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Sample records for rocuronium induced withdrawal

  1. Rocuronium-induced withdrawal movement: influence of ketorolac or a combination of lidocaine and ketorolac pretreatment

    PubMed Central

    Jeon, Younghoon; Ha, Jae Hyun; Lee, Jeong-Eun; Lee, Hyung-Chul; Ryu, Taeha

    2013-01-01

    Background Pain on injection of rocuronium is a common clinical problem. We compared the efficacy of lidocaine, ketorolac, and the 2 in combination as pretreatment for the prevention of rocuronium-induced withdrawal movement. Methods For this prospective, randomized, placebo-controlled, double-blind study a total of 140 patients were randomly allocated to one of 4 treatment groups to receive intravenously placebo (saline), lidocaine (20 mg), ketorolac (10 mg), or both (n = 35 for each group), with venous occlusion. The tourniquet was released after 2 min and anesthesia was performed using 5 mg/kg thiopental sodium followed by 0.6 mg/kg rocuronium. The withdrawal response was graded on a 4-point scale in a double-blind manner. Results The overall incidence of withdrawal movements after rocuronium was 34.3% with lidocaine (P = 0.001), 40% with ketorolac (P = 0.004), and 8.6% with both (P < 0.001), compared with 74.3% with placebo. There was a significantly lower incidence of withdrawal movements in patients receiving the lidocaine/ketorolac combination than in those receiving lidocaine or ketorolac alone (P = 0.009 and 0.002, respectively). The incidence of moderate to severe withdrawal movements was 14.3% with lidocaine, 17.2% with ketorolac, and 2.9% with lidocaine/ketorolac combination, as compared to 45.7% with the placebo. There was no significant difference in withdrawal movement between the lidocaine group and the ketorolac group. Conclusions Ketorolac pretreatment had an effect comparable to that of lidocaine in attenuating rocuronium-induced withdrawal movements and the lidocaine/ketorolac combination pretreatment, compared with lidocaine or ketorolac alone, effectively reduced withdrawal movements during rocuronium injection. PMID:23372882

  2. Pharmacological and non-pharmacological intervention for rocuronium-induced withdrawal movement in the Korean population: a meta-analysis of 41 studies including 4,742 subjects

    PubMed Central

    Choi, Geun Joo; Lee, Sangseok; Lee, Jeoung Hyuk; Park, Seul Gi

    2014-01-01

    Background We purposed to systemically review studies investigating the prophylactic effect of both pharmacological and non-pharmacological modalities against rocuronium induced withdrawal movement (RIWM) in the Korean population. Methods Literature search was performed using MEDLINE, EMBASE, CENTRAL, Koreamed, KMBASE, KISS and RISS up to March 2014. Randomized controlled trials (RCTs) comparing pharmacological and non-pharmacological interventions with placebo aimed for the Korean population were included. Outcome measures were the incidence and severity of RIWM. We conducted subgroup analyses according to each intervention method. Results Data were analyzed from 41 RCTs totaling 4,742 subjects. The overall incidence of RIWM was about 80% (range 56-100%). Incidence and severity of RIWM were significantly reduced with lidocaine (risk ratio [RR] 0.60, 95% CI 0.49-0.74; standardized mean difference [SMD] -0.74, 95% CI -1.05 to -0.44), opioids (RR 0.28, 95% CI 0.18-0.44; SMD -1.71, 95% CI -2.09 to -1.34) and hypnotics (RR 0.36, 95% CI 0.25-0.52; SMD -2.20, 95% CI -2.62 to -1.79). Regardless of tourniquet use, lidocaine showed a prophylactic effect against incidence and severity of RIWM: tourniquet (RR 0.36, 95% CI 0.21-0.62; SMD -1.51, 95% CI -2.15 to -0.86); non-tourniquet (RR 0.58, 95% CI 0.47-0.71; SMD -0.74, 95% CI -1.05 to -0.44). Dilution and slow injection of rocuronium decreased incidence and severity of RIWM: dilution (RR 0.47, 95% CI 0.39-0.56; SMD -1.64, 95% CI -2.47 to -0.81); slow injection (RR 0.34, 95% CI 0.17-0.70; SMD -2.13, 95% CI -2.74 to -1.51). Conclusions The greater part of pharmacological and non-pharmacological interventions showed prophylactic effect against the incidence and severity of RIWM in the Korean population. PMID:25006365

  3. Prevention of Withdrawal Movement Associated with the Injection of Rocuronium in Children: Comparison of Paracetamol and Lidocaine

    PubMed Central

    Polat, Reyhan; Akın, Mine; Keskin, Gülsen; Ünal, Dilek; Dönmez, Aslı

    2016-01-01

    Objective Pain from rocuronium injection is observed in 50%–80 % of patients. This study aimed to compare the effectiveness of pretreatment with paracetamol and lidocaine in preventing pain-induced withdrawal caused by the intravenous injection of rocuronium during the induction of general anaesthesia in paediatric patients. Methods Ninety children were randomized into two groups using a simple drawing from the box method: a paracetamol group (Group P, n=45) and a lidocaine group (Group L, n=45). After anaesthesia induction, venous occlusion was applied by a paediatric cuff inflated to a pressure of 75 mmHg and by 50 mg paracetamol and 0.5 mg kg−1 lidocaine was injected in Groups P and L, respectively. Venous occlusion was then released, followed by rocuronium injection (0.6 mg kg−1). Withdrawal was evaluated using a 4-point scale (1, no response; 2, movement at the wrist only; 3, movement/withdrawal involving arm only (elbow/shoulder) and 4, generalized response, movement/withdrawal in more than one extremity). Results The incidence of withdrawal movement was 42% and 26% in the Groups P and L, respectively (p=0.120). Although no significant differences were noted in the number of patients who had no withdrawal movement and mild withdrawal movement in Groups P and L, compared with Group L, the incidences of moderate withdrawal movement were significantly higher in Group P (p<0.05). No patient in either group revealed generalized movement. Conclusion Using a venous occlusion technique, pretreatment with 50 mg paracetamol can prevent withdrawal movement caused by rocuronium injection in children but is not as effective as lidocaine to prevent moderate withdrawal movement. PMID:27366564

  4. [Rocuronium anesthesia induced anaphylactic shock: a case report].

    PubMed

    Qiu, Min; Zong, Ya-nan; Lu, Jian; Ma, Lu-lin; Zheng, Qing; Guo, Xiang-yang

    2015-10-18

    Anaphylaxis is an acute and fatal systemic allergic reaction to an allergen, and it could be an unpredictable and life-threatening cause during anesthesia. The main purpose of this paper is to report a case of anaphylactic shock during the anesthesia induction and to review the prophylaxis and treatment of anaphylactic reactions and anaphylactoid reactions during the anesthesia period. A 63-year-old man, with a mass on his adrenal, was scheduled to a laparoscopic adrenal tumor excision. During the anesthesia induction period, after administrated sulfentanil, propofol and rocuronium, the blood pressure was decreased and the heart rate was increased. Then, the patient had rash on his whole body and developed an anaphylactic shock. After being treated with the anti-allergic agents and norepinephrine, the rash disappeared and the vital sign become stable. The patient felt nothing uncomfortable during the two weeks'follow-up. Anaphylactic reactions and anaphylactoid reactions are not rare during the anesthesia period. The most common inducements are muscle relaxant, latex and antibiotics. Anaphylactic reactions in the perioperative period are often serious and potentially life-threatening conditions, involving multiple organ systems in which the clinical manifestations are the consequence of the release of preformed mediators from mast cells and basophils. Before anesthesia, we should acquire the allergic history. During the anesthesia period, the vital sign and the skin should be observed carefully. PMID:26474637

  5. Effect of pretreatment with acetaminophen on withdrawal movements associated with injection of rocuronium: a prospective, randomized, double-blind, placebo controlled study

    PubMed Central

    Jeon, Younghoon; Baek, Sung-Uk; Park, Sung Sik; Kim, Si Oh; Baek, Woon-Yi

    2010-01-01

    Background Withdrawal movement during rocuronium injection is a common, unresolved adverse effect. We aimed to investigate the effect of IV acetaminophen pretreatment on withdrawal movement during rocuronium injection. Methods This study enrolled 120 American Society of Anesthesiologists (ASA) I-II patients undergoing general anesthesia. They were randomly assigned to three treatment groups. After occluding venous drainage using a tourniquet on the upper arm, the saline group received 5 ml of 0.9% sodium chloride solution, the lidocaine group received 40 mg of lidocaine, and the acetaminophen group received 50 mg of acetaminophen. During injection of pretreatment drug, pain was assessed on a four-point scale. The tourniquet was released after 120 seconds and anesthesia was performed using thiopental sodium 5 mg/kg followed by rocuronium 0.6 mg/kg. The withdrawal movement was graded on a four-point scale in a double-blind manner. Results The incidence of pain on pretreatment injection in saline, lidocaine, and acetaminophen groups was 7.7%, 5.1%, and 2.5%, respectively. The incidence of withdrawal movements was 77.5% in saline group, 32.5% in lidocaine group, and 37.5% in acetaminophen group (P < 0.05). Conclusions Acetaminophen and lidocaine reduced the incidence of withdrawal movement after rocuronium injection compared with saline. PMID:20651992

  6. A case of anaphylaxis apparently induced by sugammadex and rocuronium in successive surgeries.

    PubMed

    Yamada, Yuko; Yamamoto, Takuji; Tanabe, Kumiko; Fukuoka, Naokazu; Takenaka, Motoyasu; Iida, Hiroki

    2016-08-01

    Rocuronium is the agent most frequently involved in perioperative anaphylaxis, and sugammadex has also been known to induce anaphylactic reactions. We describe a case of successive anaphylactic episodes that seemed to be induced by clinical doses of rocuronium and sugammadex. The patient was a 19-year-old woman who had a medical history of asthma, but no history of surgery. She had been injured in a fall, and several surgeries were scheduled for multiple bone fractures. At the first surgery under general anesthesia, she developed anaphylaxis 5 min after sugammadex administration. A second general anesthesia for treatment of calcaneal fracture was induced uneventfully without neuromuscular blockade after 10 days. A third general anesthesia was scheduled to reinforce the spinal column 12 days after the first surgery. She developed anaphylaxis 8 min after rocuronium administration. The level of plasma histamine was elevated, but serum tryptase level remained normal. This surgery was canceled and rescheduled without use of a neuromuscular blockade. Skin tests were performed in a later investigation. The patient showed positive results on intradermal tests for sugammadex and rocuronium, supporting a diagnosis of allergic reactions to both drugs. Clinicians must be aware that anaphylactic reactions can be induced by both sugammadex and rocuronium. PMID:27290941

  7. [Reversal of rocuronium induced neuromuscular block with sugammadex in a patient with myasthenia gravis].

    PubMed

    Nakamori, Erisa; Nitahara, Keiichi; Sugi, Yasuyuki; Katori, Kiyoshi; Matsuzaki, Akiko; Higa, Kazuo

    2013-08-01

    We report a patient with myasthenia gravis whose rocuronium induced neuromuscular block was reversed with sugammadex. A 26-year-old man, 175 cm and 76 kg, with myasthenia gravis, was scheduled for extended thymectomy under general anesthesia. An epidural catheter was inserted at the T5-6 interspace before induction of general anesthesia. Anesthesia was induced with propofol and remifentanil. Rocuronium was given in divided doses to obtain > 95% neuromuscular block to intubate the trachea. The ED50 and ED95 of rocuronium for this patient were 0.18 mg x kg(-1) and 0.39 mg x kg(-1), respectively. The values were similar to the ED50 and ED95 of rocuronium for normal patients. General anesthesia was maintained with propofol and remifentanil. Additional doses of rocuronium were given intermittently. Sugammadex, 2 mg x kg(-1), was given at the end of the surgery. The train-of-four ratio reached 93% 105 sec later. His postoperative course was uneventful. PMID:23984578

  8. Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

    PubMed Central

    Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

    2011-01-01

    AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

  9. Magnesium-induced recurarisation after reversal of rocuronium-induced neuromuscular block with sugammadex.

    PubMed

    Unterbuchner, C; Ziegleder, R; Graf, B; Metterlein, T

    2015-04-01

    A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a sugammadex-reversed, rocuronium-induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex--particularly in combination with magnesium injection--to prevent post-operative residual curarisation. PMID:25582520

  10. Appropriate dosing of sugammadex to reverse deep rocuronium-induced neuromuscular blockade in morbidly obese patients.

    PubMed

    Loupec, T; Frasca, D; Rousseau, N; Faure, J-P; Mimoz, O; Debaene, B

    2016-03-01

    In morbidly obese patients, the speed of reversal of neuromuscular blockade with sugammadex based on ideal body weight is still matter of debate. In this single-center, randomised, double-blinded study, neuromuscular blockade was monitored in 50 patients using acceleromyography at the adductor pollicis. At the end of surgery with deep rocuronium-induced neuromuscular blockade, patients randomly received sugammadex 4 mg.kg(-1) (high dose group), 2 mg.kg(-1) (middle dose group), or 1 mg.kg(-1) (low dose group) of ideal body weight. After administration of the first dose of sugammadex, the mean (SD) recovery time (censored at 600 s) from deep neuromuscular blockade was significantly shorter (p < 0.001) in the high-dose group (n = 14; 255 (63) s) vs the middle-dose group (n = 13; 429 (102) s), or low-dose group (n = 4; 581 (154) s). Success rate from neuromuscular blockade reversal defined by a train-of-four ≥ 0.9 within 10 min after sugammadex administration, were 93%, 77% and 22% for these high, middle and low-dose groups respectively (p < 0.05 vs low-dose group). In morbidly obese patients, 4 mg.kg(-1) of ideal body weight of sugammadex allows suitable reversal of deep rocuronium-induced neuromuscular blockade. Monitoring remains essential to detect residual curarisation or recurarisation. PMID:26685122

  11. [A Case of Rocuronium-induced Anaphylaxis in Which Surgery was Subsequently Performed under General Anesthesia without Neuromuscular Blocking Agents].

    PubMed

    Horiuchi, Tatsuo; Takazawa, Tomonori; Saito, Shigeru

    2016-03-01

    We report here a case of rocuronium-induced anaphylactic shock in a 41-year-old woman. She was scheduled for partial hepatectomy due to liver metastasis of a pheochromocytoma. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was difficult, and her blood pressure fell to around 40 mmHg just after induction. Subsequently, her trachea was intubated and adrenaline was injected. However, due to the subsequent persistence of severe hypotension and hypoxia, cardiopulmonary resuscitation was necessary. Suspecting the development of pulmonary embolism or anaphylaxis, we performed transesophageal echography; however, no evidence of right heart dilatation was observed, indicating a low possibility of pulmonary embolism. Although her general condition was stabilized, surgery was canceled. Blood tests showed high serum histamine and tryptase levels, suggesting an Ig-E mediated allergic reaction. A skin test performed five weeks after anesthesia suggested that she had suffered from rocuronium-induced anaphylaxis. A skin test also showed cross-reactivity between rocuronium and vecuronium. Therefore, we did not use any neuromuscular agent for the subsequent surgery, which was completed uneventfully. Determining the drug responsible for anaphylaxis helps to prevent recurrence of anaphylaxis. PMID:27097513

  12. Relationship between first-twitch depression and train-of-four ratio during sugammadex reversal of rocuronium-induced neuromuscular blockade

    PubMed Central

    Oh, You Na; Kim, Tae Yeon; Oh, Song Yee; Sin, Yeong Hun

    2016-01-01

    Background The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex. Methods The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB. Results The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine. Conclusions If you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB. PMID:27274368

  13. Comparison of mechanomyography and acceleromyography for the assessment of rocuronium induced neuromuscular block in myotonic dystrophy type 1.

    PubMed

    Vanlinthout, L E H; Booij, L H D J; van Egmond, J; Robertson, E N

    2010-06-01

    We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies. In myotonic dystrophy type 1 patients, the dose-response curve obtained with acceleromyography was steeper and right-shifted compared with that obtained using mechanomyography. However, the effective doses to produce 95% neuromuscular block determined with both acceleromyography and mechanomyography were similar to each other and to values found in normal patients. In the three myotonic dystrophy type 1 patients with mild to moderate disease, times to recovery from block were similar to those observed in normal controls. In both patients and normal controls, neuromuscular block recovered faster with acceleromyography. However, in one patient with severe muscle wasting, recovery of neuromuscular block was prolonged. We conclude that mechanomyography and acceleromyography cannot be used interchangeably to monitor neuromuscular block in myotonic dystrophy type 1 patients. PMID:20565393

  14. The Efficacy and Safety of Topical Rocuronium Bromide to Induce Bilateral Mydriasis in Hispaniolan Amazon Parrots ( Amazona ventralis ).

    PubMed

    Baine, Katherine; Hendrix, Diane V H; Kuhn, Sonia E; Souza, Marcy J; Jones, Michael P

    2016-03-01

    The efficacy and safety of topically applied rocuronium in Hispaniolan Amazon parrots ( Amazona ventralis ) was assessed in a group of 10 adult birds. A complete ophthalmic examination (including Schirmer tear test, ocular reflexes, applanation tonometry, fluorescein staining, and slit-lamp biomicroscopy) was performed, and rocuronium bromide (0.15 mg in both eyes) was administered. Pupillary light reflex (PLR) and pupillary diameter were recorded in a darkened room at the following time points: 0, 10, 20, 30, 40, 50, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 300, and 360 minutes, and 24 hours. Fluorescein staining in both eyes was performed at 24 hours. By 10 minutes, PLR was absent in all birds (at 5 minutes, 8 birds; at 10 minutes, remaining 2 birds). Pupil diameter differed significantly from baseline at all time points. Additionally, PLR was decreased in 7/10 birds at 360 minutes and normal in all birds at 24 hours. Superficial corneal ulceration was observed at 24 hours in the left eye of 2/10 of the birds after fluorescein stain application. This study demonstrated that rocuronium bromide was an effective mydriatic agent in Hispaniolan Amazon parrots with rapid onset and prolonged duration of action. PMID:27088739

  15. Non-IgE-Dependent Hypersensitivity to Rocuronium Reversed by Sugammadex: Report of Three Cases and Hypothesis on the Underlying Mechanism.

    PubMed

    Spoerl, David; D'Incau, Stéphanie; Roux-Lombard, Pascale; Harr, Thomas; Czarnetzki, Christoph

    2016-01-01

    We present 3 cases of pseudoallergic (anaphylactoid) reactions to perioperatively administered rocuronium, which rapidly resolved after sugammadex injection. Allergological workup showed no evidence for immediate-type hypersensitivity to the drugs used for anesthesia, including rocuronium. However, rocuronium induced an irritative reaction in skin tests in all 3 patients and in 3 healthy individuals. This reaction was specifically suppressed by adding sugammadex at a 1:1 molecular proportion to rocuronium before the skin tests. This observation suggests that the patients suffered from a pseudoallergic reaction, and indicates that sugammadex might act via the inhibition of non-IgE mediated MRGPRX2 (Mas-related G-protein-coupled receptor member X2)-triggered mast cell degranulation induced by rocuronium. PMID:27240836

  16. Memantine Reverses Social Withdrawal Induced by Ketamine in Rats

    PubMed Central

    Landaeta, José; Wix, Richard; Eblen, Antonio

    2013-01-01

    The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg-1) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg-1) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia. PMID:23585718

  17. Gastrointestinal motor alterations induced by precipitated benzodiazepine withdrawal in rats.

    PubMed

    Martinez, J; Fargeas, M J; Bueno, L

    1992-03-01

    The effects of benzodiazepine withdrawal on intestinal motor activity and propulsion were investigated in two groups of diazepam-dependent rats (15 mg/kg/day for 8 days). Withdrawal was precipitated by injection of two benzodiazepine antagonists (Ro 15.1788 and PK 11.95) acting on central and peripheral-type receptors, respectively. Intestinal motor activity was assessed by implanting electrodes for long-term electromyographic recordings. Gastrointestinal transit was evaluated after gavage by a marker (51CrO4Na2) and radioactivity counting. Both RO 15.1788 (15 mg/kg) and PK 11.195 (5 mg/kg) triggered an abstinence syndrome with behavioral and autonomic signs. At the intestinal level, Ro 15.1788 induced a phase of strong irregular spiking activity (173 +/- 63 min) which remained located in the duodenum. In contrast, PK 11.195 induced a period of propagated myoelectric complexes characterized by phases II and III of high amplitude. The cecal frequency was doubled during the 1st hr after withdrawal induced by the two antagonists. Both Ro 15.1788 and PK 11.195 at this dosage had no effect per se on intestinal motility in vehicle-treated rats. In the second group of rats, gastric emptying was enhanced by 49.4 and 45.6% by Ro 15.1788 and PK 11.195, respectively. In contrast, PK 11.195 was able to accelerate the intestinal transit more than did Ro 15.1788 (geometric center, 5.9 +/- 0.43 and 5.3 +/- 0.49, respectively, vs. 4.1 +/- 0.31 in control rats). Our study shows that precipitated benzodiazepine withdrawal in diazepam-dependent rats induces alterations of the intestinal myoelectrical activity leading to an increase of the gastrointestinal transit. Central and peripheral-type receptors are involved in these effects. PMID:1312156

  18. Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium.

    PubMed

    Choi, E S; Oh, A Y; Seo, K S; Hwang, J W; Ryu, J H; Koo, B W; Kim, B G

    2016-04-01

    We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 μg.kg(-1) , 10 μg.kg(-1) , 20 μg.kg(-1) or 40 μg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 μg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 μg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade. PMID:26874258

  19. Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other neuromuscular blocking agents: a survey

    PubMed Central

    Nava-Ocampo, A A; Ramírez-Mora, J C; Moyao-García, D; Garduño-Espinosa, J; Salmerón, J

    2002-01-01

    Background Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. Material and methods The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned. Results Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. Conclusion Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice. PMID:11991809

  20. Intraoperative hemodynamics with vecuronium bromide and rocuronium for maintenance under general anesthesia

    PubMed Central

    Mathew, Alen; Sharma, Anish N. G.; Ganapathi, P.; Shankaranarayana, P.; Nazim, M.; Aiyappa, D. S.

    2016-01-01

    Aims: The present study is undertaken to compare the hemodynamic effects using vecuronium versus rocuronium for maintenance in patients undergoing general surgical procedures. Settings and Design: It is a prospective, randomized, and cohort study. Subjects and Methods: 100 patients were randomly divided into two groups. All patients were induced with 5 mg/kg of thiopentone sodium, and intubation conditions were achieved with 1.5 mg/kg of suxamethonium, using a well-lubricated cuffed endotracheal tube of appropriate size. When the patient started to breathe spontaneously, they were administered either 0.6 mg/kg of rocuronium (Group A) or 0.1 mg/kg of vecuronium (Group B). Hemodynamic parameters (heart rate and mean arterial pressure [MAP]) were monitored before administering the drug; at 1, 5, 10, 15, and 20 min after the drug and at the end of the surgery. Statistical Analysis Used: Data were compiled, analyzed and presented as frequency, proportions, mean, standard deviation, percentages, and t-test using SPSS (version 16). A P < 0.05 was considered as significant. Results: The heart rate increased significantly at 1-min and 5-min after administration of rocuronium (83.76 ± 10.37 and 86.8 ± 9.98), unlike vecuronium. However, it gradually declined towards normal, and change in heart rate with either drug was not significant beyond 10 min. The MAP decreased significantly at 1-min after administration of rocuronium (96.68 ± 7.57) which later showed a gradual increasing trend when compared to vecuronium which had no statistically significant change at any time. Conclusions: For short surgical procedures rocuronium is a good alternative to vecuronium, as the drug is reasonably cardio stable, produces excellent intubation conditions, has a shorter duration of action, and shows minimal cumulative effect. PMID:26957692

  1. Complete resistance after maximal dose of rocuronium

    PubMed Central

    Capuano, Annalisa; Sullo, Maria Giuseppa; Rafaniello, Concetta; Sportiello, Liberata; Fusco, Pierfrancesco; De Vizia, Macella; Ferraro, Fausto

    2015-01-01

    Rocuronium is a non-depolarizing neuromuscular blocking agent (NDNMBA), employed in the clinic as an adjunct to general anesthesia to facilitate tracheal intubation rapid sequence, and to provide skeletal muscle relaxation during surgery. Many cases of resistance to neuromuscular blocking agents (NMBAs) have been anecdotally reported. There are specific pathologic states, such as upper motor neuron lesions, severe thermal injuries, liver disease, renal failure, disuse atrophy, all of which show an increased resistance to the effects of nondepolarizing muscle relaxants. Also concurrent drug therapy can alter the efficacy of NMBAs such as some classes of antibiotics, furosemide, β receptor agonists, phosphodiesterase inhibitors, calcium antagonists, respiratory stimulants but also ketamine, propofol and barbiturates at high concentrations. In this scenario we describe an unusual case of 20-years-old man who showed a complete resistance to rocuronium maybe due to a glucocorticoids concomitant therapy. PMID:26312006

  2. Effect of glucocorticoid withdrawal on glucocorticoid inducing bone impairment.

    PubMed

    Shen, Gengyang; Ren, Hui; Qiu, Ting; Liang, De; Wei, Qiushi; Tang, Jingjing; Zhang, Zhida; Yao, Zhensong; Zhao, Wenhua; Jiang, Xiaobing

    2016-09-01

    Glucocorticoid (GC) withdrawal after a short-term use was common in clinical practice like immediate post-transplant period. However, previous studies without setting age-control group failed to determine whether the BMD recovery was sufficient and whether it is necessary to accept anti-osteoporosis therapy after GC withdrawal. The aim of this study was to investigate the effect of GC withdrawal on bone impairment in glucocorticoid-induced osteoporosis (GIOP) rats. Twenty-four female Sprague-Dawley rats (3 months' old) were randomly divided into two treatment groups: an untreated age-control group (Con, n = 12); another group receiving a dexamethasone injection (DEXA, n = 12). Animals in the Con group were euthanized at 3rd month (M3) and 6th month (M6), respectively. Six rats in the DEXA group were euthanized at 3rd month (M3), whereas GC intervention was withdrew in the remaining animals of DEXA group, which were euthanized at the end of 6th month (M6). Bone mass, bone microarchitecture, biomechanical properties of vertebrae, morphology, serum levels of PINP and β-CTX were evaluated. Compared with the Con(M3) group, the Con(M6) group showed significantly better bone quantity, morphology and quality. Compared with the Con(M3) group, the DEXA (M3) group showed significantly lower BMC, BMD, BS/TV, BV/TV, Tb.N, Tb.Th, vBMD, bone strength, compressive displacement, energy absorption capacity, PINP levels, β-CTX levels, and damaged trabecular morphology. And the same change trend was observed in the comparison between the Con(M6) group and DEXA (M6) group. Compared with the DEXA (M3) group, the DEXA (M6) group showed significantly higher BMC, BMD and AREA, but no significant difference in BS/TV, BV/TV, SMI, Tb.N, Tb.Th, Tb.Sp, vBMD, bone strength, bone stiffness, compressive displacement, energy absorption capacity, PINP levels, β-CTX levels, and improvement in trabecular morphology was observed. These results indicate that the reverse effect of GC withdrawal

  3. The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.

    PubMed

    Vandergriff, J; Rasmussen, K

    1999-02-01

    Naltrexone-precipitated morphine withdrawal induces hyperactivity of locus coeruleus (LC) neurons, as well as a plethora of behavioral withdrawal signs. Previous research has demonstrated that an increased release of glutamate and activation of AMPA receptors, particularly in the LC, play an important role in opiate withdrawal. LY354740 is a novel Group II metabotropic glutamate mGlu2/3 receptor agonist that decreases the release of glutamate. Therefore, we investigated the effect of LY354740 on naltrexone-precipitated morphine-withdrawal-induced activation of LC neurons and behavioral signs of morphine withdrawal. In in vivo recordings from anesthetized rats, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently attenuated the morphine-withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently suppressed the severity and occurrence of many naltrexone-precipitated morphine-withdrawal signs. These results indicate mGlu2/3 receptor agonists: (1) can attenuate the morphine-withdrawal-induced activation of LC neurons and many behavioral signs of morphine withdrawal; and (2) may have therapeutic effects in man for the treatment of opiate withdrawal. PMID:10218862

  4. Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs.

    PubMed

    Stewart, Jennifer L; McMahon, Lance R

    2010-07-01

    Marijuana-dependent individuals report using marijuana to alleviate withdrawal, suggesting that pharmacotherapy of marijuana withdrawal could promote abstinence. To identify potential pharmacotherapies for marijuana withdrawal, this study first characterized rimonabant-induced Delta(9)-tetrahydrocannabinol (Delta(9)-THC) withdrawal in rhesus monkeys by using drug discrimination and directly observable signs. Second, drugs were examined for their capacity to modify cannabinoid withdrawal. Monkeys receiving chronic Delta(9)-THC (1 mg/kg/12 h s.c.) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) under a fixed ratio schedule of stimulus-shock termination. The discriminative stimulus effects of rimonabant were dose-dependent (ED(50) = 0.25 mg/kg) and accompanied by head shaking. In the absence of chronic Delta(9)-THC treatment (i.e., in nondependent monkeys), a larger dose (3.2 mg/kg) of rimonabant produced head shaking and tachycardia. Temporary discontinuation of Delta(9)-THC treatment resulted in increased responding on the rimonabant lever, head shaking, and activity during the dark cycle. The rimonabant discriminative stimulus was attenuated fully by Delta(9)-THC (at doses larger than mg/kg/12 h) and the cannabinoid agonist CP 55940 [5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol], and partially by the cannabinoid agonist WIN 55212-2 [(R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and the alpha(2)-adrenergic agonist clonidine. In contrast, a benzodiazepine (diazepam) and monoamine agonist (cocaine) did not attenuate the rimonabant discriminative stimulus. Head shaking was attenuated by all test compounds. These results show that the discriminative stimulus effects of rimonabant in Delta(9)-THC-treated monkeys are a more pharmacologically selective measure of cannabinoid withdrawal than rimonabant-induced head shaking. These results suggest

  5. Remission of Methamphetamine-Induced Withdrawal Delirium and Craving After Electroconvulsive Therapy

    PubMed Central

    Ahmadi, Jamshid; Ekramzadeh, Sara; Pridmore, Saxby

    2015-01-01

    Introduction: The aim of this study is to describe the use of electroconvulsive therapy (ECT) in the treatment of methamphetamine-induced withdrawal delirium and craving in a single case. Case Presentation: A 44-year-old male presented to the hospital in Fars province, Iran, with Methamphetamine-Induced Withdrawal Delirium who responded to ECT. Conclusions: The electroconvulsive therapy can be a suitable option for the treatment of methamphetamine withdrawal delirium and craving. Also, it can be usefully employed in these very serious conditions which may represent a risk to life. PMID:26834801

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

    PubMed

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

    2013-08-01

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

  7. Evaluation of the relationship between anxiety during withdrawal and stress-induced reinstatement of cocaine seeking.

    PubMed

    Erb, Suzanne

    2010-06-30

    The initial termination of cocaine consumption in human addicts is associated with heightened anxiety states and low levels of craving. Craving, however, tends to increase progressively over time, remains high for extended periods of time, and can be exacerbated by stressors, leading to relapse. Laboratory rats, likewise, exhibit heightened states of anxiety after withdrawal from drug, and follow a time course of cocaine seeking that parallels the time course of craving reported in humans. In addition, laboratory rats show heightened susceptibility to relapse when exposed to stressors after extended periods of withdrawal, and exhibit persistent and heightened expressions of stress-induced anxiety. The general objective of this paper is to consider the relationship between anxiety states after withdrawal from cocaine and stress-induced reinstatement of cocaine seeking in laboratory rats, and to identify the neural substrates involved. The focus of the review is on studies addressing the roles of corticotropin-releasing factor (CRF) and noradrenaline pathways of the extended amygdala circuitry, and their direct or indirect interactions with the mesocorticolimbic dopamine system, in anxiety after withdrawal from cocaine and stress-induced reinstatement of cocaine seeking. Furthermore, the effects of time after withdrawal from cocaine and amount of cocaine exposure during self-administration on the activity of CRF, noradrenaline, and dopamine pathways of the extended amygdala and mesocorticolimbic systems will be considered. The review will highlight how changing levels of activity within these systems may serve to alter the nature of the relationship between anxiety and stress-induced reinstatement of cocaine seeking at different times after withdrawal from cocaine. PMID:19969038

  8. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain

    PubMed Central

    Van Bockstaele, Elisabeth J.; Qian, Yaping; Sterling, Robert C.; Page, Michelle E.

    2009-01-01

    experiment, animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration. PMID:18367303

  9. Antipsychotic withdrawal-induced relapse predicts future relapses in institutionalized adults with severe intellectual disability.

    PubMed

    Janowsky, David S; Barnhill, L Jarrett; Khalid, Abdul S; Davis, John M

    2008-08-01

    Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients have maintained stability. The current study evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses in those individuals where such a relapse had occurred previously. Subjects were 57 institutionalized adults with severe or profound intellectual disability. Between 1990 and 2000, each had experienced an initial activation of maladaptive aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or termination. Quarterly behavioral reports were evaluated to determine whether subsequent antipsychotic drug withdrawal attempts were also associated with future relapses. Initial relapse was followed by subsequent antipsychotic drug withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4 additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005, only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were receiving first-generation antipsychotic agents alone, 45.6% were receiving second-generation antipsychotic agents alone, and 24.6% were receiving a combination of first- and second-generation antipsychotic agents. Thus, if relapse occurs after an antipsychotic drug withdrawal attempt, subsequent attempts at withdrawal are also very likely to lead to further relapses. PMID:18626266

  10. Early skin and challenge testing after rocuronium anaphylaxis.

    PubMed

    Schulberg, E M; Webb, A R; Kolawole, H

    2016-05-01

    We present a case of early skin and challenge testing in a patient following severe anaphylaxis to rocuronium. The patient presented for semi-elective laparoscopic cholecystectomy and developed anaphylaxis with severe cardiovascular collapse after induction of anaesthesia. Surgery was cancelled but was considered necessary before the recommended four to six weeks for formal allergy testing. Limited skin and challenge testing was performed to rocuronium and cisatracurium while the patient was in the intensive care unit to identify a safe neuromuscular blocking drug for subsequent early surgery. The subsequent surgery, 48 hours after the initial reaction, was uneventful. The case highlights the difficulties when anaesthetising patients with recent anaphylaxis who have not yet had formal allergy testing and presents a potential management strategy involving early skin testing. PMID:27246945

  11. Interaction between rocuronium bromide and some drugs used during anaesthesia.

    PubMed

    Muir, A W; Anderson, K A; Pow, E

    1994-01-01

    In cats anaesthetized with i.p. chloralose and pentobarbitone, neuromuscular blockade produced by various doses of rocuronium was measured and dose response curves constructed in the presence of halothane, enflurane, nitrous oxide, propofol, alfentanil, thiopentone, ketamine, diazepam, chlorpromazine, morphine or streptomycin. In general, when a shift in the dose response curve was produced, it was a parallel shift to the left, indicating potentiation. Both halothane and enflurane produced a left shift and a small increase in the time from maximum block to 90% recovery. Nitrous oxide had no effect on the depth of block but delayed recovery. Thiopentone and ketamine potentiated the blocking effect of rocuronium but propofol and alfentanil had no effect. Chlorpromazine and morphine caused potentiation which took 1-1.5 h to develop. Streptomycin had a potentiating effect in four cats but not in two others. Diazepam displaced the dose-response curve to the right in four cats. Prior treatment with suxamethonium had no effect. PMID:7925217

  12. Stress sensitization of ethanol withdrawal-induced reduction in social interaction: inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist.

