment program settings whose treatment capacities are expanding. Organizations might benefit from routinely assessing counselor feedback about burnout and implementing feasible recommendations to attenuate burnout and promote work engagement.

  17. Regulation of extinction-related plasticity by opioid receptors in the ventrolateral periaqueductal gray matter

    Directory of Open Access Journals (Sweden)

    Ryan Parsons


    Full Text Available Recent work has led to a better understanding of the neural mechanisms underlying the extinction of Pavlovian fear conditioning. Long-term synaptic changes in the medial prefrontal cortex (mPFC are critical for extinction learning, but very little is currently known about how the mPFC and other brain areas interact during extinction. The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK in brain regions that likely participate in the consolidation of extinction learning. Inhibitors of opioid and N-methyl-D-aspartic acid (NMDA receptors were applied to the ventrolateral periaqueductal gray matter (vlPAG and amygdala shortly before extinction training. Results from these experiments show that blocking opioid receptors in the vlPAG prevented the formation of extinction memory, whereas NMDA receptor blockade had no effect. Conversely, blocking NMDA receptors in the amygdala disrupted the formation of fear extinction memory, but opioid receptor blockade in the same brain area did not. Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training. Only opioid receptor blockade in the vlPAG disrupted ERK phosphorylation in the mPFC and amygdala. These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

  18. Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function. (United States)

    Poulose, Shibu M; Miller, Marshall G; Scott, Tammy; Shukitt-Hale, Barbara


    Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging. © 2017 American Society for Nutrition.

  19. Review of environmental enrichment for broiler chickens. (United States)

    Riber, A B; van de Weerd, H A; de Jong, I C; Steenfeldt, S


    Welfare problems are commonly found in both conventional and organic production of broiler chickens. In order to reduce the extent of welfare problems, it has been suggested to provide stimulating, enriched environments. The aim of the present paper is to provide a review of the effect on behavior and welfare of the different kinds of environmental enrichments in the production of broilers that have been described in the scientific literature. Environmental enrichment is defined as an improvement of the environment of captive animals, which increases the behavioral opportunities of the animal and leads to improvements of the biological function. This definition has been broadened to include practical and economic aspects, as any enrichment strategy that adversely affects the health of animals or that has too many economic or practical constraints will never be implemented on commercial farms and thus never benefit animals. Environmental enrichment for broilers often has the purpose of satisfying behavioral needs and/or stimulating the broilers to an increased level of activity, which among others will reduce the occurrence of leg problems. Potentially successful environmental enrichments for broiler chickens are elevated resting-places, panels, barriers, and bales of straw ("point-source enrichment"), as well as covered verandas and outdoor ranges ("complex enriched environments"). Many of the ideas for environmental enrichment for broilers need to be further developed and studied, preferably in commercial trials, with respect to the use, the effect on behavior and on other welfare aspects such as leg health, and the interaction with genotype, production system, stocking density, light, and flock size. In addition, information on the practical application and the economics of the production system is often lacking, although it is important for application in practice. © 2017 Poultry Science Association Inc.

  20. Opioids Consumed in the Immediate Post-Operative Period Do Not Influence How Patients Rate Their Experience of Care After Total Hip Arthroplasty. (United States)

    Etcheson, Jennifer I; Gwam, Chukwuweike U; George, Nicole E; Virani, Sana; Mont, Michael A; Delanois, Ronald E


    Patient perception of care, commonly measured with Press Ganey (PG) surveys, is an important metric used to determine hospital and provider reimbursement. However, post-operative pain following total hip arthroplasty (THA) may negatively affect patient satisfaction. As a result, over-administration of opioids may occur, even without marked evidence of pain. Therefore, this study evaluated whether opioid consumption in the immediate postoperative period bears any influence on satisfaction scores after THA. Specifically, this study assessed the correlation between post-operative opioid consumption and 7 PG domains: (1) Overall hospital rating; (2) Communication with nurses; (3) Responsiveness of hospital staff; (4) Communication with doctors; (5) Hospital environment; (6) Pain Management; and (7) Communication about medicines. Our institutional PG database was reviewed for patients who received THA from 2011 to 2014. A total of 322 patients (mean age = 65 years; 61% female) were analyzed. Patient's opioid consumption was measured using a morphine milli-equivalent conversion algorithm. Bivariate correlation analysis assessed the association between opioid consumption and Press-Ganey survey elements. Pearson's r assessed the strength of the association. No correlation was found between total opioid consumption and Overall hospital rating (r = 0.004; P = .710), Communication with nurses (r = 0.093; P = .425), Responsiveness of hospital staff (r = 0.104; P = .381), Communication with doctors (r = 0.009; P = .940), Hospital environment (r = 0.081; P = .485), and Pain management (r = 0.075; P = .536). However, there was a positive correlation between total opioid consumption and "Communication about medicines" (r = 0.262; P = .043). Our report demonstrates that PG patient satisfaction scores are not influenced by post-operative opioid use, with the exception of PG domain, "Communication about medications." These results suggest that opioid medications should be

  1. Dispositional study of opioids in mice pretreated with sympathomimetic agents. (United States)

    Dambisya, Y M; Chan, K; Wong, C L


    Brain and plasma levels of morphine and codeine were determined by an assay method involving solid-phase extraction and ion-pair reversed phase HPLC. Detection was by a variable wavelength UV-detector (for codeine) and an amperometric electro-chemical detector (for morphine) coupled in series. Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma disposition of morphine, evidenced by overlapping plasma concentration-time profiles. Brain opioid levels were equally unaffected by sympathomimetic pretreatment. The relative ratios of brain to plasma concentrations at the time corresponding to the respective peak anti-nociceptive activity for morphine and codeine revealed no significant differences. It is concluded that single doses of ephedrine and phenylpropanolamine do not affect the disposition of morphine and codeine in mice.

  2. Pain, opioids, and sleep: implications for restless legs syndrome treatment. (United States)

    Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H; Högl, Birgit


    Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid-opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with

  3. Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

    Directory of Open Access Journals (Sweden)

    Merab G Tsagareli


    Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  4. Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, M.E.; Khachaturian, H.; Watson, S.J.


    Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.

  5. The competitive enrichment market

    International Nuclear Information System (INIS)

    Parks, J.W.; Huffman, F.C.


    With the enactment of the ''Private Ownership of Special Nuclear Materials Act'' in 1964, the U.S. Government made provisions to enter into the uranium enrichment services business. Since nuclear power was in its infancy and the Government was promoting its growth as well as trying to help U.S. industry sell reactors overseas, the initial contracts (Requirements Contracts) for enrichment services placed most of the risks associated with the supplying of the services on the Government. Projections of nuclear power additions continued to grow and in 1972 the Atomic Energy Commission (AEC) stopped contracting under Requirements Contracts in order to study which mode of contracting best suited the commercial development of the industry. In mid-1973, the AEC introduced the Long-Term Fixed Commitment (LTFC) contract which shifted the risk to the customer. By mid-1974, AEC had contracts which completely used the enrichment capacity of its complex and refused to accept requests for additional contracts. This action further convinced European nations that they should continue to develop their own enrichment capacity and resulted in the EURODIF and URENCO projects. Before this time the U.S. supplied 100% of the world market for enriching services

  6. Neurobiology of opioid withdrawal: Role of the endothelin system. (United States)

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


    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.

  7. Induction of synaptic long-term potentiation after opioid withdrawal. (United States)

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


    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.

  8. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomised controlled trial

    NARCIS (Netherlands)

    Jong, C.A.J. de; Laheij, R.J.F.; Krabbe, P.F.M.


    Aim  Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  9. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment : a randomized controlled trial

    NARCIS (Netherlands)

    De Jong, Cor A J; Laheij, Robert J F; Krabbe, Paul F M

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  10. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial.

    NARCIS (Netherlands)

    Jong, C.A.J. de; Laheij, R.J.F.; Krabbe, P.F.M.


    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  11. Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology. (United States)

    Tournier, Nicolas; Declèves, Xavier; Saubaméa, Bruno; Scherrmann, Jean-Michel; Cisternino, Salvatore


    Some of the ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp; ABCB1, MDR1), BCRP (ABCG2) and MRPs (ABCCs) that are present at the blood-brain barrier (BBB) influence the brain pharmacokinetics (PK) of their substrates by restricting their uptake or enhancing their clearance from the brain into the blood, which has consequences for their CNS pharmacodynamics (PD). Opioid drugs have been invaluable tools for understanding the PK-PD relationships of these ABC-transporters. The effects of morphine, methadone and loperamide on the CNS are modulated by P-gp. This review examines the ways in which other opioid drugs and some of their active metabolites interact with ABC transporters and suggests new mechanisms that may be involved in the variability of the response of the CNS to these drugs like carrier-mediated system belonging to the solute carrier (SLC) superfamily. Exposure to opioids may also alter the expression of ABC transporters. P-gp can be overproduced during morphine treatment, suggesting that the drug has a direct or, more likely, an indirect action. Variations in cerebral neurotransmitters during exposure to opioids and the release of cytokines during pain could be new endogenous stimuli affecting transporter synthesis. This review concludes with an analysis of the pharmacotherapeutic and clinical impacts of the interactions between ABC transporters and opioids.

  12. Laser and gas centrifuge enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Heinonen, Olli [Senior Fellow, Belfer Center for Science and International Affairs, Harvard Kennedy School, Cambridge, Massachusetts (United States)


    Principles of uranium isotope enrichment using various laser and gas centrifuge techniques are briefly discussed. Examples on production of high enriched uranium are given. Concerns regarding the possibility of using low end technologies to produce weapons grade uranium are explained. Based on current assessments commercial enrichment services are able to cover the global needs of enriched uranium in the foreseeable future.

  13. Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord (United States)


    MEDICAL CENTER WILFORD HALL AIR FORCE MEDICAL CENTER Title of Thesis: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord" Name of...that the use of any copyrighted material in the dissertation manuscript entitled: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord...University of the Health Sciences 11 Abstract Title of Thesis: Heterogenity of Opioid Binding Sites In Guinea Pig Spinal Cord Gary Dean Zarr MAJ/ANC

  14. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova


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

  15. Oxygen enrichment incineration

    International Nuclear Information System (INIS)

    Kim, Jeong Guk; Yang, Hee Chul; Park, Geun Il; Kim, Joon Hyung


    Oxygen enriched combustion technology has recently been used in waste incineration. To apply the oxygen enrichment on alpha-bearing waste incineration, which is being developed, a state-of-an-art review has been performed. The use of oxygen or oxygen-enriched air instead of air in incineration would result in increase of combustion efficiency and capacity, and reduction of off-gas product. Especially, the off-gas could be reduced below a quarter, which might reduce off-gas treatment facilities, and also increase an efficiency of off-gas treatment. However, the use of oxygen might also lead to local overheating and high nitrogen oxides (NOx) formation. To overcome these problems, an application of low NOx oxy-fuel burner and recycling of a part of off-gas to combustion chamber have been suggested

  16. Oxygen enrichment incineration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Guk; Yang, Hee Chul; Park, Geun Il; Kim, Joon Hyung


    Oxygen enriched combustion technology has recently been used in waste incineration. To apply the oxygen enrichment on alpha-bearing waste incineration, which is being developed, a state-of-an-art review has been performed. The use of oxygen or oxygen-enriched air instead of air in incineration would result in increase of combustion efficiency and capacity, and reduction of off-gas product. Especially, the off-gas could be reduced below a quarter, which might reduce off-gas treatment facilities, and also increase an efficiency of off-gas treatment. However, the use of oxygen might also lead to local overheating and high nitrogen oxides (NOx) formation. To overcome these problems, an application of low NOx oxy-fuel burner and recycling of a part of off-gas to combustion chamber have been suggested.

  17. Centrifuge enrichment program

    International Nuclear Information System (INIS)

    Astley, E.R.


    Exxon Nuclear has been active in privately funded research and development of centrifuge enrichment technology since 1972. In October of 1975, Exxon Nuclear submitted a proposal to design, construct, and operate a 3000-MT SWU/yr centrifuge enrichment plant, under the provisions of the proposed Nuclear Fuel Assurance Act of 1975. The U.S. Energy Research and Development Administration (ERDA) accepted the proposal as a basis for negotiation. It was proposed to build a 1000-MT SWU/yr demonstration increment to be operational in 1982; and after successful operation for about one year, expand the facilities into a 3000-MT SWU/yr plant. As part of the overall centrifuge enrichment plant, a dedicated centrifuge manufacturing plant would be constructed; sized to support the full 3000-MT SWU/yr plant. The selection of the centrifuge process by Exxon Nuclear was based on an extremely thorough evaluation of current and projected enrichment technology; results show that the technology is mature and the process will be cost effective. The substantial savings in energy (about 93%) from utilization of the centrifuge option rather than gaseous diffusion is a compelling argument. As part of this program, Exxon Nuclear has a large hardware R and D program, plus a prototype centrifuge manufacturing capability in Malta, New York. To provide a full-scale machine and limited cascade test capability, Exxon Nuclear is constructing a $4,000,000 Centrifuge Test Facility in Richland, Washington. This facility was to initiate operations in the Fall of 1976. Exxon Nuclear is convinced that the centrifuge enrichment process is the rational selection for emergence of a commercial enrichment industry

  18. Tobacco withdrawal among opioid-dependent smokers. (United States)

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


    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).

  19. Exercise induced asthma and endogenous opioids. (United States)

    Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F


    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

  20. US enrichment reduction studies

    International Nuclear Information System (INIS)


    A major national program, the Reduced Enrichment Research and Test Reactor (RERTR) Program, is currently under way in the U.S., centered at the Argonne National Laboratory (ANL), to reduce the potential of research and test reactor fuels for increasing the proliferation of nuclear explosive devices. The main objective of the program is to provide the technical means by which the uranium enrichment to be used in these reactors can be reduced to less than 20% without significant economic and performance penalties. The criteria, basis and goals of the program are consistent with the results of a number of case studies which have been performed as part of the program

  1. Advanced uranium enrichment processes

    International Nuclear Information System (INIS)

    Clerc, M.; Plurien, P.


    Three advanced Uranium enrichment processes are dealt with in the report: AVLIS (Atomic Vapour LASER Isotope Separation), MLIS (Molecular LASER Isotope Separation) and PSP (Plasma Separation Process). The description of the physical and technical features of the processes constitutes a major part of the report. If further presents comparisons with existing industrially used enrichment technologies, gives information on actual development programmes and budgets and ends with a chapter on perspectives and conclusions. An extensive bibliography of the relevant open literature is added to the different subjects discussed. The report was drawn up by the nuclear research Centre (CEA) Saclay on behalf of the Commission of the European Communities

  2. Uranium Conversion & Enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Karpius, Peter Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    The isotopes of uranium that are found in nature, and hence in ‘fresh’ Yellowcake’, are not in relative proportions that are suitable for power or weapons applications. The goal of conversion then is to transform the U3O8 yellowcake into UF6. Conversion and enrichment of uranium is usually required to obtain material with enough 235U to be usable as fuel in a reactor or weapon. The cost, size, and complexity of practical conversion and enrichment facilities aid in nonproliferation by design.

  3. Chronic Pain, Chronic Opioid Addiction: a Complex Nexus. (United States)

    Salsitz, Edwin A


    Over the past two decades, there has been a significant increase in the prescribing of opioids, with associated increases in opioid addiction and overdose deaths. This article reviews the evidence for the effectiveness and risk of developing an opioid use disorder (OUD) in those patients treated with chronic opioid therapy (COT) for chronic non-cancer pain (CNCP). Rates of development of OUD range from 0-50 %, and aberrant drug related behaviors (ADRBs) are reported to be 20 %. Health care providers must properly assess, screen, and carefully monitor patients on COT utilizing evidence-based tools.