    PubMed

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

    2004-03-01

    Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposure to three restraint stresses alone altered this measure of anxiety. Further, the repeatedly stressed singly withdrawn rats continued to exhibit a reduction in social interaction 16 days later, upon withdrawal from re-exposure to 5 days of chronic ethanol, consistent with a persistent adaptation by the multiple-stress/withdrawal protocol. Weekly administration of corticosterone in place of stress induced no significant change in social interaction upon withdrawal from the single chronic ethanol exposure, indicative that corticoid release is not responsible for the stress-induced reduction in anxiety-like behavior during withdrawal. In the multiple-withdrawal protocol, stress applied during withdrawal from voluntary ethanol drinking by P-rats facilitated ethanol drinking sufficiently, to induce a withdrawal-induced reduction in social interaction. Administration of a CRF-1 receptor antagonist, a benzodiazepine receptor antagonist, or a 5-HT(1A) receptor agonist prior to each stress minimized sensitization of the withdrawal-induced reduction in anxiety-like behavior. Since these pharmacological consequences on the induction of anxiety-like behavior following the stress/withdrawal protocol are like those previously seen when these drug treatments were given prior to multiple withdrawals, evidence is provided that repeated stresses and multiple withdrawals sensitize the withdrawal reduction in social interaction by similar central adaptive mechanisms. PMID:12955093

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

    PubMed Central

    Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

    2012-01-01

    Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine. PMID:23056601

  14. Loss of Prostaglandin E2-induced Extra Cortical Bone After its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-(Prostaglandin E2) induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+16%, +25% and +34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  15. Loss of Prostaglandin E2-induced Extra Cortical Bone after its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+ 16%, +25% and + 34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  16. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    PubMed

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies. PMID:26370679

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

    PubMed

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

    2010-07-01

    Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts. PMID:20566855

  18. [Rocuronium or vecuronium for intubation for short operations in the preschool age? Effects on time in the operating room and postoperative phase].

    PubMed

    Pestel, G; Uhlig, T; Unrein, H; Rothhammer, A

    2001-01-01

    This prospective randomized study compares the effects of rocuronium (R) and vecuronium (V) on the early postoperative period in infants. Forty-eight infants between the ages of three and six, scheduled for elective ENT procedures, were studied after prior approval of local ethics committee and informed parental consent. All children were premedicated with chlorprotixene and belladonna. Anaesthesia was induced with 5 mg/kg thiopentone and 1 vol.-% halothane. Subsequently, 0.4 mg/kg rocuronium or 0.075 mg/kg vecuronium were administered, respectively. Anaesthesia and post-operative care were conducted by independent anaesthetists, who were unaware of the drug used and of the relaxometric data obtained. All children were monitored in the recovery room by pulse oximetry until they reached a Steward Score of 6. Demographic data did not differ between the groups. No differences were recorded between the non-depolarizing relaxants regarding intubation time (R: 24.1 +/- 4.2 min, V: 25.8 +/- 6.8 min) and the time interval from end extubation to leaving the operating theatre (R: 2.3 +/- 0.8 min, V: 2.6 +/- 1.2 min), respectively. Similarly, no differences in SaO2 were noted during the recovery period in the recovery room. Significant differences between the non-depolarizing relaxants were found in the TOF-ratios at extubation (R: 0.73 +/- 0.31 min, V: 0.48 +/- 0.34 min) and arrival in the recovery room (R: 0.88 +/- 0.21 min, V: 0.69 +/- 0.26 min). 0.4 mg/kg Rocuronium and 0.075 mg/kg vecuronium can be used for intubation during short operations on pre-school children. Rocuronium may be the better alternative, due to its faster neuromuscular recovery properties. PMID:11455866

  19. A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.

    PubMed

    Jung, Marianna E; Metzger, Daniel B

    2016-11-01

    Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2(-), malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2's protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2's antioxidant protection for hippocampus-related behavior. PMID:27503149

  20. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

    PubMed Central

    Yildirim, Emre; Connor, David A.; Gould, Thomas J.

    2015-01-01

    Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

  1. Ethanol withdrawal induces anxiety-like effects: Role of nitric oxide synthase in the dorsal raphe nucleus of rats.

    PubMed

    Gonzaga, Natália Almeida; Batistela, Melissa Resende; Padovan, Diego; de Martinis, Bruno Spinosa; Tirapelli, Carlos Renato; Padovan, Cláudia Maria

    2016-05-01

    Nitric oxide (NO) mediated transmission in the dorsal raphe nucleus (DRN) has been shown to be involved in the modulation of anxiety-like behaviors. We investigated whether inhibition of nitric oxide synthase (NOS) in the DRN would prevent anxiety-like behavior induced by ethanol withdrawal. Male Wistar rats were treated with ethanol 2-6% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats with a guide cannula aimed at the DRN received intra-DRN injections of the non-selective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME), selective neuronal NOS (nNOS) inhibitor N(ω)-propyl-l-arginine (NPLA), or selective inhibitor of inducible NOS (iNOS) N-([3-(aminomethyl)phenyl] methyl) ethanimidamidedihydrochloride (1400W). Five minutes later, the animals were tested in the elevated plus maze (EPM). Plasma ethanol levels were determined by gas chromatography. There was a reduction in plasma ethanol levels 48 h after ethanol withdrawal. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the EPM with no change in the exploration of enclosed arms. Intra-DRN treatment with l-NAME (100 nmoles/0.2 μL) and 1400W (1 nmol/0.2 μL), but not NPLA (10 nmoles/0.2 μL) in the DRN attenuated the decrease in the exploration of the open arms of the EPM induced by ethanol withdrawal. The major new finding of the present study is that iNOS in the DRN plays a role in the anxiety-like behavior induced by ethanol withdrawal. PMID:27139232

  2. Deformation-induced changes in hydraulic head during ground-water withdrawal

    USGS Publications Warehouse

    Hsieh, Paul A.

    1996-01-01

    Ground-water withdrawal from a confined or semiconfined aquifer causes three-dimensional deformation in the pumped aquifer and in adjacent layers (overlying and underlying aquifers and aquitards). In response to the deformation, hydraulic head in the adjacent layers could rise or fall almost immediately after the start of pumping. This deformation-induced effect suggest that an adjacent layer undergoes horizontal compression and vertical extension when pumping begins. Hydraulic head initially drops in a region near the well and close to the pumped aquifer, but rises outside this region. Magnitude of head change varies from a few centimeters to more than 10 centimeters. Factors that influence the development of deformation-induced effects includes matrix rigidity (shear modulus), the arrangement of aquifer and aquitards, their thicknesses, and proximity to land surface. Induced rise in hydraulic head is prominent in an aquitard that extends from land surface to a shallow pumped aquifer. Induced drop in hydraulic head is likely observed close to the well in an aquifer that is separated from the pumped aquifer by a relatively thin aquitard. Induced effects might last for hours in an aquifer, but could persist for many days in an aquitard. Induced effects are eventually dissipated by fluid flow from regions of higher head to regions of lower head, and by propagation of drawdown from the pumped aquifer into adjacent layers.

  3. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    SciTech Connect

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

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

    PubMed

    Morisot, Nadège; Contarino, Angelo

    2016-06-01

    Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. PMID:26907806

  5. Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice.

    PubMed

    Stoker, Astrid K; Markou, Athina

    2011-09-30

    Anhedonia is a major symptom of cocaine withdrawal, whereas euphoria characterizes the effects of acute administration of this drug in humans. These mood states can be measured quantitatively in animals with brain reward thresholds obtained from the intracranial self-stimulation (ICSS) procedure. Studies have previously reported the reward-enhancing effects of acute cocaine administration using the ICSS procedure in mice, but the effects of chronic cocaine administration and withdrawal on brain reward thresholds have not been widely investigated in this species. Cocaine withdrawal was induced in C57BL/6J mice by removal of intraperitoneal osmotic minipumps that delivered cocaine (90 or 180 mg/kg/day, salt) for 72 h. Mice were tested in the ICSS procedure 3-100 h post-pump removal. Anxiety-like behavior was assessed in the light-dark box 24h post-pump removal. After an 18-day washout period, tolerance and sensitization to the reward-enhancing effects of cocaine were assessed by injecting bolus cocaine intraperitoneally (0, 2.5, 5, and 10 mg/kg). The results indicated that 72 h administration of 90 and 180 mg/kg/day cocaine significantly lowered brain reward thresholds. Withdrawal from 90 and 180 mg/kg/day of cocaine administration elevated ICSS thresholds to similar extents. No anxiety-like behavior was observed in the light-dark box during withdrawal from chronic cocaine administration, although the number of transitions between compartments and locomotion in the dark compartment markedly decreased. Chronic cocaine administration did not induce tolerance or sensitization to the reward-enhancing effects of acute cocaine. In conclusion, alterations in mood states induced by cocaine administration and withdrawal in mice can be measured using the ICSS procedure. PMID:21557971

  6. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    PubMed

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-01

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake. PMID:25486512

  7. Stress-induced suppression of the immune system after withdrawal from chronic cocaine.

    PubMed

    Avila, Albert H; Morgan, Camille A; Bayer, Barbara M

    2003-04-01

    Recent evidence suggests that withdrawal from cocaine shares similarities to the stress response. Here, we examine whether withdrawal from chronic cocaine produces immune system alterations and whether the hypothalamic-pituitary-adrenal axis is involved. Sprague-Dawley male rats received cocaine (10 mg/kg i.p., b.i.d.) or saline, followed by 2 h, 1, 2, 4, 6, and 14 days of withdrawal. Proliferation responses of peripheral blood lymphocytes to concanavalin A were significantly suppressed at the 2-h, 1- and 2-day time points, and persisted for up to 6 days during withdrawal from chronic cocaine. Flow cytometric analysis revealed no significant differences in the immunophenotype of blood lymphocytic populations of T cells, B cells, or monocytes at 2 or 6 days of withdrawal from cocaine. Consistent with the suppression in cellular immunity observed in the in vitro response, the in vivo delayed-type hypersensitivity response was also significantly decreased in cocaine withdrawing animals. Plasma corticosterone levels were significantly elevated 2 and 24 h after cessation of cocaine but returned to basal values by 2 days of withdrawal. The suppressive effects of cocaine withdrawal were no longer observed in either adrenalectomized animals or those treated with the glucocorticoid receptor antagonist mifepristone (RU486), when administered during the first 2 days of withdrawal. These data argue that repeated exposure to cocaine followed by withdrawal leads to an activation of the neuroendocrine stress response, which alters cellular immunity during the initial withdrawal phase and may contribute to an increased susceptibility to infection. PMID:12649381

  8. N-3 Polyunsaturated Fatty Acids are Selective Targets of Ethanol Withdrawal-Induced Lipid Peroxidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethanol withdrawal is a potentially life-threatening neurological syndrome owing to decreased GABA transmission and increased glutamatergic transmission resulting in a pro-excitotoxic state. Previous data indicate that ethanol withdrawal may increase CNS lipid peroxidation particularly to the n-3 fa...

  9. Mania-like reaction induced by benzodiazepine withdrawal in a patient with mental retardation.

    PubMed

    Ghaziuddin, N; Ghaziuddin, M

    1990-10-01

    Symptoms resembling mania following withdrawal of diazepam in a mentally handicapped woman are described. The importance of considering benzodiazepine withdrawal in the assessment of acute behavioural disorders of the mentally handicapped is emphasized. Attention is also drawn to the paucity of research regarding the use of antianxiety drugs in the mentally handicapped. PMID:2268841

  10. A Coulomb stress model for induced seismicity distribution due to fluid injection and withdrawal in deep boreholes

    NASA Astrophysics Data System (ADS)

    Troiano, Antonio; Di Giuseppe, Maria Giulia; Troise, Claudia; Tramelli, Anna; De Natale, Giuseppe

    2013-10-01

    Fluid injection in and withdrawal from wells are basic procedures in mining activities and deep resources exploitation, such as oil and gas extraction, permeability enhancement for geothermal exploitation and waste fluid disposal. All of these activities have the potential to induce seismicity, as exemplified by the 2006 Basel earthquake (ML 3.4). Despite several decades of experience, the mechanisms of induced seismicity are not known in detail, which prevents effective risk assessment and/or mitigation. In this study, we provide an interpretation of induced seismicity based on computation of Coulomb stress changes that result from fluid injection/withdrawal at depth, mainly focused on the interpretation of induced seismicity due to stimulation of a geothermal reservoir. Seismicity is, theoretically, more likely where Coulomb stress changes are larger. For modeling purposes, we simulate the thermodynamic evolution of a system after fluid injection/withdrawal. The associated changes in pressure and temperature are subsequently considered as sources of incremental stress changes, which are then converted to Coulomb stress changes on favourably oriented faults, taking into account the background regional stress. Numerical results are applied to the water injection that was performed to create the fractured reservoir at the enhanced-geothermal-system site, Soultz-sous-Forets (France). Our approach describes well the observed seismicity, and provides an explanation for the different behaviors of a system when fluids are injected or withdrawn.

  11. Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models

    PubMed Central

    Kwon, Jae Young; Kim, Hae-Kyu

    2016-01-01

    Background This study was conducted to investigate the pharmacodynamic interaction between rocuronium and cisatracurium using the response surface model, which is not subject to the limitations of traditional isobolographic analysis. Methods One hundred and twenty patients were randomly allocated to receive one of the fifteen predefined combinations of rocuronium and cisatracurium. To study single drugs, cisatracurium 0.2, 0.15, or 0.1 mg/kg or rocuronium 0.8, 0.6 or 0.4 mg/kg doses were administered alone. To study the pharmacodynamic interaction, drugs were applied in three types of combination ratio, i.e., half dose of each drug alone, 75% of each single dose of rocuronium and 25% of each single dose of cisatracurium, and vice versa. Train-of-four (TOF) ratio and T1% (first twitch of the TOF presented as percentage compared to the initial T1) were used as pharmacodynamic endpoints, and the Greco and Minto models were used as surface interaction models. Results The interaction term α of the Greco model for TOF ratio and T1% measurements showed synergism with values of 0.977 and 1.12, respectively. Application of the Minto model resulted in U50 (θ) values (normalized unit of concentration that produces 50% of the maximal effect in the 0 < θ < 1 region) less than 1 for both TOF ratio and T1% measurements, indicating that rocuronium and cisatracurium exhibit synergism. Conclusions Response surface modeling of the interaction between rocuronium and cisatracurium, based on considerations of their effects on muscle relaxation as measured by TOF ratio and T1%, indicated that the two drugs show considerable synergism. PMID:27482310

  12. Cocaine withdrawal

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000947.htm Cocaine withdrawal To use the sharing features on this page, please enable JavaScript. Cocaine withdrawal occurs when someone who has used a ...

  13. Anxiety-like symptoms induced by morphine withdrawal may be due to the sensitization of the dorsal periaqueductal grey.

    PubMed

    Castilho, V M; Borelli, K G; Brandão, M L; Nobre, M J

    2008-07-01

    Withdrawal from morphine leads to the appearance of extreme anxiety accompanied of several physical disturbances, most of them linked to the activation of brainstem regions such as the locus coeruleus, ventral tegmental area, hypothalamic nuclei and periaqueductal grey (PAG). As anxiety remains one of the main components of morphine withdrawal the present study aimed to evaluating the influence of the dorsal aspects of the PAG on the production of this state, since this structure is well-known to be involved in defensive behaviour elicited by anxiety-evoking stimuli. Different groups of animals were submitted to 10 days of i.p. morphine injections, challenged 2 h after with an i.p. injection of naloxone (0.1 mg/kg), and submitted to the plus-maze, open-field and light-dark transition tests. The effects of morphine withdrawal on anxiety-induced Fos immunolabelling were evaluated in four animals that passed by the light-dark transition test randomly chosen for Fos-protein analysis. Besides the PAG, Fos neural expression was conducted in other brain regions involved in the expression of anxiety-related behaviours. Our results showed that morphine withdrawn rats presented enhanced anxiety accompanied of few somatic symptoms. Increased Fos immunolabelling was noted in brain regions well-known to modulate these states as the prelimbic cortex, nucleus accumbens, amygdala and paraventricular hypothalamus. Increased Fos labelling was also observed in the ventral and dorsal aspects of the PAG, a region involved in anxiety-related processes suggesting that this region could be a common neural substrate enlisted during anxiety evoked by dangerous stimuli as well as those elicited by opiate withdrawal. PMID:18485423

  14. Withania somnifera prevents morphine withdrawal-induced decrease in spine density in nucleus accumbens shell of rats: a confocal laser scanning microscopy study.

    PubMed

    Kasture, Sanjay; Vinci, Stefania; Ibba, Federico; Puddu, Alessandro; Marongiu, Mara; Murali, Balasubramanian; Pisanu, Augusta; Lecca, Daniele; Zernig, Gerald; Acquas, Elio

    2009-11-01

    Opiate withdrawal is associated with morphological changes of dopamine neurons in the ventral tegmental area and with reduction of spine density of second-order dendrites of medium size spiny neurons in the nucleus accumbens shell but not core. Withania somnifera has long been used in the Middle East, Africa, and India as a remedy for different conditions and diseases and a growing body of evidence points to its beneficial effects on a number of experimental models of neurological disorders. Recently, many studies focused on the potential neuritic regeneration and synaptic reconstruction properties of its methanolic extract and its constituents (withanolides). This study investigates whether morphine withdrawal-induced spine reduction in the nucleus accumbens is affected by the administration of a Withania somnifera extract. To this end, rats were chronically treated with Withania somnifera extract along with morphine or saline and, upon spontaneous (1 and 3 days) or pharmacologically precipitated withdrawal, their brains were fixed in Golgi-Cox stain for confocal microscopic examination. In a separate group of animals, Withania somnifera extract was administered during three days of spontaneous withdrawal. Withania somnifera extract treatment reduced the severity of the withdrawal syndrome when given during chronic morphine but not during withdrawal. In addition, treatment with Withania somnifera extract during chronic morphine, but not during withdrawal, fully prevented the reduction of spine density in the nucleus accumbens shell in spontaneous and pharmacologically precipitated morphine withdrawal. These results indicate that pretreatment with Withania somnifera extract protects from the structural changes induced by morphine withdrawal potentially providing beneficial effects on the consequences related to this condition. PMID:19551457

  15. Modeling of fluid injection and withdrawal induced fault activation using discrete element based hydro-mechanical and dynamic coupled simulator

    NASA Astrophysics Data System (ADS)

    Yoon, Jeoung Seok; Zang, Arno; Zimmermann, Günter; Stephansson, Ove

    2016-04-01

    Operation of fluid injection into and withdrawal from the subsurface for various purposes has been known to induce earthquakes. Such operations include hydraulic fracturing for shale gas extraction, hydraulic stimulation for Enhanced Geothermal System development and waste water disposal. Among these, several damaging earthquakes have been reported in the USA in particular in the areas of high-rate massive amount of wastewater injection [1] mostly with natural fault systems. Oil and gas production have been known to induce earthquake where pore fluid pressure decreases in some cases by several tens of Mega Pascal. One recent seismic event occurred in November 2013 near Azle, Texas where a series of earthquakes began along a mapped ancient fault system [2]. It was studied that a combination of brine production and waste water injection near the fault generated subsurface pressures sufficient to induced earthquakes on near-critically stressed faults. This numerical study aims at investigating the occurrence mechanisms of such earthquakes induced by fluid injection [3] and withdrawal by using hydro-geomechanical coupled dynamic simulator (Itasca's Particle Flow Code 2D). Generic models are setup to investigate the sensitivity of several parameters which include fault orientation, frictional properties, distance from the injection well to the fault, amount of fluid withdrawal around the injection well, to the response of the fault systems and the activation magnitude. Fault slip movement over time in relation to the diffusion of pore pressure is analyzed in detail. Moreover, correlations between the spatial distribution of pore pressure change and the locations of induced seismic events and fault slip rate are investigated. References [1] Keranen KM, Weingarten M, Albers GA, Bekins BA, Ge S, 2014. Sharp increase in central Oklahoma seismicity since 2008 induced by massive wastewater injection, Science 345, 448, DOI: 10.1126/science.1255802. [2] Hornbach MJ, DeShon HR

  16. Antidepressants reduce extinction-induced withdrawal and biting behaviors: a model for depressive-like behavior.

    PubMed

    Huston, J P; van den Brink, J; Komorowski, M; Huq, Y; Topic, B

    2012-05-17

    The withholding of expected rewards results in extinction of behavior and, hypothetically, to depression-like symptoms. In a test of this hypothesis, we examined the effects of extinction of food-reinforced lever-pressing on collateral behaviors that might be indices of depression. Operant extinction is known to be aversive to the organism and results in avoidance behavior. We hypothesized that avoidance of, or withdrawal from, the former source of reward may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per group) were exposed to a Skinner box attached to a second compartment of the same size, providing opportunity for the animals to leave the operant chamber and to enter the "withdrawal" compartment. The animals spent a portion of the time during the extinction trials in this second chamber. To assess the predictive validity of this behavior as a potential marker of "despair," we tested the effects of chronic administration of two common antidepressant drugs on this measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number of entries and time spent in the withdrawal compartment. We propose that entries into and time spent in the withdrawal compartment may operationalize "avoidance," a core symptom of major depression. Rearing as well as biting behaviors during the extinction trials were also attenuated by the antidepressant treatment. These results lend support to the hypothesis that extinction of positively reinforced operants evokes behaviors that reflect elements of "despair/depression" because these behaviors are modulated by antidepressant treatment. The avoidance of the operant chamber as a consequence of extinction, together with rearing and biting behaviors, may serve as useful measures for the testing of antidepressant treatments. PMID:22410342

  17. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats.

    PubMed

    Knapp, Darin J; Overstreet, David H; Moy, Sheryl S; Breese, George R

    2004-02-01

    Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8-12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-like behavior after treatment with drugs hypothesized to have anxiolytic action. SB242084, flumazenil, and CRA1000-antagonists for 5-hydroxytryptamine (serotonin) (5-HT) 2C (5-HT(2C)), benzodiazepine, and corticotropin-releasing factor type 1 (CRF(1)) receptors, respectively-attenuated decreased social interaction without concomitant effects on activity measures. In contrast, ifenprodil, MDL 72222, and zolpidem-antagonists for N-methyl-d-aspartate (NMDA) and 5-HT(3) receptors, and agonist for benzodiazepine type 1 receptors, respectively-did not share this effect. Results for SB242084, flumazenil, and ifenprodil in the elevated plus-maze test were comparable to those in the social interaction test. These results support the suggestion that multiple neuronal systems (CRF(1), 5-HT(2C), and benzodiazepine receptors) contribute to the ethanol withdrawal sign of decreased social interaction. Furthermore, the selective effects of pharmacological agents on social interaction seem to indicate that this behavior can be dissociated from other signs. Because anxiety may be a complicating factor in alcohol withdrawal and relapse, future studies of this type are needed to provide focus for the effort to define selective and novel antianxiety agents for these disorders. PMID:15163561

  18. Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats.

    PubMed

    Hirase, Masahiro; Ishida, Takayuki; Kamei, Chiaki

    2008-11-12

    The present study was performed to examine whether or not rebound insomnia is caused by an abrupt withdrawal of benzodiazepine hypnotics and tandospirone in rats. Etizolam and triazolam caused a significant shortening of sleep latency, increase in non-REM sleep time, and decrease in wake time in a dose-dependent manner. Etizolam and triazolam caused a significant shortening of sleep latency during drug administration (for 7 days), whereas a significant prolongation of sleep latency was observed by the abrupt withdrawal of these drugs. Tandospirone caused a shortening of sleep latency, whereas no effect was observed on non-REM sleep time and wake time during drug administration (for 7 days). On the other hand, tandospirone showed no significant effect on sleep latency through its abrupt withdrawal, differing from etizolam and triazolam. From these findings, a rebound phenomenon in terms of sleep latency was confirmed with etizolam and triazolam in rats. Furthermore, the 5-HT(1A) agonist, tandospirone, caused no rebound phenomenon regarding sleep latency in rats. PMID:18789918

  19. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.

    PubMed

    Knapp, Darin J; Harper, Kathryn M; Whitman, Buddy A; Zimomra, Zachary; Breese, George R

    2016-01-01

    Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C-C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally-based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs-the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these

  20. Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa.

    PubMed

    Matsumoto, Kenjiro; Horie, Syunji; Takayama, Hiromitsu; Ishikawa, Hayato; Aimi, Norio; Ponglux, Dhavadee; Murayama, Toshihiko; Watanabe, Kazuo

    2005-11-19

    7-Hydroxymitragynine is a potent opioid analgesic alkaloid isolated from the Thai medicinal herb Mitragyna speciosa. In the present study, we investigated the opioid receptor subtype responsible for the analgesic effect of this compound. In addition, we tested whether development of tolerance, cross-tolerance to morphine and naloxone-induced withdrawal signs were observed in chronically 7-hydroxymitragynine-treated mice. Subcutaneous (s.c.) administration of 7-hydroxymitragynine produced a potent antinociceptive effect mainly through activation of mu-opioid receptors. Tolerance to the antinociceptive effect of 7-hydroxymitragynine developed as occurs to morphine. Cross-tolerance to morphine was evident in mice rendered tolerant to 7-hydroxymitragynine and vice versa. Naloxone-induced withdrawal signs were elicited equally in mice chronically treated with 7-hydroxymitragynine or morphine. 7-Hydroxymitragynine exhibited a potent antinociceptive effect based on activation of mu-opioid receptors and its morphine-like pharmacological character, but 7-hydroxymitragynine is structurally different from morphine. These interesting characters of 7-hydroxymitragynine promote further investigation of it as a novel lead compound for opioid studies. PMID:16169018

  1. Alcohol withdrawal.

    PubMed

    Manasco, Anton; Chang, Shannon; Larriviere, Joseph; Hamm, L Lee; Glass, Marcia

    2012-11-01

    Alcohol withdrawal is a common clinical condition that has a variety of complications and morbidities. The manifestations can range from mild agitation to withdrawal seizures and delirium tremens. The treatments for alcohol withdrawal include benzodiazepines, anticonvulsants, beta-blockers and antihypertensives. Although benzodiazepines are presently a first-line therapy, there is controversy regarding the efficacies of these medications compared with others. Treatment protocols often involve one of two contrasting approaches: symptom-triggered versus fixed-schedule dosing of benzodiazepines. We describe these protocols in our review and examine the data supporting symptom-triggered dosing as the preferred method for most patients in withdrawal.The Clinical Institute Withdrawal Assessment for Alcohol scoring system for alcohol withdrawal streamlines care, optimizes patient management, and is the best scale available for withdrawal assessment. Quality improvement implications for inpatient management of alcohol withdrawal include increasing training for signs of withdrawal and symptom recognition, adding new hospital protocols to employee curricula, and ensuring manageable patient-to-physician and patient-to-nurse ratios. PMID:23128805

  2. Direct Facilitatory Role of Paragigantocellularis Neurons in Opiate Withdrawal-Induced Hyperactivity of Rat Locus Coeruleus Neurons: An In Vitro Study

    PubMed Central

    Kaeidi, Ayat; Azizi, Hossein; Javan, Mohammad; Ahmadi Soleimani, S. Mohammad; Fathollahi, Yaghoub; Semnanian, Saeed

    2015-01-01

    Studies have shown that following opiate withdrawal, the spontaneous discharge rate of locus coeruleus (LC) neurons remarkably increases. Combination of intrinsic mechanisms with extrinsic excitatory modulations mediates the withdrawal-induced hyperactivity of LC neurons. The nucleus paragigantocellularis (PGi) provides the main excitatory inputs to LC and plays a pivotal role in opiate withdrawal. In the present study the direct facilitatory role of PGi on opiate withdrawal-induced hyperactivity of LC neurons was investigated using a newly developed brain slice, containing both LC and PGi. HRP retrograde neuronal tracing was used to verify the existence of both LC and PGi neurons in the developed slice. The spontaneous discharge rate (SDR), resting membrane potential (RMP) and spontaneous excitatory post-synaptic currents (sEPSCs) were recorded in LC neurons using whole cell patch clamp recording. Results showed that the net SDR and the net RMP of LC neurons in slices containing both LC and PGi neurons are significantly higher than slices lacking intact (uncut) PGi inputs. Also, the frequency of sEPSCs in those LC neurons receiving PGi inputs significantly increased compared to the slices containing no intact PGi inputs. Altogether, our results propose that increase in PGi-mediated excitatory transmission might facilitate the opiate withdrawal-induced hyperactivity of LC neurons. PMID:26230639

  3. A1-adenosine acute withdrawal response and cholecystokinin-8 induced contractures are regulated by Ca(2+)- and ATP-activated K(+) channels.

    PubMed

    Cascio, Maria Grazia; Valeri, Daniela; Tucker, Steven J; Marini, Pietro

    2015-01-01

    In isolated guinea-pig ileum (GPI), the A1-adenosine acute withdrawal response is under the control of several neuronal signalling systems, including the μ/κ-opioid and the cannabinoid CB1 systems. It is now well established that after the stimulation of the A1-adenosine system, the indirect activation of both μ/κ-opioid and CB1 systems is prevented by the peptide cholecystokinin-8 (CCk-8). In the present study, we have investigated the involvement of the Ca(2+)/ATP-activated K(+) channels in the regulation of both acute A1-withdrawal and CCk-8-induced contractures in the GPI preparation. Interestingly, we found that: (a) the A1-withdrawal contracture is inhibited by voltage dependent Ca(2+)-activated K(+) channels, Kv, while it is enhanced by the voltage independent Ca(2+)-activated K(+) channels, SKCa; (b) in the presence of CCk-8, the inhibitory effect of the A1 agonist, CPA, on the peptide induced contracture is significantly enhanced by the voltage independent Ca(2+)-activated K(+) channel, SKCa; and (c) the A1-withdrawal contracture precipitated in the presence of CCk-8 is controlled by the ATP-sensitive potassium channels, KATP. Our data suggest, for the first time, that both Ca(2+)- and ATP-activated K(+) channels are involved in the regulation of both A1-withdrawal precipitated and CCk-8 induced contractures. PMID:25836919

  4. Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats.

    PubMed

    Li, Yan; Raaby, Kasper F; Sánchez, Connie; Gulinello, Maria

    2013-11-01

    Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD) are characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. Studies demonstrated rodent models of progesterone withdrawal (PWD) have a high level of constructive and descriptive validity to model hormonally-induced mood disorders in women. Here we evaluate the effects of several classes of antidepressants in PWD female Long-Evans rats using the forced swim test (FST) as a measure of antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A) receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days of administration, amitriptyline and vortioxetine significantly reduced immobility in the FST whereas fluoxetine and duloxetine were ineffective. After 3 injections over 48 h, neither fluoxetine nor duloxetine reduced immobility, whereas amitriptyline and vortioxetine significantly reduced FST immobility during PWD. When administered acutely during PWD, the 5-HT(1A) receptor agonist, flesinoxan, significantly reduced immobility, whereas the 5-HT(1A) receptor antagonist, WAY-100635, increased immobility. The 5-HT(3) receptor antagonist, ondansetron, significantly reduced immobility, whereas the 5-HT(3) receptor agonist, SR-57227, increased immobility. The 5-HT(7) receptor antagonist, SB-269970, was inactive, although the 5-HT(7) receptor agonist, AS-19, significantly increased PWD-induced immobility. None of the compounds investigated (ondansetron, flesinoxan and SB-269970) improved the effect of fluoxetine during PWD. These data indicate that modulation of specific 5-HT receptor subtypes is critical for manipulating FST immobility in this model of hormone-induced depression. PMID:24016840

  5. Structural characterization of a degradation product of rocuronium using nanoelectrospray-high resolution mass spectrometry.

    PubMed

    Wegener, Olaf; Harms, Guido; Volmer, Dietrich A; Hayen, Heiko

    2015-09-01

    Rocuronium bromide is a non-depolarizing neuromuscular blocking agent that causes rapid muscle relaxation after intravenous injection. Regulatory authorities for registration of pharmaceuticals for human use require the evaluation of the stability of active compounds under various stress conditions. Forced degradation of rocuronium bromide was performed under hydrolytic, thermal, photolytic, and oxidative settings. HPLC-UV/vis analysis revealed an unknown degradation product under oxidative conditions (1% H2 O2 , reflux for 1 h). Investigation of the respective HPLC fraction by high resolution mass spectrometry indicated a formal loss of CH2 and an addition of one oxygen atom to the intact drug molecule. Additional multistage mass spectrometric structural elucidation experiments aided by complementary information from analysis of the intact drug and known rocuronium-related compounds showed that the morpholine moiety was unstable under oxidative stress. The data demonstrated that the morpholine ring was opened and transformed to an N-ethanoyl-formamide group. The structure was supported by appropriate mechanistic explanations. PMID:25564990

  6. D-Amphetamine withdrawal-induced decreases in brain-derived neurotrophic factor in sprague-dawley rats are reversed by treatment with ketamine.

    PubMed

    Fuller, Jasmine J L; Murray, Ryan C; Horner, Kristen A

    2015-10-01

    Withdrawal from chronic D-amphetamine (D-AMPH) can induce negative emotional states, which may contribute to relapse and the maintenance of addiction. Diminished levels of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus has been observed after exposure to stress, and recent data indicate that treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine may reverse these changes. However, it is unclear whether BDNF levels in the hippocampus or other regions of the limbic system are altered following the stress of D-AMPH withdrawal and it is not currently known if treatment with ketamine has any effect on these changes. The goals of this study were to examine BDNF levels throughout the limbic system following D-AMPH withdrawal and determine whether ketamine treatment would alter D-AMPH-induced changes in BDNF. Sprague-Dawley rats were treated with D-AMPH and BDNF protein examined in the prefrontal cortex, nucleus accumbens, amygdala and hippocampus at 24 h and 4 days of withdrawal. Our data show that at 24 h post-D-AMPH, BDNF levels were increased in the nucleus accumbens and decreased in the hippocampus. At 4 d post-D-AMPH, BDNF protein levels were decreased in all areas examined, and these decreases were reversed by treatment with ketamine. These data suggest that diminished BDNF may contribute to the negative affect seen following D-AMPH withdrawal, and that ketamine treatment could offer relief from these symptoms. PMID:25986696

  7. Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice

    PubMed Central

    Shi, Jianguo; Wu, Bin; Dang, Wei; Du, Ying; Zhou, Qiong; Wang, Jianhua; Zhang, Rui

    2013-01-01

    Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression. PMID:23823128

  8. Zolpidem withdrawal induced uncoupling of GABA(A) receptors in vitro associated with altered GABA(A) receptor subunit mRNA expression.