  4. Pain management and opioid risk mitigation in the military. (United States)

    Sharpe Potter, Jennifer; Bebarta, Vikhyat S; Marino, Elise N; Ramos, Rosemarie G; Turner, Barbara J


    Opioid analgesics misuse is a significant military health concern recognized as a priority issue by military leadership. Opioids are among those most commonly prescribed medications in the military for pain management. The military has implemented opioid risk mitigation strategies, including the Sole Provider Program and the Controlled Drug Management Analysis and Reporting Tool, which are used to identify and monitor for risk and misuse. However, there are substantial opportunities to build on these existing systems to better ensure safer opioid prescribing and monitor for misuse. Opioid risk mitigation strategies implemented by the civilian sector include establishing clinical guidelines for opioid prescribing and prescription monitoring programs. These strategies may help to inform opioid risk mitigation in the military health system. Reducing the risk of opioid misuse and improving quality of care for our Warfighters is necessary. This must be done through evidence-based approaches with an investment in research to improve patient care and prevent opioid misuse as well as its sequelae. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  5. A case of rhabdomyolysis associated with severe opioid withdrawal. (United States)

    Gangahar, Deepali


    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.

  6. Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey (United States)

    Pearson, Amy CS; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael


    Introduction Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. Materials and methods The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho. Results Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pcorrelated with the perception that treating pain patients was a “problem in my practice” (P=0.005). Conclusion In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain. PMID:28652805

  7. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast). (United States)

    Hutchinson, Mark R; Lewis, Susannah S; Coats, Benjamen D; Skyba, David A; Crysdale, Nicole Y; Berkelhammer, Debra L; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M; Judd, Charles M; Maier, Steven F; Watkins, Linda R; Johnson, Kirk W


    Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused three-to-five-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, while improving analgesia.

  8. Intentional intrathecal opioid detoxification in 3 patients: characterization of the intrathecal opioid withdrawal syndrome. (United States)

    Jackson, Tracy P; Lonergan, Daniel F; Todd, R David; Martin, Peter R


    Intrathecal (IT) drug delivery systems for patients with chronic non-malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom-triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow-up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

  9. Metacognitive Enrichment for Community College Students (United States)

    Wyre, Steven H.


    Recent research was conducted to explore how introducing metacognitive enrichment into courses containing implicit or explicit critical thinking goals would affect the students' personal epistemological maturity. At the beginning of a fall semester at a moderate sized community college in the southeastern United States, 733 students were divided…

  10. Erectile dysfunction in patients with chronic pain treated with opioids. (United States)

    Ajo, Raquel; Segura, Ana; Inda, María-Del-Mar; Margarit, César; Ballester, Pura; Martínez, Emi; Ferrández, Guillermina; Sánchez-Barbie, Ángel; Peiró, Ana M


    Chronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels. To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Prospective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. ED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. Erectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the

  11. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)


    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  12. Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

    Directory of Open Access Journals (Sweden)

    Brenton A


    Full Text Available Ashley Brenton,1 Steven Richeimer,2,3 Maneesh Sharma,4 Chee Lee,1 Svetlana Kantorovich,1 John Blanchard,1 Brian Meshkin1 1Proove Biosciences, Irvine, CA, 2Keck school of Medicine, University of Southern California, Los Angeles, CA, 3Departments of Anesthesiology and Psychiatry, University of Southern California, Los Angeles, CA, 4Interventional Pain Institute, Baltimore, MD, USA Background: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose: This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs. Patients and methods: The Proove Opioid Risk (POR algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion: The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. Keywords: opioid use disorder, addiction, personalized medicine, pharmacogenetics, genetic testing, predictive algorithm

  13. An Enriching Community. (United States)

    Holland, Nancy A.; Burroughs, Jean


    Successful school-community partnerships in Volusia (Florida) Public Schools are the results of marketing creatively, meeting community members' needs, and bringing the right people together. The 3-year old program now offers students of all ages an expanding list of enrichment classes on many subjects for a nominal fee. (MLH)

  14. Uranium enrichment techniques

    International Nuclear Information System (INIS)

    Hamdoun, N.A.


    This article includes an introduction about the isotopes of natural uranium, their existence and the difficulty of the separation between them. Then it goes to the details of a number of methods used to enrich uranium: Gaseous Diffusion method, Electromagnetic method, Jet method, Centrifugal method, Chemical method, Laser method and Plasma method.

  15. Requirements for enrichment tools

    NARCIS (Netherlands)

    Boer, A.; Winkels, R.; Trompper, M.


    This report gives a high level overview of requirements for Enrichment tools in the project. aims to initiate a platform and develop a vision for Big Open Legal Data (BOLD): an open framework for legislation, case law, and legal literature from across Europe.

  16. Enriching the Catalog (United States)

    Tennant, Roy


    After decades of costly and time-consuming effort, nearly all libraries have completed the retrospective conversion of their card catalogs to electronic form. However, bibliographic systems still are really not much more than card catalogs on wheels. Enriched content that takes for granted--such as digitized tables of contents, cover…

  17. Social Stigma Toward Persons With Prescription Opioid Use Disorder: Associations With Public Support for Punitive and Public Health-Oriented Policies. (United States)

    Kennedy-Hendricks, Alene; Barry, Colleen L; Gollust, Sarah E; Ensminger, Margaret E; Chisolm, Margaret S; McGinty, Emma E


    Prescription opioid use disorder and overdose have emerged as significant public health challenges in the past 15 years. Little is known about public attitudes toward individuals who have developed a prescription opioid use disorder and whether these attitudes affect support for policy interventions. This study examined social stigma toward individuals with prescription opioid use disorder and tested whether stigma was associated with support for various policy interventions. A nationally representative Web-based survey was conducted from January 31 to February 28, 2014. The 1,071 respondents reported on their beliefs about and attitudes toward persons affected by prescription opioid use disorder and rated their support for various policy interventions. Ordered logistic regression models estimated the association between stigma and public support for punitive and public health-oriented policies. Most respondents viewed this disorder as affecting all groups-racial and ethnic, income, and geographic area of residence groups-fairly equally, despite epidemiological data demonstrating that certain populations have been disproportionately burdened. Respondents expressed high levels of stigma toward individuals with prescription opioid use disorder. Levels of stigma were generally similar among those with and without experience with prescription opioid use disorder, either one's own or that of a relative or close friend. Higher levels of stigma were associated with greater support for punitive policies and lower support for public health-oriented policies. Reframing the issue to emphasize the structural factors contributing to prescription opioid use disorder and the barriers to accessing evidence-based treatment might improve support for policies that benefit affected individuals.

  18. Availability of enrichment services

    International Nuclear Information System (INIS)

    Svenke, E.


    The report summarizes major uncertainties which are likely to influence future demands for uranium isotopic enrichment. Since for the next decade the development of nuclear power will be largely concerned with the increment in demand the timely need for enrichment capacity will be particularly sensitive to assumptions about growth rates. Existing worldwide capacity together with capacities under construction will be sufficient well into the 1980's. However, long decision and construction leadtime, uncertainty as to future demand as well as other factors, specifically high capital need, all of which entail financial risks, create hindrances to a timely development of increment. The adequacy of current technology is well demonstrated in plant operation and new technology is under way. Technology is, however, not freely available on a purely commercial basis. Commercial willingness, which anticipates a limited degree of financial risk, is requesting both long term back-up from the utilities that would parallel their firm decisions on the acquisition of nuclear power units, and a protective government umbrella. This situation depends on the symbiotic relationship that exists between the nuclear power generating organizations, the enrichment undertakings and the governments involved. The report accordingly stresses the need for a more cooperative approach and this, moreover, at the multinational level. There is otherwise a risk that proper resources and financing means will not be allocated to the enrichment sector. Export limitations that request the highest degree of industrial processing of nuclear fuel, i.e. the compulsory enrichment of natural uranium, do not serve the interests of overall industrial efficiency

  19. Bilateral Breast Reduction Without Opioid Analgesics: A Comparative Study. (United States)

    Parsa, Fereydoun Don; Cheng, Justin; Stephan, Brad; Castel, Nikki; Kim, Leslie; Murariu, Daniel; Parsa, Alan A


    Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P opioid use (P opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. 3. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission:

  20. Promotion of uranium enrichment business

    International Nuclear Information System (INIS)

    Kurushima, Morihiro


    The Committee on Nuclear Power has studied on the basic nuclear power policy, establishing its five subcommittees, entrusted by the Ministry of Nternational Trade and Industry. The results of examination by the subcommittee on uranium enrichment business are given along with a report in this connection by the Committee. In order to establish the nuclear fuel cycle, the aspect of uranium enrichment is essential. The uranium enrichment by centrifugal process has proceeded steadily in Power Reactor and Nuclear Fuel Development Corporation. The following matters are described: the need for domestic uranium enrichment, the outlook for overseas enrichment services and the schedule for establishing domestic enrichment business, the current state of technology development, the position of the prototype enrichment plant, the course to be taken to establish enrichment business the main organization operating the prototype and commercial plants, the system of supplying centrifuges, the domestic conversion of natural uranium the subsidies for uranium enrichment business. (J.P.N.)

  1. United States uranium enrichment policies

    International Nuclear Information System (INIS)

    Roberts, R.W.


    ERDA's uranium enrichment program policies governing the manner in which ERDA's enrichment complex is being operated and expanded to meet customer requirements for separative work, research and development activities directed at providing technology alternatives for future enrichment capacity, and establishing the framework for additional domestic uranium enrichment capacity to meet the domestic and foreign nuclear industry's growing demand for enrichment services are considered. The ERDA enrichment complex consists of three gaseous diffusion plants located in Oak Ridge, Tennessee; Paducah, Kentucky; and Portsmouth, Ohio. Today, these plants provide uranium enrichment services for commercial nuclear power generation. These enrichment services are provided under contracts between the Government and the utility customers. ERDA's program involves a major pilot plant cascade, and pursues an advanced isotope separation technique for the late 1980's. That the United States must develop additional domestic uranium enrichment capacity is discussed

  2. Modelling the PKPD of oxycodone in experimental pain - impact of opioid receptor polymorphisms

    DEFF Research Database (Denmark)

    Olsen, Rasmus; Foster, David J R; Upton, Richard N


    BACKGROUND: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search...... for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. METHOD: The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies...... in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters...

  3. Anhedonia to music and mu-opioids: Evidence from the administration of naltrexone (United States)

    Mallik, Adiel; Chanda, Mona Lisa; Levitin, Daniel J.


    Music’s universality and its ability to deeply affect emotions suggest an evolutionary origin. Previous investigators have found that naltrexone (NTX), a μ-opioid antagonist, may induce reversible anhedonia, attenuating both positive and negative emotions. The neurochemical basis of musical experience is not well-understood, and the NTX-induced anhedonia hypothesis has not been tested with music. Accordingly, we administered NTX or placebo on two different days in a double-blind crossover study, and assessed participants’ responses to music using both psychophysiological (objective) and behavioral (subjective) measures. We found that both positive and negative emotions were attenuated. We conclude that endogenous opioids are critical to experiencing both positive and negative emotions in music, and that music uses the same reward pathways as food, drug and sexual pleasure. Our findings add to the growing body of evidence for the evolutionary biological substrates of music. PMID:28176798

  4. Tolerance and withdrawal from prolonged opioid use in critically ill children. (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


    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.

  5. [Hydroxylamine conversion by anammox enrichment]. (United States)

    Hu, Anhui; Zheng, Ping; Lu, Huifeng; Ding, Shuang; Wang, Caihua


    Hydroxylamine is an important intermediate product of anammox. This study was focused on the characteristics of hydroxylamine and nitrite conversions by anammox enrichment. The changes of nitrogenous substrates and related products with time were measured using batch tests with anammox enrichment as inoculum. Since hydroxylamine didn't react with nitrite in uninoculated control culture, these two compounds were chemically stable. Both of them decreased with time in anammox enrichment inoculated cultures, in which ammonia as intermediate product would be produced and converted with the maximum concentration being 0.338 mg/L. The total nitrogen concentration decreased from 4.694 mmol/L to 0.812 mmol/L with conversion rate 82.7% in the end. When hydroxylamine and nitrite concentrations were about 2.5 mmol/L respectively, the maximum specific sludge conversion rates of hydroxylamine was 0.535 mmol/(gVSS.h), which was 1.81 times bigger than that of ammonia in ammonia reaction system; the maximum specific sludge rate of total nitrogen was slightly higher than that in ammonia reaction system. When hydroxylamine concentration increased to 5.0 mmol/L, the hydroxylamine and nitrite conversion rates promoted by 26.7% and 120.7% respectively; and the maximum ammonia accumulated was 1.810 mmol/L. When nitrite concentration increased to 5.0 mmol/L, the hydroxylamine and nitrite conversion rates promoted by 6.9% and 9.0% respectively; and the maximum ammonia accumulated was 0.795 mmol/L. Anammox enrichment was capable of converting hydroxylamine and nitrite simultaneously and had the higher conversion rate of hydroxylamine than ammonia conversion rate. Hydroxylamine and nitrite conversion rates were less affected by increase in nitrite concentration, but more significantly influenced by increase in hydroxylamine. The maximum ammonia concentration accumulated would rise as the result of increasing both hydroxylamine and nitrite. The result of experiment was consistent with pathway

  6. Opioid Overdoses Treated in Emergency Departments PSA (:60)

    Centers for Disease Control (CDC) Podcasts


    This 60 second public service announcement is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.  Created: 3/6/2018 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/6/2018.

  7. Secular trends in opioid prescribing in the USA

    Directory of Open Access Journals (Sweden)

    Pezalla EJ


    Full Text Available Edmund J Pezalla,1 David Rosen,2 Jennifer G Erensen,2 J David Haddox,2,3 Tracy J Mayne2 1Bioconsult, LLC, Wethersfield, 2Purdue Pharma L.P., Stamford, CT, 3Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Abstract: Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs. The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported. Keywords: OADP, prescription, utilization trends, legislation, opioids

  8. Critical issues on opioids in chronic non-cancer pain

    DEFF Research Database (Denmark)

    Eriksen, Jørgen; Sjøgren, Per; Bruera, Eduardo


    -related quality of life (SF-36), use of the health care system, functional capabilities, satisfaction with medical pain treatment and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use...

  9. Treating opioid dependence. Growing implications for primary care. (United States)

    Krantz, Mori J; Mehler, Philip S


    Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

  10. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T


    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

  11. Opioid therapy in non-cancer chronic pain patients: Trends and efficacy in different types of pain, patients age and gender

    Directory of Open Access Journals (Sweden)

    Yasin S AlMakadma


    Full Text Available Background: In both developing and developed countries, chronic pain remains a real issue and a true disease that affects up to 42% of the population in some areas. Opioids are widely used for the management of chronic pain with variations in prescribing practices, indications and observed efficacy. Aim: to analyze trends in opioids prescribing and patient response in chronic non-cancer pain conditions. Methods: Retrospective study of 1500 casenotes of patients suffering variable non-cancer chronic pain conditions. Detailed review of those cases who were managed using opioids. Statistical analysis using "SOFA" software set. Results: The prevalence of opioids prescribing in patients suffering this condition was thus around 35% (n=526. Women older than 50 years were more likely than men to have a chronic pain condition and to be given opioid therapy for 1 year or more. Opioid efficacy on neuropathic and mixed types of pain was found to be significant with relatively low rate of drop-out and limited side-effects that are not life threatening. Overall, patients stopped or changed their opioid medication due to inefficacy in only 12.7% of cases. Conclusions: The simple fact of having pain is itself a source of self-reported disability regardless of the actual physiological or pathological mechanism. Policy makers should be aware of the huge impact of chronic pain disease and of its serious effects on social and economical well-being. In developing countries, chronic pain could represent a real challenge for all parties. Multimodal management, including opioids, appears crucial for the approach of this disease.