    PubMed

    Jembrek, Maja Jazvinšćak; Vlainić, Josipa; Šuran, Jelena

    2015-01-01

    Hypnotic zolpidem produces its effects via the benzodiazepine binding site in α1-containing GABAA receptors. The aim of the study was to assess the influence of duration of zolpidem treatment and its withdrawal, as well as the role of alpha1-containing GABAA receptors in the development of physical dependence and tolerance. Namely, recombinant receptors can be used to characterize mechanisms involved in different processes in the brain and to delineate the contribution of specific receptor subtypes. To address the influence of chronic zolpidem treatment we exposed HEK293 cells stably expressing alpha1beta2gamma2S recombinant GABAA receptors for seven consecutive days, while withdrawal periods lasted for 24, 48, 72 and 96 hours. Using radioligand binding studies we determined that chronic zolpidem treatment did not induce changes in either GABAA receptor number or in the expression of subunit mRNAs. We observed the enhancement of binding sites and upregulated expression of subunit mRNAs only following 96-hour withdrawal. Moreover, zolpidem treatment and its withdrawal (All time points) induced functional uncoupling between GABA and benzodiazepine binding sites in the GABAA receptor complex. Accordingly, it might be assumed that zolpidem withdrawal-induced uncoupling of GABAA receptors is associated with altered GABAA receptor subunit mRNA expression. The results presented here provide an insight into molecular and cellular mechanisms probably underlying adaptive changes of GABAA receptor function in response to chronic usage and withdrawal of zolpidem and perhaps the observed molecular changes could be linked to the tolerance and dependence produced upon prolonged treatment with other GABAergic drugs. PMID:26232993

  9. Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats

    PubMed Central

    Hou, Yuan-yuan; Liu, Yao; Kang, Shuo; Yu, Chuan; Chi, Zhi-qiang; Liu, Jing-gen

    2009-01-01

    Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal. Methods: NMDA receptor antagonist D-AP5 (5 μg/0.5 μL per side) or AMPA receptor antagonist NBQX (2 μg/0.5 μL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed. Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA. Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats. PMID:19767765

  10. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  11. Cocaine withdrawal

    MedlinePlus

    Cocaine withdrawal occurs when someone who has used a lot of cocaine cuts down or quits taking the drug. Symptoms ... even if the user is not completely off cocaine and still has some of the drug in ...

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

    PubMed

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

    2014-09-01

    Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways. PMID:24824948

  13. Drug Challenges Reveal Differences in Mediation of Stress Facilitation of Voluntary Alcohol Drinking and Withdrawal-Induced Anxiety in Alcohol-Preferring P Rats

    PubMed Central

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

    2010-01-01

    Background There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety. Methods P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress. Results Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety-like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5-HT1A receptor partial agonist buspirone (0.6 mg/kg), and the mixed 5-HT2C/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal-induced anxiety-like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5-HT2C receptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior. Conclusion These results suggest that stress-induced facilitation of alcohol drinking and withdrawal-induced anxiety

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

    PubMed Central

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

    2013-01-01

    Background Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g. MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine if administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Methods Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10 or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Results Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Conclusions Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. PMID:21070252

  15. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  16. Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of the stria terminalis: implications for anxiety during ethanol withdrawal.

    PubMed

    Marcinkiewcz, Catherine A; Dorrier, Cayce E; Lopez, Alberto J; Kash, Thomas L

    2015-02-01

    One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c receptor (5HT2c-R) signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 h of ethanol vapor exposure followed by an 8 h "withdrawal" period between exposures. After the 5th and final exposure, mice were withdrawn for 24 h or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field tests with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 h and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 h into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

  17. The Effect of Patient Weight and Provider Training and Experience on Dosing of Rocuronium

    PubMed Central

    Rodriguez, L.; Banks, S.; Major, B. T.; Rodriguez, Y.

    2016-01-01

    Introduction. Maintenance dosing of neuromuscular blocking agents is complex and varies with patient, procedure, and clinical situation. With this in mind, we sought to identify factors impacting the maintenance dosing of neuromuscular blockers as a step toward identifying best practice with respect to minimizing residual neuromuscular blockade. Methods. Cases utilizing rocuronium from July 1, 2010, to June 30, 2014, at the sponsoring institution were analyzed. Using a mixed model to account for repeated measures, patients were analyzed by dose and weight category as defined by the World Health Organization (eight categories ranging from very severely underweight to very severely obese) as well as by the administering provider's level of experience. Results. The study included 12,671 patients with a mean age of 49.7 (SD 16.7). Increasing weight category and higher levels of provider experience were associated with higher doses for rocuronium. There were no differences in initial dose or in frequency of maintenance dosing by weight category after controlling for case length. Discussion. The two dosing patterns identified, higher doses for overweight patients and higher doses administered by experienced providers, are modifiable factors that could enhance patient safety. PMID:27429615

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

    PubMed

    dos Santos Pereira, Maurício; Sathler, Matheus Figueiredo; Valli, Thais da Rosa; Marques, Richard Souza; Ventura, Ana Lucia Marques; Peccinalli, Ney Ronner; Fraga, Mabel Carneiro; Manhães, Alex C; Kubrusly, Regina

    2015-01-01

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

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

    PubMed Central

    dos Santos Pereira, Maurício; Sathler, Matheus Figueiredo; Valli, Thais da Rosa; Marques, Richard Souza; Ventura, Ana Lucia Marques; Peccinalli, Ney Ronner; Fraga, Mabel Carneiro; Manhães, Alex C.; Kubrusly, Regina

    2015-01-01

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

  20. The Successful Treatment of Opioid Withdrawal-Induced Refractory Muscle Spasms with 5-HTP in a Patient Intolerant to Clonidine.

    PubMed

    Dais, Jennifer; Khosia, Ankur; Doulatram, Gulshan

    2015-01-01

    Instituting drug holidays for chronic opioid using patients is becoming commonplace for pain practitioners initiating procedures such as intrathecal pump or spinal cord stimulator trials. As such, pain practitioners need to be adept in their management of acute opioid withdrawal. Successfully weaning an opioid dependent patient off of chronic opioids requires a thorough knowledge of the available adjuvants to assist in this process. However, that selection can become exhausted by adjuvant side effects or by ineffective attenuation of opioid withdrawal symptoms. In that case, novel drugs, or novel application of currently available medications must be sought after to assist in the drug holiday. We present a case in which refractory muscle spasms secondary to opioid withdrawal were successfully treated with an over-the-counter supplement that is not typically used for the attenuation of opioid withdrawal symptoms. In a patient intolerant to the side effects of clonidine, we were able to successfully wean chronic opiates by treating refractory muscle spasms with the serotonin precursor, 5-hydroxytryptophan (5-HTP). We hypothesize that our success with this medication gives further credence to the role of serotonin in opioid withdrawal somatic symptomatology, and supports the need for future research to clarify the role of serotonin precursors or serotonin modulating drugs as potential alternatives in those unable to follow standard treatment protocols. PMID:26000689

  1. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  2. Opiate and opioid withdrawal

    MedlinePlus

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

  3. Opiate and opioid withdrawal

    MedlinePlus

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

  4. [Successful anesthetic management of laparoscopic rectopexy using rocuronium and sugammadex in a patient with Becker muscular dystrophy].

    PubMed

    Yamaguchi, Satoshi; Ohno, Giichiro; Kitamura, Jiro

    2014-10-01

    A 70-year-old man with Becker muscular dystrophy (BMD) underwent laparoscopic rectopexy under general anesthesia. For anesthetic induction, we administered total 0.6 mg · kg-1 of rocuronium with titration. Eight minutes later, train-of-four (TOF) count reached to 0 and the patient was intubated smoothly. One hundred and five minutes later, TOF ratio recovered to 100% and we administered rocuronium 10 mg additionally. Surgery was finished without any problems 95 minutes after thereafter. TOF ratio was 45% and we administered sugammadex 3 mg · kg-1, reversing neuromuscular blockade to TOF ratio 100% within 1.5 minute. The patient awoke clearly and respiratory condition was good. He was extubated without remaining neuromuscular blockade. Postoperative course was stable and there was no serious adverse effect on his muscular function intra- and post-operatively. In conclusion, rocuronium and sugammadex can be used safely and effectively in general anesthetic management for patients with muscular dystrophy. However, as the onset times and durations of these agents can be longer, we should administer these agents with titration carefully under periodic neuromuscular monitoring. PMID:25693344

  5. Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    PubMed Central

    Greenberg, Gian D.; Laman-Maharg, Abigail; Campi, Katharine L.; Voigt, Heather; Orr, Veronica N.; Schaal, Leslie; Trainor, Brian C.

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females. PMID:24409132

  6. Catecholaminergic activity and 3',5'-cyclic adenosine monophosphate levels in heart right ventricle after naloxone induced withdrawal.

    PubMed

    Milanés, M V; Fuente, T; Laorden, M L

    2000-01-01

    This study evaluated the adaptive changes in noradrenergic neurons and the concomitant production of cAMP during morphine dependence and withdrawal in the right ventricle of the rat. Rats were made dependent on morphine by morphine pellet implantation for 7 days. On the day of sacrifice animals received an acute injection of saline or naloxone (1 mg/kg s.c.) and were decapitated 30 min later. Pretreatment with propranolol 15 min prior to naloxone was conducted to evaluate the possible implication of beta-adrenoceptors. The contents of noradrenaline and dopamine and their metabolites were examined. After naloxone administration to morphine-dependent rats (withdrawal) there was a pronounced increase in the content of normetanephrine and 3,4-dihydroxyphenylacetic acid and increased noradrenaline and dopamine turnover. In addition cAMP levels were increased after naloxone administration to morphine-treated rats. Propranolol did not block the hyperactivity of catecholaminergic neurons or the enhancement of cAMP observed in the heart during withdrawal. The present results indicate that heart catecholaminergic neurons play a significant role in the alterations in heart functions during morphine abstinence syndrome and suggest that those alterations are mediated through cAMP. PMID:10651148

  7. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects

    PubMed Central

    2014-01-01

    Background This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. Methods This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1–0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch® SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10–20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. Results Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5–1.7) min with sugammadex vs 9.1 (8.0–10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3–1.5) min and 6.7 (5.5–8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB. Conclusion Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT00825812. PMID:25187755

  8. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  9. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  10. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  11. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  12. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  13. Green tea polyphenol (-)-epigallocatechin-3-gallate protects rat PC12 cells from apoptosis induced by serum withdrawal independent of P13-Akt pathway.

    PubMed

    Mandel, Silvia; Reznichenko, Lydia; Amit, Tamar; Youdim, Moussa B H

    2003-01-01

    Our recent studies have demonstrated that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) exerts neuroprotective/neurorescue effects against B-amyloid toxicity and protects neuronal cells from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion (MPP+) and 6-hydroxydopamine in vitro, or from N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced nigral dopaminergic neuronal loss in mice. In the present study, we report that EGCG (0.1 and 1 microM) significantly protects rat pheochromocytoma PC12 cells from apoptosis induced by serum support withdrawal, suggesting that EGCG may play a role in the growth of PC12 cells, where it stimulates survival-promoting pathways. PMID:14715445

  14. Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

    PubMed Central

    Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

    2015-01-01

    Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

  15. Leflunomide-induced lung injury that developed after its withdrawal, coinciding with peripheral blood lymphocyte count decrease.

    PubMed

    Otsuka, Takeshi; Koyama, Takako; Ohtani, Ryoko; Niiro, Hiroaki; Yoshizawa, Seiji; Harada, Mine; Inokuma, Shigeko

    2008-01-01

    A 60-year-old rheumatoid arthritis (RA) female with lung fibrosis was treated with leflunomide (LEF) for only 12 days, and responded well. Twenty-five days after the withdrawal of the drug, she had fever, dyspnea, and an elevated serum C-reactive protein level. Chest CT revealed ground-glass opacities (GGOs) and consolidations forming a mosaic pattern, in lung fields including the upper, anterior and central areas, and honeycomb patterns in the lung bases and backs. The level of plasma A771726, an active metabolite of LEF, was still as high as that usually noted under LEF therapy. After pulsed steroid and cholestyramine administration, A771726 was depleted and she recovered. The peripheral blood lymphocyte count that had been approximately 1,000/microL, decreased to 220/microL just at the onset of lung injury, and rapidly and steadily returned to the preinjury level preceding recovery from the injury. Serum albumin level decreased in association with lung injury, and gradually returned to the preinjury level. Special caution is necessary when prescribing leflunomide to elderly patients with preexisting interstitial lung disease, and remains necessary until at least 1 month after its withdrawal. PMID:18161003

  16. Enhanced striatial /sup 3/H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase

    SciTech Connect

    Bhargava, H.N.

    1984-02-27

    Chronic intragastric administration of haloperidol (1.5 mg/kg/day) for 21 days followed by a 3-day withdrawal period resulted in the development of enhanced locomotor activity response to apomorphine, and an increase in the number of binding sites for /sup 3/H-spiroperidol in the striatal membranes of the rat brain. Subcutaneous administration of Pro-Leu-Gly-NH/sub 2/ or cyclo-(Leu-Gly) in doses of 2 mg/kg/day given for 3-days after termination of haloperidol treatment inhibited the enhanced response to apomorphine, as well as the increases in the number of /sup 3/H-spiroperidol binding sites in the striatum. If indeed, the supersensitivity of striatal dopamine receptors is one of the mechanisms in the development of tardive dyskinesia symptoms, the present results suggest that the above peptides may be helpful in ameliorating some of the symptoms of tardive dyskinesia induced by neuroleptic drugs. 31 references, 3 figures.

  17. Abruption-Induced Preterm Delivery Is Associated with Thrombin-Mediated Functional Progesterone Withdrawal in Decidual Cells

    PubMed Central

    Lockwood, Charles J.; Kayisli, Umit A.; Stocco, Carlos; Murk, William; Vatandaslar, Emre; Buchwalder, Lynn F.; Schatz, Frederick

    2013-01-01

    Plasma progesterone levels remain elevated throughout human pregnancy, suggesting that reduced reproductive-tract progesterone receptor (PR) initiates labor. Placental abruption and excess thrombin generation elicit preterm delivery (PTD). PR, glucocorticoid receptor (GR), and total and p-ERK1/2 in decidual cells (DCs) and interstitial trophoblasts (IT) were assessed via immunohistochemical staining in abruption-associated PTD versus gestational-age matched control placentas, and in cultured DCs incubated with estradiol (E2) ± medroxyprogesterone acetate (MPA) ± thrombin. Immunostaining for PR was lower in DC nuclei in abruption versus control decidua and was absent from ITs; GR was higher in IT than DCs, with no abruption-related changes in either cell type; p-ERK1/2 was higher in DCs in abruption than control decidua, with total ERK 1/2 unchanged. Immunoblotting of cultured DCs demonstrated strong E2, weak MPA, and intermediate E2+MPA mediated elevation of PR-A and PR-B levels, with constitutive GR expression. In cultured DCs, thrombin inhibited PR but not GR mRNA levels, reduced PR binding to DNA and [3H]progesterone binding to PR, and enhanced phosphorylated but not total ERK1/2 levels. Coincubation with a specific p-ERK1/2 inhibitor reversed thrombin-enhanced p-ERK1/2 and lowered PR levels. Thus, abruption-associated PTD is initiated by functional progesterone withdrawal, as indicated by significantly reduced DC nuclear expression of PR-A and PR-B. Functional withdrawal of progesterone results in increased p-ERK1/2, and is thus one pathway initiating abruption-associated PTD. PMID:23058370

  18. Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a β-lactam antibiotic during cocaine withdrawal.

    PubMed

    Kovalevich, Jane; Corley, Gladys; Yen, William; Rawls, Scott M; Langford, Dianne

    2012-12-01

    We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss. PMID:23031254

  19. Cocaine-Induced Loss of White Matter Proteins in the Adult Mouse Nucleus Accumbens Is Attenuated by Administration of a β-Lactam Antibiotic during Cocaine Withdrawal

    PubMed Central

    Kovalevich, Jane; Corley, Gladys; Yen, William; Rawls, Scott M.; Langford, Dianne

    2013-01-01

    We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss. PMID:23031254

  20. [A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

    PubMed

    Naruse, Satoshi; Iwata, Hiroki; Suzuki, Kota; Uraoka, Masahiro; Katoh, Takasumi; Sato, Shigehito

    2016-06-01

    We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug. PMID:27483667

  1. The relationship between the target effective site concentration of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients

    PubMed Central

    Fan, Xiaochong; Ma, Minyu; Li, Zhisong; Gong, Shengkai; Zhang, Wei; Wen, Yuanyuan

    2015-01-01

    Objective: To study the relationship between the target effective site concentration (Ce) of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients. Methods: 50 elderly patients (ASA grade II) scheduled for selective surgical procedure under general anaesthesia were randomly divided into two groups, A and B, with 25 cases in each group. The Ce of rocuronium for intubation was 3 μg·ml-1 in both groups, and the Ce during operation were 0.8 and 1.0 μg·ml-1 in group A and B, respectively. When target controlled infusion of rocuronium was stopped, without the administration of reversal agents for neuromuscular blockade, the relationship between Ce and the first twitch height (T1) was studied by regression analysis. Results: There was a significant linear relationship between Ce and T1, and there was no statistical difference in regression coefficient and interception between group A and B (P>0.05). Conclusion: The degree of recovery from neuromuscular blockade could be judged by the target effective site concentration of rocuronium at the time of reversal from neuromuscular blockade in the elderly patients. PMID:26629159

  2. Effect of low dose rocuronium in preventing ventilation leak for flexible laryngeal mask airway during radical mastectomy

    PubMed Central

    Gong, Ya-Hong; Yi, Jie; Zhang, Qian; Xu, Li

    2015-01-01

    The flexible laryngeal mask airway (FLMA) is becoming more and more popular in general anesthesia during surgery of head, neck and upper chest. But very limited information has been published about whether muscle relaxant was necessary or not for anesthesia with FLMA. To investigate whether low-dose muscle relaxant is necessary in preventing ventilation leak of FLMA in radical mastectomy, forty-eight female patients undergoing radical mastectomy were enrolled in the study. They were randomly divided into low-dose muscle relaxant (LD-MR) group and non-muscle relaxant (non-MR) group. All the included patients received total intravenous anesthesia (with propofol, fentanyl and remifentanil) and controlled mechanical ventilation with FLMA during the surgery. Patients in LD-MR group received 0.4 mg/kg rocuronium during anesthesia induction, while patients in non-MR group received equivalent volumes of physiological saline. Insertion time was shorter in LD-MR group than that in non-MR group (P < 0.05). Peak airway pressures and ventilation leak volumes at 10, 20 and 30 minutes were lower in LD-MR group than those in non-MR group (P < 0.05). No difference was found between LD-MR and non-MR group in terms of emergence time, FLMA extraction time, and maximum tidal volumes before FLMA extraction. The results show that low-dose rocuronium could reduce the ventilation leak for mechanical ventilation with FLMA during radical mastectomy without prolonging the emergence time. PMID:26550303

  3. Withdrawal strategies for outpatients

    PubMed Central

    Mezciems, Edgar

    1996-01-01

    This article discusses outpatient withdrawal strategies for patients addicted to alcohol, benzodiazepines, barbiturates, and opiates and describes some practical ways to support recovery. PMID:8828877

  4. Ethanol-induced impairments in receptor-mediated endocytosis of asialoorosomucoid in isolated rat hepatocytes: Time course of impairments and recovery after ethanol withdrawal

    SciTech Connect

    Casey, C.A.; Kragskow, S.L.; Sorrell, M.F.; Tuma, D.J.

    1989-04-01

    Chronic ethanol administration markedly impairs the process of receptor-mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver. In this study, we further characterized these impairments by identifying the time of onset for ethanol-induced changes in RME as well as establishing the time course for recovery to normal endocytotic values after ethanol withdrawal. Ethanol administration for 3 days did not alter any aspect of endocytosis examined in this study. After feeding ethanol to rats for 7 days, however, significant decreases in amounts of ligand bound, internalized, and degraded were apparent. These impairments persisted throughout the 5-week feeding study although the effects were somewhat attenuated with more prolonged ethanol feeding. In addition, an accumulation of intracellular receptors was observed in ethanol-fed animals relative to controls after 7 days of ethanol feeding. In all cases, recovery of endocytotic values to control levels was partially completed after 2 to 3 days of refeeding control diet and was fully completed after 7 days of refeeding. These results indicate that ethanol feeding for as little as 7 days profoundly impairs the process of RME by the liver. These impairments can be reversed after refeeding control diet for 7 days.

  5. The effect of rocuronium and sugammadex on neuromuscular blockade in a child with congenital myotonic dystrophy type 1.

    PubMed

    Pickard, Amelia; Lobo, Clinton; Stoddart, Peter A

    2013-09-01

    Myotonic dystrophy type 1 (MD1) is the commonest muscular dystrophy found in adults; however, it may present in the neonatal period with hypotonia, talipes, poor feeding, and respiratory failure. Inheritance is autosomal dominant with a defect in the DMPK gene found on the long arm of chromosome 19 with variable expansion of the cytosine-thymine-guanine (CTG) triplet repeat. A 14-month-old boy with congenital MD type 1 was scheduled for percutaneous endoscopic gastrostomy (PEG) insertion, orchidopexy, and division of tongue-tie. Following induction of anesthesia, acceleromyography was used to monitor neuromuscular function. This revealed a very rapid onset of profound neuromuscular block which lasted significantly longer than would be expected in a child without MD1. Sugammadex reversed the block rapidly. The anesthetic management of children with MD1 has been well described but not the acceleromyographic monitored use of rocuronium and its subsequent reversal with the new cyclodextrin sugammadex. PMID:23763618

  6. Anxiogenic effects of cocaine withdrawal in zebrafish.

    PubMed

    López-Patiño, Marcos A; Yu, Lili; Cabral, Howard; Zhdanova, Irina V

    2008-01-28

    Continued usage of cocaine is determined by genetic, conditioned and homeostatic factors, while it is reinforced by drug-induced reward and the emotionally negative state of drug withdrawal, which includes anxiety. The molecular mechanisms of these long-term behavioral and physiological alterations have yet to be fully elucidated. Here we demonstrate that in zebrafish, a wide range of non-anesthetic cocaine doses, 0.015-15 muM, does not result in acute alterations in locomotor activity, in spite of the high brain cocaine levels induced (7-120 pg/microg protein). Conversely, cocaine withdrawal causes hyperactivity associated with stereotypy. The behavioral hyperactivity is progressively increased during the initial period of withdrawal (24-72 h) and is maintained for at least 5 days. Such effect of cocaine withdrawal is aggravated by environmental stimulation and attenuated in the home environment. Administration of cocaine (1.5 microM) or a non-sedative dose of diazepam (5 microM, immersion) acutely counteracts withdrawal-associated hyperactivity and stereotypy in zebrafish, with the magnitude of these effects positively correlating with the degree of prior increase in basal activity. Administration of an anxiogenic benzodiazepine inverse agonist, FG-7142, results in zebrafish behavior similar to that observed during cocaine withdrawal. Together, the results suggest that cocaine withdrawal produces long-lasting behavioral effects in zebrafish which are consistent with an anxiety-like state. Thus, zebrafish, a powerful model for the study of vertebrate genetics, could provide insights into the molecular mechanisms of drug withdrawal. PMID:17889042

  7. Freshwater withdrawals in Texas, 1985

    USGS Publications Warehouse

    Lurry, Dee L.; Barber, Nancy L.

    1990-01-01

    Freshwater withdrawal data was compiled for the 254 counties in Texas for 1985. Major categories of withdrawal are presented by county on maps of the State. Withdrawals are also shown by source, aquifer, and major river basin. Total freshwater withdrawals in Texas during 1985 were about 20, 100 million gal/day. Surface-water withdrawals were about 12,900 million gal/day or 64% of the total, and groundwater withdrawals were about 7,190 million gal/day or 36% of the total. More water was withdrawn for irrigation than for any other purpose, accounting for 40% of total freshwater withdrawals and for 75% of groundwater withdrawals. (USGS)

  8. [Clozapine withdrawal. A review].

    PubMed

    Szafrański, T; Gmurkowski, K

    1999-01-01

    The article describes the symptoms of withdrawal of clozapine and their possible causes as well as research on switching from clozapine to another antipsychotic drug. A computerised search was conducted using MEDLINE (1966-1997) to retrieve reports of clozapine withdrawal. Fifteen case reports and sixteen withdrawal studies (only one of them double-blind and two single-blind) were identified. Clozapine multi-receptors profile seems to be responsible for withdrawal symptoms--several specific mechanisms are suggested: cholinergic supersensitivity, dopaminergic supersensivity, special role of D4 receptors, possibilities of serotonergic, noradrenergic and GABA-ergic involvement. Risk of relapse after withdrawal of clozapine seems to be greater than after withdrawal of classical neuroleptics. Some patients might become de novo neuroleptic resistant for at least several weeks after withdrawal. Therefore, clozapine should be stopped only due to strong clinical indications, and if only possible, the withdrawal should be slow (50 mg/week). To prevent relapse of psychosis some experts advocate starting new antipsychotic drugs in therapeutic dosage before withdrawal of clozapine is completed. In case of emergency, when clozapine (high dosage) must be withdrawn immediately, patient must be hospitalised and cholinergics might be considered to prevent, cholinergic rebound". There are no established guidelines which antipsychotic to choose after withdrawal of clozapine. In general, classical antipsychotics are ineffective. Thioridazine is suggested because of its prominent anticholinergic activity, but there is no clinical evidence of advantage of this treatment in comparison to classical drugs. Risperidon and especially olanzapine are promising possibilities, but initial data are disappointing. Benzamides might be another possibility but clinical data are scarce. These important issues require further studies. PMID:10786215

  9. Lung function and sputum characteristics of patients with severe asthma during an induced exacerbation by double-blind steroid withdrawal.

    PubMed

    in't Veen, J C; Smits, H H; Hiemstra, P S; Zwinderman, A E; Sterk, P J; Bel, E H

    1999-07-01

    Some patients with severe asthma are difficult to control and suffer from frequent exacerbations, whereas others remain stable with anti-inflammatory therapy. To investigate mechanisms of exacerbations, we compared 13 patients 20 to 51 yr of age (11 female, two male) with difficult-to-control asthma (two or more exacerbations during the previous year) and 15 patients 20 to 47 yr of age (13 female, two male) with severe but stable asthma (no exacerbations) after matching for sex, age, atopy, lung function, airway responsiveness, and medication. Exacerbations were induced by double-blind, controlled tapering of inhaled corticosteroids (fluticasone propionate) at weekly intervals. FEV1, airway responsiveness for methacholine (PC20MCh) and hypertonic saline (HYP slope), eosinophils and soluble markers (ECP, albumin, IL-6, IL-8) in induced sputum were assessed at baseline and during exacerbation (peak flow < 60% of personal best), or after 5 wk if no exacerbation occurred. Steroid tapering caused a decrease (mean +/- SEM) in FEV1 (12.1 +/- 3.1% pred; p = 0.045), PC20MCh (2.1 +/- 0.4 doubling dose; p = 0.004) and HYP slope (1.7 +/- 0.3 doubling dose; p = 0.001), and an increase in sputum eosinophils (10 +/- 3%; p = 0.008) and soluble markers for the two groups combined, without significant differences between the groups. Patients with difficult-to-control asthma had more exacerbations than did the stable asthmatics during both steroid tapering (7 versus 2; p = 0.022) and corticosteroid treatment (6 versus 0; p = 0.003). Exacerbations during steroid treatment in the patients with difficult-to-control asthma were associated with a decrease in FEV1 and PC20MCh, but not in HYP slope or increase in sputum eosinophils. We conclude that tapering of inhaled corticosteroids induces a rapid, reversible flare-up of eosinophilic airway inflammation. Patients with difficult-to-control asthma may develop exacerbations despite treatment with inhaled corticosteroids, which appear to

  10. Alcohol-induced persistent mild cognitive impairment with successful withdrawal from alcohol dependence--a case report.

    PubMed

    Harada, Toshihide; Ishizaki, Fumiko; Horie, Nobuko; Katsuoka, Hiroyuki; Nitta, Yumiko; Yamada, Tohru; Nitta, Kohsaku; Ito, Makoto

    2011-03-01

    An 81-year-old man diagnosed with alcohol-induced persistent mild cognitive impairment consulted our clinic presenting with gait disturbance. Between the ages of 20 and 53 years, his alcohol consumption was 1.8 liters of alcoholic sake per day. However, from the age of 53 years onward, his consumption decreased to 360 ml per day. The patient had alcoholic neuropathy, mild cognitive impairment, and alcoholic cerebellar disorder. His score on the revised version of Hasegawa's Dementia Scale (HDS-R) was 22 and his clinical dementia rating (CDR) was 0.5. His score on the Japanese version of the Mini-Mental State Examination (MMSE) was 22. These scores indicated mild cognitive impairment (MCI). He had delusions and confabulations, without impairment of date and place orientation. Magnetic resonance imaging (MRI) demonstrated enlarged ventricles, sulcal widening, and brain atrophy. He was provided with medication and counseling to treat his alcohol abuse. He accepted our treatment and is presently doing well after 1 year 2 months of treatment. PMID:21675042

  11. Neurotoxic Consequences of Chronic Alcohol Withdrawal: Expression Profiling Reveals Importance of Gender Over Withdrawal Severity

    PubMed Central

    Hashimoto, Joel G; Wiren, Kristine M

    2011-01-01

    While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways were more altered by alcohol. Examination of ethanol-regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse. PMID:17593928

  12. Withdrawing Nutrition, Hydration

    Cancer.gov

    Module eleven of the EPEC-O Self-Study Original Version discusses the general aspects of withholding or withdrawing of life-sustaining therapies, and presents a specific application to artificial nutrition and hydration.

  13. Inflated reward value in early opiate withdrawal.

    PubMed

    Wassum, Kate M; Greenfield, Venuz Y; Linker, Kay E; Maidment, Nigel T; Ostlund, Sean B

    2016-03-01

    Through incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again. Opiate withdrawal has been proposed as a need state in which, through experience, opiate value can be increased, resulting in escalated opiate self-administration. Endogenous opioid transmission plays anatomically dissociable roles in the positive emotional experience of reward consumption and incentive learning. We, therefore, sought to determine if chronic opiate exposure and withdrawal produces a disruption in the fundamental incentive learning process such that reward seeking, even for non-opiate rewards, can become maladaptive, inconsistent with the emotional experience of reward consumption and irrespective of need. Rats trained to earn sucrose or water on a reward-seeking chain were treated with morphine (10-30 mg/kg, s.c.) daily for 11 days prior to testing in withdrawal. Opiate-withdrawn rats showed elevated reward-seeking actions, but only after they experienced the reward in withdrawal, an effect that was strongest in early (1-3 days), as opposed to late (14-16 days), withdrawal. This was sufficient to overcome a negative reward value change induced by sucrose experience in satiety and, in certain circumstances, was inconsistent with the emotional experience of reward consumption. Lastly, we found that early opiate withdrawal-induced inflation of reward value was blocked by inactivation of basolateral amygdala mu opioid receptors. These data suggest that in early opiate withdrawal, the incentive learning process is disrupted, resulting in maladaptive reward seeking. PMID:25081350

  14. Effect of cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement, and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats.

    PubMed

    Grimm, J W; Shaham, Y; Hope, B T

    2002-09-01

    Lever pressing during tests for resistance to extinction and cue-induced reinstatement of cocaine seeking in rats progressively increases over the first 2 months of withdrawal. In the present report, we investigated the generality of these findings in rats trained to self-administer sucrose, a non-drug reinforcer. We also examined whether the time-dependent changes in cocaine seeking correlate with the levels of the dopamine transporter (DAT) and tyrosine hydroxylase (TH) proteins in the amygdala, nucleus accumbens, prefrontal cortex and orbitofrontal cortex. Rats were trained to self-administer cocaine (0.5 mg/kg/i.v. infusion) or 10% sucrose (0.2 ml/infusion into a liquid drop receptacle) for 10 days (6 h/day); each reward delivery was paired with a tone+light cue. Tests for cocaine seeking were conducted following 1 or 15 reward-free days. On the test day, rats were initially tested for resistance to extinction during 6-7 60-min extinction sessions in the absence of the tone-light cue, until they reached the extinction criterion of less than 15 responses/60 min. Subsequently, rats were tested for cue-induced reinstatement during a 60-min session in which each lever press led to a contingent presentation of the tone-light cue. Lever pressing during the tests for reward seeking was significantly greater on day 15 than on day 1 following withdrawal from both cocaine and sucrose self-administration training. The levels of DAT, but not TH, were greater in the prefrontal cortex of cocaine-trained rats than in sucrose-trained rats on both days 1 and 15 of withdrawal. The levels of DAT and TH in other brain areas were not altered following withdrawal from cocaine or sucrose self-administration. These data suggest that the withdrawal can modulate reward seeking of both drug and non-drug reinforcers, and that alterations in DAT and TH levels in the brain regions examined do not mediate this effect. PMID:12394414

  15. Cyclosporine alters opiate withdrawal in rodents.

    PubMed

    Dafny, N; Wagle, V G; Drath, D B

    1985-05-01

    Opiates exert numerous effects on all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristics of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal. Therefore, success in modifying the withdrawal syndrome may shed light on the dynamics of opiate addiction. The present study demonstrates that cyclosporine, a widely used immunosuppressive drug, considerably modified the behavioral signs of a naloxone-induced abstinence syndrome in morphine-addicted rats. In previous experiments, alpha-interferon has shown similar results. The similarity in actions of these two immunomodulator drugs is discussed and we suggest that opiate addiction may involve the immune system. PMID:4039025

  16. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? PMID:25559647

  17. The alcohol withdrawal syndrome.

    PubMed

    McKeon, A; Frye, M A; Delanty, Norman

    2008-08-01

    The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients. PMID:17986499

  18. Alcohol Abuse: Alcohol Withdrawal Syndrome

    MedlinePlus

    ... they quit drinking. What are the symptoms of alcohol withdrawal syndrome? Symptoms can be mild or severe, and may include: Shakiness Sweats Anxiety Irritability Fatigue Depression Headaches Insomnia Nightmares Decreased appetite More severe withdrawal symptoms ...