  12. Future of uranium enrichment

    International Nuclear Information System (INIS)

    Hosmer, C.


    The increasing amount of separative work being done in government facilities to produce low-enriched uranium fuel for nuclear utilities again raises the question: should this business-type, industrial function be burned over the private industry. The idea is being looked at by the Reagan administration, but faces problems of national security as well as from the unique nature of the business. This article suggests that a joint government-private venture combining enriching, reprocessing, and waste disposal could be the answer. Further, a separate entity using advanced laser technology to deplete existing uranium tails and lease them for fertile blankets in breeder reactors might earn substantial revenues to help reduce the national debt

  13. South Australia, uranium enrichment

    International Nuclear Information System (INIS)


    The Report sets out the salient data relating to the establishment of a uranium processing centre at Redcliff in South Australia. It is conceived as a major development project for the Commonwealth, the South Australian Government and Australian Industry comprising the refining and enrichment of uranium produced from Australian mines. Using the data currently available in respect of markets, demand, technology and possible financial return from overseas sales, the project could be initiated immediately with hexafluoride production, followed rapidly in stages by enrichment production using the centrifuge process. A conceptual development plan is presented, involving a growth pattern that would be closely synchronised with the mining and production of yellowcake. The proposed development is presented in the form of an eight-and-half-year programme. Costs in this Report are based on 1975 values, unless otherwise stated. (Author)

  14. Nutrient enrichment increases mortality of mangroves.

    Directory of Open Access Journals (Sweden)

    Catherine E Lovelock

    Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

  15. Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus. (United States)

    Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz


    Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  16. Addiction to opioids in chronic pain patients: a literature review

    DEFF Research Database (Denmark)

    Højsted, Jette; Sjøgren, Per


    , incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... long-term opioid treatment, and specialised treatment facilities for pain management or addiction medicine should be consulted in these cases....

  17. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng


    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  18. Opioid prescriptions before and after high-energy trauma

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Hallas, Jesper; Larsen, Morten S


    OBJECTIVE: To describe the legal use of opioids in adult patients before and after high-energy trauma. DESIGN: The study was a retrospective database study. SETTING: Clinical care outside hospitals. PATIENTS: All patients who suffered high-energy trauma and were brought to Odense University...... Hospital (OUH), Denmark, in 2007 and 2008 were retrieved from the trauma database. These patients were linked with data on opioid use from the regional prescription database. In all, 938 patients were included. MAIN OUTCOME MEASURE: Redemption of opioid prescription during the 6 months prior...... to a multitrauma or redemption of two or more prescriptions for opioids 6 months or later after a multitrauma. RESULTS: Of the 938 patients brought to OUH with severe trauma within the study period, 61 patients died (7 percent) and six of these had redeemed prescriptions for opioids within 6 months prior...

  19. The role of the opioid system in alcohol dependence. (United States)

    Nutt, David J


    The role of the brain opioid system in alcohol dependence has been the subject of much research for over 25 years. This review explores the evidence: firstly describing the opioid receptors in terms of their individual subtypes, neuroanatomy, neurophysiology and ligands; secondly, summarising emerging data from specific neurochemical, behavioural and neuroimaging studies, explaining the characteristics of addiction with a focus on alcohol dependence and connecting the opioid system with alcohol dependence; and finally reviewing the known literature regarding opioid antagonists in clinical use for alcohol dependence. Further interrogation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase our insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.

  20. Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids. (United States)

    Skovlund, Eva; Handal, Marte; Selmer, Randi; Brandlistuen, Ragnhild Eek; Skurtveit, Svetlana


    An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice. (United States)

    Sheikhi, Mehdi; Shirzadian, Armin; Dehdashtian, Amir; Amiri, Shayan; Ostadhadi, Sattar; Ghasemi, Mehdi; Dehpour, Ahmad Reza


    Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Long-term evaluation of opioid treatment in fibromyalgia. (United States)

    Peng, Xiaomei; Robinson, Rebecca L; Mease, Philip; Kroenke, Kurt; Williams, David A; Chen, Yi; Faries, Douglas; Wohlreich, Madelaine; McCarberg, Bill; Hann, Danette


    In a 12-month observational study, we evaluated the effect of opioid use on the outcomes in 1700 adult patients with fibromyalgia. Data were evaluated using propensity score matching after patients were divided into cohorts based on their baseline medication use: (1) taking an opioid (concurrent use of tramadol was permitted); (2) taking tramadol (but no opioids); and (3) not taking opioids or tramadol. Changes in outcomes were assessed using the Brief Pain Inventory for severity and pain-related interference (BPI-S, BPI-I), Fibromyalgia Impact Questionnaire (FIQ), Patient Health Questionnaire for depression (PHQ-8), Insomnia Severity Index (ISI), Sheehan Disability Scale (SDS), 7-item Generalized Anxiety Disorder Scale (GAD-7), and economic factors. Time-to-opioid or tramadol discontinuation was analyzed using Kaplan-Meier survival analyses. Compared with the opioid cohort, the nonopioid cohort demonstrated significantly greater reductions (PFIQ, PHQ-8, SDS, and ISI; the tramadol cohort compared with the opioid group showed greater reductions on FIQ and ISI. Reductions in BPI-S and GAD-7 did not differ significantly among cohorts. Compared with the opioid cohort, patients in the tramadol cohort had fewer outpatient visits to health care providers. Few significant differences were found between the tramadol and nonopioid cohorts across outcomes. Although pain severity was reduced over time in all cohorts, opioid users showed less improvement in pain-related interference with daily living, functioning, depression, and insomnia. Overall, the findings show little support for the long-term use of opioid medications in patients with fibromyalgia given the poorer outcomes across multiple assessment domains associated with this cohort.

  3. Opioid Prescriptions by Specialty in Ohio, 2010-2014. (United States)

    Weiner, Scott G; Baker, Olesya; Rodgers, Ann F; Garner, Chad; Nelson, Lewis S; Kreiner, Peter W; Schuur, Jeremiah D


    The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty. We extracted prescriptions for pill versions of opioids written in the calendar years 2010 to 2014. The main outcomes were the number of filled prescriptions, pill counts, MMEs, and extended-released opioids written by physicians in each specialty, and annual prescribing trends. There were 56,873,719 prescriptions for the studied opioids dispensed, for which 41,959,581 (73.8%) had prescriber specialty type available. Mean number of pills per prescription and MMEs were highest for physical medicine/rehabilitation (PM&R; 91.2 pills, 1,532 mg, N = 1,680,579), anesthesiology/pain (89.3 pills, 1,484 mg, N = 3,261,449), hematology/oncology (88.2 pills, 1,534 mg, N = 516,596), and neurology (84.4 pills, 1,230 mg, N = 573,389). Family medicine (21.8%) and internal medicine (17.6%) wrote the most opioid prescriptions overall. Time trends in the average number of pills and MMEs per prescription also varied depending on specialty. The numbers of pills and MMEs per opioid prescription vary markedly by prescriber specialty, as do trends in prescribing characteristics. Pill count and MME values define each specialty's contribution to overall opioid prescribing more accurately than the number of prescriptions alone.

  4. Medication-Assisted Treatment For Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43 (United States)

    Tinkler, Emily; Vallejos Bartlett, Catalina; Brooks, Margaret; Gilbert, Johnatnan Max; Henderson, Randi; Shuman, Deborah, J.


    TIP 43 provides best-practice guidelines for medication-assisted treatment of opioid addiction in opioid treatment programs (OTPs). The primary intended audience for this volume is substance abuse treatment providers and administrators who work in OTPs. Recommendations in the TIP are based on both an analysis of current research and determinations…

  5. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides. (United States)

    Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina


    During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the

  6. Genetisk polymorfisme har betydning for 
opioiders smertestillende effekt efter kirurgi

    DEFF Research Database (Denmark)

    Frydshou, Andreas; Hansen, Egon Godthåb; Gögenur, Ismail


    Post-operative pain-management (PPM) should first of all be decided by the specific surgical procedure in each case, but it also seems that genetic polymorphism affects the clinical effects of the pharmacological treatment. In this article we summarize the existing evidence of the hypothesis...... that the A118G-variant of the µ-opioidreceptor-gene OPRM1 affects clinical response to opioids after gynaecological and abdominal surgery. If the genetic profile of each patient becomes easier accessible in the future, PPM might be planned accordingly to surgical procedure as well as to genetic profile...... to avoid post-operative pain and pharmacological adverse effects....


    Todadze, Kh; Mosia, S


    Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

  8. Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol. (United States)

    Bennett, Marsha; Bonanno, Laura; Kuhn, William


    The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

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

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


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

  10. Opioid system of the brain and ethanol. (United States)

    Gogichadze, M; Mgaloblishvili-Nemsadze, M; Oniani, N; Emukhvary, N; Basishvili, T


    Influence of blocking of opioid receptors with concomitant intraperitoneal injections of Naloxone (20 mg/kg) (non-selective antagonist of opioid system) on the outcomes of anesthetic dose of ethanol (4,25 ml /kg 25% solution) was investigated in the rats. The sleep-wakefulness cycle (SWC) was used as a model for identification of the effects. Alterations of the SWC structure adequately reflect the neuro-chemical changes, which may develop during pharmacological and non-pharmacological impact. Administration of anesthetic dose of ethanol evoked considerable modification of spontaneous EEG activity of the neocortex. The EEG activity was depressed and full inhibition of spinal reflexes and somatic muscular relaxation did occur. During EEG depression regular SWC did not develop. All phases of SWC were reduced. The disturbances of SWC, such as decrease of slow wave sleep and paradoxical sleep duration and increase of wakefulness, remained for several days. At concomitant administration of Naloxone and ethanol, duration of EEG depression decreased significantly. Generation of normal SWC was observed on the same experimental day. However, it should be noted that complete abolishment of ethanol effects by Naloxone was not observed. The results obtained suggest that Naloxone partially blocks ethanol depressogenic effects and duration of this effect is mediated by GABA-ergic system of the brain.

  11. A Motion Videogame for Opioid Relapse Prevention. (United States)

    Abroms, Lorien C; Leavitt, Leah E; Van Alstyne, Judy M; Schindler-Ruwisch, Jennifer M; Fishman, Marc J; Greenberg, Daniel


    This study examined the feasibility and acceptability of a body motion-activated videogame, targeting the prevention of opioid relapse among youth in the context of outpatient treatment. Participants attended four weekly gameplay sessions. Surveys were conducted at baseline and following each week's gameplay and assessed satisfaction with gameplay, craving intensity, and self-efficacy to refuse opioids. Participants expressed a high level of satisfaction with the videogame throughout the 4 weeks and agreed with the statement that they would be more likely to attend treatment sessions if the game was present (mean=4.6; standard deviation [SD]=0.7) and would recommend the videogame to other people in treatment (mean=4.2; SD=0.8). All participants recommended playing the videogame as part of treatment at least weekly, with a third recommending playing daily. Self-reported cravings declined over the 4-week period from baseline (mean=12.7; SD=8.4) to Week 4 (mean=9.8; SD=8.3), although the decline was not significant. Although participants stated that they liked the game, one-third of participants had dropped out of the study by the fourth session of gameplay. Preliminary evidence indicates that a motion videogame for addiction recovery may be feasible and acceptable within the context of outpatient treatment, although additional efforts are needed to keep youth in treatment. Future studies are needed to assess the impact of the game on long-term abstinence, treatment adherence, and engagement.

  12. Possible role of a dysregulation of the endogenous opioid system in antisocial personality disorder. (United States)

    Bandelow, Borwin; Wedekind, Dirk


    Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an "endorphin rush" by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Extensive changes in the expression of the opioid genes between humans and chimpanzees. (United States)

    Cruz-Gordillo, Peter; Fedrigo, Olivier; Wray, Gregory A; Babbitt, Courtney C


    The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes. Copyright © 2010 S. Karger AG, Basel.

  14. Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis. (United States)

    Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj


    The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

  15. The Comprehensive Addiction and Recovery Act: Opioid Use Disorder and Midwifery Practice. (United States)

    Murphy, Jeanne; Goodman, Daisy; Johnson, M Christina; Terplan, Mishka


    The federal response to the opioid use disorder crisis has included a mobilization of resources to encourage office-based pharmacotherapy with buprenorphine, an effort culminating in the 2016 Comprehensive Addiction and Recovery Act, signed into law as Public Law 114-198. The Comprehensive Addiction and Recovery Act was designed to increase access to treatment with special emphasis on services for pregnant women and follow-up for infants affected by prenatal substance exposure. In this effort, the Comprehensive Addiction and Recovery Act laudably expands eligibility for obtaining a waiver to prescribe buprenorphine to nurse practitioners and physician assistants. However, certified nurse-midwives and certified midwives, who care for a significant proportion of pregnant and postpartum women and attend a significant proportion of births in the United States, were not included in the Comprehensive Addiction and Recovery Act legislation. In this commentary, we argue that an "all-hands" approach to providing office-based medication-assisted treatment for opioid use disorder is essential to improving access to treatment. Introduced in the House of Representatives in September 2017, the Addiction Treatment Access Improvement Act (H.R. 3692) would allow midwives to apply for the federal waiver to prescribe buprenorphine and is supported by the American College of Obstetricians and Gynecologists and the American College of Nurse-Midwives. We support this change and encourage the U.S. Congress to act quickly to allow midwives to prescribe medication-assisted treatment for pregnant women with opioid use disorder.

  16. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats. (United States)

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


    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.

  17. Association between Opioid Receptor mu 1 (OPRM1 Gene Polymorphisms and Tobacco and Alcohol Consumption in a Spanish Population

    Directory of Open Access Journals (Sweden)

    Francesc Francès


    Full Text Available Evidence gained from animals and humans suggests that the encephalic opioid system might be involved in the development of drug addiction through its role in reward. Our aim is to assess the influence of genetic variations in the opioid receptor mu 1 on alcohol and tobacco consumption in a Spanish population. 763 unrelated individuals (465 women, 298 men aged 18-85 years were recruited between October 2011 and April 2012. Participants were requested to answer a 35-item questionnaire on tobacco and alcohol consumption, as well as to complete the AUDIT and Fagerström tests. Individuals were genotyped for three polymorphisms in the opioid receptor mu 1 (OPRM1 gene, using a TaqMan® protocol. In males, the rs10485057 polymorphism was associated with total pure ethanol intake and with the risk of being an alcohol consumer. Also, this polymorphism was significantly associated with higher Fagerström scores. Rs1799971 had a different influence on adaptive and maladaptive patterns of alcohol use. Despite the limited sample size, our study might enrich current knowledge on patterns of alcohol use, because it encompasses both extreme and adaptive phenotypes, providing thus a wider perspective on this subject.

  18. Beta activity of enriched uranium

    International Nuclear Information System (INIS)

    Nambiar, P.P.V.J.; Ramachandran, V.