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

    PubMed

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

    2015-06-01

    Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence. PMID:25129124

  20. Intubating conditions and side effects of propofol, remifentanil and sevoflurane compared with propofol, remifentanil and rocuronium: a randomised, prospective, clinical trial

    PubMed Central

    2014-01-01

    Background Tracheal intubation without muscle relaxants is usually performed with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 μg·kg-1 and propofol 2.0-3.0 mg·kg-1 or sevoflurane up to 8.0 Vol% provide acceptable, i.e. excellent or good intubating conditions. We hypothesized that sevoflurane 1.0 MAC would provide acceptable intubating conditions when combined with propofol and remifentanil. Methods Eighty-three patients to be intubated were randomised to two groups. The SEVO group received propofol 1.5 mg kg-1, remifentanil 0.30 μg kg min-1 and sevoflurane 1.0 MAC; the MR group received the same doses of propofol and remifentanil plus rocuronium 0.45 mg kg-1. We evaluated intubation and extubation conditions, mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). The vocal cords were examined for injury by videolaryngoscopy before and 24 hours after surgery. Results Acceptable intubating conditions were seen more frequently with rocuronium than with sevoflurane: 97% versus 82%; p = 0.03; the subscore for vocal cords was comparable: 100% versus 98%. MAP before intubation decreased significantly compared with the MAP at baseline to the same extent in both groups; ephedrine IV was given in 15 (SEVO) versus 16 (MR) patients; p = 0.93. BIS at tracheal intubation was 27 (13-65) in the SEVO group, 29 (14-62) in the MR group; p = 0.07. Vocal cord injuries (oedema, haematoma) were similar: 4 patients in each group. Conclusions Overall intubating conditions were better when rocuronium was used; the subscore for vocal cords was comparable. The incidence of side effects was the same in the two groups. Trial registration ClinicalTrials.Gov: NCT 01591031. PMID:24860256

  1. Adenosine kinase inhibitors attenuate opiate withdrawal via adenosine receptor activation.

    PubMed

    Kaplan, G B; Coyle, T S

    1998-11-27

    Previous studies have demonstrated a role for adenosine in mediating opiate effects. This study examines the effects of indirect activation of adenosine receptors, via treatment with adenosine kinase inhibitors, on the expression of opiate withdrawal in mice. Mice receive chronic morphine treatment via implantation of subcutaneous morphine pellets (75 mg) for 72 h. Mice then receive parenteral treatment with adenosine kinase inhibitors, either 5'-amino-5'-deoxyadenosine (2, 5, 20, 40 mg/kg, intraperitoneal or i.p.) or iodotubericidin (1, 2, 5 mg/kg, i.p.), followed by naloxone injection and opiate withdrawal signs are measured over 20 min. Both adenosine kinase inhibitors significantly reduce the following opiate withdrawal signs in a dose-dependent manner compared to vehicle: withdrawal jumps, teeth chattering, forepaw tremors, and forepaw treads. Additionally, 5'-amino-5'-deoxyadenosine significantly reduces withdrawal-induced diarrhea and weight loss. Effects of 5'-amino-5'-deoxyadenosine (40 mg/kg) on opiate withdrawal signs appear to be mediated via adenosine receptor activation as they are reversed by pretreatment by adenosine receptor antagonist caffeine (20 mg, i.p.) but not by selective phosphodiesterase inhibitor Ro 20-1724 (10 mg/kg, i.p.). Adenosine receptor activation via adenosine kinase inhibitor treatment attenuates opiate withdrawal and these agents may be generally useful in the treatment of drug withdrawal syndromes. PMID:9865523

  2. Changes in monoamine concentrations in mouse brain associated with ethanol dependence and withdrawal

    PubMed Central

    Griffiths, P.J.; Littleton, J.M.; Ortiz, A.

    1974-01-01

    1 Chronic administration of ethanol to mice by inhalation induced tolerance to ethanol and produced an increase in the concentration of brain monoamines. 2 Withdrawal of ethanol from dependent mice caused behavioural changes associated with a further transient rise in brain monoamine concentrations which then declined to control levels. 3 Inhibition of the withdrawal syndrome by the administration of ethanol postponed the changes in monoamines associated with withdrawal. 4 Administration of inhibitors of catecholamine synthesis before withdrawal of ethanol modified the withdrawal syndrome. PMID:4475606

  3. Insomnia related to biperiden withdrawal in two schizophrenic patients.

    PubMed

    Hirose, S

    2000-11-01

    It is not uncommon for patients who are receiving antipsychotic medication to be given anticholinergic agents, such as biperiden, despite the relative absence of neurological side-effects. Two cases of schizophrenia are reported in which insomnia developed after biperiden withdrawal or reduction. The insomnia continued until biperiden treatment was reinstated, despite the fact that the patients did not exhibit signs or report symptoms indicative of antipsychotic drug-induced neurological side-effects. The occurrence of insomnia following the withdrawal of biperiden or reduction in the dose has not been previously reported. One potential explanation for the insomnia is cholinergic rebound following the withdrawal of biperiden. PMID:11110012

  4. Social Withdrawal in Childhood

    PubMed Central

    Rubin, Kenneth H.; Coplan, Robert J.; Bowker, Julie C.

    2013-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  5. Social withdrawal in childhood.

    PubMed

    Rubin, Kenneth H; Coplan, Robert J; Bowker, Julie C

    2009-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  6. Transitions in viscous withdrawal

    NASA Astrophysics Data System (ADS)

    Zhang, Wendy W.

    2008-11-01

    A process analogous to flow-focusing occurs in extended and stably stratified layers of immiscible, viscous liquids. In viscous withdrawal, an axisymmetric converging flow is imposed in the upper layer. When the upper layer flow is weak, the interface forms a hump. No liquid from the lower layer is entrained. When the upper layer flow is strong, liquid from the lower layer is entrained and the interface becomes a spout. Here I summarize recent results on the fundamental mechanisms controlling these regimes. For selective withdrawal, a clear picture has emerged, with good agreement between theory, simulation and experiment. The regime ends when the viscous stress exerted by the upper layer flow overcomes surface tension, creating a saddle-node bifurcation in the hump solution. Less is understood about viscous entrainment. A long-wavelength model including only local information is degenerate, possessing many solutions for the same withdrawal condition. Including information about the global geometry removes this degeneracy but also makes the surprising prediction that global geometry can change the nature of the transition. First-order, weakly first-order or continuous transitions are all possible. How these results relate to the variety of experimental phenomena, such as stable, micron-sized spouts, intricate patterns of hysteresis and multiple stable spout states under the same condition, is at present unclear. (Includes material from joint works with Blanchette, Cohen, Kleine Berkenbusch, and Schmidt.)

  7. Opiate withdrawal behavior after focal brain stimulation.

    PubMed

    Williams, D A; Thorn, B E

    1984-11-01

    Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal. PMID:6542676

  8. Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture

    PubMed Central

    Wu, Jin; Jin, Tian; Wang, Hong; Li, Shi-Tong

    2016-01-01

    Background: The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP). Methods: A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction. Results: Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChET mRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET). Conclusions: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the

  9. Stereochemistry and neuropharmacology of a ‘bath salt’ cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates

    PubMed Central

    Vouga, Alexandre; Gregg, Ryan A.; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K.; Tallarida, Christopher S.; Grizzanti, David; Raffa, Robert B.; Smith, Garry R.; Reitz, Allen B.; Rawls, Scott M.

    2015-01-01

    Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100–1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10–100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10–250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own. PMID:25496724

  10. In Vivo Evidence for Alcohol-Induced Neurochemical Changes in Rat Brain Without Protracted Withdrawal, Pronounced Thiamine Deficiency, or Severe Liver Damage

    PubMed Central

    Zahr, Natalie M; Mayer, Dirk; Vinco, Shara; Orduna, Juan; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2009-01-01

    Magnetic resonance spectroscopy (MRS) studies in human alcoholics report decreases in N-acetylaspartate (NAA) and choline-containing (Cho) compounds. Whether alterations in brain metabolite levels are attributable to alcohol per se or to physiological effects of protracted withdrawal or impaired nutritional or liver status remains unclear. Longitudinal effects of alcohol on brain metabolites measured in basal ganglia with single-voxel MRS were investigated in sibling pairs of wild-type Wistar rats, with one rat per pair exposed to escalating doses of vaporized alcohol, the other to vapor chamber air. MRS was conducted before alcohol exposure and twice during exposure. After 16 weeks of alcohol exposure, rats achieved average blood alcohol levels (BALs) of ~ 293 mg per 100 ml and had higher Cho and a trend for higher glutamine + glutamate (Glx) than controls. After 24 weeks of alcohol exposure, BALs rose to ~ 445 mg per 100 ml, and alcohol-exposed rats had higher Cho, Glx, and glutamate than controls. Thiamine and thiamine monophosphate levels were significantly lower in the alcohol than the control group but did not reach levels low enough to be considered clinically relevant. Histologically, livers of alcohol-exposed rats exhibited greater steatosis and lower glycogenosis than controls, but were not cirrhotic. This study demonstrates a specific pattern of neurobiochemical changes suggesting excessive membrane turnover or inflammation, indicated by high Cho, and alterations to glutamate homeostasis in the rat brain in response to extended vaporized alcohol exposure. Thus, we provide novel in vivo evidence for alcohol exposure as causing changes in brain chemistry in the absence of protracted withdrawal, pronounced thiamine deficiency, or severe liver damage. PMID:18704091

  11. Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.

    PubMed

    Vouga, Alexandre; Gregg, Ryan A; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K; Tallarida, Christopher S; Grizzanti, David; Raffa, Robert B; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

    2015-04-01

    Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own. PMID:25496724

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

    PubMed

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

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. PMID:25961814

  13. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist

    PubMed Central

    Tai, Sherrica; Nikas, Spyros P.; Shukla, Vidyanand G.; Vemuri, Kiran; Makriyannis, Alexandros; Järbe, Torbjörn U.C.

    2015-01-01

    Rationale Previous reports shows rimonabant's inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation neutral antagonists were developed, to address mechanisms by which an inverse agonist and neutral antagonist elicit withdrawal. Objective Introduces an animal model to study cannabinoid dependence by incorporating traditional methodologies and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral endpoints. Methods The cannabinergic AM2389 was acutely characterized in the tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test and temperature); with some comparisons made to Δ9-tetrahydrocannabinol (THC). Tolerance was measured in mice repeatedly administered AM2389. Antagonist-precipitated withdrawal was characterized in cannabinoid-adapted mice induced by either centrally acting antagonists, rimonabant and AM4113, or an antagonist with limited brain penetration, AM6545. Results In the tetrad, AM2389 was more potent and longer acting than THC, suggesting a novel approach for inducing dependence. Repeated administration of AM2389 led to tolerance by attenuating hypothermia that was induced by acute AM2389 administration. Antagonist-precipitated withdrawal signs were induced by rimonabant or AM4113, but not by AM6545. Antagonist-precipitated withdrawal was reversed by reinstating AM2389 or THC. Conclusions These findings suggest cannabinoid-precipitated withdrawal may not be ascribed to the inverse properties of rimonabant, but rather to rapid competition with the agonist at the CB1R. This withdrawal syndrome is likely centrally-mediated, since only the centrally acting CB1R antagonists elicited withdrawal, i.e., such responses were absent after the purported peripherally selective CB1R antagonist AM6545. PMID:25772338

  14. Assessment of groundwater/surface-water interaction and simulation of potential streamflow depletion induced by groundwater withdrawal, Uinta River near Roosevelt, Utah

    USGS Publications Warehouse

    Lambert, P.M.; Marston, T.; Kimball, B.A.; Stolp, B.J.

    2011-01-01

    Roosevelt City, Utah, asserts a need for an additional supply of water to meet municipal demands and has identified a potential location for additional groundwater development at the Sprouse well field near the West Channel of the Uinta River. Groundwater is commonly hydraulically linked to surface water and, under some conditions, the pumpage of groundwater can deplete water in streams and other water bodies. In 2008, the U.S. Geological Survey, in cooperation with Roosevelt City, the Utah Department of Natural Resources, and the Ute Indian Tribe, began a study to improve understanding of the local interconnection between groundwater and surface water and to assess the potential for streamflow depletion from future groundwater withdrawals at a potential Roosevelt City development location-the Sprouse well field near the West Channel of the Uinta River. In the study, streamflow gains and losses at the river/aquifer boundary near the well field and changes in those conditions over time were assessed through (1) synoptic measurement of discharge in the stream at multiple sites using tracer-dilution methods, (2) periodic measurement of the vertical hydraulic gradient across the streambed, and (3) continuous measurement of stream and streambed water temperature using heat as a tracer of flow across the streambed. Although some contradictions among the results of the three assessment methods were observed, results of the approaches generally indicated (1) losing streamflow conditions on the West Channel of the Uinta River north of and upstream from the Sprouse well field within the study area, (2) gaining streamflow conditions south of and downstream from the well field, and (3) some seasonal changes in those conditions that correspond with seasonal changes in stream stage and local water-table altitudes. A numerical groundwater flow model was developed on the basis of previously reported observations and observations made during this study, and was used to estimate

  15. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    PubMed

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. PMID:26786746

  16. Consequences of multiple withdrawals from alcohol.

    PubMed

    Duka, Theodora; Gentry, John; Malcolm, Robert; Ripley, Tamzin L; Borlikova, Gilyanna; Stephens, Dai N; Veatch, Lynn M; Becker, Howard C; Crews, Fulton T

    2004-02-01

    This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL, organized by Theodora Duka and chaired by Dai Stephens. The purpose of the symposium was to examine the effects of multiple experiences of withdrawal from alcohol in animals made dependent on alcohol and in humans who are alcohol dependent. Parallels were drawn to the effects of repeated short-lived high-content alcohol exposures in animals and in humans who are social drinkers but indulge in binge drinking. The presentations were (1) Multiple detoxifications and risk of relapse in abstinent alcoholics, by John Gentry and Robert Malcolm; (2) Emotional and cognitive impairments after long-term use of alcohol: relationship to multiple detoxifications and binge drinking, by Theodora Duka; (3) The effect of repeated withdrawal from ethanol on conditioning to appetitive stimuli, by Tamzin Ripley, Gilyanna Borlikova, and Dai Stephens; (4) Alcohol withdrawal kindling: electrographic measures in a murine model of behavioral seizure sensitization, by Lynn Veatch and Howard Becker; and (5) Binge drinking induced changes in CNS, by Fulton Crews. PMID:15112931

  17. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  18. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  19. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  20. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  1. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  2. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Withdrawal. 74.18 Section 74.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE OPT-INS Permitting Procedures § 74.18 Withdrawal. (a) Withdrawal through administrative amendment. An opt-in source may request to withdraw...

  3. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  4. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  5. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  6. Role of calcium in morphine dependence and naloxone-precipitated withdrawal in mice

    PubMed Central

    Seth, Vikas; Upadhyaya, Prerna; Moghe, Vijay; Ahmad, Mushtaq

    2011-01-01

    Purpose To explore the role of calcium in morphine withdrawal syndrome using various agents affecting calcium levels in cytoplasm. Methods Mice were rendered dependent on morphine by subcutaneous injection of morphine, and withdrawal was induced 4 hours later by injecting the opioid antagonist, naloxone. Mice were observed for 30 minutes for signs of withdrawal, ie, characteristic jumping, hyperactivity, urination, and diarrhea. Various calcium channel blockers were injected intraperitoneally 30 minutes before naloxone to evaluate their influence on the severity of the withdrawal syndrome. We also tested the effect of combination levodopa-carbidopa pretreatment and its interaction with a selective alpha-1 blocker, terazosin, on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Results A significant dose-dependent attenuation of naloxone-induced morphine withdrawal syndrome was observed with calcium channel blockers, ie, verapamil 20 mg/kg (P < 0.05) and diltiazem 30 mg/kg (P < 0.01). Combination levodopa-carbidopa pretreatment facilitated the morphine withdrawal syndrome, and this was found to be blocked by terazosin, although not to a statistically significant (P > 0.05) extent. Conclusion The results indicate that calcium plays an important role in the genesis of morphine dependence and withdrawal, and suggest the usefulness of calcium channel blockers in the management of morphine withdrawal syndrome.

  7. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  8. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

    PubMed

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

    2015-01-01

    . The resultant PR and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding. PMID:26436918

  9. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding

    PubMed Central

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A.; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J.

    2015-01-01

    . The resultant PR and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding. PMID:26436918

  10. Restlessness related to SSRI withdrawal.

    PubMed

    Hirose, S

    2001-02-01

    There are reports that abrupt withdrawal of various selective serotonin re-uptake inhibitors, such as fluvoxamine, can elicit in patients various withdrawal symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year. However, there have been no case reports of withdrawal symptoms following abrupt fluvoxamine discontinuation in Japan. The author reports a case where the abrupt discontinuation of fluvoxamine produced restlessness in a depressed patient. The restlessness disappeared soon after the reinstatement of treatment with fluvoxamine. This case report suggests that clinicians should carefully scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms observed following abrupt discontinuation might be regarded as a relapse of depression or side-effects of the medicine. PMID:11235863

  11. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-01-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  12. Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

  13. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    PubMed

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-01

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. PMID:25744879

  14. Who withdraws? Psychological individual differences and employee withdrawal behaviors.

    PubMed

    Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G

    2016-04-01

    Psychological individual differences, such as personality, affectivity, and general mental ability, have been shown to predict numerous work-related behaviors. Although there is substantial research demonstrating relationships between psychological individual differences and withdrawal behaviors (i.e., lateness, absenteeism, and turnover), there is no integrative framework providing scholars and practitioners a guide for conceptualizing how, why, and under what circumstances we observe such relationships. In this integrative conceptual review we: (a) utilize the Cognitive-Affective Processing System framework (Mischel & Shoda, 1995) to provide an overarching theoretical basis for how psychological individual differences affect withdrawal behaviors; (b) create a theoretical model of the situated person that summarizes the existing empirical literature examining the effect of psychological differences on withdrawal behavior; and (c) identify future research opportunities based on our review and integrative framework. (PsycINFO Database Record PMID:26595754

  15. 29 CFR 4219.18 - Withdrawal in a plan year in which substantially all employers withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal in a plan year in which substantially all employers withdraw. 4219.18 Section 4219.18 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS NOTICE, COLLECTION, AND REDETERMINATION OF WITHDRAWAL LIABILITY Redetermination...

  16. A Detection Model of College Withdrawal

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Keeney, Jessica; Merritt, Stephanie M.; Schmitt, Neal; Oswald, Frederick L.

    2011-01-01

    Many students during their college careers consider withdrawing from their respective college or university. Understanding why some students decide to withdraw yet others persist has implications for both the well being of students as well as for institutes of higher education. The present study develops a model of the decision to withdraw drawing…

  17. 5 CFR 1604.7 - Withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Withdrawals. A service member may withdraw all or a portion of his or her account under the rules in 5 CFR... exception to them) are explained at 5 CFR part 1650. (c) Combat zone contributions. If a service member account contains combat zone contributions, the withdrawal will be distributed pro rata from all...

  18. Withdrawal severity after chronic intermittent ethanol in inbred mouse strains

    PubMed Central

    Metten, Pamela; Sorensen, Michelle L.; Cameron, Andy Jade; Yu, Chia-Hua; Crabbe, John C.

    2010-01-01

    Background To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and in ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Methods Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Results Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 ± 0.02 mg/ml and we restricted the range of this value to 1.00 to 2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, Low Dose (1.29 ± 0.1 mg/ml) and High Dose (1.71 ± 0.02 mg/ml). After the third inhalation exposure, ethanol- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at hr 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. Conclusion The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the High Dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hrs) ethanol withdrawal studies, supporting the influence of common

  19. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  20. OPIATE EXPOSURE AND WITHDRAWAL DYNAMICALLY REGULATE mRNA EXPRESSION IN THE SEROTONERGIC DORSAL RAPHE NUCLEUS

    PubMed Central

    Lunden, Jason; Kirby, Lynn G.

    2013-01-01

    Previous results from our lab suggest that hypofunctioning of the serotonergic (5-HT) dorsal raphe nucleus (DRN) is involved in stress-induced opiate reinstatement. To further investigate the effects of morphine dependence and withdrawal on the 5-HT DRN system, we measured gene expression at the level of mRNA in the DRN during a model of morphine dependence, withdrawal and post withdrawal stress exposure in rats. Morphine pellets were implanted for 72h and then either removed or animals were injected with naloxone to produce spontaneous or precipitated withdrawal, respectively. Animals exposed to these conditions exhibited withdrawal symptoms including weight loss, wet dog shakes and jumping behavior. Gene expression for brain-derived neurotrophic factor (BDNF), TrkB, corticotrophin releasing-factor (CRF)-R1, CRF-R2, GABAA-α1, μ-opioid receptor (MOR), 5-HT1A, tryptophan hydroxylase2 and the 5-HT transporter was then measured using quantitative real-time PCR at multiple time-points across the model of morphine exposure, withdrawal and post withdrawal stress. Expression levels of BDNF, TrkB and CRF-R1 mRNA were decreased during both morphine exposure and following seven days of withdrawal. CRF-R2 mRNA expression was elevated after seven days of withdrawal. 5-HT1A receptor mRNA expression was decreased following 3 hours of morphine exposure, while TPH2 mRNA expression was decreased after seven days of withdrawal with swim stress. There were no changes in the expression of GABAA-α1, MOR or 5-HT transporter mRNA. Collectively these results suggest that alterations in neurotrophin support, CRF-dependent stress signaling, 5-HT synthesis and release may underlie 5-HT DRN hypofunction that can potentially lead to stress-induced opiate relapse. PMID:24055683

  1. Estimated freshwater withdrawals in Texas, 1990

    USGS Publications Warehouse

    Lurry, Dee L.

    1994-01-01

    Freshwater withdrawals in Texas during 1990 were estimated as part of the U.S. Geological Survey's National Water Use Information Program. Estimates of freshwater withdrawals were made for five categories of use: irrigation, thermoelectric- power generation, water supply, industrial and mining, and domestic/commercial/livestock. Total freshwater withdrawals for the State were estimated to be 20,100 Mgal/d (million gallons per day). Ground water was estimated to account for 37 percent (7,390 Mgal/d), and surface water was estimated to account for 63 percent (12,700 Mgal/d) of total withdrawals. The largest withdrawals of freshwater were for irrigation purposes.

  2. Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats.

    PubMed

    Gonzaga, Natalia A; Mecawi, André S; Antunes-Rodrigues, José; De Martinis, Bruno S; Padovan, Claudia M; Tirapelli, Carlos R

    2015-02-01

    We analyzed the effects of ethanol withdrawal on the vascular and systemic renin-angiotensin system (RAS) and vascular oxidative stress. Male Wistar rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the elevated-plus maze (EPM) and increased plasma corticosterone levels. Ethanol withdrawal significantly increased systolic blood pressure and plasma angiotensin II (ANG II) levels without an effect on plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, or plasma angiotensin I (ANG I) levels. No differences in vascular ANG I, ANG II levels, and ACE activity/expression and AT1 and AT2 receptor expression were detected among the experimental groups. Plasma osmolality, as well as plasma sodium, potassium, and glucose levels were not affected by ethanol withdrawal. Ethanol withdrawal induced systemic and vascular oxidative stress, as evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels and the vascular generation of superoxide anion. Ethanol withdrawal significantly decreased plasma and vascular nitrate/nitrite levels. Major new findings of the present study are that ethanol withdrawal induces vascular oxidative stress and reduces nitric oxide (NO) levels in the vasculature. Additionally, our study provides novel evidence that ethanol withdrawal does not affect the vascular ANG II generating system while stimulating systemic RAS. These responses could predispose individuals to the development of cardiovascular diseases. PMID:25557835

  3. Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome.

    PubMed

    Kaplan, G B; Bharmal, N H; Leite-Morris, K A; Adams, W R

    1999-10-01

    The role of adenosine receptor-mediated signaling was examined in the alcohol withdrawal syndrome. CD-1 mice received a liquid diet containing ethanol (6.7%, v/v) or a control liquid diet that were abruptly discontinued after 14 days of treatment. Mice consuming ethanol showed a progressive increase in signs of intoxication throughout the drinking period. Following abrupt discontinuation of ethanol diet, mice demonstrated reversible signs of handling-induced hyperexcitability that were maximal between 5-8 h. Withdrawing mice received treatment with adenosine receptor agonists at the onset of peak withdrawal (5.5 h) and withdrawal signs were blindly rated (during withdrawal hours 6 and 7). Adenosine A1-receptor agonist R-N6(phenylisopropyl)adenosine (0.15 and 0.3 mg/ kg) reduced withdrawal signs 0.5 and 1.5 h after drug administration in a dose-dependent fashion. Adenosine A2A-selective agonist 2-p-(2-carboxyethyl)phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (0.3 mg/kg) reduced withdrawal signs at both time points. In ethanol-withdrawing mice, there were significant decreases in adenosine transporter sites in striatum without changes in cortex or cerebellum. In ethanol-withdrawing mice, there were no changes in adenosine A1 and A2A receptor concentrations in cortex, striatum, or cerebellum. There appears to be a role for adenosine A1 and A2A receptors in the treatment of the ethanol withdrawal syndrome. Published by Elsevier Science Inc. PMID:10548160

  4. Regional cerebral glucose utilization during morphine withdrawal in the rat.

    PubMed Central

    Wooten, G F; DiStefano, P; Collins, R C

    1982-01-01

    Regional cerebral glucose utilization was studied by 2-deoxy[14C]glucose autoradiography in morphine-dependent rats and during naloxone-induced morphine withdrawal. In morphine-dependent rats, glucose utilization was increased compared with naive controls uniformly (23-54%) in hippocampus, dentate gyrus, and subiculum and reduced in frontal cortex, striatum, anterior ventral thalamus, and medial habenular nucleus. On precipitation of morphine withdrawal by subcutaneous administration of naloxone at 0.5 mg/kg to morphine-dependent rats, glucose utilization was increased in the central nucleus of amygdala (51%), lateral mammillary nucleus (40%), lateral habenular nucleus (39%), medial mammillary nucleus (35%), and medial septal nucleus (35%) (all, P less than 0.01). Significant increases also occurred in several other limbic structures including interpeduncular nucleus, anterior medial and ventral thalamic nuclei, and lateral septal nucleus. Knowledge of the functional cerebral anatomy of the morphine-withdrawal syndrome should facilitate studies directed toward understanding the molecular mechanisms of opiate withdrawal. Images PMID:6954484

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

    PubMed Central

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

    2009-01-01

    Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. To investigate the role for the CRF2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF2 receptor (CRF2−/−). We employed a novel, clinically relevant mouse model of ‘spontaneous’ opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20–100 mg/kg, i.p.). We found that 8–128 h after the last opiate injection, CRF2−/− mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF2−/− mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF2−/− mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus–pituitary–adrenal axis in the CRF2 receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF2 receptor pathway in opiate withdrawal. The CRF2 receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake. PMID:18288089

  6. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    PubMed

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists. PMID:11425504

  7. [Extension of the concept of withdrawal signs].

    PubMed

    Kato, Shin

    2015-12-01

    If the conditions including normal-dose dependence in which withdrawal signs are observed in the absence of definite psychic dependence are classified as dependence, this classification should be regarded as inappropriate extension of the concept of drug dependence. These conditions should be diagnosed as 'withdrawal' as specified by the DSM-5 or ICD-10. Advancements of research have clarified that an increased number of drugs cause withdrawal signs. Some Japanese researchers use the concept of 'withdrawal signs of psychic dependence.' Their definition of drug dependence and concept of withdrawal signs, however, are different from the definition established by the WHO and the researchers specializing in this field. Thus, the concept of 'withdrawal signs of psychic dependence' raises a lot of questions. PMID:26964289

  8. Estimated freshwater withdrawals in Washington, 2010

    USGS Publications Warehouse

    Lane, Ron C.; Welch, Wendy B.

    2015-01-01

    The amount of public- and self-supplied water used for domestic, irrigation, livestock, aquaculture, industrial, mining, and thermoelectric power was estimated for state, county, and eastern and western regions of Washington during calendar year 2010. Withdrawals of freshwater for offstream uses were estimated to be about 4,885 million gallons per day. The total estimated freshwater withdrawals for 2010 was approximately 15 percent less than the 2005 estimate because of decreases in irrigation and thermoelectric power withdrawals.

  9. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  10. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  11. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  12. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  13. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  14. Improving Nursing Knowledge of Alcohol Withdrawal

    PubMed Central

    Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. (See CE Video, Supplemental Digital Content 1, http://links.lww.com/JNPD/A9) PMID:25816126

  15. Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.

    PubMed

    Bray, Brenna; Scholl, Jamie L; Tu, Wenyu; Watt, Michael J; Renner, Kenneth J; Forster, Gina L

    2016-08-01

    Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippocampus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal. Contrary to our prediction, microdialysis samples from freely-moving rats revealed that restraint stress-induced corticosterone levels in the ventral hippocampus are enhanced by amphetamine withdrawal relative to controls. In separate groups of rats, plasma corticosterone levels increased immediately after 20min of restraint and decreased to below stress-naïve levels after 1h, indicating negative feedback regulation of corticosterone following stress. However, plasma corticosterone responses were similar in amphetamine-withdrawn and control rats. Neither amphetamine nor stress exposure significantly altered protein expression or enzyme activity of the steroidogenic enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD1) or hexose-6-phosphate dehydrogenase (H6PD) in the ventral hippocampus. Our findings demonstrate for the first time that amphetamine withdrawal potentiates stress-induced corticosterone in the ventral hippocampus, which may contribute to increased behavioral stress sensitivity previously observed during amphetamine withdrawal. However, this is not mediated by either changes in plasma corticosterone or hippocampal steroidogenic enzymes. Establishing enhanced ventral hippocampal corticosterone as a direct cause of greater stress sensitivity may identify the glucocorticoid system as a novel target for treating behavioral symptoms of amphetamine withdrawal. PMID:27208490

  16. Withdrawing benzodiazepines in primary care.

    PubMed

    Lader, Malcolm; Tylee, Andre; Donoghue, John

    2009-01-01

    assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one. PMID:19062773

  17. The kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), decreases morphine withdrawal and the consequent conditioned place aversion in rats.

    PubMed

    Kelsey, John E; Verhaak, Allison M S; Schierberl, Kathryn C

    2015-04-15

    Much data suggest that the binding of dynorphin-like peptides to kappa-opioid receptors (KORs) during the administration of and withdrawal from a variety of addictive drugs is aversive and serves to limit the reinforcing properties of those drugs and to enhance tolerance, withdrawal, and the probability of stress-induced relapse. In this study, we examined the role of KORs in mediating opioid withdrawal and its aversive consequences in rats. We found that selective blockade of KORs by i.p. administration of 20mg/kg nor-binaltorphimine (nor-BNI) 5h prior to naltrexone-precipitated withdrawal in morphine-dependent rats decreased feces excreted during a 30-min withdrawal session. More critically, this injection of nor-BNI decreased the subsequent conditioned place aversion (CPA) for the withdrawal chamber 2 days later. The subsequent finding that administration of nor-BNI 2h following withdrawal did not affect the CPA 2 days later suggested that nor-BNI reduced the CPA in the prior experiment because it reduced the aversive effects of withdrawal, not because it reduced the aversive/anxiogenic effects of the withdrawal chamber at the time of CPA testing. These data indicate that the binding of dynorphin-like peptides to KORs during opioid withdrawal serves to enhance withdrawal and its aversive consequences and suggest that selective KOR antagonists may be useful in reducing these aversive effects and consequent relapse. PMID:25591478

  18. Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat.

    PubMed

    Antkiewicz-Michaluk, Lucyna; Wąsik, Agnieszka; Możdżeń, Edyta; Romańska, Irena; Michaluk, Jerzy

    2015-03-01

    Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2) and monoamine releaser, so it can be used as a pharmacological model of depression. In the present paper, we investigated the behavioral and neurochemical effects of withdrawal from acute and repeated administration of a low dose of reserpine (0.2 mg/kg) in Wistar Han rats. We demonstrated the behavioral and receptor oversensitivity (postsynaptic dopamine D1) during withdrawal from chronic reserpine. It was accompanied by a significant increase in motility in the locomotor activity test and climbing behavior in the forced swim test (FST). Neurochemical studies revealed that repeated but not acute administration the a low dose of reserpine triggered opposing adaptive changes in the noradrenergic and serotonin system function analyzed during reserpine withdrawal, i.e. 48 h after the last injection. The tissue concentration of noradrenaline was significantly decreased in the hypothalamus and nucleus accumbens only after repeated drug administration (by about 20% and 35% vs. control; p<0.05, respectively). On the other hand, the concentration of its extraneuronal metabolite, normetanephrine (NM) increased significantly in the VTA during withdrawal both from acute and chronic reserpine. The serotonin concentration was significantly reduced in the VTA after chronic reserpine (by about 40% vs. the control group, p<0.05) as well as its main metabolite, 5-HIAA (by about 30% vs. control; p<0.05) in the VTA and hypothalamus. Dopamine and its metabolites were not changed after acute or chronic reserpine administration. In vivo microdialysis studies clearly evidenced the lack of the effect of a single dose of reserpine, and its distinct effects after chronic treatment on the release of noradrenaline and serotonin in the rat striatum. In fact, the withdrawal from repeated administration of reserpine significantly increased an extraneuronal concentration of noradrenaline in the rat striatum but at the same

  19. Oxidative Stress During Alcohol Withdrawal and its Relationship with Withdrawal Severity

    PubMed Central

    Parthasarathy, Ramamourty; Kattimani, Shivanand; Sridhar, M. G.

    2015-01-01

    Background: Oxidative parameters are altered during alcohol withdrawal and are said to contribute towards withdrawal symptoms in alcoholic patients. Aims: To study levels of five selected oxidative parameters during alcohol withdrawal state and after treatment of the withdrawal state and to assess the association of the oxidative parameters with the severity of alcohol withdrawal. Materials and Methods: This was a case-control study done in a De-addiction clinic of a tertiary teaching centre, Southern India. 50 persons having alcohol withdrawal symptoms were included. The oxidative stress parameters malondialdehyde, protein carbonyl, glutathione peroxidase, superoxide dismutase and catalase were assessed in during the withdrawal phase and again after the withdrawal had subsided. The same oxidative stress parameters were measured in the control group. Statistical analysis: Statistical analysis was done using SPSS version 17.0. One way ANOVA and Pearson correlation test were used for finding the association between the oxidative stress parameters levels and the severity of alcohol withdrawal. Multiple linear regression analysis done to predict variables associated with level of oxidative parameters. Results: During alcohol withdrawal the pro-oxidant malondialdehyde was elevated compared to that in the control group. Among the antioxidant enzymes the superoxide dismutase was higher and catalase was lower than the control group levels. After remission of the alcohol withdrawal both malondialdehyde remained higher and superoxide dismutase lower than in the control group. The levels of oxidative stress parameters not correlated with the severity of alcohol withdrawal. Conclusions: oxidative stress parameters show changes during alcohol withdrawal and during the remission of withdrawal. However, levels of oxidative stress parameters not correlated with the severity of withdrawal. PMID:25969603

  20. Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice

    PubMed Central

    Gamage, Thomas F.; Ignatowska-Jankowska, Bogna M.; Muldoon, Pretal P.; Cravatt, Benjamin F.; Damaj, M. Imad; Lichtman, Aron H.