    Use of enriched uranium as reactor fuel necessitates its handling in various forms. For purposes of planning and organising radiation protection measures in enriched uranium handling facilities, it is necessary to have a basic knowledge of the radiation status of enriched uranium systems. The theoretical variations in beta activity and energy with U 235 enrichment are presented. Depletion is considered separately. Beta activity build up is also studied for two specific enrichments, in respect of which experimental values for specific alpha activity are available. (author)

  19. Blueprint for domestic uranium enrichment

    International Nuclear Information System (INIS)


    The AEC advisory committee on domestic production of uranium enrichment has studied for more than a year how to achieve the domestic enrichment of uranium by the construction and operation of a commercial enriching plant using centrifugal separation method, and the report was submitted to the Atomic Energy Commission on August 18, 1980. Japan has depended wholly on overseas services for her uranium enrichment needs, but the development of domestic enrichment has been carried on in parallel. The AEC decided to construct a uranium enrichment pilot plant using centrifuges, and it has been forwarded as a national project. The plant is operated by the Power Reactor and Nuclear Fuel Development Corp. since 1979. The capacity of the plant will be raised to approximately 75 ton SWU a year. The centrifuges already operated have provided the first delivery of fuel of about 1 ton for the ATR ''Fugen''. The demand-supply balance of uranium enrichment service, the significance of the domestic enrichment of uranium, the evaluation of uranium enrichment technology, the target for domestic enrichment plan, the measures to promote domestic uranium enrichment, and the promotion of the construction of a demonstration plant are reported. (Kako, I.)

  20. An ethnographic study of barriers to cancer pain management and opioid availability in India. (United States)

    Lebaron, Virginia; Beck, Susan L; Maurer, Martha; Black, Fraser; Palat, Gayatri


    The world's global cancer burden disproportionally affects lower income countries, where 80% of patients present with late-stage disease and have limited access to palliative care and effective pain-relieving medications, such as morphine. Consequently, millions die each year with unrelieved pain. Objective. The objective of this study was to examine barriers to opioid availability and cancer pain management in India, with an emphasis on the experiences of nurses, who are often the front-line providers of palliative care. Methods. Fifty-nine participants were recruited using a purposive, snowball sampling strategy. Ethnographic data collection included in-depth, semistructured interviews (n = 54), 400+ hours of participant observation, and review of documents over 9 months at a government cancer hospital in South India. Systematic qualitative analysis led to identification of key barriers that are exemplified by representative quotes. Results. Morphine is more available at this study site than in most of India, but access is limited to patients seen by the palliative care service, and significant gaps in supply still occur. Systems to measure and improve pain outcomes are largely absent. Key barriers related to pain management include the role of nursing, opioid misperceptions, bureaucratic hurdles, and sociocultural/infrastructure challenges. Implications. Interventions must streamline process details of morphine procurement, work within the existing sociocultural infrastructure to ensure opioids reach patients most in need, target unexpected audiences for symptom management education, and account for role expectations of health care providers. Conclusion. Macro- and micro-level policy and practice changes are needed to improve opioid availability and cancer pain management in India.

  1. Diagnostic Performance of Self-Assessment for Constipation in Patients With Long-Term Opioid Treatment. (United States)

    Tafelski, Sascha; Bellin, Felicitas; Denke, Claudia; Beutlhauser, Torsten; Fritzsche, Thomas; West, Christina; Schäfer, Michael


    Constipation is a prevalent comorbidity affecting ∼50% of patients with long-term opioid therapy. In clinical routine different diagnostic instruments are in use to identify patients under risk. The aim of this study was to assess the diagnostic performance of an 11-item Likert scale for constipation used as a self-assessment in opioid-treated patients. This trial was conducted as a retrospective cohort study in Berlin, Germany. Patients with long-term opioid therapy treated in 2 university-affiliated outpatient pain facilities at the Charité hospital were included from January 2013 to August 2013. Constipation was rated in a self-assessment using a numeric rating scale from 0 to 10 (Con-NRS) and compared with results from a structured assessment based on ROME-III criteria. Altogether, 171 patients were included. Incidence of constipation was 49% of patients. The receiver-operating characteristic of Con-NRS achieved an area under the curve of 0.814 (AUC 95% confidence interval 0.748-0.880, P < 0.001). Con-NRS ≥ 1 achieved sensitivity and specificity of 79.7% and 77.2%, respectively. The positive predictive value and the negative predictive value were 70.3% and 81.6%, respectively. Overall diagnostic performance of a concise 11-item Likert scale for constipation was moderate. Although patients with long-term opioid therapy are familiar with numeric rating scales, a significant number of patients with constipation were not identified. The instrument may be additionally useful to facilitate individualized therapeutic decision making and to control therapeutic success when measured repetitively.

  2. Doctors and patients in pain: Conflict and collaboration in opioid prescription in primary care. (United States)

    Esquibel, Angela Y; Borkan, Jeffrey


    Use of chronic opioid therapy (COT) for chronic noncancer pain has dramatically increased in the United States. Patients seek compassionate care and relief while physicians struggle to manage patients' pain effectively without doing harm. This study explores the narratives of chronic noncancer pain patients receiving chronic opioid therapy and those of their physicians to better understand the effects of COT on the doctor-patient relationship. A mixed method study was conducted that included in-depth interviews and qualitative analysis of 21 paired patients with chronic pain and their physicians in the following groups: patients, physicians, and patient-physician pairs. Findings revealed that patients' narratives focus on suffering from chronic pain, with emphasis on the role of opioid therapy for pain relief, and physicians' narratives describe the challenges of treating patients with chronic pain on COT. Results elucidate the perceptions of ideal vs difficult patients and show that divergent patterns surrounding the consequences, utility, and goals of COT can negatively affect the doctor-patient relationship. The use of paired interviews through a narrative lens in this exploratory study offers a novel and informative approach for clinical practice and research. The findings have significant implications for improving doctor-patient communication and health outcomes by encouraging shared decision making and goal-directed health care encounters for physicians and patients with chronic pain on COT. This study found patterns of understanding pain, opioid pain medications, and the doctor-patient relationship for patients with chronic pain and their physicians using a narrative lens. Thematic findings in this exploratory study, which include a portrayal of collaborative vs conflictual relationships, suggest areas of future intervention and investigation. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  3. Comorbid Post-Traumatic Stress Disorder and Opioid Dependence. (United States)

    Patel, Rikinkumar S; Elmaadawi, Ahmed; Nasr, Suhayl; Haskin, John


    Post-traumatic stress disorder (PTSD) is predominant amongst individuals addicted to opioids and obscures the course of illness and the treatment outcome. We report the case of a patient with major depressive disorder and opioid dependence, who experienced post-traumatic stress disorder symptoms during a recent visit to the inpatient unit. The similarity of symptoms between post-traumatic stress disorder and opioid dependence is so high that, sometimes, it is a challenge to differentiate between these conditions. Since opioid withdrawal symptoms mimic hyper vigilance, this results in an exaggeration of the response of patients with post-traumatic stress disorder. This comorbidity is associated with worse health outcomes, as its pathophysiology involves a common neurobiological circuit. Opioid substitution therapy and psychotherapeutic medications in combination with evidence-based cognitive behavioral therapy devised for individuals with comorbid post-traumatic stress disorder and opioid dependence may improve treatment outcomes in this population. Therefore, we conclude that the screening for post-traumatic stress disorder in the opioid-abusing population is crucial. To understand the underlying mechanisms for this comorbidity and to improve the treatment response, further research should be encouraged.

  4. Pain in the management of opioid use disorder

    Directory of Open Access Journals (Sweden)

    Sirohi S


    Full Text Available Sunil Sirohi,1 Amit K Tiwari21Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, 2Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USAOpioids remain the drug of choice for the clinical management of moderate to severe pain. However, in addition to their most effective analgesic actions, opioids also produce a sense of well-being and euphoria, which may trigger significant concerns associated with their use.1 In fact, there has been an alarming increase in prescription opioid use, abuse and illicit use; and according to the National Center for Health Statistics, the total number of deaths related to opioid overdose has more than tripled from 2011 to 2014.2–5 Although representing 5.0 % of the global population, studies report that Americans consume 80% of the global opioid supply,3 and the United States is experiencing an opioid abuse epidemic.6 Considering this unprecedented rise in opioid consumption, the United States Centers for Disease Control and Prevention has listed prescription opioid overdose among one of the 10 most important public health problems in all the 50 states.7

  5. Risk Factors for Opioid-Use Disorder and Overdose. (United States)

    Webster, Lynn R


    Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

  6. Comparison of periodontal manifestations in amphetamine and opioids' consumers

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi


    Full Text Available Background: Drug abuse is one of the most important etiologic and deteriorating factors in periodontal disease. Amphetamines and opioids, the most commonly used drugs worldwide, play an important role in this regard. The aim of this study was to compare the periodontal status of amphetamines and opioids consumers in Kermanshah city, Iran in 1393. Methods: Three drug rehabilitation clinics were selected randomly in Kermanshah. According to inclusion and exclusion criteria, 20 amphetamine consumers and 20 opioid consumers were selected randomly and participated in this study. A questionnaire for drug use and periodontal variables was designed. The collected data were entered into SPSS-18 software and Mann-Whitney and t-test were used for statistical analysis. Results: Pocket depth, gingival index and gingival bleeding in amphetamines users were more than those in opioids consumers (P<0.021. Plaque index and gingival recession in opioids users were more than those of amphetamines consumers (P<0.001. The number of periodontal disease cases in amphetamines group were 13 persons (65% and in opioids group 8 persons (40%. Conclusion: Our study showed that periodontal hygine in amphetamine consumers was worse than opioid consumers.

  7. Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets. (United States)

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


    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.

  8. Methylnaltrexone in the treatment of opioid-induced constipation

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld


    Full Text Available Beverley Greenwood-Van Meerveld1, Kelly M Standifer21Veterans Affairs Medical Center, Oklahoma Center for Neuroscience, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Department of Pharmaceutical Sciences, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic usefulness of a μ opioid receptor antagonist, methylnaltrexone in the treatment of opioid-induced constipation. The review highlights methylnaltrexone bromide (RelistorTM; Progenics/Wyeth a quaternary derivative of naltrexone, which was recently approved in the United States, Europe and Canada. The Food and Drug Administration in the United States approved a subcutaneous injection for the treatment of opioid bowel dysfunction in patients with advanced illness who are receiving palliative care and when laxative therapy has been insufficient. Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral–cecal transit in patients with opioidinduced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal. An analysis of the mechanism of action and the potential benefits of using methylnaltrexone is based on data from published basic research and recent clinical studies.Keywords: methylnaltrexone, constipation, opioid

  9. Uranium enrichment by gas centrifuge

    International Nuclear Information System (INIS)

    Heriot, I.D.


    After recalling the physical principles and the techniques of centrifuge enrichment the report describes the centrifuge enrichment programmes of the various countries concerned and compares this technology with other enrichment technologies like gaseous diffusion, laser, aerodynamic devices and chemical processes. The centrifuge enrichment process is said to be able to replace with advantage the existing enrichment facilities in the short and medium term. Future prospects of the process are also described, like recycled uranium enrichment and economic improvements; research and development needs to achieve the economic prospects are also indicated. Finally the report takes note of the positive aspect of centrifuge enrichment as far as safeguards and nuclear safety are concerned. 27 figs, 113 refs

  10. Radiometric enrichment of nonradioactive ores

    International Nuclear Information System (INIS)

    Mokrousov, V.A.; Lileev, V.A.


    Considered are the methods of mineral enrichment based on the use of the radioation of various types. The physical essence of enrichment processes is presented, their classification is given. Described are the ore properties influencing the efficiency of radiometric enrichment, methods of the properties study and estimation of ore enrichment. New possibilities opened by radiometric enrichment in the technology of primary processing of mineral raw materials are elucidated. A considerable attention is paid to the main and auxiliary equipment for radiometric enrichment. The foundations of the safety engineering are presented in a brief form. Presented are also results of investigations and practical works in the field of enrichment of ores of non-ferrous, ferrous and non-metallic minerals with the help of radiometric methods

  11. Satiety and the role of μ-opioid receptors in the portal vein. (United States)

    De Vadder, Filipe; Gautier-Stein, Amandine; Mithieux, Gilles


    Mu-opioid receptors (MORs) are known to influence food intake at the brain level, through their involvement in the food reward system. MOR agonists stimulate food intake. On the other hand, MOR antagonists suppress food intake. MORs are also active in peripheral organs, especially in the small intestine where they control the gut motility. Recently, an indirect role in the control of food intake was ascribed to MORs in the extrinsic gastrointestinal neural system. MORs present in the neurons of the portal vein walls sense blood peptides released from the digestion of dietary protein. These peptides behave as MOR antagonists. Their MOR antagonist action initiates a gut-brain circuitry resulting in the induction of intestinal gluconeogenesis, a function controlling food intake. Thus, periportal MORs are a key mechanistic link in the satiety effect of protein-enriched diets. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. The world enrichment market

    International Nuclear Information System (INIS)

    Gunter, L.; McCants, C.; Rutkowski, E.


    The enrichment market can be divided into two periods: the near-term market (1991 to 1995) and the long-term market (1995 and beyond). The near-term market is characterized by limited unfilled requirements of 4% per year, to be supplied by national stockpiles and excess inventories. This low-cost material will be drawn down by about 1993, causing a subsequent price rise. As the price rises, primary supplier activity is expected to increase. In the near-term, two contracting activities are apparent: spot; and intermediate-term. The current spot market is expected to last until available low cost inventories are drawn down. Recently, in attempts to gain market share, suppliers have offered attractively priced intermediate-term (3 year) contracts for 1996 to 1998. While a small spot market will continue after 1995, it is anticipated that utilities will prefer a mix of medium- and long-term (5 to 10 year) contracts from primary suppliers for most of their enrichment requirements. As national stockpiles and utility inventories are consumed, low-cost supply available to the spot market is expected to diminish. Consequently, with little low-cost supply available, the only apparent source of material will be from primary suppliers, and the resulting competition over market share is expected to be intense. (author)

  13. Motif enrichment tool. (United States)

    Blatti, Charles; Sinha, Saurabh


    The Motif Enrichment Tool (MET) provides an online interface that enables users to find major transcriptional regulators of their gene sets of interest. MET searches the appropriate regulatory region around each gene and identifies which transcription factor DNA-binding specificities (motifs) are statistically overrepresented. Motif enrichment analysis is currently available for many metazoan species including human, mouse, fruit fly, planaria and flowering plants. MET also leverages high-throughput experimental data such as ChIP-seq and DNase-seq from ENCODE and ModENCODE to identify the regulatory targets of a transcription factor with greater precision. The results from MET are produced in real time and are linked to a genome browser for easy follow-up analysis. Use of the web tool is free and open to all, and there is no login requirement. ADDRESS: © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Opioid-induced preconditioning: recent advances and future perspectives. (United States)

    Peart, Jason N; Gross, Eric R; Gross, Garrett J


    Opioids, named by Acheson for compounds with morphine-like actions despite chemically distinct structures, have received much research interest, particularly for their central nervous system (CNS) actions involved in pain management, resulting in thousands of scientific papers focusing on their effects on the CNS and other organ systems. A more recent area which may have great clinical importance concerns the role of opioids, either endogenous or exogenous compounds, in limiting the pathogenesis of ischemia-reperfusion injury in heart and brain. The role of endogenous opioids in hibernation provides tantalizing evidence for the protective potential of opioids against ischemia or hypoxia. Mammalian hibernation, a distinct energy-conserving state, is associated with depletion of energy stores, intracellular acidosis and hypoxia, similar to those which occur during ischemia. However, despite the potentially detrimental cellular state induced with hibernation, the myocardium remains resilient for many months. What accounts for the hypoxia-tolerant state is of great interest. During hibernation, circulating levels of opioid peptides are increased dramatically, and indeed, are considered a "trigger" of hibernation. Furthermore, administration of opioid antagonists can effectively reverse hibernation in mammals. Therefore, it is not surprising that activation of opioid receptors has been demonstrated to preserve cellular status following a hypoxic insult, such as ischemia-reperfusion in many model systems including the intestine [Zhang, Y., Wu, Y.X., Hao, Y.B., Dun, Y. Yang, S.P., 2001. Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine. Life Sci. 68, 1013-1019], skeletal muscle [Addison, P.D., Neligan, P.C., Ashrafpour, H., Khan, A., Zhong, A., Moses, M., Forrest, C.R., Pang, C.Y., 2003. Noninvasive remote ischemic preconditioning for global protection of skeletal muscle against infarction. Am. J. Physiol. Heart Circ

  15. Health service utilisation by people living with chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study. (United States)

    Nielsen, Suzanne; Campbell, Gabrielle; Peacock, Amy; Smith, Kimberly; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Degenhardt, Louisa


    used among those with CNCP and the demographic and clinical characteristics that may be associated with the use of different types of treatments. Understanding the use of non-drug therapy among people with CNCP is crucial given the potential to improve pain control for these patients. What does this paper add? The present study found that a wide range of non-opioid treatments was accessed by the study sample, both before and after commencing opioids, indicating that in this sample opioids were not the sole strategy used for pain management. The most common treatment (other than opioids) was CAM, reported by two-fifths of the sample. Having private health insurance was associated with increased use of non-opioid treatments for pain, highlighting the importance of considering how treatments are paid for and potential financial barriers to effective treatments. What are the implications for practitioners? Patients' beliefs and financial barriers may affect the uptake of different treatments. Many patients may be using complementary and alternative approaches with limited evidence to support their use, highlighting the need for clinicians to discuss with patients the range of prescribed and non-prescribed treatments they are accessing and to help them understand the benefits and risks of treatments that have not been tested sufficiently, or have inconsistent evidence, as to their efficacy in improving pain outcomes.