    2014-01-01

    Background Inhibition of endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) reduces somatic morphine withdrawal signs, but its effects on aversive aspects of withdrawal are unknown. The present study investigated whether Δ9-tetrahydrocannabinol (THC), the MAGL inhibitor JZL184, the FAAH inhibitor PF-3845, or the dual FAAH/MAGL inhibitor SA-57 would reduce acquisition of morphine withdrawal-induced conditioned place avoidance (CPA) and jumping. Methods Mice were implanted with placebo or 75 mg morphine pellets, 48 h later injected with naloxone or saline and placed in the conditioning apparatus, and assessed for CPA at 72 h. Subjects were also observed for jumping behavior following naloxone challenge. Results Naloxone (0.056 mg/kg) produced robust CPA in morphine-pelleted, but not placebo-pelleted, mice. Morphine pretreatment prevented the occurrence of withdrawal CPA and withdrawal jumping, while clonidine (an α2 adrenergic receptor agonist) only blocked withdrawal CPA. THC, JZL184, and SA-57 significantly reduced the percentage of mice that jumped during the conditioning session, but did not affect acquisition of withdrawal CPA. PF-3845 did not reduce morphine withdrawal CPA or jumping. Finally, neither THC nor the endocannabinoid catabolic enzyme inhibitors in non-dependent mice elicited a conditioned place preference or aversion. Conclusions These findings suggest that inhibiting endocannabinoid catabolic enzymes reduces somatic morphine withdrawal signs, but not aversive aspects as inferred in the CPA paradigm. The observation that non-dependent mice administered inhibitors of endocannabinoid degradation did not display place preferences is consistent with the idea that that endocannabinoid catabolic enzymes might be targeted therapeutically, with reduced risk of abuse. PMID:25479915

  1. Withdrawal

    MedlinePlus

    ... for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch ...

  2. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome. PMID:25307572

  3. Geomechanics of subsurface water withdrawal and injection

    NASA Astrophysics Data System (ADS)

    Gambolati, Giuseppe; Teatini, Pietro

    2015-06-01

    Land subsidence and uplift, ground ruptures, and induced seismicity are the principal geomechanic effects of groundwater withdrawal and injection. The major environmental consequence of groundwater pumping is anthropogenic land subsidence. The first observation concerning land settlement linked to subsurface processes was made in 1926 by the American geologists Pratt and Johnson, who wrote that "the cause of subsidence is to be found in the extensive extraction of fluid from beneath the affected area." Since then, impressive progress has been made in terms of: (a) recognizing the basic hydrologic and geomechanic principles underlying the occurrence; (b) measuring aquifer compaction and ground displacements, both vertical and horizontal; (c) modeling and predicting the past and future event; and (d) mitigating environmental impact through aquifer recharge and/or surface water injection. The first milestone in the theory of pumped aquifer consolidation was reached in 1923 by Terzaghi, who introduced the principle of "effective intergranular stress." In the early 1970s, the emerging computer technology facilitated development of the first mathematical model of the subsidence of Venice, made by Gambolati and Freeze. Since then, the comprehension, measuring, and simulation of the occurrence have improved dramatically. More challenging today are the issues of ground ruptures and induced/triggered seismicity, which call for a shift from the classical continuum approach to discontinuous mechanics. Although well known for decades, anthropogenic land subsidence is still threatening large urban centers and deltaic areas worldwide, such as Bangkok, Jakarta, and Mexico City, at rates in the order of 10 cm/yr.

  4. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  5. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  6. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  7. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  8. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  9. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Withdrawal. 1008.40 Section 1008.40 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OIG AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal....

  10. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  11. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  12. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  13. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  14. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  15. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review...

  16. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  17. 14 CFR 93.223 - Slot withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Allocation of Commuter and Air Carrier IFR... essential air service operations or eliminating slots. Before withdrawing any slots under this section to... service operations shall be exempt from withdrawal for use for other international or essential...

  18. 14 CFR 93.223 - Slot withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Allocation of Commuter and Air Carrier IFR... essential air service operations or eliminating slots. Before withdrawing any slots under this section to... service operations shall be exempt from withdrawal for use for other international or essential...

  19. 49 CFR 107.111 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Withdrawal. 107.111 Section 107.111 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION... PROCEDURES Special Permits § 107.111 Withdrawal. An application may be withdrawn at any time before...

  20. 49 CFR 107.111 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Withdrawal. 107.111 Section 107.111 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION... PROCEDURES Special Permits § 107.111 Withdrawal. An application may be withdrawn at any time before...

  1. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  2. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  3. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  4. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  5. 49 CFR 365.123 - Applicant withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Applicant withdrawal. 365.123 Section 365.123 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... APPLICATIONS FOR OPERATING AUTHORITY How To Apply for Operating Authority § 365.123 Applicant withdrawal....

  6. Atorvastatin withdrawal elicits oxidative/nitrosative damage in the rat cerebral cortex.

    PubMed

    de Oliveira, Clarissa Vasconcelos; Funck, Vinícius Rafael; Pereira, Letícia Meier; Grigoletto, Jéssica; Rambo, Leonardo Magno; Ribeiro, Leandro Rodrigo; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2013-05-01

    Statins are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting step in cholesterol biosynthesis. Statins effectively prevent and reduce the risk of coronary artery disease through lowering serum cholesterol, and also exert anti-thrombotic, anti-inflammatory and antioxidant effects independently of changes in cholesterol levels. On the other hand, clinical and experimental evidence suggests that abrupt cessation of statin treatment (i.e. statin withdrawal) is associated with a deleterious rebound phenomenon. In fact, statin withdrawal increases the risk of thrombotic vascular events, causes impairment of endothelium-dependent relaxation and facilitates experimental seizures. However, evidence for statin withdrawal-induced detrimental effects to the brain parenchyma is still lacking. In the present study adult male Wistar rats were treated with atorvastatin for seven days (10mg/kg/day) and neurochemical assays were performed in the cerebral cortex 30 min (atorvastatin treatment) or 24h (atorvastatin withdrawal) after the last atorvastatin administration. We found that atorvastatin withdrawal decreased levels of nitric oxide and mitochondrial superoxide dismutase activity, whereas increased NADPH oxidase activity and immunoreactivity for the protein nitration marker 3-nitrotyrosine in the cerebral cortex. Catalase, glutathione-S-transferase and xanthine oxidase activities were not altered by atorvastatin treatment or withdrawal, as well as protein carbonyl and 4-hydroxy-2-nonenal immunoreactivity. Immunoprecipitation of mitochondrial SOD followed by analysis of 3-nitrotyrosine revealed increased levels of nitrated mitochondrial SOD, suggesting the mechanism underlying the atorvastatin withdrawal-induced decrease in enzyme activity. Altogether, our results indicate the atorvastatin withdrawal elicits oxidative/nitrosative damage in the rat cerebral cortex, and that changes in NADPH oxidase activity and mitochondrial superoxide

  7. Treatment of acute opioid withdrawal with ibogaine.

    PubMed

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  8. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal

    PubMed Central

    Li, Hao; Scholl, Jamie L.; Tu, Wenyu; Hassell, James; Watt, Michael J.; Forster, Gina L.; Renner, Kenneth J.

    2014-01-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, increases in stress-induced ventral hippocampal serotonin have been linked to coping mechanisms. The goal of this study is to understand neurobiological changes induced by amphetamine that contribute to stress-sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pre-treated with amphetamine (2.5 mg/kg, ip.) followed by two weeks withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced a greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular serotonin, stress-induced increases in serotonin were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced serotonin increase in saline pre-treated rats, suggesting that glucocorticoid receptors mediate stress-induced serotonin increases in the ventral hippocampus. However, mifepristone had no effect on stress-induced serotonin increases in the central amygdala, indicating that stress increases serotonin in this region independent of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampus serotonin combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening stress responsiveness. PMID:25234335

  9. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal.

    PubMed

    Li, Hao; Scholl, Jamie L; Tu, Wenyu; Hassell, James E; Watt, Michael J; Forster, Gina L; Renner, Kenneth J

    2014-12-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, which are factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, stress-induced increases in ventral hippocampal serotonin (5-HT) levels have been linked to coping mechanisms. The goal of this study was to investigate the neurobiological changes induced by amphetamine that contribute to stress sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pretreated with amphetamine (2.5 mg/kg, intraperitoneal) and then subjected to 2 weeks of withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular 5-HT, stress-induced increases in 5-HT levels were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced increase in 5-HT levels in saline-pretreated rats, suggesting that glucocorticoid receptors mediate stress-induced increases in 5-HT levels in the ventral hippocampus. However, mifepristone had no effect on stress-induced increases in 5-HT levels in the central amygdala, indicating that stress increases 5-HT levels in this region independently of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampal 5-HT levels combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening

  10. Amphetamine withdrawal and sleep disturbance.

    PubMed

    Gossop, M R; Bradley, B P; Brewis, R K

    1982-01-01

    Sleep duration and indices of disturbed sleep, such as night-time waking and day-time sleep, were investigated in amphetamine users following hospital admission and withdrawal from the drug. Compared to controls, the amphetamine group showed an initial period of oversleeping and, towards the end of the first week, they showed a considerable degree of reduced sleep which persisted for the 20 days of this study. There was greater variability in sleep duration within the amphetamine group on almost all nights, and the variability in sleep duration from one night to the next was also greater. More night-time sleep disturbance was evident among the amphetamine ex-users. These results are discussed with respect to previous work and the pattern is seen to be more complex than had been imagined. A tentative neurochemical model is suggested and clinical implications are considered. PMID:7166130

  11. Baclofen reestablishes striatal and cortical dopamine concentrations during naloxone-precipitated withdrawal.

    PubMed

    Diaz, Silvina L; Kemmling, Alma K; Balerio, Graciela N

    2003-03-01

    The present study analyzes the effects of baclofen (BAC) on mice brain neurochemical alterations during the morphine (MOR) withdrawal syndrome. Male Swiss-Webster albino mice (27-33 g) were rendered dependent by intraperitoneal (i.p.) injection of MOR (2mg/kg), twice daily for 9 days. On day 10, the dependent animals were divided into two groups: one receiving naloxone (NAL; 6 mg/kg i.p.) to precipitate the withdrawal syndrome 60 min after the last dose of MOR and the other received BAC (2mg/kg, i.p.) followed by NAL (6 mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Ten minutes after these treatments, mice were killed by decapitation and the striatum, cortex and hippocampus were dissected to determine endogenous concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites using HPLC with electrochemical detection. Striatal DA, dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentrations as well as cortical DA concentrations of the withdrawal groups decreased significantly with respect to the control groups. BAC attenuated the decrease in DA and DOPAC concentrations observed during the withdrawal, without modifying per se the control DA concentrations. No changes on 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) concentrations were observed during the MOR abstinence syndrome. The prevention caused by BAC on the decreased concentrations of DA induced by MOR withdrawal could have a therapeutic interest for the management of withdrawal syndrome. PMID:12470702

  12. Employing mirtazapine to aid benzodiazepine withdrawal.

    PubMed

    Chandrasekaran, P K

    2008-06-01

    Insomnia and depression are frequently encountered in patients during withdrawal from substances. While there are no approved medications for treating them, off-label attempts to address these phenomena with mirtazapine have shown some promising results. This case describes the use of mirtazapine as an aid in benzodiazepine withdrawal and its potential benefits in alleviating insomnia and depression in a 32-year-old man. It was found to ameliorate sleep myoclonus that was thought to be associated with his withdrawal syndrome. It is hoped this report will generate interest and stimulate further research in this area of psychopharmacology. PMID:18581012

  13. 12 CFR 925.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Voluntary withdrawal from membership. 925.26... ASSOCIATES MEMBERS OF THE BANKS Withdrawal and Removal From Membership § 925.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank...

  14. 19 CFR 144.31 - Right to withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Withdrawals from Warehouse § 144.31 Right to withdraw. Withdrawals from bonded warehouse may be made only by the person primarily liable for the payment of duties on the merchandise being withdrawn, i.e., the importer of record on the warehouse...

  15. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal from warehouse by transferee. 144.27...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time...

  16. Involvement of nuclear factor-kB in the expression of opiate withdrawal.

    PubMed

    Capasso, A

    2001-08-01

    1. To investigate the role of NF-kB in the expression of opiate withdrawal, the effects of PDTC, an inhibitor of NF-kB activation, was studied on acute opiate withdrawal induced by morphine in vitro. 2. After a 4 min in vitro exposure to morphine, a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. 3. PDTC (1x10(-8)-5x10(-8)-1x10(-7) M) was able to reduce the naloxone-induced contracture after exposure to the opioid agonist in a concentration-dependent fashion. 4. The results of the present study indicate that NF-kB is involved in the expression of opiate withdrawal thus extending and explaining previous papers performed with dexamethasone and selective arachidonic acid metabolites inhibitors. PMID:11474844

  17. Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge.

    PubMed

    Gancarz-Kausch, Amy M; Adank, Danielle N; Dietz, David M

    2014-01-01

    Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences. PMID:25363133

  18. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  19. Estimated Freshwater Withdrawals in Oklahoma, 1990

    USGS Publications Warehouse

    Lurry, Dee L.; Tortorelli, Robert L.

    1996-01-01

    This report presents 1990 freshwater withdrawal estimates for Oklahoma by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: irrigation, water supply, livestock, thermoelectric-power generation, domestic and commercial, and industrial and mining. Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, water supply, livestock, and thermoelectric-power generation are illustrated in this report, although data for all categories are tabulated. The U.S. Geological Survey (USGS) established the National Water-Use Information Program in 1977 to collect uniform, current, and reliable information on water use. The Oklahoma District of the USGS and the Oklahoma Water Resources Board participate in a cooperative program to collect and publish water-use information for Oklahoma. Data contained in this report were made available through the cooperative program.

  20. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat

    PubMed Central

    Paterson, Neil E.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    Rationale Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence. Objectives To evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats. Methods A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic minipumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via minipump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing minipumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure. Results Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding. Conclusions The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal, and may alter the rewarding effects of nicotine and food. PMID:18438738

  1. [Asymmetry and spatial specificity of auditory aftereffects following adaptation to signals simulating approach and withdrawal of sound sources].

    PubMed

    Malinina, E S

    2014-01-01

    The spatial specificity of auditory approaching and withdrawing aftereffects was investigated in an anechoic chamber. The adapting and testing stimuli were presented from loudspeakers located in front of the subject at the distance of 1.1 m (near) and 4.5 m (far) from the listener's head. Approach and withdrawal of stimuli were simulated by increasing or decreasing the amplitude of the wide-noise impulse sequence. The listeners were required to determine the movement direction of test stimulus following each 5-s adaptation period. The listeners' "withdrawal" responses were used for psychometric functions plotting and for quantitative assessment of auditory aftereffect. The data summarized for all 8 participants indicated that the asymmetry of approaching and withdrawing aftereffects depended on spatial localization of adaptor and test. The asymmetry of aftereffects was largest when adaptor and test were presented from the same loudspeaker (either near or far). Adaptation to the approach induced a directionally dependent displacement of the psychometric functions relative to control condition without adaptation and adaptation to the withdrawal was not. The magnitude of approaching aftereffect was greater when adaptor and test were located in near spatial domain than when they came from far domain. When adaptor and test were presented from the distinct loudspeakers, magnitude approaching aftereffect was decreasing in comparison to the same spatial localization, but after adaptation to withdrawal it was increasing. As a result, the directionally dependent displacements of the psychometric functions relative to control condition were observed after adaptation as to approach and to withdrawal. The discrepancy of the psychometric functions received after adaptation to approach and to withdrawal at near and far spatial domains was greater under the same localization of adaptor and test in comparison to their distinct localization. We assume that the peculiarities of

  2. Withdrawing Benzodiazepines in Patients With Anxiety Disorders.

    PubMed

    Lader, Malcolm; Kyriacou, Andri

    2016-01-01

    The large class of CNS-depressant medications-the benzodiazepines-have been extensively used for over 50 years, anxiety disorders being one of the main indications. A substantial proportion (perhaps up to 20-30 %) of long-term users becomes physically dependent on them. Problems with their use became manifest, and dependence, withdrawal difficulties and abuse were documented by the 1980s. Many such users experience physical and psychological withdrawal symptoms on attempted cessation and may develop clinically troublesome syndromes even during slow tapering. Few studies have been conducted to establish the optimal withdrawal schedules. The usual management comprises slow withdrawal over weeks or months together with psychotherapy of various modalities. Pharmacological aids include antidepressants such as the SSRIs especially if depressive symptoms supervene. Other pharmacological agents such as the benzodiazepine antagonist, flumazenil, and the hormonal agent, melatonin, remain largely experimental. The purpose of this review is to analyse the evidence for the efficacy of the usual withdrawal regimes and the newer agents. It is concluded that little evidence exists outside the usual principles of drug withdrawal but there are some promising leads. PMID:26733324

  3. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  4. Antiepileptic Drug Withdrawal in Dogs with Epilepsy

    PubMed Central

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication. PMID:26664952

  5. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond.

    PubMed

    Sachdeva, Ankur; Choudhary, Mona; Chandra, Mina

    2015-09-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on 'Alcohol withdrawal syndrome' in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  6. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    SciTech Connect

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  7. 19 CFR 19.6 - Deposits, withdrawals, blanket permits to withdraw and sealing requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... withdrawal permit has been issued. Duty-paid or unconditionally duty-free merchandise which has been... withdrawal for transportation to another port by a duty-free sales enterprise which meets the requirements...-free merchandise intended for passengers' on-board purchases when expressly authorized in writing...

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

    ERIC Educational Resources Information Center

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

    2004-01-01

    Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic…

  9. Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice.

    PubMed

    Kumarnsit, Ekkasit; Keawpradub, Niwat; Nuankaew, Watcharin

    2007-04-01

    Administration of the aqueous extract of Mitragyna speciosa at a dose of 300 mg/kg significantly inhibited ethanol withdrawal-induced behaviors that included rearing, displacement and head weaving. The results also showed that at doses of 100, 300 and 500 mg/kg M. speciosa showed antidepressant activity without effect on the spontaneous motor activity. PMID:17335995

  10. Carisoprodol: abuse potential and withdrawal syndrome.

    PubMed

    Reeves, Roy R; Burke, Randy S

    2010-03-01

    Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate) is a centrally acting skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well established abuse potential similar to that of benzodiazepines. A number of reports show that carisoprodol has been abused for its sedative and relaxant effects, to augment or alter the effects of other drugs, and by the intentional combination of carisoprodol and other noncontrolled medications because of the relative ease (as compared to controlled substances) of obtaining prescriptions. The diversion and abuse of carisoprodol and its adverse health effects appear to have dramatically increased over the last several years. Clinicians have begun to see a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia in patients who abruptly cease intake of large doses of carisoprodol. Hallucinations and delusions may also occur. The withdrawal symptoms are very similar to those previously described for meprobamate withdrawal, suggesting that what may actually be occurring is withdrawal from meprobamate accumulated as a result of intake of excessive amounts of carisoprodol. However carisoprodol itself is capable of modulating GABA(A) function, and this may contribute both to the drugs abuse potential and to the occurrence of a withdrawal syndrome with abrupt cessation of intake. Carisoprodol has been classified as a controlled substance in several states in the US and restrictions on the use of the drug have been imposed in some European countries. Carisoprodol is metabolized to a controlled substance, has clear evidence of abuse potential and increasing incidence of abuse, and has shown evidence of a withdrawal syndrome with abrupt cessation from intake. This article will discuss the abuse potential of carisoprodol and the associated withdrawal syndrome, and consider implications for future use of the drug. PMID

  11. Improving Alcohol Withdrawal Outcomes in Acute Care

    PubMed Central

    Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry

    2014-01-01

    Context Excessive alcohol consumption is the nation’s third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%–12.9%). In patients with DT, restraint use decreased (60.4%–44.4%) and transfers to the ICU decreased (21.6%–15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes. PMID:24867561

  12. Accentuated Decrease in Social Interaction in Rats Subjected to Repeated Ethanol Withdrawals

    PubMed Central

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

    2010-01-01

    changes in body weight could account for these behavioral differences. Conclusion Repeated withdrawal from ethanol can lead to accentuated or more persistent anxiety-like behavior in rats, as indicated by a decrease in social interaction. The withdrawal-induced decrease in locomotor activity is not accentuated by repeated withdrawals. This model of repeated withdrawals from ethanol may prove useful in defining the neurochemical basis of this accentuation. PMID:12198403

  13. Intra-administration associations and withdrawal symptoms: morphine-elicited morphine withdrawal.

    PubMed

    McDonald, Robert V; Siegel, Shepard

    2004-02-01

    On the basis of a conditioning analysis, some drug "withdrawal symptoms" are conditional responses elicited by stimuli paired with the drug effect. Prior demonstrations of conditional elicitation of withdrawal symptoms evaluated the role of environmental cues; however, pharmacological cues also typically signal a drug effect. Within each administration, early drug onset cues (DOCs) may become associated with the later, larger drug effect (intra-administration associations). This experiment evaluated the contribution of intra-administration associations to withdrawal symptoms. The results indicated that (a). 5 mg/kg morphine elicited behavioral and thermic withdrawal symptoms in rats previously injected on a number of occasions with 50 mg/kg morphine and that (b). DOC-elicited withdrawal symptoms are not a sensitized response to the opiate but rather an associative phenomenon. PMID:14769091

  14. Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats

    PubMed Central

    Fadaei-Kenarsary, Meisam; Farbood, Yaghoob; Taghi Mansouri, Seyed Mohammad; Fathi Moghaddam, Hadi

    2015-01-01

    Introduction: Methadone has been used as a drug to detoxify opioid tolerance. Naloxane precipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant. On the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the present study aimed to examine the effects of chronic methadone (70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) and their combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity. Methods: Twenty eight young male Sprague-Dawley rats were randomly divided into 4 groups: control, venlafaxine treated, methadone treated and venlafaxine + methadone treated. Morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. Then primary withdrawal behaviours and tail flick test were performed. The test was then followed by methadone or its vehicle administration. Second intervention was venlafaxine or its vehicle injection. Then final withdrawal behaviours and tail flick test were performed. Results: Combination of chronic methadone substitution and venlafaxine administration, significantly reduced freezing behaviour of spontaneous morphine withdrawal syndrome (P<0.01, 379±144%). Chronic methadone administration (P<0.05, 35±8% difference with venlafaxine treated group) induced hyperalgesia. A positive correlation (P=0.001, +63%) was observed between the animals final freezing scores and their response latencies to the painful stimulus. Discussion: Combination of chronic methadone and venlafaxine administrations reduces freezing withdrawal behaviour. Further investigations on analgesic interventions are needed to overcome this hyperalgesia.

  15. Drug withdrawal conceptualized as a stressor

    PubMed Central

    Chartoff, Elena H.; Carlezon, William A.

    2015-01-01

    Drug withdrawal is often conceptualized as an aversive state that motivates drug-seeking and drug-taking behaviors in humans. Stress is more difficult to define, but is also frequently associated with aversive states. Here we describe evidence for the simple theory that drug withdrawal is a stress-like state, on the basis of common effects on behavioral, neurochemical, and molecular endpoints. We also describe data suggesting a more complex relationship between drug withdrawal and stress. As one example, we will highlight evidence that, depending on drug class, components of withdrawal can produce effects that have characteristics consistent with mood elevation. In addition, some stressors can act as positive reinforcers, defined as having the ability to increase the probability of a behavior that produces it. As such, accumulating evidence supports the general principles of opponent process theory, whereby processes that have an affective valence are followed in time by an opponent process that has the opposite valence. Throughout, we identify gaps in knowledge and propose future directions for research. A better understanding of the similarities, differences, and overlaps between drug withdrawal and stress will lead to the development of improved treatments for addiction, as well as for a vast array of neuropsychiatric conditions that are triggered or exacerbated by stress. PMID:25083570

  16. Inpatient management of acute alcohol withdrawal syndrome.

    PubMed

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

  17. Fast Conducting Mechanoreceptors Contribute to Withdrawal Behavior in Normal and Nerve Injured Rats

    PubMed Central

    Boada, M. Danilo; Martin, Thomas J.; Peters, Christopher M.; Hayashida, Kenichiro; Harris, Michael H.; Houle, Timothy T.; Boyden, Edward S.; Eisenach, James C.; Ririe, Douglas G.

    2014-01-01

    Fast conducting myelinated high threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an AAV8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype specific with only AHTMR neurons being inhibited. One week following nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve injured animals were also increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states. PMID:25267211

  18. Thymus Daenensis Extract and Essential Oils Effects on Morphine Withdrawal Signs in Mice

    PubMed Central

    Khodayar, Mohammad Javad; Taherzadeh, Esmaeil; Siahpoosh, Amir; Mansourzadeh, Zahra; Tabatabaei, Seyed Amir Hossein

    2014-01-01

    Background: Thymus species are well known medicinal plants which the previous studies suggested the involvement of the opioid system in them. Objectives: This study aimed to investigate the effects of methanolic extract and essential oil of aerial parts of Thymus daenensis (TD), an endemic aromatic medicinal plant of Iran, on morphine withdrawal syndrome in mice. Materials and Methods: Experiments were performed in two groups of five, each group treated with extracts or essential oils of TD. Dependency was induced by subcutaneous injection of morphine for three consecutive days. On the fourth day, the last dose of morphine was injected two hours prior to intraperitoneal injection of naloxone while the extract or essential oil of TD was administered 30 minutes before naloxone. A period of 20 minutes after naloxone injection was considered the critical period of the withdrawal syndrome. The number of jumps, standing, leaning, and the weight of stools were recorded as withdrawal signs. Results: The 200 mg/kg and 400 mg/kg doses of extract and all doses of essential oil decreased significantly the number of jumps, standing, leaning and the weight of stool. Administration of 100 mg/kg of extract only decreased the weight of stool and had no effect on the other factors. Conclusions: Extract and essential oil of TD attenuates morphine withdrawal behaviors in mice and may be useful in alleviating the signs and symptoms of opiate withdrawal syndrome in human. PMID:25237649

  19. Fast-conducting mechanoreceptors contribute to withdrawal behavior in normal and nerve injured rats.

    PubMed

    Boada, M Danilo; Martin, Thomas J; Peters, Christopher M; Hayashida, Kenichiro; Harris, Michael H; Houle, Timothy T; Boyden, Edward S; Eisenach, James C; Ririe, Douglas G

    2014-12-01

    Fast-conducting myelinated high-threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and in nerve injury-induced hyperalgesia are less well accepted. Modulation of this subpopulation of peripheral neurons would help define their roles in withdrawal behaviors. The optically active proton pump, ArchT, was placed in an adeno-associated virus-type 8 viral vector with the CAG promoter and was administered by intrathecal injection resulting in expression in myelinated neurons. Optical inhibition of peripheral neurons at the soma and transcutaneously was possible in the neurons expressing ArchT, but not in neurons from control animals. Receptive field characteristics and electrophysiology determined that inhibition was neuronal subtype-specific with only AHTMR neurons being inhibited. One week after nerve injury the AHTMR are hyperexcitable, but can still be inhibited at the soma and transcutaneously. Withdrawal thresholds to mechanical stimuli in normal and in hyperalgesic nerve-injured animals also were increased by transcutaneous light to the affected hindpaw. This suggests that AHTMR neurons play a role not only in threshold-related withdrawal behavior in the normal animal, but also in sensitized states after nerve injury. This is the first time this subpopulation of neurons has been reversibly modulated to test their contribution to withdrawal-related behaviors before and after nerve injury. This technique may prove useful to define the role of selective neuronal populations in different pain states. PMID:25267211

  20. Baclofen and Gamma-Hydroxybutyrate Withdrawal

    PubMed Central

    LeTourneau, Jennifer L.; Hagg, Daniel S.; Smith, Stephen M.

    2008-01-01

    Introduction Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABAB agonists, such as baclofen, will be a more effective strategy. Methods A case report from the medical intensive care unit (ICU) of the university tertiary care hospital. Results A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB use. This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines. The addition of baclofen allowed the rapid sequential decreases in the GHB dose without seizure or delirium and resulted in long-term improvement of her tremor. Conclusions Baclofen, a GABAB agonist, may be a useful agent in the treatment of severe GHB withdrawal. PMID:18266111

  1. Complications of alcohol withdrawal: pathophysiological insights.

    PubMed

    Trevisan, L A; Boutros, N; Petrakis, I L; Krystal, J H

    1998-01-01

    Disease processes or events that accompany acute alcohol withdrawal (AW) can cause significant illness and death. Some patients experience seizures, which may increase in severity with subsequent AW episodes. Another potential AW complication is delirium tremens, characterized by hallucinations, mental confusion, and disorientation. Cognitive impairment and delirium may lead to a chronic memory disorder (i.e., Wernicke-Korsakoff syndrome). Psychiatric problems associated with withdrawal include anxiety, depression, and sleep disturbance. In addition, alterations in physiology, mood, and behavior may persist after acute withdrawal has subsided, motivating relapse to heavy drinking. Recent advances in neurobiology may support the development of improved medications to decrease the risk of AW complications and support long-term sobriety. PMID:15706735

  2. Morphine withdrawal, treatments 1900-30.

    PubMed

    Malcolm, M T

    1999-03-01

    The treatments used between 1900 and 1930 for morphine withdrawal are discussed. The accounts are mainly taken from contemporary textbooks which contain fascinating descriptions of their authors' preferred methods and criticisms of regimes given by other therapists. Delirium, produced by atropine or similar substances, is advocated to cover withdrawal symptoms. The present paper draws parallels with current issues, e.g. withdrawal of opiate under cover of general anaesthesia, follow-up studies and cost-benefit analyses. The particular problems of addicted doctors in 1900-1930 are addressed as are the comparisons then made with non-medically qualified addicts. It is important we keep in mind past mistakes and over-valued ideas so as to reduce any similarly misplaced optimism in our current treatment options. PMID:11623818

  3. Drug withdrawals and the lessons within.

    PubMed

    Smith, Dennis A; Schmid, Esther F

    2006-01-01

    Drug withdrawals over recent decades have triggered changes in the way that drug targets and screening programs are researched and designed. In the cases having the greatest impact, the reason for withdrawal was the reversible interaction of a drug or its metabolite with a single receptor, ion channel or enzyme (primary or secondary pharmacology). Once this interaction is identified, screens can be established and validated. When the mechanism is complex (eg, organ toxicity), however, such screens are difficult to implement and usually examine only the initial step, leading to considerable problems in extrapolation and risk definition. This review classifies drugs withdrawn from the US market over the last 25 years by their reasons for withdrawal, and examines how drug discovery programs have been modified in response to these events. PMID:16445116

  4. Divalproex in the treatment of alcohol withdrawal.

    PubMed

    Myrick, H; Brady, K T; Malcolm, R

    2000-02-01

    The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal. PMID:10718170

  5. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  6. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat

    PubMed Central

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2010-01-01

    BACKGROUND Alcohol withdrawal, refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with N/OFQ significantly reduces alcohol consumption and attenuates alcohol-seeking behaviour induced by environmental conditioning factors or by stress in rats. In the present study we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS For this purpose animals were subjected to a 6 day chronic alcohol intoxication (by intragastric administration) and at 8, 10 and 12 hours following cessation of alcohol exposure they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0 and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety another group of rats was subjected to ethanol intoxication and after one week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12-h later were tested in the EPM following ICV N/OFQ (0.0, 1.0 and 2.0μg/rat). RESULTS Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS The present findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. PMID:21223310

  7. Hostility as a Predictor of Affective Changes During Acute Tobacco Withdrawal

    PubMed Central

    Quinn, Austin; Sekimura, Stephanie

    2014-01-01

    Introduction: Hostility—a personality trait reflective of cynical attitudes and a general mistrust of others—is associated with smoking status and relapse risk. Yet, the mechanisms linking hostility and smoking are not entirely clear. In this lab study, we tested a socioaffective model that purports that high-hostility individuals smoke to cope with maladaptive social mood states (i.e., anger and low friendliness), which become expressed and exacerbated during acute tobacco withdrawal. Methods: Following a baseline visit at which trait hostility was assessed, adult smokers (n = 153, ≥10 cig/day) attended two counterbalanced lab visits: a deprived session following 16hr of deprivation, and a nondeprived session. At both lab visits, affect and withdrawal symptoms were assessed at a single time point. Results: Higher trait hostility predicted larger deprivation-induced increases in several forms of negative affect (anxiety, depression, confusion; βs ≥ .20, ps ≤ .01) and a composite tobacco withdrawal symptom index (β = .16, p = .04) but did not predict changes in positive emotions. These effects persisted after statistically controlling for gender, nicotine dependence, and depression. Other aspects of trait aggression (i.e., verbal aggression, physical aggression, anger) did not predict deprivation-induced changes in affect and withdrawal other than state anger. Discussion: High-hostility individuals appear to experience generalized exacerbations in several negative affective states during acute tobacco withdrawal. Increases in negative affect during tobacco withdrawal may motivate negative reinforcement-mediated smoking and could underlie tobacco addiction in high-hostility smokers. PMID:24113928

  8. Does Melissa Officinalis Cause Withdrawal or Dependence?

    PubMed Central

    Demirci, Kadir; Akgönül, Mehmet; Demirdaş, Arif; Akpınar, Abdullah

    2015-01-01

    Introduction: Melissa officinalis is a medical and aromatic plant that is used for its hypnotic, sedative, and spasmolytic effects. This report presents a case study of30-year-old patient who was admitted to an emergency department with restlessness, tremor, distractibility, and sweating following a discontinuation of Melissa officinalis consumption. Case report: In this case, withdrawal symptoms may be related to the dependence effect caused by long-term use of Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many patients as an alternative to pharmaceutical drugs, patients should be made aware that it may have a risk of dependency and can lead to withdrawal symptoms. PMID:25870482

  9. [Late-onset alcohol withdrawal syndrome].

    PubMed

    Batel, P; Larivière, P

    2000-10-01

    The alcoholic withdrawal syndrome (AWS) arises variably within hours following the hospitalization of an alcohol dependent patient. Delay usually observed between admission and the first symptoms depends above all on alcohol serum level concentration at arrival and on the degree of severity of physical dependence. The case reported here describes the very late onset severe alcoholic withdrawal syndrome observed in a 57-year-old alcohol dependent patient hospitalized for leg trauma and operated within hours followed admission. The first symptoms of AWS appeared only the 4-th day after hospitalization and the patient quickly developed a clinical state of delirium tremens. Delay in the onset of this AWS is discussed. PMID:11104941

  10. 5 CFR 1650.16 - Required withdrawal date.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.16 Required withdrawal date. (a) A... date described in paragraph (a) of this section, but is not required to do so. (c) In the event that...