  16. Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain. (United States)

    Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando


    Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

  17. Health-Related Quality of Life among Chronic Opioid Users, Nonchronic Opioid Users, and Nonopioid Users with Chronic Noncancer Pain. (United States)

    Hayes, Corey J; Li, Xiaocong; Li, Chenghui; Shah, Anuj; Kathe, Niranjan; Bhandari, Naleen Raj; Payakachat, Nalin


    Evaluate the association between opioid therapy and health-related quality of life (HRQoL) in participants with chronic, noncancer pain (CNCP). Medical Expenditure Panel Survey Longitudinal, Medical Conditions, and Prescription Files. Using a retrospective cohort study design, the Mental Health Component (MCS12) and Physical Health Component (PCS12) scores of the Short Form-12 Version 2 were assessed to measure mental and physical HRQoL. Chronic, noncancer pain participants were classified as chronic, nonchronic, and nonopioid users. One-to-one propensity score matching was employed to match chronic opioid users to nonchronic opioid users plus nonchronic opioid users and chronic opioid users to nonopioid users. A total of 5,876 participants were identified. After matching, PCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = -0.98, 95% CI: -2.07, 0.10), chronic versus nonopioid users (LSM Diff = -2.24, 95% CI: -4.58, 0.10), or chronic versus nonchronic opioid users (LSM Diff = -2.23, 95% CI: -4.53, 0.05). Similarly, MCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = 0.76, 95% CI: -0.46, 1.98), chronic versus nonopioid users (LSM Diff = 1.08, 95% CI: -1.26, 3.42), or chronic versus nonchronic opioid users (LSM Diff = -0.57, 95% CI: -2.90, 1.77). Clinicians should evaluate opioid use in participants with CNCP as opioid use is not correlated with better HRQoL. © Health Research and Educational Trust.

  18. Modular enrichment measurement system for in-situ enrichment assay

    International Nuclear Information System (INIS)

    Stewart, J.P.


    A modular enrichment measurement system has been designed and is in operation within General Electric's Nuclear Fuel Fabrication Facility for the in-situ enrichment assay of uranium-bearing materials in process containers. This enrichment assay system, which is based on the ''enrichment meter'' concept, is an integral part of the site's enrichment control program and is used in the in-situ assay of the enrichment of uranium dioxide (UO 2 ) powder in process containers (five gallon pails). The assay system utilizes a commercially available modular counting system and a collimnator designed for compatability with process container transport lines and ease of operator access. The system has been upgraded to include a microprocessor-based controller to perform system operation functions and to provide data acquisition and processing functions. Standards have been fabricated and qualified for the enrichment assay of several types of uranium-bearing materials, including UO 2 powders. The assay system has performed in excess of 20,000 enrichment verification measurements annually and has significantly contributed to the facility's enrichment control program

  19. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P


    significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  20. Enrichment of boron 10

    International Nuclear Information System (INIS)

    Coutinho, C.M.M.; Rodrigues Filho, J.S.R.; Umeda, K.; Echternacht, M.V.


    A isotopic separation pilot plant with five ion exchange columns interconnected in series were designed and built in the IEN. The columns are charged with a strong anionic resin in its alkaline form. The boric acid solution is introduced in the separation columns until it reaches a absorbing zone length which is sufficient to obtain the desired boron-10 isotopic concentration. The boric acid absorbing zone movement is provided by the injection of a diluted hydrochloric acid solution, which replace the boric acid throughout the columns. The absorbing zone equilibrium length is proportional to its total length. The enriched boron-10 and the depleted boron are located in the final boundary and in the initial position of the absorbing zones, respectively. (author)

  1. Thermal breeder fuel enrichment zoning

    International Nuclear Information System (INIS)

    Capossela, H.J.; Dwyer, J.R.; Luce, R.G.; McCoy, D.F.; Merriman, F.C.


    A method and apparatus for improving the performance of a thermal breeder reactor having regions of higher than average moderator concentration are disclosed. The fuel modules of the reactor core contain at least two different types of fuel elements, a high enrichment fuel element and a low enrichment fuel element. The two types of fuel elements are arranged in the fuel module with the low enrichment fuel elements located between the high moderator regions and the high enrichment fuel elements. Preferably, shim rods made of a fertile material are provided in selective regions for controlling the reactivity of the reactor by movement of the shim rods into and out of the reactor core. The moderation of neutrons adjacent the high enrichment fuel elements is preferably minimized as by reducing the spacing of the high enrichment fuel elements and/or using a moderator having a reduced moderating effect. 1 figure

  2. Advanced Neutron Source enrichment study

    International Nuclear Information System (INIS)

    Bari, R.A.; Ludewig, H.; Weeks, J.R.


    A study has been performed of the impact on performance of using low-enriched uranium (20% 235 U) or medium-enriched uranium (35% 235 U) as an alternative fuel for the Advanced Neutron Source, which was initially designed to use uranium enriched to 93% 235 U. Higher fuel densities and larger volume cores were evaluated at the lower enrichments in terms of impact on neutron flux, safety, safeguards, technical feasibility, and cost. The feasibility of fabricating uranium silicide fuel at increasing material density was specifically addressed by a panel of international experts on research reactor fuels. The most viable alternative designs for the reactor at lower enrichments were identified and discussed. Several sensitivity analyses were performed to gain an understanding of the performance of the reactor at parametric values of power, fuel density, core volume, and enrichment that were interpolations between the boundary values imposed on the study or extrapolations from known technology

  3. Opioid Epidemic: Cellular & Molecular Anesthesia as a Key Solution

    Directory of Open Access Journals (Sweden)

    Ali Dabbagh


    Full Text Available Opioids are one of the most important arsenals armamentarium of physicians for fighting against pain. During the decades, opioids have been used in a wide range of indications; both for treatment of acute and chronic pain; as natural and synthetic compounds and in a variety of delivery forms from intravenous infusion to intrathecal adjuvants of local anesthetics or as transdermal patches. There is no doubt that we are in an opioid misuse epidemic status; whether in the US or other countries; but if we want to resolve this miserable multilateral complication, there is no doubt that Cellular and Molecular aspects of Anesthesia has a key role in resolving the problem; through creating an opioid free pain management era.

  4. Opioid interruptions, pain, and withdrawal symptoms in nursing home residents. (United States)

    Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S


    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

  5. Opioid Overdose Prevention: Safety Advice for Patients & Family Members (United States)

    ... the effects of opioids. Naloxone works by blocking opiate receptor sites. It is not effective in treating ... agitation, anxiety, confusion, or ringing in your ears.  Seizures (convulsions).  Feeling that you might pass out.  Slow ...

  6. Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  7. Although Relatively Few, "Doctor Shoppers" Skew Opioid Prescribing (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  8. Fentanyl and Other Synthetic Opioids Drug Overdose Deaths (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  9. Polyglycerol-opioid conjugate produces analgesia devoid of side effects. (United States)

    González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph


    Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

  10. The endogenous opioid system: a common substrate in drug addiction. (United States)

    Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael


    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

  11. Addiction to opioids in chronic pain patients: a literature review

    DEFF Research Database (Denmark)

    Højsted, Jette; Sjøgren, Per


    , incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... treatment as addiction may result in poor pain control. Several screening tools were identified, but only a few were thoroughly validated with respect to validity and reliability. Most of the identified guidelines mention addiction as a potential problem. The guidelines in cancer pain management...

  12. Influence of intravenous opioid dose on postoperative ileus. (United States)

    Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J


    Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  14. The Neuroanatomy of Sexual Dimorphism in Opioid Analgesia (United States)


    2012 for review). Studies utilizing orofacial , somatosensory or visceral pain assays typically report that morphine produces a significantly greater...Review The neuroanatomy of sexual dimorphism in opioid analgesia Dayna R. Loyd a, Anne Z. Murphy b,⁎ a Pain Management Research Area, United 13 April 2014 Keywords: Pain Periaqueductal gray Morphine Mu opioid receptor The influence of sex has been neglected in clinical studies on pain

  15. Safety of oral dronabinol during opioid withdrawal in humans. (United States)

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


    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.

  16. Is there a role for opioids in the treatment of fibromyalgia? (United States)

    Littlejohn, Geoffrey O; Guymer, Emma K; Ngian, Gene-Siew


    The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.

  17. Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance

    Directory of Open Access Journals (Sweden)

    Zhao Jing


    Full Text Available Abstract The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

  18. Medication-assisted recovery from opioid addiction: historical and contemporary perspectives. (United States)

    White, William L


    Recovery is being used as a conceptual fulcrum for the redesign of addiction treatment and related support services in the United States. Efforts by policy, research, and clinical leaders to define recovery and calls for assertive models of long-term recovery management raise critical questions about how transformation efforts of recovery-focused systems will affect the pharmacotherapeutic treatment of opioid addiction and the status of patients participating in such treatment. This article highlights recent work advocating a recovery-oriented approach to medication-assisted treatment.

  19. A nationwide pharmacy chain responds to the opioid epidemic. (United States)

    Shafer, Emily; Bergeron, Nyahne; Smith-Ray, Renae; Robson, Chester; O'Koren, Rachel

    To describe the 3-pronged approach taken by a large national retail pharmacy chain to address the opioid epidemic and associated overdoses. Large national retail pharmacy chain with more than 8200 stores in 50 states. Eight million customer interactions daily through in-store and digital settings. This is a company with a long history of responding to public health crises. Initiated 3 programs to respond to the opioid crisis: 1) provide safe medication disposal kiosks; 2) expand national access to naloxone; and 3) provide education on the risk and avoidance of opioid overdose. Used the RE-AIM framework to evaluate and enhance the quality, speed, and public health impact of the interventions. Not applicable. Early results are safe medication disposal kiosks in more than 43 states, naloxone-dispensing program in 33 states, and patient and support system education using the Opioid Overdose Toolkit from the Substance Abuse and Mental Health Services Administration. The availability of safe drug-disposal kiosks, naloxone dispensing at pharmacies, and patient education are key prevention initiatives to address the opioid epidemic and reduce the increasing national burden of opioid overdose. Early results are quantitatively and qualitatively promising. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Clinical implications of patient-provider agreements in opioid prescribing. (United States)

    Kraus, Carl N; Baldwin, Alan T; Curro, Frederick A; McAllister, R G


    In June, 2012 the United States Food and Drug Administration (FDA) developed a "blueprint" for prescriber education as a means of directing Certified Medical Education (CME) activities that included content which would meet the regulatory requirements of the class-wide, longacting/ extended-release (LA-ER) opioid Risk Evaluation Mitigation Strategies (REMS). Within the blueprint is the suggested adoption of Patient-Provider Agreements (PPAs) to be used in association with opioid prescribing, but, to our knowledge, there have been no reported evaluations of the role played by opioid-agent PPAs in clinical practice, or of the perceptions of this regulatory mandate by clinicians. Therefore, we conducted a survey regarding PPA perceptions by opioid prescribers that was posted for five weeks on a well-trafficked online CME service provider (Medscape). Of the 1,232 respondents (reflecting a 99.5% completion rate), 52.4% treat acute or chronic pain with opioids. The survey identified an improvement of opioid safe-use education (21% of respondents) as the most frequently selected beneficial element of PPAs. Conversely, the challenges to adoption included time constraints (21% of physicians) as well as lack of evidence that PPAs will reduce drug misuse, and the lack of a uniform, patient-friendly PPA. Based on our survey, clinicians consider the PPA of potential value, but data regarding the utility of such an instrument are lacking.

  1. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    Neumaier, J.F.


    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

  2. Reviewing opioid use, monitoring, and legislature: Nursing perspectives

    Directory of Open Access Journals (Sweden)

    Deniece A. Jukiewicz


    Full Text Available The phenomena of prescription opioid misuse and abuse have a complicated history of contributing factors including policies, practices, and prescribing leading to contemporary phenomena. Some factors implicated in the opioid drug abuse problem include inefficient prescribing and improper use, lack of knowledge related to interpretation and assessment of pain levels, and decreased oversight and regulation from government and policy agents. Nurses, often frontline providers, need to be knowledgeable and embrace the guidelines, and necessary implications associated with both prescribing and administration of opioids. Additionally, all providers including physicians, physician assistants, nurse practitioners, and bedside nurses must have a firm understanding of the improper use and abuse of opioids. The examination and review of opioid policies at the state and federal level has revealed inconsistency with regulations, policies, and guidelines that have lead to the current situation. The use of an interdisciplinary team with nurses and various other practitioners is a good strategy to help reduce this problem. Keywords: Abuse, Administration, Legislature, Nursing, Opioid, Overdose, Policy, Prescribing

  3. Preference or fat? Revisiting opioid effects on food intake. (United States)

    Taha, Sharif A


    It is well established that opioid signaling in the central nervous system constitutes a powerful stimulus for food intake. The role of opioids in determining food preference, however, is less well defined. Opioids have been proposed to promote intake of preferred foods, or, alternatively, to preferentially increase consumption of fat. In the present manuscript, I comprehensively review results from previous studies investigating this issue. Data from these studies suggests a mechanism for opioid action that may reconcile the previously proposed hypotheses: opioid effects on food intake do appear to be largely specific for fat consumption, but individual animals' sensitivity to this effect may be dependent on baseline food preferences. In addition, I highlight the possibility that the selectivity of endogenous opioid effects may importantly differ from that of exogenous agonists in the degree to which baseline preferences, rather than macronutrient intake, are altered. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. 2010 Elsevier Inc. All rights reserved.

  4. Yiguanjian cataplasm attenuates opioid dependence in a mouse (United States)

    Gao, Shuai; Gao, Hong; Fan, Yuchen; Zhang, Guanghua; Sun, Fengkai; Zhao, Jing; Li, Feng; Yang, Yang; Wang, Kai


    To investigate the effect of Yiguanjian (YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. One hundred Swiss albino mice, of equal male to female ratio, were randomly and equally divided into 10 groups. A portion (3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment. Morphine (5 mg/kg) was intraperitoneally administered twice daily for 5 days. YGJ cataplasm was prepared and pasted on the bare region of the mice immediately before morphine administration on day 3 and subsequently removed at the end day 5. On day 6, naloxone (8 mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome. Behavioral observation was performed in two 30-min phases immediately after naloxone injection. The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone- induced experimental opioid withdrawal, in terms of withdrawal severity score and the frequencies of jumping, rearing, forepaw licking, and circling behaviors. However, YGJ cataplasm treatment did not alter the acute analgesic effect of morphine. YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms. Therefore, YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.

  5. Enrichment plants. A survey of major new uranium enriching projects

    International Nuclear Information System (INIS)

    Kovan, D.


    The work enrichment situation is reported. The development of enrichment in the U.S. and in Europe is outlined. A brief description is given of the technology of separation by diffusion and by centrifugation and the advantages and disadvantages of the two processes are compared. Finally the supply and demand situation is briefly considered. (U.K.)

  6. Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons. (United States)

    Ardianto, C; Yonemochi, N; Yamamoto, S; Yang, L; Takenoya, F; Shioda, S; Nagase, H; Ikeda, H; Kamei, J


    The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 μg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 μg/side) outside of the LH did not affect food intake. The injection of β-FNA (2 μg/side), naltrindole (1 μg/side) or norBNI (2 μg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 μg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 μg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy

    DEFF Research Database (Denmark)

    Søndergaard, Jens; Christensen, Helene Nordahl; Ibsen, Rikke


    -based cohort study including patients ≥18 years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. A measure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain....../acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age...... characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31% versus 19%) compared to those without OIC (P 

  8. Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

    Directory of Open Access Journals (Sweden)

    Tara Gomes


    Full Text Available Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily, moderate (900 to 1,799 mg daily, or high (≥1,800 mg daily. A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256 and 6.8% of controls (313 of 4,619 were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI

  9. Role of the brain dopaminergic and opioid system in the regulation of "child's" (maternal bonding) behavior of newborn albino rats. (United States)

    Stovolosov, I S; Dubynin, V A; Kamensky, A A


    Administration of D(2) receptor antagonist clebopride in a dose not affecting locomotor activity was followed by a decrease in maternal bonding behavior of 10-day-old and 15-day-old albino rat pups. D(1) receptor antagonist SCH23390 had a stimulatory effect only on the behavior of 10-day-old newborns. Opioid peptide β-casomorphin-7 abolished the effect of clebopride in rat pups of the older age group.

  10. Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

    Directory of Open Access Journals (Sweden)

    Yuqing Mao


    Full Text Available Background/Aims: Irritable bowel syndrome (IBS, defined as recurrent abdominal pain and changes in bowel habits, seriously affects quality of life and ability to work. Ghrelin is a brain-gut hormone, which has been reported to show antinociceptive effects in peripheral pain. We investigated the effect of ghrelin on visceral hypersensitivity and pain in a rat model of IBS. Methods: Maternal deprivation (MD was used to provide a stress-induced model of IBS in Wistar rats. Colorectal distension (CRD was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR scores. Rats that were confirmed to have visceral hypersensitivity after MD were injected with ghrelin (10 µg/kg subcutaneously twice a week from weeks 7 to 8. [D-Lys3]-GHRP-6 (100 nmol/L and naloxone (100 nmol/L were administered subcutaneously to block growth hormone secretagogue receptor 1α (GHS-R1α and opioid receptors, respectively. Expression of transient receptor potential vanilloid type 1 (TRPV1 and µ and κ opioid receptors (MOR and KOR in colon, dorsal root ganglion (DRG and cerebral cortex tissues were detected by western blotting, quantitative real-time polymerase chain reaction (qRT-PCR, immunohistochemical analyses and immunofluorescence. Results: Ghrelin treatment increased expression of opioid receptors and inhibited expression of TRPV1 in colon, dorsal root ganglion (DRG and cerebral cortex. The antinociceptive effect of ghrelin in the rat model of IBS was partly blocked by both the ghrelin antagonist [D-Lys3]-GHRP-6 and the opioid receptor antagonist naloxone. Conclusion: The results indicate that ghrelin exerted an antinociceptive effect, which was mediated via TRPV1/opioid systems, in IBS-induced visceral hypersensitivity. Ghrelin might potentially be used as a new treatment for IBS.

  11. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Parvaz Madadi

    Full Text Available The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity.This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed.Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359. Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch, 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer.These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.

  12. Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic. (United States)

    Chakrabarti, Sumita; Liu, Nai-Jiang; Zadina, James E; Sharma, Tarak; Gintzler, Alan R


    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.

  13. Effects of Enrichment Presentation and Other Factors on Behavioral Welfare of Pantropical Spotted Dolphin (Stenella attenuata). (United States)

    Perez, Barbara C; Mehrkam, Lindsay R; Foltz, Amanda R; Dorey, Nicole R


    Environmental enrichment is a crucial element of promoting welfare for animals in captivity. However, enrichment programs are not always formally evaluated for their efficacy. Furthermore, there is little empirical evidence of enrichment evaluation for species of small cetaceans in zoological settings. A wide range of variables may potentially influence enrichment efficacy and how it in turn affects behavior. The purpose of this study was to determine the most preferred environmental enrichment, and method of presentation, for a species that has not been well studied in captivity, the pantropical spotted dolphin (Stenella attenuata). In order to determine which enrichment items and method of presentation were most effective at eliciting enrichment interaction, we systematically examined how several variables of enrichment influenced enrichment interaction. The results suggested that presenting enrichment after training sessions influenced interaction with the enrichment. The results also indicated preference for enrichment type and a specific enrichment device. Finally, factors that influenced interaction were also found to influence aberrant behavior. The results support the premise that enrichment be "redefined" for each species and each individual.

  14. Functional properties of pasta enriched with variable cereal brans. (United States)

    Kaur, Gurkirat; Sharma, Savita; Nagi, H P S; Dar, Basharat N


    To explore the potentiality of cereal brans for preparation of fiber enriched pasta, various cereal brans (Wheat, Rice, Barley and Oat) were added at 0, 5, 10, 15, 20 and 25 per cent to durum wheat semolina. The effect of cereal bran enrichment on the colour, cooking, sensory quality and shelf life of enriched pasta was assessed at ambient temperature. Pasta prepared with added fiber at 25 per cent level had the highest protein and dietary fiber content as compared to control. Enrichment with variable fiber sources improved the brightness of pasta, as colour of pasta enhanced significantly. Addition of cereal brans resulted an increase in the water absorption and cooking losses of pasta. This effect was dependent on the level and type of cereal brans. Significant correlation (r = 0.80) was obtained between water absorption and volume expansion in all types of bran enriched pasta. At 25 per cent level of supplementation, maximum solids were leached into cooking water. Bran enriched pasta required less cooking time for complete gelatinization of starch. Increasing level of cereal brans had significantly affected the overall acceptability of enriched pasta. Cooking quality of pasta remained constant during storage. Non significant effect of storage was found on water activity, free fatty acids. Enriched pasta (15 per cent level of wheat, rice and oat bran and 10 per cent barley bran) was highly acceptable upto 4 months of storage with respect to quality.


    Directory of Open Access Journals (Sweden)

    O. E. Dudu


    Full Text Available The study was carried out to determine the microbiological and nutritional quality, organoleptic, rheological and textural effect as well as the effect on the shelf life of wheat bread enriched with West African cottage cheese (warankashi at different substitution levels (1 %, 3 % and 5 %. The protein and fat content of wheat bread significantly increased but carbohydrate levels decreased significantly as enrichment with Warankashi increased. The amino acid profile of the wheat bread increased with increasing enrichment. The incorporation of Warankashi into wheat flour affected the rheological and textural properties of wheat flour; the rate of water absorption of the wheat flour decreased as Warankashi incorporation levels increased. Also, the dough stability time of the enriched flours was lesser than that of the wheat flour. The 3 % enrichment level had the highest dough consistency (520 BU. The extensibility of 1 % and 3 % wara bread dough were the same while that of wheat flour bread and 5 % Warankashi were the same. The 3 % wara bread dough had the highest resistance to extension. Shelf life of the bread remained unaffected by Warankashi incorporation but the rate of bacteria and fungi (yeast and mould growth decreased significantly (P < 0.05 as enrichment levels increased. There was no significant difference between the organoleptic properties of wheat bread to that of the enriched breads but the 3 % Warankshi enriched bread had the highest consumer acceptability.

  16. Review of uranium enrichment prospects in Canada, 1976

    International Nuclear Information System (INIS)

    Developments since 1971 which affect the prospects for uranium enrichment in Canada from the federal government point of view are reviewed. The market for enriched uranium to the year 2000 is similar to that projected in 1971. The committed enrichment capacity of the world will be sufficient until 1990. The Canadian uranium mining capability may be adequate to supply an enrichment plant, but the present reserves policy along with the currently known resources are likely to restrict exports of its products during the plant life. Prices for enriched uranium produced in Canada would be higher than those reported by other proposed new plants; however, newer enrichment techniques have some potential for cost reductions. Application of enrichment with U235 (or plutonium and U233/thorium) to CANDU offers some uranium resource conservation and possible slight power cost reductions. Construction of an enrichment plant in Canada to supply the export market is less attractive in 1976 than in 1971, but there is potential for such a business in the future. (L.L.)

  17. Undertreatment of pain and low use of opioids in Latin America. (United States)

    García, César Amescua; Santos Garcia, Joao Batista; Rosario Berenguel Cook, María Del; Colimon, Frantz; Flores Cantisani, José Alberto; Guerrero, Carlos; Rocío Guillén Núnez, María Del; Hernández Castro, John Jairo; Kraychete, Durval Campos; Lara-Solares, Argelia; Lech, Osvandré; Rico Pazos, María Antonieta; Gallegos, Manuel Sempértegui; Marcondes, Lizandra Pattaro


    Pain is highly prevalent among the adult Latin American population. However, many patients with moderate to severe pain do not have access to effective pain management with opioids due to limited access to healthcare, overuse of nonopioid analgesics, regulatory barriers and lack of appropriate information about opioids. There is scarce training on use of opioids among physicians and other healthcare providers, which leads to misconceptions, mainly related to a fear of prescribing opioids. Although opioids are safe and effective drugs for the treatment of moderate to severe chronic pain, the use of opioids in Latin American nations is clearly below standards compared with developed countries.

  18. Novel meat-enriched foods for older consumers. (United States)

    Farouk, Mustafa M; Yoo, Michelle J Y; Hamid, Nazimah S A; Staincliffe, Maryann; Davies, Briar; Knowles, Scott O


    Red meat enriched versions of bread, spaghetti, yoghurt, ice cream and chocolate were prototyped and assessed for some of their physical, chemical and microbiological properties, as well as sensory appeal. The protein content of the products were significantly increased and their colour went darker with meat enrichment (pice cream meltability and yoghurt apparent viscosity decreased with meat enrichment (pice cream and spaghetti were not affected (p>0.05) but that of non-flavoured ice cream and yoghurt went down (pindustry stretch its established business models, and encouraging further development of novel food choices for elderly and other groups of consumers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Buckwheat-enriched wheat bread: National market placement possibilities

    Directory of Open Access Journals (Sweden)

    Sakač Marijana B.


    Full Text Available Quality parameters and the possibility of successful placement of buckwheat-enriched wheat bread on the national market are presented in this paper. Analysis of the market position of buckwheat-enriched wheat bread includes demands, offer and competition. Elements that affect the overall retail price of buckwheat-enriched wheat bread are given in details, along with SWOT analysis and marketing plan including target market, market supply and product marketing mix. According to all performed analyses it could be concluded that this product should be positioned on the national market, especially for people with special needs and requirements.

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

    LENUS (Irish Health Repository)

    Fanning, Rebecca A


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

  1. Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review. (United States)

    Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana


    Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

  2. Nucleus accumbens opioid, GABaergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat. (United States)

    Zhang, Min; Balmadrid, Christian; Kelley, Ann E


    The current studies were designed to evaluate whether incentive motivation for palatable food is altered after manipulations of opioid, GABAergic, and dopaminergic transmission within the nucleus accumbens. A progressive ratio schedule was used to measure lever-pressing for sugar pellets after microinfusion of drugs into the nucleus accumbens in non-food-deprived rats. The mu opioid agonist D-Ala2, NMe-Phe4, Glyo15-enkephalin and the indirect dopamine agonist amphetamine induced a marked increase in break point and correct lever-presses; the GABA(A) agonist muscimol did not affect breakpoint or lever-presses. The data suggest that opioid, dopaminergic, and GABAergic systems within the accumbens differentially modulate food-seeking behavior through mechanisms related to hedonic evaluation of food, incentive salience, and control of motor feeding circuits, respectively.

  3. Industrial aspects in uranium enrichment

    International Nuclear Information System (INIS)

    Mezin, M.


    Characteristics of isotope separation processes in operation and under development are discussed. These include the number of stages in series, the number of components, the component unit capacity and enery requirements. The implementation of an enrichment process and the question of an enrichment plant in Australia are also considered

  4. City model enrichment (United States)

    Smart, Philip D.; Quinn, Jonathan A.; Jones, Christopher B.

    The combination of mobile communication technology with location and orientation aware digital cameras has introduced increasing interest in the exploitation of 3D city models for applications such as augmented reality and automated image captioning. The effectiveness of such applications is, at present, severely limited by the often poor quality of semantic annotation of the 3D models. In this paper, we show how freely available sources of georeferenced Web 2.0 information can be used for automated enrichment of 3D city models. Point referenced names of prominent buildings and landmarks mined from Wikipedia articles and from the OpenStreetMaps digital map and Geonames gazetteer have been matched to the 2D ground plan geometry of a 3D city model. In order to address the ambiguities that arise in the associations between these sources and the city model, we present procedures to merge potentially related buildings and implement fuzzy matching between reference points and building polygons. An experimental evaluation demonstrates the effectiveness of the presented methods.

  5. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report


    Lalanne, Laurence; Nicot, Chloe; Lang, Jean-Philippe; Bertschy, Gilles; Salvat, Eric


    Background Opioids are good painkillers, but many patients treated with opioids as painkillers developed a secondary addiction. These patients need to stop misusing opioids, but the mild-to-severe clinical symptoms associated with opioid withdrawal risk increasing their existing pain. In such cases, ketamine, which is used by anaesthetists and pain physicians to reduce opioid medication, may be an effective agent for managing opioid withdrawal. Case presentation We describe the case of a woma...

  6. AEC determines uranium enrichment policy

    International Nuclear Information System (INIS)



    The Advisory Committee on Uranium Enrichment of the Atomic Energy Commission (AEC) has submitted a report to AEC chairman concerning the promotion of the introduction of advanced material, high performance centrifuges to replace conventional metallic drum centrifuges, and the development of next generation advanced centrifuges. The report also called for the postponement until around 1997 of the decision whether the development should be continued or not on atomic vapor laser isotope separation (AVLIS) and molecular laser isotope separation (MLIS) processes, as well as the virtual freezing of the construction of a chemical process demonstration plant. The report was approved by the AEC chairman in August. The uranium enrichment service market in the world will continue to be characterized by oversupply. The domestic situation of uranium enrichment supply-demand trend, progress of the expansion of Rokkasho enrichment plant, the trend in the development of gas centrifuge process and the basic philosophy of commercializing domestic uranium enrichment are reported. (K.I.)