  11. 5 CFR 1650.16 - Required withdrawal date.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.16 Required withdrawal date. (a) A... date described in paragraph (a) of this section, but is not required to do so. (c) In the event that...

  12. 5 CFR 1650.16 - Required withdrawal date.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.16 Required withdrawal date. (a) A... date described in paragraph (a) of this section, but is not required to do so. (c) In the event that...

  13. 5 CFR 1650.16 - Required withdrawal date.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.16 Required withdrawal date. (a) A... date described in paragraph (a) of this section, but is not required to do so. (c) In the event that...

  14. 17 CFR 41.47 - Withdrawal of margin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... after such withdrawal is sufficient to satisfy the required margin for the security futures and related... PRODUCTS Customer Accounts and Margin Requirements § 41.47 Withdrawal of margin. (a) By the...

  15. 29 CFR 102.104 - Withdrawal of petition.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion....

  16. 48 CFR 14.303 - Modification or withdrawal of bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Submission of Bids 14.303 Modification or withdrawal of... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not...

  17. 29 CFR 102.104 - Withdrawal of petition.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion....

  18. 29 CFR 102.104 - Withdrawal of petition.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion....

  19. 29 CFR 102.104 - Withdrawal of petition.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Orders and Advisory Opinions Regarding Board Jurisdiction § 102.104 Withdrawal of petition. The petitioner may withdraw his petition at any time prior to issuance of the Board's advisory opinion....

  20. Neuronal metabolomics by ion mobility mass spectrometry in cocaine self-administering rats after early and late withdrawal.

    PubMed

    Zhang, Xing; Chiu, Veronica M; Todd, Ryan P; Sorg, Barbara A; Hill, Herbert H

    2016-06-01

    The neuronal metabolomes in rat striatum (STR), prefrontal cortex (PFC), and nucleus accumbens (NAC) were analyzed by Hadamard transform ion mobility mass spectrometry (HT-IMMS) in order to reveal global and specific metabolic changes induced by cocaine self-administration after 1-day or 3-week withdrawal. Metabolite features were comprehensively separated and detected using HPLC-IMMS within minutes. Global metabolic differences were observed by PCA for comparisons between cocaine and saline treatments at 1-day withdrawal time. Metabolite features that were significantly changed were selected using PCA loadings' plot and unpaired LLL test and then tentatively identified by accurate m/z, yielding a complete profile of metabolic changes induced by cocaine self-administration. The majority of these changes were found at the 1-day withdrawal time, but several of them endured even after 3-week withdrawal from cocaine, and these changes were generally brain region specific. Putatively identified metabolites associated with oxidative stress and energy metabolism were also specifically investigated. We discovered that the dysregulation of creatine/creatinine was different between the STR and NAC, demonstrating that metabolic alterations are brain region specific. Glutathione and adenosine were also changed in their abundance, and the results agreed with previous studies. In general, this study provided a high-throughput analytical platform to perform metabolomics analyses with putative identifications for altered metabolite features induced by cocaine treatment, therefore revealing additional metabolic targets of cocaine-induced changes after early and extended withdrawal times. PMID:27108279

  1. 5 CFR 1650.31 - Age-based withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Age-based withdrawals. 1650.31 Section 1650.31 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN In-Service Withdrawals § 1650.31 Age-based withdrawals. (a) A participant who has reached age 591/2 and who has...

  2. 5 CFR 1650.31 - Age-based withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Age-based withdrawals. 1650.31 Section 1650.31 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN In-Service Withdrawals § 1650.31 Age-based withdrawals. (a) A participant who has reached age 591/2 and who has...

  3. Improving Nursing Knowledge of Alcohol Withdrawal: Second Generation Education Strategies.

    PubMed

    Berl, Kimberly; Collins, Michelle L; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. PMID:25816126

  4. 76 FR 16017 - Withdrawal of Regulatory Guide 8.5

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... COMMISSION Withdrawal of Regulatory Guide 8.5 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.5, ``Criticality and Other Interior Evacuation Signals.'' FOR FURTHER INFORMATION CONTACT... The U.S. Nuclear Regulatory Commission (NRC) is withdrawing Regulatory Guide 8.5, ``Criticality...

  5. Dynamics of Lip Dyskinesia Associated with Neuroleptic Withdrawal.

    ERIC Educational Resources Information Center

    Newell, Karl M.; Bodfish, James W.; Mahorney, Steven L.; Sprague, Robert L.

    2000-01-01

    The lip movements associated with dyskinesia in six adults with mental retardation were investigated through analysis at medication baseline, at the highest level of withdrawal dyskinesia, and at the lowest level of dyskinesia following medication withdrawal. Lip oscillations following withdrawal were linked to changes in structural complexity of…

  6. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of fuel alcohol..., DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for Use, Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  7. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of fuel alcohol..., DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for Use, Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  8. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  9. 20 CFR 408.355 - Can you withdraw your application?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Can you withdraw your application? 408.355 Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your...

  10. 20 CFR 408.355 - Can you withdraw your application?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Can you withdraw your application? 408.355 Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your...

  11. 20 CFR 408.355 - Can you withdraw your application?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Can you withdraw your application? 408.355 Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your...

  12. 20 CFR 408.355 - Can you withdraw your application?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Can you withdraw your application? 408.355 Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your...

  13. 12 CFR 341.5 - Withdrawal from registration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Withdrawal from registration. 341.5 Section 341... POLICY REGISTRATION OF SECURITIES TRANSFER AGENTS § 341.5 Withdrawal from registration. (a) Notice of withdrawal from registration. Any transfer agent registered under this part that ceases to engage in...

  14. 5 CFR 330.1001 - Withdrawal from competition.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Withdrawal from competition. 330.1001... RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Prohibited Practices § 330.1001 Withdrawal from competition... applicant or eligible to withdraw from competition or eligibility, for a position in the competitive...

  15. 5 CFR 330.1001 - Withdrawal from competition.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Withdrawal from competition. 330.1001... RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Prohibited Practices § 330.1001 Withdrawal from competition... applicant or eligible to withdraw from competition or eligibility, for a position in the competitive...

  16. 5 CFR 330.1001 - Withdrawal from competition.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Withdrawal from competition. 330.1001... RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Prohibited Practices § 330.1001 Withdrawal from competition... applicant or eligible to withdraw from competition or eligibility, for a position in the competitive...

  17. 5 CFR 330.1001 - Withdrawal from competition.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Withdrawal from competition. 330.1001... RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Prohibited Practices § 330.1001 Withdrawal from competition... applicant or eligible to withdraw from competition or eligibility, for a position in the competitive...

  18. 5 CFR 330.1001 - Withdrawal from competition.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Withdrawal from competition. 330.1001... RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Prohibited Practices § 330.1001 Withdrawal from competition... applicant or eligible to withdraw from competition or eligibility, for a position in the competitive...

  19. Factors Associated with Student Withdrawal from Community College

    ERIC Educational Resources Information Center

    Scoggin, Donna; Styron, Ronald

    2006-01-01

    Research was designed to identify commonalities of personal, enrollment, withdrawal, and evaluative factors as they relate to student withdrawal from community college. The study sought to identify interrelationships between identified reasons for student withdrawal and the variables of gender, race, classification status, degree sought, plans for…

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Can you withdraw your application? 408.355 Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your...

  1. Teachers' Withdrawal Behaviors and Their Relationship with Work Ethic

    ERIC Educational Resources Information Center

    Erdemli, Özge

    2015-01-01

    Problem Situation: People experience ups and downs in their job satisfaction and motivation levels at different points of their work lives for various reasons. One of the outputs of low job satisfaction and motivation is defined as "withdrawal behaviors" in the literature. Withdrawal behaviors are any employee behavior of withdrawal from…

  2. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  3. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  4. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  5. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw...

  6. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw...

  7. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw...

  8. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  9. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw...

  10. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  11. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at...

  12. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at...

  13. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at...

  14. Teachers' Withdrawal Behaviors: Integrating Theory and Findings

    ERIC Educational Resources Information Center

    Shapira-Lishchinsky, Orly

    2012-01-01

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

  15. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  16. 21 CFR 601.43 - Withdrawal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Withdrawal procedures. 601.43 Section 601.43 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Accelerated Approval of Biological Products for Serious or Life-Threatening Illnesses §...

  17. Design of withdrawal-weighted SAW filters.

    PubMed

    Lee, Youngjin; Lee, Seunghee; Roh, Yongrae

    2002-03-01

    This paper presents a new design algorithm for a withdrawal-weighted surface acoustic wave (SAW) transversal filter. The proposed algorithm is based on the effective transmission loss theory and a delta function model of a SAW transversal filter. The design process consists of three steps, which eventually determine eight geometrical design parameters for the filter in order to satisfy given performance specifications. First, the number of fingers in the input and output interdigital transducers (IDTs), plus their geometrical sizes is determined using the insertion loss specification. Second, the number and positions of the polarity reverses in the output IDT are determined using the bandwidth and ripple specifications. Third, the number and position for withdrawing and switching specific fingers in the output IDT and attached electrode area are determined to achieve the desired sidelobe level. The efficiency of the technique is illustrated using a sample design of an IF filter consisting of a uniform input IDT and withdrawal-weighted output IDT. The proposed algorithm is distinct from conventional techniques in that it can optimize the structural geometry of a withdrawal-weighted SAW filter in a direct manner by considering all the performance specifications simultaneously. PMID:12322883

  18. Cohort Survival and Withdrawal Study District Report.

    ERIC Educational Resources Information Center

    Shainline, Michael

    At the completion of the 1986-87 school year, the Albuquerque (New Mexico) Public Schools (APS) conducted a cohort survival and withdrawal study to follow-up 5,976 students who had begun the ninth grade within the district in 1983-84. Current records were matched with those from the 1983-84 school year to determine whether members of the…

  19. 75 FR 22868 - Withdrawal of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... Safe Shutdown Earthquake Ground Motion.'' FOR FURTHER INFORMATION CONTACT: Rebecca L. Karas... Determination of Safe Shutdown Earthquake Ground Motion,'' dated March 1997. RG 1.165 provides general...-Specific Earthquake Ground Motion.'' The withdrawal of Regulatory Guide 1.165 does not alter the...

  20. Helping Individuals Withdraw from Psychiatric Drugs

    ERIC Educational Resources Information Center

    Cohen, David

    2007-01-01

    Many counselors, psychologists, and social workers assist clients to take psychotropic drugs but recoil from helping clients to rethink drug use or stop taking drugs. They might fear resisting the prevailing ideology, violating "standards of care," or contradicting physicians' advice. This article discusses withdrawal emergent reactions from…

  1. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Withdrawal process. 457.170 Section 457.170 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction; State Plans for Child Health Insurance Programs...

  2. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Withdrawal process. 457.170 Section 457.170 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction; State Plans for Child Health Insurance Programs...

  3. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Withdrawal process. 457.170 Section 457.170 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction; State Plans for Child Health Insurance Programs...

  4. 46 CFR 390.9 - Qualified withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., construction or reconstruction its fair market value. The party must obtain the prior written permission of the... CONSTRUCTION FUND § 390.9 Qualified withdrawals. (a) In general—(1) Defined. In accordance with 46 U.S.C. 53509...: (i) The acquisition, construction or reconstruction of a qualified agreement vessel; (ii)...

  5. 46 CFR 390.9 - Qualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., construction or reconstruction its fair market value. The party must obtain the prior written permission of the... CONSTRUCTION FUND § 390.9 Qualified withdrawals. (a) In general—(1) Defined. In accordance with 46 U.S.C. 53509...: (i) The acquisition, construction or reconstruction of a qualified agreement vessel; (ii)...

  6. 21 CFR 314.530 - Withdrawal procedures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Withdrawal procedures. 314.530 Section 314.530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses §...

  7. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Withdrawal procedures. 314.620 Section 314.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible...

  8. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Approval of New Drugs When Human... approval. For new drugs approved under this subpart, FDA may withdraw approval, following a hearing...

  9. 21 CFR 314.530 - Withdrawal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses § 314.530 Withdrawal procedures. (a) For new drugs approved...

  10. Suppressive effects of rosa damascena essential oil on naloxone- precipitated morphine withdrawal signs in male mice.

    PubMed

    Abbasi Maleki, Navid; Abbasi Maleki, Saeid; Bekhradi, Reza

    2013-01-01

    This research was done to test the effect of Rosa damascena essential oil on withdrawal signs of naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection (IP) three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4, after the last administration of morphine, Rosa damascena essential oil was administered at different concentrations (5, 2 and 40%, IP) 30 min before administration of naloxone (5 mg/kg, IP). The following actions were taken as signs of withdrawal and records taken for jumping as a number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing, writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed that different concentrations of Rosa damascena essential oil significantly reduced signs of morphine withdrawal compared to the control group in terms of number of jumps (p < 0.05 and p < 0.01), grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea (p < 0.05). In conclusion it seems that GABAergic activity induced by flavonoids from Rosa damascena essential oil can alleviate signs of morphine withdrawal, but further studies need to be done to better understand this mechanism. PMID:24250642

  11. Estrogen withdrawal from osteoblasts and osteocytes causes increased mineralization and apoptosis.

    PubMed

    Brennan, M Á; Haugh, M G; O'Brien, F J; McNamara, L M

    2014-07-01

    Recent studies have demonstrated increased bone mineral heterogeneity following estrogen withdrawal in vivo. Such changes likely contribute to fracture risk during post-menopausal osteoporosis since tissue mineralization is correlated with bone strength and stiffness. However, the cellular mechanisms responsible for increased mineral variability have not yet been distinguished. The objective of this study is to elucidate how alterations in mineral distribution are initiated during estrogen depletion. Specifically, we tested two separate hypotheses; (1) estrogen deficiency directly alters osteoblast mineralization and (2) estrogen deficiency increases bone cell apoptosis. Osteoblast-like cells (MC3T3-E1) and osteocyte-like cells (MLO-Y4) were pretreated with or without estrogen (17β-estradiol) for 14 days. Estrogen deficiency was subsequently induced by either withdrawing estrogen from cells or blocking estrogen receptors using an estrogen antagonist, fulvestrant (ICI 182,780). Cell number (Hoechst DNA), alkaline phosphatase activity (p-NPP), mineralization (alizarin red) and apoptosis (Caspase 3/7) were evaluated. Whether estrogen withdrawal altered apoptosis rates in the presence of an apoptosis promoting agent (etoposide) was also determined. Interestingly, estrogen withdrawal from cells accustomed to estrogen exposure caused significantly increased osteoblast mineralization and osteocyte apoptosis compared with continued estrogen treatment. In contrast, blocking estrogen receptors with fulvestrant abrogated the mineralization induced by estrogen treatment. When apoptosis was induced using etoposide, cells undergoing estrogen withdrawal increased apoptosis compared to cells with continued estrogen treatment. Recognizing the underlying mechanisms regulating bone cell mineralization and apoptosis during estrogen deficiency and their consequences is necessary to further our knowledge of osteoporosis. PMID:24446157

  12. Blockade of Endocannabinoid Hydrolytic Enzymes Attenuates Precipitated Opioid Withdrawal Symptoms in MiceS⃞

    PubMed Central

    Ramesh, Divya; Ross, Gracious R.; Schlosburg, Joel E.; Owens, Robert A.; Abdullah, Rehab A.; Kinsey, Steven G.; Long, Jonathan Z.; Nomura, Daniel K.; Sim-Selley, Laura J.; Cravatt, Benjamin F.; Akbarali, Hamid I.

    2011-01-01

    Δ9-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB1 receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB1 receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate

  13. N-acetylcysteine decreased nicotine reward-like properties and withdrawal in mice

    PubMed Central

    Bowers, M.S.; Jackson, A.; Maldoon, P.P.; Damaj, M. I.

    2016-01-01

    Rationale N-acetylcysteine can increase extrasynaptic glutamate and reduce nicotine self-administration in rats and smoking rates in humans. Objectives The aim of this study was to determine if N-acetylcysteine modulates the development of nicotine place conditioning and withdrawal in mice. Methods N-acetylcysteine was given to nicotine-treated male ICR mice. Experiment 1: reward-like behavior. N-acetylcysteine (0, 5, 15, 30, or 60 mg/kg, i.p.) was given 15 min before nicotine (0.5 mg/kg, s.c.) or saline (10 ml/kg, s.c.) in an unbiased conditioned place preference (CPP) paradigm. Conditioning for highly palatable food served as control. Experiment 2: spontaneous withdrawal. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on anxiety-like behavior, somatic signs, and hyperalgesia were measured 18 - 24 hrs after continuous nicotine (24 mg/kg/day, 14 days). Experiment 3: Mecamylamine-precipitated, withdrawal-induced aversion. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on mecamylamine (3.5 mg/kg, i.p.) precipitated withdrawal was determined after continuous nicotine (24 mg/kg, i.p., 28 days) using the conditioned place aversion (CPA) paradigm. Results Dose-related reductions in the development of nicotine CPP, somatic withdrawal signs, hyperalgesia, and CPA were observed after N-acetylcysteine pretreatment. No effect of N-acetylcysteine were found on palatable food CPP, anxiety-like behavior, or motoric capacity (crosses between plus maze arms). Finally, N-acetylcysteine did not affect any measure in saline-treated mice at doses effective in nicotine-treated mice. Conclusions These are the first data suggesting that N-acetylcysteine blocks specific mouse behaviors associated with nicotine reward and withdrawal, which adds to the growing appreciation that N-acetylcysteine may have high clinical utility in combating nicotine dependence. PMID:26676982

  14. The effects of adenosine ligands R-PIA and CPT on ethanol withdrawal.

    PubMed

    Gatch, M B; Wallis, C J; Lal, H

    1999-08-01

    The potential anxiogenic or anxiolytic effects of R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), an adenosine agonist, and 8-cyclopentyl-1,3,dimethylxanthine (CPT), an adenosine antagonist, were tested during chronic exposure to ethanol and to ethanol-induced withdrawal in rats. Effects on anxiety were measured by the elevated plus maze and dark-light box. Ethanol consumption and preference was tested in an additional experiment. In testing of elevated plus maze performance during withdrawal from ethanol, R-PIA produced no change in the anxiety-related behaviors of total arm entries and percent open arm entries, but produced a significant decrease in percent open arm time. CPT produced at least partial recovery from the anxiogenic effects of ethanol withdrawal on all three measures of elevated plus maze performance, although peak effects were seen at the intermediate dose of CPT (0.08 mg/kg) for total arm entries and percent open arm time. CPT also showed anxiolytic effects at low to intermediate doses (0.04, 0.08 mg/kg) in the dark-light box. CPT did not reduce the preference for ethanol over water or the total consumption of ethanol over a range of ethanol doses. In summary, the adenosine agonist, R-PIA, exacerbated the effects of ethanol withdrawal, whereas the adenosine antagonist, CPT, at least partially blocked the anxiogenic effects produced by ethanol withdrawal. These results suggest that adenosine antagonists, at least at some doses, may be useful for ameliorating the anxiogenic effects produced by ethanol withdrawal, although it does not appear useful for reducing consumption. PMID:10487382

  15. Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.

    PubMed

    Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed

    2016-05-01

    Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. PMID:26969766

  16. Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review

    PubMed Central

    Harris, Zachary M.; Alonso, Alvaro; Kennedy, Thomas P.

    2016-01-01

    Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy. PMID:27006838

  17. Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation.

    PubMed

    Kutlu, Munir Gunes; Oliver, Chicora; Huang, Peng; Liu-Chen, Lee-Yuan; Gould, Thomas J

    2016-10-01

    Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. PMID:27378334

  18. Affective and somatic aspects of spontaneous and precipitated nicotine withdrawal in C57BL/6J and BALB/cByJ mice

    PubMed Central

    Stoker, Astrid K.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    The aversive aspects of nicotine withdrawal are powerful motivational forces contributing to the tobacco smoking habit. We evaluated measures of affective and somatic aspects of nicotine withdrawal in C57BL/6J and BALB/cByJ mice. Nicotine withdrawal was induced by termination of chronic nicotine delivery through osmotic minipumps or precipitated with the nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine or dihydro-β-erythroidine (DHβE). A rate-independent discrete-trial intracranial self-stimulation threshold procedure was used to assess brain reward function. Anxiety-like behavior and sensorimotor gating were assessed in the light-dark box and prepulse inhibition (PPI) tests, respectively. Acoustic startle response and somatic signs of withdrawal were also evaluated. Spontaneous nicotine withdrawal after 14-day exposure to 10–40 mg/kg/day nicotine induced no alterations in anxiety-like behavior, startle reactivity, PPI, or somatic signs in either strain, and no changes in thresholds in C57BL/6J mice. Extended 28-day exposure to 40 mg/kg/day nicotine induced threshold elevations, increased somatic signs, and anxiety-like behavior 24 h post-nicotine in C57BL/6J mice; thresholds returned to baseline levels by day 4 in nicotine-exposed mice. Mecamylamine or DHβE administration induced threshold elevations in nicotine-exposed C57BL/6J mice compared with saline-exposed mice. In conclusion, administration of relatively high nicotine doses over prolonged periods of time induces both the affective and somatic aspects of spontaneous nicotine withdrawal in the mouse, while exposure to nicotine for shorter periods of time is sufficient for nAChR antagonist-precipitated nicotine withdrawal. The current study is one of the first to demonstrate reward deficits associated with both spontaneous and nAChR antagonist-precipitated nicotine withdrawal in C57BL/6J mice. PMID:18452957

  19. Identification and management of alcohol withdrawal syndrome.

    PubMed

    Mirijello, Antonio; D'Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2015-03-01

    Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed. PMID:25666543

  20. Dexmedetomidine for Sedation during Withdrawal of Support

    PubMed Central

    O’Hara, Chris; Tamburro, Robert F; Ceneviva, Gary D

    2015-01-01

    Agents used to control end-of-life suffering are associated with troublesome side effects. The use of dexmedetomidine for sedation during withdrawal of support in pediatrics is not yet described. An adolescent female with progressive and irreversible pulmonary deterioration was admitted. Despite weeks of therapy, she did not tolerate weaning of supplemental oxygen or continuous bilevel positive airway pressure. Given her condition and the perception that she was suffering, the family requested withdrawal of support. Despite opioids and benzodiazepines, she appeared to be uncomfortable after support was withdrawn. Ketamine was initiated. Relief from ketamine was brief, and its use was associated with a “wide-eyed” look that was distressing to the family. Ketamine was discontinued and a dexmedetomidine infusion was initiated. The patient’s level of comfort improved greatly. The child died peacefully 24 hours after initiating dexmedetomidine from her underlying disease rather than the effects of the sedative. PMID:26339188

  1. [Insomnia therapy and withdrawal of hypnotics].

    PubMed

    Garma, L; Widlöcher, D; Scherrer, J

    1982-11-18

    The aim of this study is to evaluate the efficiency of a treatment prescribed, in the course of an hospital consultation for sleep pathology, to patients suffering from chronic insomnia not improved by longstanding and sustained medication with hypnotic drugs. The basis of the treatment is a progressive but total withdrawal of hypnotics in so far taken regularly. The withdrawal of hypnotics was prescribed to 79 patients: 33 aged 17 to 39 years (group 1, mean age 30) and 46 aged 40 to 70 years (group 2, mean age 51). 41 showed primary psychophysiological insomnia and 28 showed insomnia associated with psychiatric disorders. In patients of group 1, the average durations were 8 years for insomnia and 3 years for sustained hypnotic use; these durations were 15 and 5 years respectively in patients of group 2. Hypnotic drug withdrawal was achieved without placebos in 3 months in group 1 patients and 5 months in group 2 patients. 65 patients completely stopped the continual use of hypnotics. Subjective improvement of insomnia was reported by 51 of these patients (as well as by 6 patients who were given simultaneous antidepressant therapy). 16 of the 51 improved patients have resorted to hypnotics occasionally (at intervals of 10 days or more). After complete withdrawal, patients went on consulting for various lengths of time: 5 months average for group 1, 14 months average for group 2. This study of a fairly large group of insomniacs shows the frequent ineffectiveness of a sustained use of currently available hypnotics. It also shows that two times out of three the complete stop of sustained hypnotic medication proved beneficial to the patient. PMID:6297032

  2. Cardiovascular collapse with attempted pericardial drain withdrawal

    PubMed Central

    Kraus, Molly B; Spitznagel, Rachel A; Kugler, Jane A

    2016-01-01

    Cardiac tamponade is a rare but serious emergency condition in the pediatric population. As treatment, a pericardial drain is often placed to evacuate the fluid. We present a case of a 4-year-old girl with cardiac tamponade secondary to renal failure. After the tamponade resolved, she suffered cardiovascular collapse upon attempted drain withdrawal. This case highlights an unusual cause for cardiovascular collapse, which occurred on blind removal of a pericardial drain. PMID:27625522

  3. Ground-Water-Withdrawal Component of the Michigan Water-Withdrawal Screening Tool

    USGS Publications Warehouse

    Reeves, Howard W.; Hamilton, David A.; Seelbach, Paul W.; Asher, A. Jeremiah

    2009-01-01

    A water-withdrawal assessment process and Internet-based screening tool have been developed to evaluate proposed new or increased high-capacity water withdrawals in Michigan. Michigan legislation defines high capacity withdrawals as those capable of removing an average of 100,000 gallons per day for a consecutive 30-day period. This report describes the ground-water component of the screening tool, provides background information used to develop the screening tool, and documents how this component of the screening tool is implemented. The screening tool is based on application of an analytical model to estimate streamflow depletion by a proposed pumping well. The screening tool is designed to evaluate intermittent pumping, to account for the dynamics of stream-aquifer interaction, and to apportion streamflow depletion among neighboring streams. The tool is to be used for an initial screening of a proposed new or increased high-capacity withdrawal in order to identify withdrawals that may cause adverse resource impacts. The screening tool is not intended to be a site-specific design tool. Results of an example application of the screening tool in Kalamazoo County, Mich., are compared to streamflow depletion estimated by use of a regional ground-water-flow model to demonstrate its performance.

  4. Hyposensitivity to gamma-aminobutyric acid in the ventral tegmental area during alcohol withdrawal: reversal by histone deacetylase inhibitors.

    PubMed

    Arora, Devinder S; Nimitvilai, Sudarat; Teppen, Tara L; McElvain, Maureen A; Sakharkar, Amul J; You, Chang; Pandey, Subhash C; Brodie, Mark S

    2013-08-01

    Putative dopaminergic (pDAergic) ventral tegmental area (VTA) neurons have an important role in alcohol addiction. Acute ethanol increases the activity of pDAergic neurons, and withdrawal from repeated ethanol administration produces a decreased sensitivity of pDAergic VTA neurons to GABA. Recent studies show that behavioral changes induced by chronic alcohol are reversed by inhibitors of histone deacetylases (HDACs). Whether HDAC-induced histone modifications regulate changes in GABA sensitivity of VTA pDAergic neurons during withdrawal is unknown. Here, we investigated modulation of withdrawal-induced changes in GABA sensitivity of pDAergic VTA neurons by HDAC inhibitors (HDACi), and also measured the levels of HDAC2, histone (H3-K9) acetylation, and GABA-Aα1 receptor (GABA (A-α1) R) subunit in VTA during ethanol withdrawal. Mice were injected intraperitoneally (ip) with either ethanol (3.5 g/kg) or saline twice daily for 3 weeks. In recordings from pDAergic VTA neurons in brain slices from ethanol-withdrawn mice, sensitivity to GABA (50-500 μM) was reduced. In brain slices from ethanol-withdrawn mice incubated with the HDACi SAHA (vorinostat) or trichostatin A (TSA) for 2 h, the hyposensitivity of pDAergic VTA neurons to GABA was significantly attenuated. There was no effect of TSA or SAHA on GABA sensitivity of pDAergic VTA neurons from saline-treated mice. In addition, ethanol withdrawal was associated with an increase in levels of HDAC2 and a decrease in histone (H3-K9) acetylation and levels of GABA (A-α1) R subunits in the VTA. Therefore, blockade of upregulation of HDAC2 by HDACi normalizes GABA hyposensitivity of pDAergic neurons developed during withdrawal after chronic ethanol treatment, which suggests the possibility that inhibition of HDACs can reverse ethanol-induced neuroadaptational changes in reward circuitry. PMID:23474591

  5. Clinical management of alcohol withdrawal: A systematic review.

    PubMed

    Kattimani, Shivanand; Bharadwaj, Balaji

    2013-07-01

    Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed. PMID:25013309

  6. FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal.

    PubMed

    Haemmerle, Monika; Bottsford-Miller, Justin; Pradeep, Sunila; Taylor, Morgan L; Choi, Hyun-Jin; Hansen, Jean M; Dalton, Heather J; Stone, Rebecca L; Cho, Min Soon; Nick, Alpa M; Nagaraja, Archana S; Gutschner, Tony; Gharpure, Kshipra M; Mangala, Lingegowda S; Rupaimoole, Rajesha; Han, Hee Dong; Zand, Behrouz; Armaiz-Pena, Guillermo N; Wu, Sherry Y; Pecot, Chad V; Burns, Alan R; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K

    2016-05-01

    Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management. PMID:27064283

  7. Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse.

    PubMed

    Meye, Frank J; Soiza-Reilly, Mariano; Smit, Tamar; Diana, Marco A; Schwarz, Martin K; Mameli, Manuel

    2016-08-01

    Cocaine withdrawal produces aversive states and vulnerability to relapse, hallmarks of addiction. The lateral habenula (LHb) encodes negative stimuli and contributes to aversive withdrawal symptoms. However, it remains unclear which inputs to LHb promote this and what the consequences are for relapse susceptibility. We report, using rabies-based retrolabeling and optogenetic mapping, that the entopeduncular nucleus (EPN, the mouse equivalent of the globus pallidus interna) projects to an LHb neuronal subset innervating aversion-encoding midbrain GABA neurons. EPN-to-LHb excitatory signaling is limited by GABAergic cotransmission. This inhibitory component decreases during cocaine withdrawal as a result of reduced presynaptic vesicular GABA transporter (VGAT). This shifts the EPN-to-LHb GABA/glutamate balance, disinhibiting EPN-driven LHb activity. Selective virally mediated VGAT overexpression at EPN-to-LHb terminals during withdrawal normalizes GABAergic neurotransmission. This intervention rescues cocaine-evoked aversive states and prevents stress-induced reinstatement, used to model relapse. This identifies diminished inhibitory transmission at EPN-to-LHb GABA/glutamate synapses as a mechanism contributing to the relapsing feature of addictive behavior. PMID:27348214

  8. FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal

    PubMed Central

    Haemmerle, Monika; Bottsford-Miller, Justin; Pradeep, Sunila; Taylor, Morgan L.; Hansen, Jean M.; Dalton, Heather J.; Stone, Rebecca L.; Cho, Min Soon; Nick, Alpa M.; Nagaraja, Archana S.; Gutschner, Tony; Gharpure, Kshipra M.; Mangala, Lingegowda S.; Han, Hee Dong; Zand, Behrouz; Armaiz-Pena, Guillermo N.; Wu, Sherry Y.; Pecot, Chad V.; Burns, Alan R.; Lopez-Berestein, Gabriel; Afshar-Kharghan, Vahid; Sood, Anil K.

    2016-01-01

    Recent studies in patients with ovarian cancer suggest that tumor growth may be accelerated following cessation of antiangiogenesis therapy; however, the underlying mechanisms are not well understood. In this study, we aimed to compare the effects of therapy withdrawal to those of continuous treatment with various antiangiogenic agents. Cessation of therapy with pazopanib, bevacizumab, and the human and murine anti-VEGF antibody B20 was associated with substantial tumor growth in mouse models of ovarian cancer. Increased tumor growth was accompanied by tumor hypoxia, increased tumor angiogenesis, and vascular leakage. Moreover, we found hypoxia-induced ADP production and platelet infiltration into tumors after withdrawal of antiangiogenic therapy, and lowering platelet counts markedly inhibited tumor rebound after withdrawal of antiangiogenic therapy. Focal adhesion kinase (FAK) in platelets regulated their migration into the tumor microenvironment, and FAK-deficient platelets completely prevented the rebound tumor growth. Additionally, combined therapy with a FAK inhibitor and the antiangiogenic agents pazopanib and bevacizumab reduced tumor growth and inhibited negative effects following withdrawal of antiangiogenic therapy. In summary, these results suggest that FAK may be a unique target in situations in which antiangiogenic agents are withdrawn, and dual targeting of FAK and VEGF could have therapeutic implications for ovarian cancer management. PMID:27064283

  9. Reliable Diameter Control of Carbon Nanotube Nanobundles Using Withdrawal Velocity.

    PubMed

    Shin, Jung Hwal; Kim, Kanghyun; An, Taechang; Choi, WooSeok; Lim, Geunbae

    2016-12-01

    Carbon nanotube (CNT) nanobundles are widely used in nanoscale imaging, fabrication, and electrochemical and biological sensing. The diameter of CNT nanobundles should be controlled precisely, because it is an important factor in determining electrode performance. Here, we fabricated CNT nanobundles on tungsten tips using dielectrophoresis (DEP) force and controlled their diameters by varying the withdrawal velocity of the tungsten tips. Withdrawal velocity pulling away from the liquid-air interface could be an important, reliable parameter to control the diameter of CNT nanobundles. The withdrawal velocity was controlled automatically and precisely with a one-dimensional motorized stage. The effect of the withdrawal velocity on the diameter of CNT nanobundles was analyzed theoretically and compared with the experimental results. Based on the attachment efficiency, the withdrawal velocity is inversely proportional to the diameter of the CNT nanobundles; this has been demonstrated experimentally. Control of the withdrawal velocity will play an important role in fabricating CNT nanobundles using DEP phenomena. PMID:27581602

  10. Dipeptides delay the onset of morphine withdrawal in the mouse.

    PubMed

    Kovács, G L; Szontágh, L; Baláspiri, L; Telegdy, G

    1984-01-01

    The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine. PMID:6540034

  11. The interpersonal process model of demand/withdraw behavior.

    PubMed

    Baucom, Brian R; Dickenson, Janna A; Atkins, David C; Baucom, Donald H; Fischer, Melanie S; Weusthoff, Sarah; Hahlweg, Kurt; Zimmermann, Tanja

    2015-02-01

    The demand/withdraw interaction pattern is a destructive cycle of relationship communication behavior that is associated with negative individual and relationship outcomes. Demand/withdraw behavior is thought to be strongly linked to partners' emotional reactions, but current theories are inconsistent with empirical findings. The current study proposes the interpersonal process model of demand/withdraw behavior, which includes linkages between each partners' emotional reactions and the interpersonal behavior of demanding and withdrawing. Data come from problem solving discussions of 55 German couples with observationally coded demand/withdraw behavior and fundamental frequency (f₀) to measure vocally encoded emotional arousal. Actor-partner interdependence models (Kenny, Kashy, & Cook, 2006) were used to examine associations among demand/withdraw behavior and f₀ in the overall discussion and 5-min segments. Significant cross-partner associations emerged for demanding and withdrawing behavior across the whole conversation as well as within 5-min segments, and these associations are partially accounted for by each individual's f₀. When behaviorally coded demanders expressed more vocal arousal, they demanded more and withdrew less while their partners withdrew more. In contrast, when behaviorally coded withdrawers expressed more vocal arousal, their partners demanded less and withdrew more. Findings demonstrate that demand/withdraw behavior varies between couples (i.e., some couples engage in a stronger demand/withdraw cycle than others) and between segments (i.e., when 1 partner increases demanding, the other increases withdrawing). Findings support key elements of the interpersonal process model, showing intra- and interpersonal pathways linking demand/withdraw behavior and emotion and demonstrate the importance of partners' behavioral roles in these linkages. PMID:25495639

  12. Fluid injection and withdrawal in deep geothermal borehole.

    NASA Astrophysics Data System (ADS)

    Troiano, A.; Di Giuseppe, M. G.; Troise, C.; Tramelli, A.; De Natale, G.