  7. IAEA statement on Iranian enrichment announcement

    International Nuclear Information System (INIS)


    Full text: The following is a statement attributable to IAEA Spokesperson Gill Tudor: 'The IAEA can confirm that it has received a letter from the Atomic Energy Organization of Iran (AEOI) on 8 February 2010, in which the AEOI informed the Agency that production of less than 20% enriched uranium is being foreseen at the Pilot Fuel Enrichment Plant at Natanz for fuel for the Tehran Research Reactor'. 'IAEA Director General Yukiya Amano noted with concern this decision, as it may affect, in particular, ongoing international efforts to ensure the availability of nuclear fuel for the Tehran Research Reactor.' 'The Director General reiterated the Agency's readiness to play an intermediary role on the issue of the Tehran Research Reactor.' (IAEA)

  8. New generation enrichment monitoring technology for gas centrifuge enrichment plants

    International Nuclear Information System (INIS)

    Ianakiev, Kiril D.; Alexandrov, Boian S.; Boyer, Brian D.; Hill, Thomas R.; Macarthur, Duncan W.; Marks, Thomas; Moss, Calvin E.; Sheppard, Gregory A.; Swinhoe, Martyn T.


    The continuous enrichment monitor, developed and fielded in the 1990s by the International Atomic Energy Agency, provided a go-no-go capability to distinguish between UF 6 containing low enriched (approximately 4% 235 U) and highly enriched (above 20% 235 U) uranium. This instrument used the 22-keV line from a 109 Cd source as a transmission source to achieve a high sensitivity to the UF 6 gas absorption. The 1.27-yr half-life required that the source be periodically replaced and the instrument recalibrated. The instrument's functionality and accuracy were limited by the fact that measured gas density and gas pressure were treated as confidential facility information. The modern safeguarding of a gas centrifuge enrichment plant producing low-enriched UF 6 product aims toward a more quantitative flow and enrichment monitoring concept that sets new standards for accuracy stability, and confidence. An instrument must be accurate enough to detect the diversion of a significant quantity of material, have virtually zero false alarms, and protect the operator's proprietary process information. We discuss a new concept for advanced gas enrichment assay measurement technology. This design concept eliminates the need for the periodic replacement of a radioactive source as well as the need for maintenance by experts. Some initial experimental results will be presented.

  9. Characteristics of prescribers whose patients shop for opioids: results from a cohort study. (United States)

    Cepeda, M Soledad; Fife, Daniel; Berlin, Jesse A; Mastrogiovanni, Gregory; Yuan, Yingli


    Little is known about the prevalence of opioid shoppers in clinical practices and the relation between prescriber characteristics and the risk of having opioid shoppers. Describe the prevalence of opioid shoppers in prescribers' practices. Assess the relation between prescribers' characteristics and patient opioid shopping behavior. Retrospective cohort study using a large US retail prescription database. Patients with ≥1 opioid dispensing were followed 18 months. These patients' prescribers are the focus of the study. A patient was a "shopper" if he or she had opioid prescriptions written by ≥1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies and a "heavy shopper" if he or she had ≥5 shopping episodes. The proportions of shoppers by prescriber and the proportion of prescribers with ≥1 shopper or heavy shopper were calculated. Among 858,290 opioid prescribers, most (87 percent) had no shoppers and 98 percent had no heavy shoppers. Prescribers who were aged 70-79 years, male, or who prescribed schedule II opioids had an increased likelihood of having shoppers. As the number of patients for whom a prescriber prescribed opioids increased, the proportion of shoppers also increased. Prescribers with 66 or more patients receiving opioids, who represented 25 percent of prescribers, prescribed for 82 percent of all shoppers. The great majority of opioid prescribers appear to have no shoppers in their practice. Any educational program will be more cost effective if targeted to prescribers of schedule II opioids with a large volume of patients requiring opioids.

  10. Advances in the delivery of buprenorphine for opioid dependence

    Directory of Open Access Journals (Sweden)

    Rosenthal RN


    Full Text Available Richard N Rosenthal,1 Viral V Goradia2 1Department of Psychiatry, Addiction Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 2Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA Abstract: Opioid use disorders (OUDs have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. Keywords: opioid use disorder, buprenorphine, drug diversion, drug implants, depot medications, maintenance therapy, treatment adherence

  11. Review of Opioid Pharmacogenetics and Considerations for Pain Management. (United States)

    Owusu Obeng, Aniwaa; Hamadeh, Issam; Smith, Michael


    Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics. © 2017

  12. Impact of opioid therapy on gonadal hormones: focus on buprenorphine. (United States)

    Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali


    Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

  13. Variability in prescription opioid intake and reinforcement amongst 129 substrains. (United States)

    Jimenez, S M; Healy, A F; Coelho, M A; Brown, C N; Kippin, T E; Szumlinski, K K


    Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  14. Hydrogen-enriched fuels

    Energy Technology Data Exchange (ETDEWEB)

    Roser, R. [NRG Technologies, Inc., Reno, NV (United States)


    NRG Technologies, Inc. is attempting to develop hardware and infrastructure that will allow mixtures of hydrogen and conventional fuels to become viable alternatives to conventional fuels alone. This commercialization can be successful if the authors are able to achieve exhaust emission levels of less than 0.03 g/kw-hr NOx and CO; and 0.15 g/kw-hr NMHC at full engine power without the use of exhaust catalysts. The major barriers to achieving these goals are that the lean burn regimes required to meet exhaust emissions goals reduce engine output substantially and tend to exhibit higher-than-normal total hydrocarbon emissions. Also, hydrogen addition to conventional fuels increases fuel cost, and reduces both vehicle range and engine output power. Maintaining low emissions during transient driving cycles has not been demonstrated. A three year test plan has been developed to perform the investigations into the issues described above. During this initial year of funding research has progressed in the following areas: (a) a cost effective single-cylinder research platform was constructed; (b) exhaust gas speciation was performed to characterize the nature of hydrocarbon emissions from hydrogen-enriched natural gas fuels; (c) three H{sub 2}/CH{sub 4} fuel compositions were analyzed using spark timing and equivalence ratio sweeping procedures and finally; (d) a full size pick-up truck platform was converted to run on HCNG fuels. The testing performed in year one of the three year plan represents a baseline from which to assess options for overcoming the stated barriers to success.

  15. Irradiation exposure modulates central opioid functions

    International Nuclear Information System (INIS)

    Dougherty, P.M.; Dafny, N.


    Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets

  16. Irradiation exposure modulates central opioid functions

    Energy Technology Data Exchange (ETDEWEB)

    Dougherty, P.M.; Dafny, N.


    Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets.

  17. Endogenous opioids regulate moment-to-moment neuronal communication and excitability (United States)

    Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.


    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

  18. Effect of Intravenous Acetaminophen on Postoperative Opioid Use in Bariatric Surgery Patients


    Wang, Shan; Saha, Ronik; Shah, Neal; Hanna, Adel; DeMuro, Jonas; Calixte, Rose; Brathwaite, Collin


    Opioids are often used to relieve pain after surgery, but they are associated with serious adverse effects. In this retrospective chart-review analysis, the use of intravenous acetaminophen did not reduce opioid use following bariatric surgery.

  19. South African guideline for the use of chronic opioid therapy for ...

    African Journals Online (AJOL)

    pain and chronic pain associated with cancer and at the end of life. Although .... Opioid drugs are agonists that bind to endogenous opioid receptors and mimic ..... interstitial cystitis/painful bladder syndrome, chronic prostate pain, and irritable ...

  20. The challenge of perioperative pain management in opioid-tolerant patients (United States)

    Coluzzi, Flaminia; Bifulco, Francesca; Cuomo, Arturo; Dauri, Mario; Leonardi, Claudio; Melotti, Rita Maria; Natoli, Silvia; Romualdi, Patrizia; Savoia, Gennaro; Corcione, Antonio


    The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. PMID:28919771

  1. 77 FR 44695 - Revised Meeting Notice: Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and... (United States)


    ... maternal prescription drug abuse and dependence and resulting increases in opioid exposed babies with NAS and possibly other consequences. Misuse and abuse of, and dependence upon, prescription opioid drugs... access treatment through family medicine and gynecological practitioners, and specialty treatment...

  2. Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay


    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.

  3. Age differences in heroin and prescription opioid abuse among enrolees into opioid treatment programs

    Directory of Open Access Journals (Sweden)

    Fong Chunki


    Full Text Available Abstract Background In the United States, among those entering opioid treatment programs (OTPs, prescription opioid (PO abusers tend to be younger than heroin users. Admissions of older persons to OTPs have been increasing, and it is important to understand typical patterns of use among those older enrolees. Methods To disentangle the effect of age on recent heroin and PO abuse 29,114 enrolees into 85 OTPs were surveyed across 34 states from 2005-2009. OTPs where PO use was prevalent were oversampled. Results Mean age was 34; 28% used heroin only. Younger enrolees had increased odds of using POs relative to using heroin only but mixed model analysis showed that much of the total variability in type of use was attributed to variation in age between OTPs rather than within OTPs. Conclusions Organizational and cultural phenomena (e.g., OTP characteristics must be examined to better understand the context of individual characteristics (e.g., age. If nesting of enrolees within OTPs is ignored, then associations that primarily operate at the OTP level may be misinterpreted as exclusively dependent on individuals.

  4. Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies. (United States)

    Melichar, Jan K; Hume, Susan P; Williams, Tim M; Daglish, Mark R C; Taylor, Lindsay G; Ahmad, Rabia; Malizia, Andrea L; Brooks, David J; Myles, Judith S; Lingford-Hughes, Anne; Nutt, David J


    Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

  5. High enrichment to low enrichment core's conversion. Technical securities

    International Nuclear Information System (INIS)

    Abbate, P.; Madariaga, M.R.


    This work presents the fulfillment of the technical securities subscribed by INVAP S.E. for the conversion of a high enriched uranium core. The reactor (of 5 thermal Mw), built in the 50's and 60's, is of the 'swimming pool' type, with light water and fuel elements of the curve plates MTR type, enriched at 93.15 %. These are neutronic and thermohydraulic securities. (Author) [es

  6. Safety of uranium enrichment plant

    International Nuclear Information System (INIS)

    Yonekawa, Shigeru; Morikami, Yoshio; Morita, Minoru; Takahashi, Tsukasa; Tokuyasu, Takashi.


    With respect to safety evaluation of the gas centrifuge enrichment facility, several characteristic problems are described as follows. Criticality safety in the cascade equipments can be obtained to maintain the enrichment of UF 6 below 5 %. External radiation dose equivalent rate of the 30B cylinder is low enough, the shield is not necessary. Penetration ratio of the two-stage HEPA filters for UF 6 aerosol is estimated at 10 -9 . From the experimental investigation, vacuum tightness is not damaged by destruction of gas centrifuge rotor. Carbon steel can be used for uranium enrichment equipments under the condition below 100degC. (author)

  7. Environmental enrichment for aquatic animals. (United States)

    Corcoran, Mike


    Aquatic animals are the most popular pets in the United States based on the number of owned pets. They are popular display animals and are increasingly used in research settings. Enrichment of captive animals is an important element of zoo and laboratory medicine. The importance of enrichment for aquatic animals has been slower in implementation. For a long time, there was debate over whether or not fish were able to experience pain or form long-term memories. As that debate has reduced and the consciousness of more aquatic animals is accepted, the need to discuss enrichment for these animals has increased. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. World enrichment requirements to 2005

    International Nuclear Information System (INIS)



    The primary enrichment suppliers-Eurodif, Techsnabexport, Urenco, and the US DOE - are positioning themselves to take advantage of the post - 1995 market. Overall, unfilled requirements represent about 40 percent of world requirements in the year 2000. The USA will be the primary market, as US utilities' unfilled enrichment requirements account for over 60 percent of the world's total unfilled requirements. The enrichment market is moving toward more global competition, as each supplier tries to maintain its current regional market base and then to capture additional market share in other regions

  9. Buprenorphine implants in medical treatment of opioid addiction. (United States)

    Chavoustie, Steven; Frost, Michael; Snyder, Ole; Owen, Joel; Darwish, Mona; Dammerman, Ryan; Sanjurjo, Victoria


    Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

  10. Reducing the health consequences of opioid addiction in primary care. (United States)

    Bowman, Sarah; Eiserman, Julie; Beletsky, Leo; Stancliff, Sharon; Bruce, R Douglas


    Addiction to prescription opioids is prevalent in primary care settings. Increasing prescription opioid use is largely responsible for a parallel increase in overdose nationally. Many patients most at risk for addiction and overdose come into regular contact with primary care providers. Lack of routine addiction screening results in missed treatment opportunities in this setting. We reviewed the literature on screening and brief interventions for addictive disorders in primary care settings, focusing on opioid addiction. Screening and brief interventions can improve health outcomes for chronic illnesses including diabetes, hypertension, and asthma. Similarly, through the use of screening and brief interventions, patients with addiction can achieve improved health outcome. A spectrum of low-threshold care options can reduce the negative health consequences among individuals with opioid addiction. Screening in primary care coupled with short interventions, including motivational interviewing, syringe distribution, naloxone prescription for overdose prevention, and buprenorphine treatment are effective ways to manage addiction and its associated risks and improve health outcomes for individuals with opioid addiction. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. [Management of opioid maintenance treatments when analgesic treatments are required]. (United States)

    Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund


    Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity

    Directory of Open Access Journals (Sweden)

    Allison Doyle Brackley


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

  13. Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence (United States)

    Yang, Cheng; Chen, Yan; Tang, Lei


    Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

  14. Pennsylvania State Core Competencies for Education on Opioids and Addiction. (United States)

    Ashburn, Michael A; Levine, Rachel L


    The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain. Specific competencies were developed for each domain. These competencies will be incorporated into the educational process at all Pennsylvania medical schools. It is hoped that these curriculum changes will improve student knowledge and attitudes in these areas, thus improving patient outcomes. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail:

  15. Benzodiazepines, opioids and driving: an overview of the experimental research. (United States)

    Leung, Stefanie Y


    Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the driver's blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  16. Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors (United States)


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

  17. Evaluation of the Tolerability of Switching Patients on Chronic Full ?-Opioid Agonist Therapy to Buccal Buprenorphine


    Webster, Lynn; Gruener, Daniel; Kirby, Todd; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew


    Objective?Assess whether patients with chronic pain receiving 80 to 220?mg oral morphine sulfate equivalent of a full ?-opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy. Methods.?A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent...

  18. Changing Trends in Opioid Use Among Patients With Rheumatoid Arthritis in the United States. (United States)

    Curtis, Jeffrey R; Xie, Fenglong; Smith, Christian; Saag, Kenneth G; Chen, Lang; Beukelman, Timothy; Mannion, Melissa; Yun, Huifeng; Kertesz, Stefan


    Opioid prescribing recently has come under intense scrutiny. However, longitudinal patterns of prescription opioid receipt in a population-based cohort of patients with chronic pain, such as those with rheumatoid arthritis (RA), have not been well characterized. The aim of this study was to examine both trends over time and variability in individual physician prescribing of short-term and long-term use of opioids. We identified a cohort of RA patients based on 2006-2014 Medicare data and evaluated longitudinal time trends in "regular" use of opioids. A separate analysis conducted in 2014 assessed rheumatologist-specific variability in regular use of opioid prescriptions in patients with RA. We identified 97,859 RA patients meeting the eligibility criteria. The mean age of the patients was 67 years, 80% were female, 82% were white, and 12% were African American. The most commonly used opioids were those that combined acetaminophen with hydrocodone or propoxyphene. Regular opioid prescribing increased slowly but peaked in 2010 before propoxyphene was withdrawn from the market. Following the withdrawal of propoxyphene, receipt of hydrocodone and tramadol increased commensurately, and overall opioid use declined only slightly. Factors associated with regular use of opioids included younger age, female sex, African American race, back pain, fibromyalgia, anxiety, and depression. Variability between US rheumatologists (n = 4,024) in prescribing the regular use of opioids for their RA patients was high; in the average rheumatologist's practice, 40% of RA patients used prescription opioids regularly. In almost half of the patients, at least some opioid prescriptions were written by a rheumatologist, and 14% received opioids that were co-prescribed concurrently by more than 1 physician. In the US, opioid use in older patients with RA peaked in 2010 and is now declining slightly. Withdrawal of propoxyphene from the US market in 2010 had minimal effect on overall opioid

  19. Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome


    McLemore, Gabrielle L.; Lewis, Tamorah; Jones, Catherine H.; Gauda, Estelle B.


    The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care...

  20. Environmental Enrichment for Broiler Breeders: An Undeveloped Field

    Directory of Open Access Journals (Sweden)

    Anja B. Riber


    Full Text Available Welfare problems, such as hunger, frustration, aggression, and abnormal sexual behavior, are commonly found in broiler breeder production. To prevent or reduce these welfare problems, it has been suggested to provide stimulating enriched environments. We review the effect of the different types of environmental enrichment for broiler breeders, which have been described in the scientific literature, on behavior and welfare. Environmental enrichment is defined as an improvement of the environment of captive animals, which increases the behavioral opportunities of the animal and leads to improvements in biological function. This definition has been broadened to include practical and economic aspects as any enrichment strategy that adversely affects the health of animals (e.g., environmental hygiene, or that has too many economic or practical constraints will never be implemented on commercial farms and thus never benefit animals. Environmental enrichment for broiler breeders often has the purpose of satisfying the behavioral motivations for feeding and foraging, resting, and/or encouraging normal sexual behavior. Potentially successful enrichments for broiler breeders are elevated resting places, cover panels, and substrate (for broiler breeders housed in cage systems. However, most of the ideas for environmental enrichment for broiler breeders need to be further developed and studied with respect to the use, the effect on behavior and welfare, and the interaction with genotype and production system. In addition, information on practical use and the economics of the production system is often lacking although it is important for application in practice.

  1. The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy

    Directory of Open Access Journals (Sweden)

    Gudin JA


    Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care

  2. The effects of auditory enrichment on gorillas. (United States)

    Robbins, Lindsey; Margulis, Susan W


    Several studies have demonstrated that auditory enrichment can reduce stereotypic behaviors in captive animals. The purpose of this study was to determine the relative effectiveness of three different types of auditory enrichment-naturalistic sounds, classical music, and rock music-in reducing stereotypic behavior displayed by Western lowland gorillas (Gorilla gorilla gorilla). Three gorillas (one adult male, two adult females) were observed at the Buffalo Zoo for a total of 24 hr per music trial. A control observation period, during which no sounds were presented, was also included. Each music trial consisted of a total of three weeks with a 1-week control period in between each music type. The results reveal a decrease in stereotypic behaviors from the control period to naturalistic sounds. The naturalistic sounds also affected patterns of several other behaviors including locomotion. In contrast, stereotypy increased in the presence of classical and rock music. These results suggest that auditory enrichment, which is not commonly used in zoos in a systematic way, can be easily utilized by keepers to help decrease stereotypic behavior, but the nature of the stimulus, as well as the differential responses of individual animals, need to be considered. © 2014 Wiley Periodicals, Inc.

  3. Centar's gas centrifuge enrichment project

    International Nuclear Information System (INIS)

    Abajian, V.V.; Fishman, A.M.


    Plans for the building and operating of Centar Associates gas centrifuge uranium enrichment plant are described. Operating costs and machine manufacture are considered. Commitments with the utilities are summarised. (U.K.)

  4. Extraosseus enrichments in bone scintigraphy

    International Nuclear Information System (INIS)

    Jochens, R.; Schumacher, T.; Amthauer, H.; Wolter, M.; Stock, W.; Stroszczynski, C.; Moersler, J.P.; Eichstaedt, H.


    Extraosseus enrichments are common findings in bone scintigraphy. Main causes are artifacts by skin or cloth contamination, paravenous and subcutaneous injection. Physical examination, removal of cloths, skin cleaning or further images in differing projections lead to the correct diagnosis artefact or extraosseous enrichments. Further on, extraosseous enrichments are seen in physiological variants. In different diseases extraosseous enrichments are common, especially in urinary tract, liver and extremities. Further diagnostics, e.g. conventional radiologic procedures, sonography and CT scans, have to be performed. In individual cases side results in bone scintigraphy lead to formerly unknown diagnosis, further diagnostic procedure is influenced decisively. Own cases show for example a cerebral apoplectic insult, formerly unknown liver metastasis or metastasis in extraosseous Ewings's sarcoma. (orig.) [de

  5. Behavioral intervention to reduce opioid overdose among high-risk persons with opioid use disorder: A pilot randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Phillip Oliver Coffin

    Full Text Available The United States is amidst an opioid epidemic, including synthetic opioids that may result in rapid death, leaving minimal opportunity for bystander rescue. We pilot tested a behavioral intervention to reduce the occurrence of opioid overdose among opioid dependent persons at high-risk for subsequent overdose.We conducted a single-blinded randomized-controlled trial of a repeated dose motivational interviewing intervention (REBOOT to reduce overdose versus treatment as usual, defined as information and referrals, over 16 months at the San Francisco Department of Public Health from 2014-2016. Participants were 18-65 years of age, had opioid use disorder by Structured Clinical Interview, active opioid use, opioid overdose within 5 years, and prior receipt of naloxone kits. The intervention was administered at months 0, 4, 8, and 12, preceded by the assessment which was also administered at month 16. Dual primary outcomes were any overdose event and number of events, collected by computer-assisted personal interview, as well as any fatal overdose events per vital records.A total of 78 persons were screened and 63 enrolled. Mean age was 43 years, 67% were born male, 65% White, 17% African-American, and 14% Latino. Ninety-two percent of visits and 93% of counseling sessions were completed. At baseline, 33.3% of participants had experienced an overdose in the past four months, with a similar mean number of overdoses in both arms (p = 0.95; 29% overdosed during follow-up. By intention-to-treat, participants assigned to REBOOT were less likely to experience any overdose (incidence rate ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019 and experienced fewer overdose events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023, findings that were robust to sensitivity analyses. There were no differences between arms in days of opioid use, substance use treatment, or naloxone carriage.REBOOT reduced the occurrence of any opioid overdose and the number of overdoses

  6. Effect Of A “No Superuser Opioid Prescription” Policy On ED Visits And Statewide Opioid Prescription

    Directory of Open Access Journals (Sweden)

    Zachary P. Kahler


    Full Text Available Introduction: The U.S. opioid epidemic has highlighted the need to identify patients at risk of opioid abuse and overdose. We initiated a novel emergency department- (ED based interventional protocol to transition our superuser patients from the ED to an outpatient chronic pain program. The objective was to evaluate the protocol’s effect on superusers’ annual ED visits. Secondary outcomes included a quantitative evaluation of statewide opioid prescriptions for these patients, unique prescribers of controlled substances, and ancillary testing. Methods: Patients were referred to the program with the following inclusion criteria: ≥ 6 visits per year to the ED; at least one visit identified by the attending physician as primarily driven by opioid-seeking behavior; and a review by a committee comprising ED administration and case management. Patients were referred to a pain management clinic and informed that they would no longer receive opioid prescriptions from visits to the ED for chronic pain complaints. Electronic medical record (EMR alerts notified ED providers of the patient’s referral at subsequent visits. We analyzed one year of data pre- and post-referral. Results: A total of 243 patients had one year of data post-referral for analysis. Median annual ED visits decreased from 14 to 4 (58% decrease, 95% CI [50 to 66]. We also found statistically significant decreases for these patients’ state prescription drug monitoring program (PDMP opioid prescriptions (21 to 13, total unique controlled-substance prescribers (11 to 7, computed tomography imaging (2 to 0, radiographs (5 to 1, electrocardiograms (12 to 4, and labs run (47 to 13. Conclusion: This program and the EMR-based alerts were successful at decreasing local ED visits, annual opioid prescriptions, and hospital resource allocation for this population of patients. There is no evidence that these patients diverted their visits to neighboring EDs after being informed that they

  7. European Pain Federation position paper on appropriate opioid use in chronic pain management

    DEFF Research Database (Denmark)

    O'Brien, T; Christrup, L L; Drewes, A M


    rests with the primary care physician and other non-specialist opioid prescribers. There is much confusing and conflicting information available to non-specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent...

  8. Information on risk of constipation for Danish users of opioids, and their laxative use

    DEFF Research Database (Denmark)

    Pottegård, Anton; Knudsen, Thomas Bøllingtoft; van Heesch, Kim


    of opioids by the time of the first prescription regarding the risk of constipation. Method Interviews with patients filling an opioid at a community pharmacy were performed by the dispensing pharmacist or pharmaconomist at the pharmacy. Information collected concerned the patient, the opioid, information...

  9. Perceived stigma and social support in treatment for pharmaceutical opioid dependence. (United States)

    Cooper, Sasha; Campbell, Gabrielle; Larance, Briony; Murnion, Bridin; Nielsen, Suzanne


    The dramatic increase in pharmaceutical opioid (PO) use in high-income countries is a growing public health concern. Stigma and social support are important as they may influence treatment uptake and outcomes, yet few studies exist regarding perceived stigma and social support among people with PO dependence. The aims of the study are to: (i) compare characteristics of those with PO dependence from iatrogenic and non-iatrogenic causes; (ii) document perceived stigma and its correlates in people in treatment for PO dependence; and (iii) examine correlates of social support in people in treatment for PO dependence. This prospective cohort study included (n = 108) PO-dependent people referred from treatment services. Telephone interviews were conducted at baseline, 3, 12 and 24 months. Multivariate linear regression was used to examine correlations. Mean age was 41 (SD = 10.5). Half (n = 56, 52%) were female. Two in five met the criteria for iatrogenic dependence (n = 41, 38%), with iatrogenic dependence associated with chronic pain, and no history of injection or heroin use. One quarter of study subjects reported past month unsanctioned opioid use (n = 25, 23%). Being married/de facto or female was associated with higher levels of perceived stigma. Unsanctioned opioid use, iatrogenic dependence and mental health conditions were associated with lower social support. Stigma affects all people in treatment. Those who are married/de facto and female may benefit from interventions to address stigma. The association of low social support with poorer mental health and ongoing substance use indicate that treatment could focus more on this area. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  10. NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction. (United States)

    Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee


    Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

  11. Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat. (United States)

    Tung, Kenneth H; Angus, James A; Wright, Christine E


    Morphine and methadone share the property of μ-opioid receptor agonism yet have markedly different cardiovascular actions suggesting additional properties are at play. We investigated the i.v. dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone. In vitro tissue assays were employed to define more clearly cardiac and vascular mechanisms of action. Morphine (9, 30, 90mg/kg i.v.) decreased heart rate (HR) and mean arterial pressure (MAP) - responses that were blocked by naloxone pretreatment (10mg/kg i.v.). In contrast, methadone (3, 10, 30mg/kg i.v.) caused dramatic short-lived (1-3min) bradycardia, hypotension and lengthening of the QT interval before stabilising 5min after i.v. dosing. Only the steady-state responses of HR and MAP were blocked by naloxone. Mepyramine (10mg/kg i.v.) and cimetidine (100mg/kg i.v.) also blocked the naloxone-sensitive components. In isolated small mesenteric arteries precontracted by K(+) 62mM or endothelin-1, methadone (1-30μM) relaxed vessels while morphine (1-100μM) had no effect. Pretreatment with naloxone (10μM), indomethacin (30μM) or nitro-l-arginine (100μM) did not affect the relaxation to methadone. In rat isolated left atria, morphine and methadone inhibited inotropic responses at high concentrations (100μM). In rat papillary muscle and right atria, methadone was more than 30 times more potent at lengthening the refractory period and slowing the atrial rate than morphine. We conclude that methadone is a potent vasodilator agent, possibly through blocking L-type calcium channels. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Response of the μ-opioid system to social rejection and acceptance. (United States)

    Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Wang, H; Ni, L; Walker, S J; Mickey, B J; Korycinski, S T; Koeppe, R A; Crocker, J K; Langenecker, S A; Zubieta, J-K


    The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.

  13. Uranium enrichment: an evolving market

    International Nuclear Information System (INIS)

    Longenecker, J.; Witzel, R.


    With over half of the world uranium enrichment market uncommitted to any supplier early in the next century, competition is certain to be fierce. In the meantime the outlood remains unclear, with the market dominated by a number of developments -privatisation of the United States Enrichment Corp (USEC), increasing availability of Russian and US military inventories, the deployment of advanced technology and the closure of nuclear power plants due to deregulation. (author)

  14. Unjust enrichment in business law


    Vydrová, Zuzana


    This thesis analyses the concept of unjust enrichment under the business law. First of all the thesis explains the term of business law. Business law is a complex of legal rules concerning the contractual relationships between entrepreneurs arising from their business activities. Business law is a comprehensive field of law which extends into many other fields of law, both private and public law. Equally the regulation of unjust enrichment within the business law expands into many other laws ...

  15. Detecting aberrant opioid behavior in the emergency department: a prospective study using the screener and Opioid Assessment for Patients with Pain-Revised (SOAPP®-R), Current Opioid Misuse Measure (COMM)™, and provider gestalt. (United States)

    Varney, Shawn M; Perez, Crystal A; Araña, Allyson A; Carey, Katherine R; Ganem, Victoria J; Zarzabal, Lee A; Ramos, Rosemarie G; Bebarta, Vikhyat S


    Emergency department (ED) providers have limited time to evaluate patients at risk for opioid misuse. A validated tool to assess the risk for aberrant opioid behavior may mitigate adverse sequelae associated with prescription opioid misuse. We sought to determine if SOAPP-R, COMM, and provider gestalt were able to identify patients at risk for prescription opioid misuse as determined by pharmacy records at 12 months. We conducted a prospective observational study of adult patients in a high volume US ED. Patients completed the SOAPP-R and COMM, and treating EM providers evaluated patients' opioid misuse risk. We performed variable-centered, person-centered, and hierarchical cluster analyses to determine whether provider gestalt, SOAPP-R, or COMM, or a combination, predicted higher misuse risk. The primary outcome was the number of opioid prescriptions at 12 months according to pharmacy records. For 169 patients (mean age 43 years, 51% female, 73% white), correlation analysis showed a strong relationship between SOAPP-R and COMM with predicting the number of opioid prescriptions dispensed at 12 months. Provider scores estimating opioid misuse were not related to SOAPP-R and only weakly associated with COMM. In our adjusted regression models, provider gestalt and SOAPP-R uniquely predicted opioid prescriptions at 6 and 12 months. Using designated cutoff scores, only SOAPP-R detected a difference in the number of opioid prescriptions. Cluster analysis revealed that provider gestalt, SOAPP-R, and COMM scores jointly predicted opioid prescriptions. Provider gestalt and self-report instruments uniquely predicted the number of opioid prescriptions in ED patients. A combination of gestalt and self-assessment scores can be used to identify at-risk patients who otherwise miss the cutoff scores for SOAPP-R and COMM.

  16. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H


    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  17. Substitution treatment for opioid addicts in Germany

    Directory of Open Access Journals (Sweden)

    Gerlach Ralf


    Full Text Available Abstract Background After a long and controversial debate methadone maintenance treatment (MMT was first introduced in Germany in 1987. The number of patients in MMT – first low because of strict admission criteria – increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP, who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. Results The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65 % to 85 % in the first years, up to 50 % after more than seven years and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10 % of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. Conclusion In Germany, a

  18. Substitution treatment for opioid addicts in Germany. (United States)

    Michels, Ingo Ilja; Stöver, Heino; Gerlach, Ralf


    After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT--first low because of strict admission criteria--increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP), who has com