    2012-04-01

    Geothermal systems represents a large resource that can provide, with a reasonable investment, a very high and cost-competitive power generating capacity. Considering also the very low environmental impact, their development represents, in the next decades, an enormous perspective. Despite this unquestionable potential, geothermal exploitation has always been perceived as limited, mainly because of the dependance of a site usefulness on several pre-existing conditions, mainly correlated to the reservoir rock's permeability and porosity, the amount of fluid saturation and, first of all, a convenient temperature-depth relationship. However, this major barrier it is not insurmountable and a notable progress in recent tests is achieved with the Enhanced Geothermal System (EGS), where massive fluid injection and withdrawal were performed to enlarge the natural fracture system of the basement rock. The permeability of the surrounding rocks results highly increased by pressurized fluids circulation and geothermal resources, in such way, become accessible in areas where deep reservoir exploitation, otherwise, could be not advantageous or even possible. Still problematic remains, however, most of the key technical requirements as, firstly, deep fluid injection, that represents a necessary field practice in EGS development. This kind of procedure have often strong and uncontrolled physical effects on the neighboring environment, involving possibly even large areas and, in particular, they represent one of the most important sources of seismicity induced by human activities. In some cases, seismicity reaches level that can not be sustained, as in the paradigmatic case of the 2006 M=3.4 earthquake induced in the Basel city (Swiss), with the consequent EGS project early termination. We test a numerical procedure that models deep fluid injection and withdrawal, during well stimulation, and its effects on induced seismicity. We propose such a procedure as a way to estimate how

  13. Evidence for a peripheral mechanism in cardiac opioid withdrawal.

    PubMed

    Milanés, M V; Martinez, M D; González-Cuello, A; Laorden, M L

    2001-09-01

    Studies involving heart catecholaminergic systems in morphine-dependent rats have not established whether the adaptive changes observed in the heart during morphine withdrawal are mediated peripherally or centrally. In this study, naloxone (Nx), naloxone methiodide (NxM) and N-methyl levallorphan (NML), quaternary derivatives of Nx and levallorphan, respectively, that do not cross the blood-brain barrier, were administered to morphine-dependent rats and catecholamines and their metabolites determined in the right ventricle. Rats were made dependent on morphine by implantation of morphine pellets for 7 days. On day 8 animals received s.c. injections of saline, Nx (1 mg/kg), NxM (5 mg/kg) or NML (5 mg/kg) and were decapitated 30 min later. Noradrenaline (NA) and its metabolites normetanephrine (NMN) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined by high-performance liquid chromatography with electrochemical detection. After NxM or NML administration to morphine-dependent rats there was a pronounced increase in NMN and DOPAC levels, as well as in NA and DA turnovers (as estimated by NMN/NA and DOPAC/DA ratios, respectively) in the right ventricle. Similarly, giving Nx to morphine-dependent rats increased NMN and DOPAC levels and NA and DA turnovers. In addition, in the paraventricular nucleus of the hypothalamus (PVN) NA and DA turnover, measured as the MHPG/NA or DOPAC/DA ratios, increased after Nx administration but not after NxM or NML These results suggest that the changes in cardiac sympathetic activity observed during morphine withdrawal are due to intrinsic mechanisms outside the central nervous system. These data may be important for understanding the adaptive changes induced in the heart in subjects dependent on opioids. PMID:11521160

  14. Ethanol withdrawal in mice precipitated and exacerbated by hyperbaric exposure

    SciTech Connect

    Alkana, R.L.; Finn, D.A.; Galleisky, G.G.; Syapin, P.J.; Malcolm, R.D.

    1985-01-01

    Mice were fed an ethanol-containing liquid diet for 9 days. On removal of the diet, exposure to 12 atmospheres absolute of a mixture of helium and oxygen precipitated earlier withdrawal, increased withdrawal scores for the first 6 hours, and increased the peak withdrawal intensity compared to dependent animals exposed to control conditions. The enhanced withdrawal did not appear to reflect alterations in ethanol elimination, oxygen or helium partial pressures, body temperature, or general excitability. These results extend to chronically treated animals the evidence that hyperbaric exposure antagonizes the membrane actions of ethanol.

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

    PubMed

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

    2016-02-01

    Internet gaming disorder (IGD) is currently positioned in the appendix of the DSM-5 as a condition requiring further study. The aim of this review was to examine the state of current knowledge of gaming withdrawal symptomatology, given the importance of withdrawal in positioning the disorder as a behavioral addiction. A total of 34 studies, including 10 qualitative studies, 17 research reports on psychometric instruments, and 7 treatment studies, were evaluated. The results indicated that the available evidence on Internet gaming withdrawal is very underdeveloped. Internet gaming withdrawal is most consistently referred to as 'irritability' and 'restlessness' following cessation of the activity. There exists a concerning paucity of qualitative studies that provide detailed clinical descriptions of symptoms arising from cessation of internet gaming. This has arguably compromised efforts to quantify withdrawal symptoms in empirical studies of gaming populations. Treatment studies have not reported on the natural course of withdrawal and/or withdrawal symptom trajectory following intervention. It is concluded that many more qualitative clinical studies are needed, and should be prioritised, to develop our understanding of gaming withdrawal. This should improve clinical descriptions of problematic internet gaming and in turn improve the quantification of IGD withdrawal and thus treatments for harmful internet gaming. PMID:26704173

  16. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Logan, J. ||

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  17. Adolescent Anabolic/Androgenic Steroids: Aggression and Anxiety During Exposure Predict Behavioral Responding During Withdrawal in Syrian Hamsters (Mesocricetus auratus)

    PubMed Central

    Ricci, Lesley A.; Morrison, Thomas R.; Melloni, Richard H.

    2014-01-01

    In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety- eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. PMID:24126136

  18. Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal

    PubMed Central

    Kaufling, Jennifer

    2015-01-01

    Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA–VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA–VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. SIGNIFICANCE STATEMENT Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons

  19. Withdrawal from intermittent ethanol exposure increases probability of burst firing in VTA neurons in vitro.

    PubMed

    Hopf, F Woodward; Martin, Miquel; Chen, Billy T; Bowers, M Scott; Mohamedi, Maysha M; Bonci, Antonello

    2007-10-01

    Changing the activity of ventral tegmental area (VTA) dopamine neurons from pacemaker to burst firing is hypothesized to increase the salience of stimuli, such as an unexpected reward, and likely contributes to withdrawal-associated drug-seeking behavior. Accordingly, pharmacological, behavioral, and electrophysiological data suggest an important role of the VTA in mediating alcohol-dependent behaviors. However, the effects of repeated ethanol exposure on VTA dopamine neuron ion channel function are poorly understood. Here, we repeatedly exposed rats to ethanol (2 g/kg ethanol, ip, twice per day for 5 days), then examined the firing patterns of VTA dopamine neurons in vitro after 7 days withdrawal. Compared with saline-treated animals, the function of the small conductance calcium-dependent potassium channel (SK) was reduced in ethanol-treated animals. Consistent with a role for SK in regulation of burst firing, NMDA applied during firing facilitated the transition to bursting in ethanol-treated but not saline-treated animals; NMDA consistently induced bursting only in saline-treated animals when SK was inhibited. Also, enhanced bursting in ethanol-treated animals was not a result of differences in NMDA-induced depolarization. Further, I(h) was also reduced in ethanol-treated animals, which delayed recovery from hyperpolarization, but did not account for the increased NMDA-induced bursting in ethanol-treated animals. Finally, repeated ethanol exposure and withdrawal also enhanced the acute locomotor-activating effect of cocaine (15 mg/kg, ip). Thus withdrawal after repeated ethanol exposure produced several alterations in the physiological properties of VTA dopamine neurons, which could ultimately increase the ability of VTA neurons to produce burst firing and thus might contribute to addiction-related behaviors. PMID:17699688

  20. Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats.

    PubMed

    Grasing, K; He, S

    2005-02-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding

  1. Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors.

    PubMed

    Pang, Xueyan; Liu, Liwang; Ngolab, Jennifer; Zhao-Shea, Rubing; McIntosh, J Michael; Gardner, Paul D; Tapper, Andrew R

    2016-08-01

    Cholinergic neurons in the medial habenula (MHb) modulate anxiety during nicotine withdrawal although the molecular neuroadaptation(s) within the MHb that induce affective behaviors during nicotine cessation is largely unknown. MHb cholinergic neurons are unique in that they robustly express neuronal nicotinic acetylcholine receptors (nAChRs), although their behavioral role as autoreceptors in these neurons has not been described. To test the hypothesis that nAChR signaling in MHb cholinergic neurons could modulate anxiety, we expressed novel "gain of function" nAChR subunits selectively in MHb cholinergic neurons of adult mice. Mice expressing these mutant nAChRs exhibited increased anxiety-like behavior that was alleviated by blockade with a nAChR antagonist. To test the hypothesis that anxiety induced by nicotine withdrawal may be mediated by increased MHb nicotinic receptor signaling, we infused nAChR subtype selective antagonists into the MHb of nicotine naïve and withdrawn mice. While antagonists had little effect on nicotine naïve mice, blocking α4β2 or α6β2, but not α3β4 nAChRs in the MHb alleviated anxiety in mice undergoing nicotine withdrawal. Consistent with behavioral results, there was increased functional expression of nAChRs containing the α6 subunit in MHb neurons that also expressed the α4 subunit. Together, these data indicate that MHb cholinergic neurons regulate nicotine withdrawal-induced anxiety via increased signaling through nicotinic receptors containing the α6 subunit and point toward nAChRs in MHb cholinergic neurons as molecular targets for smoking cessation therapeutics. PMID:27020042

  2. 50 CFR 259.33 - Constructive deposits and withdrawals; ratification of withdrawals (as qualified) made without...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... “Period (cc)”. (b) Constructive deposits and withdrawals (before Interim CCF Agreement effectiveness date..., before the end of Period (cc). If, however, the Secretary receives the completed application in proper... the consent given before the end of Period (bb) or Period (cc), whichever applies, then the burden...

  3. 50 CFR 259.33 - Constructive deposits and withdrawals; ratification of withdrawals (as qualified) made without...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... “Period (cc)”. (b) Constructive deposits and withdrawals (before Interim CCF Agreement effectiveness date..., before the end of Period (cc). If, however, the Secretary receives the completed application in proper... the consent given before the end of Period (bb) or Period (cc), whichever applies, then the burden...

  4. 50 CFR 259.33 - Constructive deposits and withdrawals; ratification of withdrawals (as qualified) made without...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... “Period (cc)”. (b) Constructive deposits and withdrawals (before Interim CCF Agreement effectiveness date..., before the end of Period (cc). If, however, the Secretary receives the completed application in proper... the consent given before the end of Period (bb) or Period (cc), whichever applies, then the burden...

  5. The effect of repeated withdrawal episodes on acquisition and loss of tolerance to ethanol in ethanol-treated rats.

    PubMed

    Maier, D M; Pohorecky, L A

    1987-01-01

    Male rats were administered ethanol via an intragastric catheter (8.0-12.0 g/kg/day) either continuously for 8 weeks or on a binge schedule with four 2 week cycles of drug administration separated from each successive cycle by a 2 week period of no drug treatment. Older rats were administered ethanol for 2 weeks, to provide an age control for the binge-treated animals as age can alter an animal's sensitivity to ethanol. Acquisition and loss of tolerance to ethanol-induced motor impairment were measured on a dowel task while acquisition and loss of tolerance to ethanol-induced hypothermia were assessed by measuring rectal temperature. Acceleration of tolerance development to both ethanol-induced motor impairment and hypothermia was observed in animals subjected to repeated withdrawal episodes (binge-Study 1) but not in the controls for total dose and duration of drug treatment who experienced withdrawal only once (continuous-Study 2). Persistence of tolerance to ethanol-induced motor impairment occurred in both binge and continuously treated animals while persistence of tolerance to ethanol-induced hypothermia was seen only in the binge treated animals. Age (3 to 7 months) did not affect tolerance development or decay. After three cycles of drug treatment (three withdrawal episodes), binge treated animals showed an impairment in motor ability when blood ethanol levels were near zero. This impairment disappeared when the animals were administered ethanol, indicating a normalizing effect of ethanol on motor behavior in animals subjected to repeated episodes of withdrawal. A similar, but not significant, effect was seen in continuously treated animals. Thus, in an animal exposed to prolonged ethanol treatment, persistent changes in responding to the drug were found. The persistence of these changes was enhanced by the experience of withdrawal from ethanol. PMID:3628538

  6. Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: an in vitro model of neocytolysis

    NASA Technical Reports Server (NTRS)

    Trial, J.; Rice, L.; Alfrey, C. P.

    2001-01-01

    BACKGROUND: We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen. METHODS: We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal. RESULTS: A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO. CONCLUSIONS: HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.

  7. Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal

    PubMed Central

    Almela, Pilar; García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2013-01-01

    G protein-coupled receptors (GPCRs) comprise a large family of membrane receptors involved in signal transduction. These receptors are linked to a variety of physiological and biological processes such as regulation of neurotransmission, growth, and cell differentiation among others. Some of the effects of GPCRs are known to be mediated by the activation of mitogen-activated extracellular kinase (MAPK) pathways. Cross-talk among various signal pathways plays an important role in activation of intracellular and intranuclear signal transduction cascades. Naloxone-induced morphine withdrawal leads to an up-regulation of adenyl cyclase-mediated signaling, resulting in high expression of protein kinase (PK) A. In addition, there is also an increased expression of extracellular signal regulated kinase (ERK), one member of MAPK. For this reason, the crosstalk between these GPCRs and receptors with tyrosine kinase activity (TKR) can be considered a possible mechanism for adaptive changes that occurs after morphine withdrawal. Morphine withdrawal activates ERK1/2 and phosphorylated tyrosine hydroxylase (TH) at Ser31 in the right and left ventricle. When N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a PKA inhibitor was infused, the ability of morphine withdrawal to activate ERK, which phosphorylates TH at Ser31, was reduced. The present finding demonstrated that the enhancement of ERK1/2 expression and the phosphorylation state of TH at Ser31 during morphine withdrawal are dependent on PKA and suggest cross-talk between PKA and ERK1/2 transduction pathway mediating morphine withdrawal-induced activation of TH. Increasing understanding of the mechanisms that interconnect the two pathway regulated by GPCRs and TKRs may facilitate the design of new therapeutic strategies. PMID:24409147

  8. Marijuana withdrawal syndrome in the animal model.

    PubMed

    Lichtman, Aron H; Martin, Billy R

    2002-11-01

    Although the proposition that repeated marijuana use can lead to marijuana dependence has long been accepted, only recently has evidence emerged suggesting that abstinence leads to clinically significant withdrawal symptoms. Converging evidence from human and animal studies has increased our understanding of cannabinoid dependence. One of the most powerful tools to advance this area of research is the CB1 cannabinoid receptor antagonist SR 141716A, which reliably precipitates withdrawal syndromes in mice, rats, and dogs that have been treated repeatedly with cannabinoids. In addition, the use of CB1 receptor knockout mice has revealed that not only cannabinoid dependence is mediated through a CB1 receptor mechanism of action, but CB1 receptors also modulate opioid dependence. Moreover, the results of other genetically altered mouse models suggest the existence of a reciprocal relationship between cannabinoid and opioid systems in drug dependence. Undoubtedly, these animal models will play pivotal roles in further characterizing cannabinoid dependence and elucidating the mechanisms of action, as well as developing potential pharmacotherapies for cannabinoid dependence. PMID:12412832

  9. 78 FR 28163 - Zentox Corporation; Withdrawal of Food Additive Petition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ... Register of September 3, 2008 (73 FR 51490), we announced that Zentox Corp., c/o Burdock Group, 801 North... HUMAN SERVICES Food and Drug Administration 21 CFR Part 173 Zentox Corporation; Withdrawal of Food Additive Petition AGENCY: Food and Drug Administration, HHS. ACTION: Notice of withdrawal. SUMMARY:...

  10. 8 CFR 1003.4 - Withdrawal of appeal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Withdrawal of appeal. 1003.4 Section 1003.4 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Board of Immigration Appeals § 1003.4 Withdrawal of appeal. In...

  11. 8 CFR 1003.4 - Withdrawal of appeal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Withdrawal of appeal. 1003.4 Section 1003.4 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Board of Immigration Appeals § 1003.4 Withdrawal of appeal. In...

  12. 8 CFR 1003.4 - Withdrawal of appeal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Withdrawal of appeal. 1003.4 Section 1003.4 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Board of Immigration Appeals § 1003.4 Withdrawal of appeal. In...

  13. 8 CFR 1003.4 - Withdrawal of appeal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Withdrawal of appeal. 1003.4 Section 1003.4 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Board of Immigration Appeals § 1003.4 Withdrawal of appeal. In...

  14. 8 CFR 1003.4 - Withdrawal of appeal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Withdrawal of appeal. 1003.4 Section 1003.4 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE GENERAL PROVISIONS EXECUTIVE OFFICE FOR IMMIGRATION REVIEW Board of Immigration Appeals § 1003.4 Withdrawal of appeal. In...

  15. 75 FR 60113 - Pesticide Science Policy; Notice of Withdrawal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ... pesticides, the Agency uses a variety of data and different models. This science policy document was... AGENCY Pesticide Science Policy; Notice of Withdrawal AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA announces the withdrawal of the pesticide science policy document ``Use...

  16. 19 CFR 177.6 - Withdrawal of ruling requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal of ruling requests. 177.6 Section 177.6 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ADMINISTRATIVE RULINGS General Ruling Procedure § 177.6 Withdrawal of ruling...

  17. 75 FR 43208 - Withdrawal of Regulatory Guide 5.17

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... because the guidance is outdated. Former Sec. 73.31(e) has been deleted (44 FR 68184; November 28, 1979... COMMISSION Withdrawal of Regulatory Guide 5.17 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 5.17, ``Truck Identification Markings''. FOR FURTHER INFORMATION CONTACT: Robert...

  18. 30 CFR 74.18 - Withdrawal of certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Withdrawal of certification. 74.18 Section 74.18 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH COAL MINE DUST SAMPLING DEVICES General Requirements for All Devices § 74.18 Withdrawal...

  19. 21 CFR 900.6 - Withdrawal of approval.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Withdrawal of approval. 900.6 Section 900.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY Accreditation § 900.6 Withdrawal of approval. If FDA...

  20. 21 CFR 900.6 - Withdrawal of approval.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Withdrawal of approval. 900.6 Section 900.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY Accreditation § 900.6 Withdrawal of approval. If FDA...

  1. 21 CFR 900.6 - Withdrawal of approval.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Withdrawal of approval. 900.6 Section 900.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY Accreditation § 900.6 Withdrawal of approval. If FDA...

  2. Who Withdraws from Initial Teacher Preparation Programmes and Why?

    ERIC Educational Resources Information Center

    Hobson, Andrew J.; Giannakaki, Marina-Stefania; Chambers, Gary N.

    2009-01-01

    Background: In recent years, withdrawal from initial teacher preparation (ITP) programmes, in England and elsewhere, has become a cause for concern amongst both ITP providers and policy-makers. Purpose: This paper seeks to enhance the presently underdeveloped evidence base on the causes of withdrawal from ITP and on the characteristics of student…

  3. 75 FR 2894 - Withdrawal of Regulatory Guide 1.148

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... From the Federal Register Online via the Government Publishing Office ] NUCLEAR REGULATORY COMMISSION Withdrawal of Regulatory Guide 1.148 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.148, ``Functional Specification for Active Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' FOR...

  4. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  5. 30 CFR 23.13 - Withdrawal of approval.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Withdrawal of approval. 23.13 Section 23.13 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS TELEPHONES AND SIGNALING DEVICES § 23.13 Withdrawal of approval. MSHA...

  6. 19 CFR 10.80 - Remission of duty; withdrawal; bond.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Remission of duty; withdrawal; bond. 10.80 Section 10.80 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... for Curing Fish § 10.80 Remission of duty; withdrawal; bond. Imported salt in bond may be used...

  7. 5 CFR 831.406 - Withdrawal of voluntary contributions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of...

  8. 5 CFR 831.406 - Withdrawal of voluntary contributions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of voluntary contributions. (a) Before receiving...

  9. 5 CFR 831.406 - Withdrawal of voluntary contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of...

  10. 5 CFR 831.406 - Withdrawal of voluntary contributions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Withdrawal of voluntary contributions. 831.406 Section 831.406 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Voluntary Contributions § 831.406 Withdrawal of voluntary contributions. (a) Before receiving...

  11. 49 CFR 386.51 - Amendment and withdrawal of pleadings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Amendment and withdrawal of pleadings. 386.51 Section 386.51 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR... HAZARDOUS MATERIALS PROCEEDINGS General Rules and Hearings § 386.51 Amendment and withdrawal of...

  12. 17 CFR 3.51 - Withdrawal of application for registration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Withdrawal of application for registration. 3.51 Section 3.51 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION REGISTRATION Denial, Suspension or Revocation of Registration § 3.51 Withdrawal of application for...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... part. Nonqualified withdrawals for research, development, and design expenses incident to new and... determination and publication is made, the latest published percentage shall apply for any taxable year... withdrawals for research and development and payments against indebtedness in excess of basis) or in the...

  14. 46 CFR 391.7 - Tax treatment of nonqualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... part. Nonqualified withdrawals for research, development, and design expenses incident to new and... determination and publication is made, the latest published percentage shall apply for any taxable year... withdrawals for research and development and payments against indebtedness in excess of basis) or in the...

  15. 26 CFR 3.7 - Tax treatment of nonqualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Nonqualified withdrawals for research, development, and design expenses incident to new and advanced ship... nearest one-hundredth of 1 percent. If such a determination and publication is made, the latest published...)(2) (i) and (ii) of the Act (relating to withdrawals for research and development and...

  16. 26 CFR 3.7 - Tax treatment of nonqualified withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Tax treatment of nonqualified withdrawals. 3.7 Section 3.7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) CAPITAL CONSTRUCTION FUND § 3.7 Tax treatment of nonqualified withdrawals. (a) In general. Section 607(h) of the Act provides...

  17. 42 CFR 411.378 - Withdrawing a request.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Withdrawing a request. 411.378 Section 411.378 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... requesting an advisory opinion may withdraw the request before CMS issues a formal advisory opinion....

  18. 42 CFR 411.378 - Withdrawing a request.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Withdrawing a request. 411.378 Section 411.378 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... requesting an advisory opinion may withdraw the request before CMS issues a formal advisory opinion....

  19. 42 CFR 411.378 - Withdrawing a request.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Withdrawing a request. 411.378 Section 411.378 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... requesting an advisory opinion may withdraw the request before CMS issues a formal advisory opinion....

  20. 42 CFR 411.378 - Withdrawing a request.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Withdrawing a request. 411.378 Section 411.378 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... requesting an advisory opinion may withdraw the request before CMS issues a formal advisory opinion....

  1. 42 CFR 411.378 - Withdrawing a request.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Withdrawing a request. 411.378 Section 411.378 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... requesting an advisory opinion may withdraw the request before CMS issues a formal advisory opinion....

  2. 30 CFR 74.18 - Withdrawal of certification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Withdrawal of certification. 74.18 Section 74.18 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH COAL MINE DUST SAMPLING DEVICES General Requirements for All Devices § 74.18 Withdrawal...

  3. 30 CFR 74.18 - Withdrawal of certification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Withdrawal of certification. 74.18 Section 74.18 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH COAL MINE DUST SAMPLING DEVICES General Requirements for All Devices § 74.18 Withdrawal...

  4. 30 CFR 74.18 - Withdrawal of certification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Withdrawal of certification. 74.18 Section 74.18 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH COAL MINE DUST SAMPLING DEVICES General Requirements for All Devices § 74.18 Withdrawal...

  5. Anhedonia as a component of the tobacco withdrawal syndrome.

    PubMed

    Cook, Jessica W; Piper, Megan E; Leventhal, Adam M; Schlam, Tanya R; Fiore, Michael C; Baker, Timothy B

    2015-02-01

    Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this topic has not been addressed definitively in research with humans. This research sought to determine whether anhedonia is (a) an element of the tobacco withdrawal syndrome in humans and (b) an impediment to successful tobacco cessation. Data were from 1,175 smokers (58.3% women; 85.5% White) participating in a randomized double-blind, placebo-controlled trial of smoking cessation pharmacotherapies. Ecological momentary assessments for 5 days before and 10 days after the target quit day were used to assess anhedonia and other established withdrawal symptoms. Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change in response to tobacco cessation and was associated with the severity of other withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated with decreased latency to relapse (hazard ratio = 1.09, 95% confidence interval [CI] [1.02, 1.17]) and with lower 8-week point-prevalence abstinence (odds ratio = .91, 95% CI [.86, .97])-relations that remained significant when other withdrawal symptoms were included as predictors. Finally, nicotine replacement therapy nearly fully suppressed the increase in abstinence-related anhedonia (β = -.66, p < .001), suggesting agonist suppression of withdrawal. Results suggest that anhedonia is a unique and motivationally significant element of the tobacco withdrawal syndrome in humans. These results have implications for defining and assessing tobacco use disorder and for understanding and treating tobacco addiction. PMID:25384069

  6. 27 CFR 22.111 - Withdrawals under permit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawals under permit...-Free Alcohol § 22.111 Withdrawals under permit. (a) General. The permit, Form 5150.9, issued under... distilled spirits plant or, under the provisions of 26 U.S.C. 5688(a)(2)(B), receive alcohol from...

  7. The Longitudinal Impact of Demand and Withdrawal during Marital Conflict.

    ERIC Educational Resources Information Center

    Heavey, Christopher L.; And Others

    1995-01-01

    Couples (n=48) completed a measure of relationship satisfaction and participated in two videotaped problem-solving interactions. Thirty-six men and women completed the same satisfaction measure 2.5 years later. Withdrawal by men and woman-demand-man withdrawal in issues identified by the women reliably predicted decline in wives' relationship…

  8. 20 CFR 416.1555 - Withdrawing charges against a representative.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... When we consider withdrawing charges brought under § 416.1545(d) or (e) based on the representative's assertion that, before or after our filing of charges, the representative has been reinstated to practice by... representative. We will withdraw charges if the representative files an answer, or we obtain evidence,...

  9. 20 CFR 404.1755 - Withdrawing charges against a representative.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... When we consider withdrawing charges brought under § 404.1745(d) or (e) based on the representative's assertion that, before or after our filing of charges, the representative has been reinstated to practice by... representative. We will withdraw charges if the representative files an answer, or we obtain evidence,...

  10. 17 CFR 242.405 - Withdrawal of margin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... account after such withdrawal is sufficient to satisfy the required margin for the security futures and...) REGULATIONS M, SHO, ATS, AC, AND NMS AND CUSTOMER MARGIN REQUIREMENTS FOR SECURITY FUTURES Customer Margin Requirements for Security Futures § 242.405 Withdrawal of margin. (a) By the customer. Except as...

  11. 39 CFR 761.5 - Withdrawal of Postal Service securities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Withdrawal of Postal Service securities. 761.5 Section 761.5 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.5 Withdrawal of Postal Service securities. (a)...

  12. 39 CFR 761.5 - Withdrawal of Postal Service securities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Withdrawal of Postal Service securities. 761.5 Section 761.5 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.5 Withdrawal of Postal Service securities. (a)...

  13. 39 CFR 761.5 - Withdrawal of Postal Service securities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Withdrawal of Postal Service securities. 761.5 Section 761.5 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.5 Withdrawal of Postal Service securities. (a)...

  14. 39 CFR 761.5 - Withdrawal of Postal Service securities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Withdrawal of Postal Service securities. 761.5 Section 761.5 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.5 Withdrawal of Postal Service securities. (a)...

  15. 39 CFR 761.5 - Withdrawal of Postal Service securities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Withdrawal of Postal Service securities. 761.5 Section 761.5 Postal Service UNITED STATES POSTAL SERVICE POSTAL SERVICE DEBT OBLIGATIONS; DISBURSEMENT POSTAL MONEY ORDERS BOOK-ENTRY PROCEDURES § 761.5 Withdrawal of Postal Service securities. (a)...

  16. 16 CFR 803.12 - Withdraw and refile notification.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Federal Trade Commission and the Antitrust Division in writing of such withdrawal. (b) Upon public... withdrawal of a tender offer or the termination of an agreement or letter of intent is made by the acquiring... SEC filing indicating a desire to recommence the tender offer or enter into a new or amended...

  17. 29 CFR 528.5 - Proceedings for withdrawal or annulment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.5 Proceedings for withdrawal or... 29 Labor 3 2012-07-01 2012-07-01 false Proceedings for withdrawal or annulment. 528.5 Section 528.5 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  18. 29 CFR 528.5 - Proceedings for withdrawal or annulment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.5 Proceedings for withdrawal or... 29 Labor 3 2014-07-01 2014-07-01 false Proceedings for withdrawal or annulment. 528.5 Section 528.5 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  19. 29 CFR 528.3 - Withdrawal and annulment of certificates.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.3 Withdrawal and annulment of... 29 Labor 3 2011-07-01 2011-07-01 false Withdrawal and annulment of certificates. 528.3 Section 528.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  20. 29 CFR 528.3 - Withdrawal and annulment of certificates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.3 Withdrawal and annulment of... 29 Labor 3 2014-07-01 2014-07-01 false Withdrawal and annulment of certificates. 528.3 Section 528.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  1. 29 CFR 528.5 - Proceedings for withdrawal or annulment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.5 Proceedings for withdrawal or... 29 Labor 3 2013-07-01 2013-07-01 false Proceedings for withdrawal or annulment. 528.5 Section 528.5 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  2. 29 CFR 528.5 - Proceedings for withdrawal or annulment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.5 Proceedings for withdrawal or... 29 Labor 3 2010-07-01 2010-07-01 false Proceedings for withdrawal or annulment. 528.5 Section 528.5 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  3. 29 CFR 528.5 - Proceedings for withdrawal or annulment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.5 Proceedings for withdrawal or... 29 Labor 3 2011-07-01 2011-07-01 false Proceedings for withdrawal or annulment. 528.5 Section 528.5 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  4. 29 CFR 528.3 - Withdrawal and annulment of certificates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.3 Withdrawal and annulment of... 29 Labor 3 2010-07-01 2010-07-01 false Withdrawal and annulment of certificates. 528.3 Section 528.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  5. 29 CFR 528.3 - Withdrawal and annulment of certificates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.3 Withdrawal and annulment of... 29 Labor 3 2012-07-01 2012-07-01 false Withdrawal and annulment of certificates. 528.3 Section 528.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  6. 29 CFR 528.3 - Withdrawal and annulment of certificates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RETAIL OR SERVICE ESTABLISHMENTS AT SPECIAL MINIMUM WAGE RATES § 528.3 Withdrawal and annulment of... 29 Labor 3 2013-07-01 2013-07-01 false Withdrawal and annulment of certificates. 528.3 Section 528.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  7. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  8. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  9. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  10. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  11. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  12. 37 CFR 1.313 - Withdrawal from issue.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Withdrawal from issue. 1.313... COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Allowance and Issue of Patent § 1.313 Withdrawal from issue. (a) Applications may be withdrawn from issue for further action...

  13. Anhedonia as a Component of the Tobacco Withdrawal Syndrome

    PubMed Central

    Cook, Jessica W.; Piper, Megan E.; Leventhal, Adam M.; Schlam, Tanya R.; Fiore, Michael C.; Baker, Timothy B.

    2015-01-01

    Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this topic has not been addressed definitively in research with humans. This research sought to determine whether anhedonia is: 1) an element of the tobacco withdrawal syndrome in humans and 2) an impediment to successful tobacco cessation. Data were from 1175 smokers (58.3% women; 85.5% white) participating in a randomized, double blind, placebo-controlled trial of smoking cessation pharmacotherapies. Ecological momentary assessments for 5 days before and 10 days after the target quit day were used to assess anhedonia and other established withdrawal symptoms. Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change in response to tobacco cessation and was associated with the severity of other withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated with decreased latency to relapse (HR=1.09, 95%CI[1.02,1.17]) and with lower 8-week point prevalence abstinence (OR=.91, 95%CI[.86,.97])—relations that remained significant when other withdrawal symptoms were included as predictors. Finally, nicotine replacement therapy nearly fully suppressed the increase in abstinence-related anhedonia (β = −.66, p<.001), suggesting agonist suppression of withdrawal. Results suggest that anhedonia is a unique and motivationally significant element of the tobacco withdrawal syndrome in humans. These results have implications for defining and assessing tobacco use disorder and for understanding and treating tobacco addiction. PMID:25384069

  14. 15 CFR 10.13 - Withdrawal of a published standard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.13 Withdrawal of a published standard. (a) Standards published... organization, or that lack of government sponsorship would result in significant public disadvantage for legal... advantages and disadvantages of amendment, revision, development of a new standard, or withdrawal with...

  15. The Relationship of Personality Variables to Organizational Withdrawal

    ERIC Educational Resources Information Center

    Bernardin, H. John

    1977-01-01

    Investigates the relationship of personality characteristics to organizational withdrawal and tests the Porter and Steers "polar" hypothesis, i.e., employees with high levels of emotional instability, anxiety, achievement orientation, aggression, independence, self-confidence and sociability were more apt to withdraw from organizations than…

  16. 21 CFR 900.6 - Withdrawal of approval.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal of approval. 900.6 Section 900.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY Accreditation § 900.6 Withdrawal of approval. If FDA...

  17. Why Students Drop Classes and Withdraw from American River College.

    ERIC Educational Resources Information Center

    Rasor, Richard A.; And Others

    In an effort to determine the causes of student attrition, a study was conducted at American River College (ARC) in December 1979, involving: (1) a survey of 1,174 students who had dropped at least one class while at ARC, and (2) a categorization of the reasons for college withdrawal indicated by 591 students on ARC's standardized withdrawal form.…

  18. 17 CFR 41.47 - Withdrawal of margin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Withdrawal of margin. 41.47... PRODUCTS Customer Accounts and Margin Requirements § 41.47 Withdrawal of margin. (a) By the customer... deposited as margin for positions in an account may be withdrawn, provided that the equity in the...

  19. 17 CFR 242.405 - Withdrawal of margin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Withdrawal of margin. 242.405...) REGULATIONS M, SHO, ATS, AC, AND NMS AND CUSTOMER MARGIN REQUIREMENTS FOR SECURITY FUTURES Customer Margin Requirements for Security Futures § 242.405 Withdrawal of margin. (a) By the customer. Except as...

  20. 27 CFR 19.536 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... free of tax. 19.536 Section 19.536 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawal of Spirits Free of Tax § 19.536 Authorized withdrawals free of tax. Pursuant to the regulations in this chapter, spirits may be withdrawn from bonded premises free of tax— (a) On receipt of a...

  1. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of disability retirement applications. (a) OPM will honor, without question, an applicant's request to...

  2. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of disability retirement applications. (a) OPM will honor, without question, an applicant's request to...

  3. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of disability retirement applications. (a) OPM will honor, without question, an applicant's request to...

  4. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of disability retirement applications. (a) OPM will honor, without question, an applicant's request to...

  5. 46 CFR 287.10 - Withdrawals from fund.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OPERATORS ESTABLISHMENT OF CONSTRUCTION RESERVE FUNDS § 287.10 Withdrawals from fund. (a) Withdrawals for... contract for the construction or acquisition of new vessel or vessels or for the liquidation of existing or... contract for the construction or acquisition of a new vessel or vessels or for the liquidation of...

  6. 26 CFR 2.1-10 - Withdrawals from fund.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MARITIME CONSTRUCTION RESERVE FUND § 2.1-10 Withdrawals from fund. (a) Withdrawals for obligations or... the construction or acquisition of a new vessel or vessels or for the liquidation of existing or... contract for the construction or acquisition of a new vessel or vessels or for the liquidation of...

  7. 46 CFR 287.10 - Withdrawals from fund.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OPERATORS ESTABLISHMENT OF CONSTRUCTION RESERVE FUNDS § 287.10 Withdrawals from fund. (a) Withdrawals for... contract for the construction or acquisition of new vessel or vessels or for the liquidation of existing or... contract for the construction or acquisition of a new vessel or vessels or for the liquidation of...

  8. 26 CFR 2.1-10 - Withdrawals from fund.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MARITIME CONSTRUCTION RESERVE FUND § 2.1-10 Withdrawals from fund. (a) Withdrawals for obligations or... the construction or acquisition of a new vessel or vessels or for the liquidation of existing or... contract for the construction or acquisition of a new vessel or vessels or for the liquidation of...

  9. 49 CFR 450.16 - Withdrawal of delegation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 6 2011-10-01 2011-10-01 false Withdrawal of delegation. 450.16 Section 450.16 Transportation Other Regulations Relating to Transportation (Continued) COAST GUARD, DEPARTMENT OF HOMELAND SECURITY SAFETY APPROVAL OF CARGO CONTAINERS GENERAL Procedure for Delegation to Approval Authorities § 450.16 Withdrawal of delegation. (a)...

  10. 20 CFR 702.225 - Withdrawal of a claim.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Withdrawal of a claim. 702.225 Section 702.225 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT AND RELATED STATUTES ADMINISTRATION AND PROCEDURE Claims Procedures Claims § 702.225 Withdrawal of a claim....

  11. 5 CFR 831.1207 - Withdrawal of disability retirement applications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Withdrawal of disability retirement...) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1207 Withdrawal of disability retirement applications. (a) OPM will honor, without question, an applicant's request to...

  12. Challenges of withdrawal from chronic antidepressant medication: a healing odyssey.

    PubMed

    Whedon, James M; Rugo, Nancy A; Lux, Kenneth

    2013-01-01

    We report the case of a woman with posttraumatic stress disorder secondary to childhood sexual assault who attempted withdrawal from long-term use of antidepressant medication and experimented with a plethora of different therapies. The complex case history illustrates the potential difficulty of withdrawal from chronic antidepressant medication and the role of integrative therapies for posttraumatic stress disorder. PMID:23452714

  13. 24 CFR 13.3 - Withdrawal of data.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Withdrawal of data. 13.3 Section 13.3 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 13.3 Withdrawal of data....

  14. 24 CFR 13.3 - Withdrawal of data.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Withdrawal of data. 13.3 Section 13.3 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 13.3 Withdrawal of data....

  15. 24 CFR 13.3 - Withdrawal of data.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Withdrawal of data. 13.3 Section 13.3 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 13.3 Withdrawal of data....

  16. 24 CFR 13.3 - Withdrawal of data.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Withdrawal of data. 13.3 Section 13.3 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 13.3 Withdrawal of data....

  17. Phencyclidine withdrawal disrupts episodic-like memory in rats: reversal by donepezil but not clozapine.

    PubMed

    Le Cozannet, Romain; Fone, Kevin C F; Moran, Paula M

    2010-09-01

    Episodic memory is the capacity to recall an event in time and place (What? Where? When?). Impaired episodic memory is a debilitating cognitive symptom in schizophrenia but is poorly controlled by currently available antipsychotic drugs. Consistent with glutamatergic abnormality in schizophrenia, the NDMA receptor antagonist, phencyclidine (PCP), induces persistent 'schizophrenia-like' symptoms including memory deficits in humans and rodents and is widely used as an animal model of the disorder. However, in contrast to humans, PCP and PCP withdrawal-induced memory deficits in rodents are reversed by antipsychotic drugs such as clozapine. One possible explanation is that the memory tasks used in animal studies do not simultaneously test the What? Where? When? components that characterize episodic memory in human tasks. We investigated whether subchronic PCP withdrawal disrupts memory in rats in a task that requires simultaneous integration of memory for object, place and context. Rats learn to discriminate objects under specific spatial and contextual conditions analogous to the What? Where? When? components of human episodic memory. We found that PCP withdrawal impaired performance on this task and that the atypical antipsychotic drug clozapine did not reverse this impairment. However the acetylcholinesterase inhibitor (AChEI) donepezil, which has been shown to improve episodic memory in humans did reverse the effect of PCP. This suggests that PCP withdrawal disruption of object-place-context recognition in rats may prove to be a useful model to investigate episodic memory impairment in schizophrenia and supports the suggestion that AChEIs could prove to be a useful pharmacological strategy to specifically treat episodic memory problems in schizophrenia. PMID:20236574

  18. Are withholding and withdrawing therapy always morally equivalent?

    PubMed

    Sulmasy, D P; Sugarman, J

    1994-12-01

    Many medical ethicists accept the thesis that there is no moral difference between withholding and withdrawing life-sustaining therapy. In this paper, we offer an interesting counterexample which shows that this thesis is not always true. Withholding is distinguished from withdrawing by the simple fact that therapy must have already been initiated in order to speak coherently about withdrawal. Provided that there is a genuine need and that therapy is biomedically effective, the historical fact that therapy has been initiated entails a claim to continue therapy that cannot be attributed to patients who have not yet received therapy. This intrinsic difference between withholding and withdrawing therapy is of moral importance. In many instances, patients will waive this claim. But when one considers withdrawing therapy from one patient to help another in a setting of scarce resources, this intrinsic moral difference comes into sharp focus. In an era of shrinking medical resources, this difference cannot be ignored. PMID:7861426

  19. Are withholding and withdrawing therapy always morally equivalent?

    PubMed Central

    Sulmasy, D P; Sugarman, J

    1994-01-01

    Many medical ethicists accept the thesis that there is no moral difference between withholding and withdrawing life-sustaining therapy. In this paper, we offer an interesting counterexample which shows that this thesis is not always true. Withholding is distinguished from withdrawing by the simple fact that therapy must have already been initiated in order to speak coherently about withdrawal. Provided that there is a genuine need and that therapy is biomedically effective, the historical fact that therapy has been initiated entails a claim to continue therapy that cannot be attributed to patients who have not yet received therapy. This intrinsic difference between withholding and withdrawing therapy is of moral importance. In many instances, patients will waive this claim. But when one considers withdrawing therapy from one patient to help another in a setting of scarce resources, this intrinsic moral difference comes into sharp focus. In an era of shrinking medical resources, this difference cannot be ignored. PMID:7861426

  20. Cognitive Function During Nicotine Withdrawal: Implications for Nicotine Dependence Treatment

    PubMed Central

    Ashare, Rebecca L.; Falcone, Mary; Lerman, Caryn

    2013-01-01

    Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition. Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts. A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment. We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects. We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity. We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal. PMID:23639437

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  2. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol. PMID:25790020

  3. Progestin withdrawal at parturition in the mare.

    PubMed

    Legacki, Erin L; Corbin, C J; Ball, B A; Wynn, M; Loux, S; Stanley, S D; Conley, A J

    2016-10-01

    Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3β, 20α-diol (3β,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry. The biopotency of dominant metabolites was assessed using luciferase reporter assays. Stable transfected Chinese hamster ovarian cells expressing the equine progesterone receptor (ePGR) were transfected with an MMTV-luciferase expression plasmid responsive to steroid agonists. Cells were incubated with increasing concentrations (0-100nM) of progesterone, 20αDHP and 3α,20βDHP. The concentrations of circulating pregnanes in periparturient mares were (highest to lowest) 3α,20βDHP and 20αDHP (800-400ng/mL respectively), DHP and allopregnanolone (90 and 30ng/mL respectively), and pregnenolone and progesterone (4-2ng/mL). Concentrations of all measured pregnanes declined on average by 50% from prepartum peaks to the day before foaling. Maximum activation of the ePGR by progesterone occurred at 30nM; 20αDHP and 3α,20βDHP were significantly less biopotent. At prepartum concentrations, both 20αDHP and 3α,20βDHP exhibited significant ePGR activation. Progestogenic support of pregnancy declines from 3 to 5days before foaling. Prepartum peak concentrations indicate that DHP is the major progestin, but other pregnanes like 20αDHP are present in sufficient concentrations to play a physiological role in the absence of DHP. The authors conclude that progestin withdrawal associated with parturition in mares involves cessation of pregnane synthesis by the placenta. PMID:27568209

  4. 75 FR 74743 - Notice of Proposed Withdrawal Extension, Corrections to Existing Withdrawal, and Opportunity for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... application to extend the withdrawal established by PLO No. 6849 (56 FR 16278), for an additional 20-year term... subsequently corrected by Federal Register notice 56 FR 24119, and PLO Nos. 6849 and 6907. The corrections to.... 10, N\\1/2\\N\\1/2\\, SE\\1/4\\NE\\1/4\\, and E\\1/2\\SE\\1/4\\; Secs. 11 to 14, inclusive; Sec. 15, NE\\1/4\\,...

  5. Attenuation of Morphine Withdrawal Syndrome by Various Dosages of Curcumin in Comparison with Clonidine in Mouse: Possible Mechanism

    PubMed Central

    Motaghinejad, Majid; Bangash, Mohammad Yasan; Hosseini, Pantea; Karimian, Seyed Morteza; Motaghinejad, Ozra

    2015-01-01

    Background Herbal medical compounds and their major constituent have been used in the management and treatment of opioid withdrawal syndrome and pain. This study was carried out to clarify the effect of curcumin, the major compound of turmeric, on morphine withdrawal syndrome in mouse model and its possible mechanisms of pain relieving activity by assessing in writhing test as a model of visceral pain. Methods Due to two separate protocols (withdrawal syndrome and pain), 144 male albino mice were divided in two major groups. In withdrawal syndrome group, test effect of various dosages of curcumin (10, 20, and 40 mg/kg) was assessed on withdrawal signs and compared with positive and negative control and standard treatment (clonidine 0.4 mg/kg) groups. In pain groups, to determine the mechanism of pain relieving activity of curcumin, various dosages of curcumin (10, 20, and 40 mg/kg) in three separated groups, were used against acetic acid induced writhing (which is a constriction) test. The most effective dose (40 mg/kg) was used in writhing test and compared with groups pretreated with antagonist of major neurotransmitters involved in pain; and compared with group pretreated with vehicle (DMSO, 0.05%) as control. Results Curcumin attenuates withdrawal syndrome in a dose dependent manner in comparison with the dependent positive control group (P<0.05). It also indicated that pretreatment with naloxone and cyproheptadine significantly attenuate antinociception effect of curcumin (P<0.05). Conclusion This study advocate that antinociception of curcumin was mediated by opioidergic and adrenergic system. PMID:25821292

  6. Progesterone receptor expression declines in the guinea pig uterus during functional progesterone withdrawal and in response to prostaglandins.

    PubMed

    Welsh, Toni N; Hirst, Jonathan J; Palliser, Hannah; Zakar, Tamas

    2014-01-01

    Progesterone withdrawal is essential for parturition, but the mechanism of this pivotal hormonal change is unclear in women and other mammals that give birth without a pre-labor drop in maternal progesterone levels. One possibility suggested by uterine tissue analyses and cell culture models is that progesterone receptor levels change at term decreasing the progesterone responsiveness of the myometrium, which causes progesterone withdrawal at the functional level and results in estrogen dominance enhancing uterine contractility. In this investigation we have explored whether receptor mediated functional progesterone withdrawal occurs during late pregnancy and labor in vivo. We have also determined whether prostaglandins that induce labor cause functional progesterone withdrawal by altering myometrial progesterone receptor expression. Pregnant guinea pigs were used, since this animal loses progesterone responsiveness at term and gives birth in the presence of high maternal progesterone level similarly to primates. We found that progesterone receptor mRNA and protein A and B expression decreased in the guinea pig uterus during the last third of gestation and in labor. Prostaglandin administration reduced while prostaglandin synthesis inhibitor treatment increased progesterone receptor A protein abundance. Estrogen receptor-1 protein levels remained unchanged during late gestation, in labor and after prostaglandin or prostaglandin synthesis inhibitor administration. Steroid receptor levels were higher in the non-pregnant than in the pregnant uterine horns. We conclude that the decreasing expression of both progesterone receptors A and B is a physiological mechanism of functional progesterone withdrawal in the guinea pig during late pregnancy and in labor. Further, prostaglandins administered exogenously or produced endogenously stimulate labor in part by suppressing uterine progesterone receptor A expression, which may cause functional progesterone withdrawal, promote

  7. Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

    PubMed Central

    Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

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

    PubMed

    Khor, Beng-Siang; Jamil, Mohd Fadzly Amar; Adenan, Mohamad Ilham; Shu-Chien, Alexander Chong

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

  9. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  10. CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

    PubMed Central

    Wills, Kiri L.; Vemuri, Kiran; Kalmar, Alana; Lee, Alan; Limebeer, Cheryl L.; Makriyannis, Alexandros

    2014-01-01

    Rationale Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal. PMID:24770676

  11. Estimated Withdrawals from Stream-Valley Aquifers and Refined Estimated Withdrawals from Selected Aquifers in the United States, 2000

    USGS Publications Warehouse

    Sargent, B. Pierre; Maupin, Molly A.; Hinkle, Stephen R.

    2008-01-01

    The U.S. Geological Survey National Water Use Information Program compiles estimates of fresh ground-water withdrawals in the United States on a 5-year interval. In the year-2000 compilation, withdrawals were reported from principal aquifers and aquifer systems including two general aquifers - Alluvial and Other aquifers. Withdrawals from a widespread aquifer group - stream-valley aquifers - were not specifically identified in the year-2000 compilation, but they are important sources of ground water. Stream-valley aquifers are alluvial aquifers located in the valley of major streams and rivers. Stream-valley aquifers are long but narrow aquifers that are in direct hydraulic connection with associated streams and limited in extent compared to most principal aquifers. Based in large part on information published in U.S. Geological Survey reports, preliminary analysis of withdrawal data and hydrogeologic and surface-water information indicated areas in the United States where possible stream-valley aquifers were located. Further assessment focused on 24 states and the Commonwealth of Puerto Rico. Withdrawals reported from Alluvial aquifers in 16 states and withdrawals reported from Other aquifers in 6 states and the Commonwealth of Puerto Rico were investigated. Two additional States - Arkansas and New Jersey - were investigated because withdrawals reported from other principal aquifers in these two States may be from stream-valley aquifers. Withdrawals from stream-valley aquifers were identified in 20 States and were about 1,560 Mgal/d (million gallons per day), a rate comparable to withdrawals from the 10 most productive principal aquifers in the United States. Of the 1,560 Mgal/d of withdrawals attributed to stream-valley aquifers, 1,240 Mgal/d were disaggregated from Alluvial aquifers, 150 Mgal/d from glacial sand and gravel aquifers, 116 Mgal/d from Other aquifers, 28.1 Mgal/d from Pennsylvanian aquifers, and 24.9 Mgal/d from the Mississippi River Valley alluvial

  12. Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of alpha-lipoic acid administration.

    PubMed

    Pinelli, Arnaldo; Cighetti, Giuliana; Trivulzio, Silvio

    2008-08-01

    A number of experimental studies have found that reactive oxygen species are involved during morphine treatment or withdrawal. The aims of this study were to analyse whether morphine administration and/or removal are related to peroxide generation and/or signs of withdrawal in rats, and whether the changes in antioxidant status induced by the administration of an antioxidant may modify peroxide levels and behavioural signs. We injected morphine or morphine and naloxone into rats and evaluated the plasma levels of peroxide malondialdehyde (MDA) and the appearance of withdrawal signs. We also investigated the effects on these parameters induced by the administration of the antioxidant alpha-lipoic acid (LA). Morphine treatment increased MDA levels. Abrupt naloxone-induced morphine withdrawal caused a further and significant increase in MDA, and the appearance of withdrawal signs such as abnormal fecal excretion, shortened latency times and jumping. The administration of LA lowered MDA levels in the rats treated with morphine or morphine plus naloxone, and also decreased MDA values and abstinence signs in the animals treated with morphine plus naloxone. The effects of LA were attributed to its capacity to scavenge peroxides and interfere with the biogenesis of the arachidonic acid metabolites involved in the expression of abstinence symptoms. PMID:18705754

  13. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

    PubMed

    Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

    2015-10-21

    Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

  14. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  15. Change in bone mineral density at one year following glucocorticoid withdrawal in kidney transplant recipients.

    PubMed

    Ing, Steven W; Sinnott, Loraine T; Donepudi, Sirisha; Davies, Elizabeth A; Pelletier, Ronald P; Lane, Nancy E

    2011-01-01

    Glucocorticoid (GC) therapy induces deleterious effects on the skeleton in kidney transplantation but studies of GC discontinuation in this population are limited. This study evaluated changes in areal bone mineral density (BMD) with GC withdrawal. Subjects were enrolled one yr after renal transplantation and randomized to continue or stop prednisone; all subjects continued cyclosporine and mycophenolate mofetil. BMD measured by dual-energy X-ray absorptiometry was performed at enrollment and repeated at one yr and values were standardized. Mean ± standard deviation of annualized change in standardized BMD between GC withdrawal vs. continuation group at the lumbar spine was +4.7% ± 5.5 vs. +0.9% ± 5.3 (p = 0.0014); total hip +2.4% ± 4.2 vs. -0.4% ± 4.2 (p = 0.013), and femoral neck +2.1% ± 4.6 vs. +1.0% ± 6.0 (p = 0.37). There was no confounding by prednisone dose prior to enrollment, change in creatinine clearance, weight, or use of bone-active medications following study entry. Multivariate analysis determined that the change in BMD was positively associated with baseline alkaline phosphatase and creatinine clearance and negatively associated with baseline BMD. BMD improves with GC withdrawal after renal transplantation, and this gain in BMD is dependent on the baseline bone turnover, renal function, and BMD. PMID:20961333

  16. Volatile oil of Artemisia santolina decreased morphine withdrawal jumping in mice

    PubMed Central

    Gohari, Ahmad R.; Kurepaz-Mahmoodabadi, Mahdieh; Saeidnia, Soodabeh

    2013-01-01

    Introduction: Flowered aerial parts of Artemisia santolina Schrenk (Asteraceae), which is found in the central and western regions of Iran were collected from Khorasan province and the volatile oil extracted by hydro distillation. Materials and Methods: The oil (0.5% v/w) was analyzed by GC and GC/MS using DB-5 column. The effect of this oil on the withdrawal syndrome was determined in mice. After induction of dependency by morphine, mice were intraperitoneally administered different concentrations of the oil. Morphine-withdrawal inducing by naloxone was assessed by recording the incidence of escape jumps for 60 min. Results: The results indicated that a significant difference between the essential oil received group (at dose of 3.6 mg/kg) and control group was shown but the lower doses were not effective. Essential oil analysis showed that there were forty-six components, representing 95.4% of the oil. Conclusion: The oil of A. santolina which is rich in oxygenated monoterpenes with the major components, trans-verbenol (34.6%) and p-mentha3-en-8-ol (13.1%), can decreased the number of withdrawal jumping in addicted mice. PMID:23798887

  17. The effect of chronic morphine or methadone exposure and withdrawal on clock gene expression in the rat suprachiasmatic nucleus and AA-NAT activity in the pineal gland.

    PubMed

    Pačesová, D; Novotný, J; Bendová, Z

    2016-07-18

    The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine. PMID:27070740

  18. Reversal of caffeine withdrawal by ingestion of a soft beverage.

    PubMed

    Watson, J M; Lunt, M J; Morris, S; Weiss, M J; Hussey, D; Kerr, D

    2000-05-01

    Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects. PMID:10837839

  19. Reactivation of hepatitis B virus after withdrawal of erlotinib

    PubMed Central

    Bui, N.; Wong-Sefidan, I.

    2015-01-01

    Reactivation of hepatitis B virus (hbv) is a reported complication for patients undergoing chemotherapy, particularly immunochemotherapy with anti-CD20 agents such as rituximab. However, as the use of molecularly targeted agents increases, the risk of viral reactivation is less clearly defined. Here, we present the case of a 62-year-old woman with newly diagnosed EGFR mutation–positive metastatic non-small-cell lung cancer (nsclc). Per interview, our patient had a remote history of hbv infection. She was started on erlotinib and developed profound diarrhea leading to renal failure that required hospital admission and temporary discontinuation of erlotinib. At 8 days after erlotinib cessation, she had a marked spike in her liver function tests, with viral serologies that were consistent with hbv reactivation. Although erlotinib and other tyrosine kinase inhibitors (tkis) are not classically associated with hbv reactivation, hbv reactivation can occur even in the setting of tki withdrawal. Before tki initiation, careful patient screening in those at risk for hbv should be performed to attenuate preventable hepatotoxicity and to differentiate between other causes of hepatotoxicity (for example, drug-induced toxicity). PMID:26715877

  20. Reduced emotional signs of opiate withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake

    PubMed Central

    Radke, Anna K.; Holtz, Nathan A.; Gewirtz, Jonathan C.; Carroll, Marilyn E.

    2013-01-01

    Rationale Rats bred for high (HiS) and low (LoS) saccharin intake exhibit divergent behavioral responses to multiple drugs of abuse, with HiS rats displaying greater vulnerability to drug taking. Previous research indicates that this effect may be due to increased sensitivity to reward in HiS rats and to the aversive effects of acute drug administration in LoS rats. Objective The current study investigated whether HiS and LoS rats also exhibit different behavioral signs of withdrawal following one or repeated opiate exposures. Methods Emotional signs of opiate withdrawal were assessed with potentiation of the acoustic startle reflex and conditioned place aversion (CPA) in male and female HiS and LoS rats. Startle was measured before and 4 h after a 10 mg/kg injection of morphine on days 1, 2, and 7 of opiate exposure. CPA was induced with a two-day, naloxone-precipitated conditioning paradigm. Somatic signs of withdrawal and weight loss were used also measured. Results Male and female LoS rats exhibited lower startle potentiation than HiS rats on the seventh day of morphine exposure. LoS male rats also failed to develop a CPA to morphine withdrawal. No differences in physical withdrawal signs were observed between HiS and LoS rats, but males of both lines had more physical signs of withdrawal than females. Conclusions These results suggest that LoS rats are less vulnerable to the negative emotional effects of morphine withdrawal than HiS rats. A less severe withdrawal syndrome may contribute to decreased levels of drug taking in the LoS line. PMID:23254375

  1. 77 FR 11554 - Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ... HUMAN SERVICES Food and Drug Administration Final Decision on Withdrawal of Breast Cancer Indication for... final decision withdrawing approval of the breast cancer indication for AVASTIN (Bevacizumab). The... proposal to withdraw the approval. DATES: Withdrawal of AVASTIN's breast cancer indication was...

  2. Stop-out or Drop-out? An Examination of College Withdrawals and Re-Enrollments

    ERIC Educational Resources Information Center

    Woosley, Sherry

    2004-01-01

    The withdrawal policies of many universities are based on the supposition that being able to withdraw without grade point repercussions will encourage students to return to the institution at a later date. This study focused on withdrawing students and examined the differences between those who re-enroll after a withdrawal and those who do not.…

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

    PubMed

    Chan, Hung-Yu; Lee, Kuan-I

    2015-03-01

    Alcohol withdrawal syndrome is a commonly seen problem in psychiatric practice. Alcohol withdrawal delirium is associated with significant morbidity and mortality. Withdrawal symptoms usually include tremulousness, psychotic and perceptual symptoms, seizures, and consciousness disturbance. Herein, we report a case involving a 63-year-old man who had alcohol withdrawal delirium that was manifested mainly by manic symptoms. PMID:25515164

  4. Feed Withdrawal and Transport Interactions with Intestinal and Peripheral Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple stressors associated with transporting finishing pigs to slaughter can result in increased shedding of pathogens. Previously we found feed withdrawal by itself or followed by transportation increased Salmonella concentrations in ileal contents. However, no difference was found among treatm...

  5. 24 CFR 13.3 - Withdrawal of data.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a three month period from the date the National Center receives information or notice that a child... Center of the need to withdraw from circulation penalty mail envelopes and other materials related to...

  6. 7 CFR 160.26 - Withdrawal of request.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) NAVAL STORES REGULATIONS AND STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.26 Withdrawal of request....

  7. 21 CFR 900.24 - Withdrawal of approval.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY States as Certifiers § 900.24 Withdrawal of approval. If FDA... the agency, has failed to achieve the MQSA goals of quality mammography and access, or has...

  8. 18 CFR 341.13 - Withdrawal of proposed tariff publications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE INTERSTATE COMMERCE ACT OIL PIPELINE TARIFFS: OIL PIPELINE COMPANIES SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.13 Withdrawal...

  9. A Case Report of Kratom Addiction and Withdrawal.

    PubMed

    Galbis-Reig, David

    2016-02-01

    Kratom, a relatively unknown herb among physicians in the western world, is advertised on the Internet as an alternative to opioid analgesics, as a potential treatment for oploid withdrawal and as a "legal high" with minimal addiction potential. This report describes a case of kratom addiction in a 37-year-old woman with a severe oploid-like withdrawal syndrome that was managed successfully with symptom-triggered clonidine therapy and scheduled hydroxyzine. A review of other case reports of kratom toxicity, the herb's addiction potential, and the kratom withdrawal syndrome is discussed. Physicians in the United States should be aware of the growing availability and abuse of kratom and the herb's potential adverse health effects, with particular attention to kratom's toxicity, addictive potential, and associated withdrawal syndrome. PMID:27057581

  10. Astronaut's tool for withdrawing/replacing computer cards

    NASA Technical Reports Server (NTRS)

    West, R. L.

    1969-01-01

    Symmetrical tool allows astronauts to withdraw and replace Apollo Telescope Mount control computer cards. It is easily manipulated by a gloved hand, provides positive locking of a withdrawn card, and has a visible locking device.

  11. Dying on dialysis: the case for a dignified withdrawal.

    PubMed

    Schmidt, Rebecca J; Moss, Alvin H

    2014-01-01

    Acceleration of comorbid illness in patients undergoing long-term maintenance hemodialysis may be manifested by clinical deterioration that is subtle and not immediately life-threatening. Nonetheless, it is emotionally debilitating for patients and families in addition to being medically and ethically challenging for treating nephrologists. A marked decline in clinical status warrants review of the balance of benefits to burdens dialysis is providing to a given patient and should trigger conversation about the option of withdrawal using an individualized patient-centered, rather than disease-oriented, approach. This paper presents a rationale for and an objective approach to initiating and managing dialysis withdrawal for patients who wish to withdraw because of unsatisfactory quality of life and those (many with significant cognitive impairment) for whom withdrawal is deemed appropriate because the burdens of continuing treatment substantially outweigh the benefits. PMID:23970133

  12. 5 CFR 1650.32 - Financial hardship withdrawals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., unexpected, or unusual event, such as an earthquake, hurricane, tornado, flood, storm, fire, or theft. (4... participant must certify that he or he has a financial hardship as described on the hardship withdrawal...

  13. 21 CFR 900.24 - Withdrawal of approval.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MAMMOGRAPHY QUALITY STANDARDS ACT MAMMOGRAPHY States as Certifiers § 900.24 Withdrawal of approval. If FDA... the agency, has failed to achieve the MQSA goals of quality mammography and access, or has...

  14. Estimated withdrawals and use of freshwater in Vermont, 1990

    USGS Publications Warehouse

    Horn, M.A.; Medalie, Laura

    1996-01-01

    Estimated freshwater withdrawals during 1990 in Vermont totaled about 632 million gallons per day. The largest withdrawals were for thermoelectric- power generation (82 percent), industrial use (7 percent), and public supply (6 percent). Most withdrawals, 587 million gallons per day, were made from surface-water sources as compared to 44.9 million gallons per day from ground-water sources. The largest withdrawals were in the Upper Connecticut-Mascomo River Basin (525 million gallons per day). About 17,700 million gallons per day were used instream for hydroelectric-poser generation, the largest of which were in the Upper Connecticut-Mascoma and Otter River Basins. Other information describing water-use patters is shown in tables, bar graphs, pie charts, maps, and accompanying text. The data are aggregated by river basin (hydrologic cataloging unit), and all amounts are reports in million gallons per day.

  15. The time course and significance of cannabis withdrawal.

    PubMed

    Budney, Alan J; Moore, Brent A; Vandrey, Ryan G; Hughes, John R

    2003-08-01

    Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. Criteria for cannabis withdrawal are proposed. PMID:12943018

  16. BDNF–TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms

    PubMed Central

    Ren, Q; Ma, M; Yang, C; Zhang, J-C; Yao, W; Hashimoto, K

    2015-01-01

    Depression is a core symptom of methamphetamine (METH) withdrawal during the first several weeks of abstinence. However, the precise mechanisms underlying METH withdrawal symptoms remain unknown. Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), have a role the in pathophysiology of depression. In this study, we examined the role of BDNF–TrkB signaling in different brain regions of male mice with METH withdrawal symptoms. Repeated METH (3 mg kg−1 per day for 5 days) administration to mice caused a long-lasting depression-like behavior including anhedonia. Western blot analysis showed that BDNF levels in the nucleus accumbens (NAc) of METH-treated mice were significantly higher than those of control mice whereas BDNF levels in other regions, including the prefrontal cortex and hippocampus, were not altered. METH-induced depression-like behavior, behavioral sensitization and dendritic changes in the NAc shell were improved by subsequent subchronic administration of TrkB antagonist ANA-12 (0.5 mg kg−1 per day for 14 days), but not TrkB agonist 7,8-dihydroxyflavone (10 mg kg−1 per day for 14 days). In vivo microdialysis showed that METH (1 mg kg−1)-induced dopamine release in NAc shell of METH-treated mice was attenuated after subsequent subchronic ANA-12 administration. Interestingly, a single bilateral infusion of ANA-12 into the NAc shell, but not NAc core, showed a rapid and long-lasting therapeutic effect. However, ketamine and paroxetine had no effect. These findings suggest that increased BDNF–TrkB signaling in the NAc shell has an important role in the behavioral abnormalities after withdrawal from repeated METH administration, and that TrkB antagonists are potential therapeutic drugs for withdrawal symptoms in METH abusers. PMID:26506052

  17. [What happened after meprobamate's withdrawal? Survey in two nursing homes].

    PubMed

    Lounis, Yacine; Bonnet-Zamponi, Dominique; Pautas, Éric; Gaubert-Dahan, Marie-Line

    2016-01-01

    We have conducted in two nursing homes a survey to study the impact of meprobamate's withdrawal, at the beginning of 2012, in terms of extent of prescribing to others psychotropic drugs and occurrence of adverse events. After meprobamate's withdrawal, 65 % of residents did not receive alternative medication and within three months after meprobamate stopping, adverse events (drowsiness, falls and hospitalization) decreased while agitation did not increase. PMID:26976315

  18. Status Cataplecticus Precipitated by Abrupt Withdrawal of Venlafaxine

    PubMed Central

    Wang, Janice; Greenberg, Harly

    2013-01-01

    Status cataplecticus is a rare manifestation of narcolepsy with cataplexy episodes recurring for hours or days, without a refractory period, in the absence of emotional triggers. This case highlights a narcoleptic patient who developed status cataplecticus after abrupt withdrawal of venlafaxine. Citation: Wang J; Greenberg H. Status cataplecticus precipitated by abrupt withdrawal of venlafaxine. J Clin Sleep Med 2013;9(7):715-716. PMID:23853567

  19. Differential long-term neuroadaptations of glutamate receptors in the basolateral and central amygdala after withdrawal from cocaine self-administration in rats.

    PubMed

    Lu, Lin; Dempsey, Jack; Shaham, Yavin; Hope, Bruce T

    2005-07-01

    Humans and laboratory animals remain highly vulnerable to relapse to cocaine-seeking after prolonged periods of withdrawal from the drug. It has been hypothesized that this persistent cocaine relapse vulnerability involves drug-induced alterations in glutamatergic synapses within the mesolimbic dopamine reward system. Previous studies have shown that cocaine self-administration induces long-lasting neuroadaptations in glutamate neurons of the ventral tegmental area and nucleus accumbens. Here, we determined the effect of cocaine self-administration and subsequent withdrawal on glutamate receptor expression in the amygdala, a component of the mesolimbic dopamine system that is involved in cocaine seeking and craving induced by drug-associated cues. Rats were trained for 10 days to self-administer intravenous cocaine (6 h/day) or saline (a control condition) and were killed after one or 30 withdrawal days. Basolateral and central amygdala tissues were assayed for protein expression of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits (GluR1 and GluR2) and the NMDA receptor subunits (NR1, NR2A and NR2B). In the basolateral amygdala, GluR1 but not GluR2 levels were increased on days 1 and 30, NR2A levels were increased on day 1, and NR2B levels were decreased on day 30 of withdrawal from cocaine. In the central amygdala, GluR2 but not GluR1 levels were increased on days 1 and 30, NR1 levels were increased on day 30 and NR2A or NR2B levels were not altered after withdrawal from cocaine. These results indicate that cocaine self-administration and subsequent withdrawal induces long-lasting and differential neuroadaptations in basolateral and central amygdala glutamate receptors. PMID:15953359

  20. Gamma-hydroxybutyrate withdrawal syndrome: a case report

    PubMed Central

    2009-01-01

    Introduction To raise awareness among health care workers of the risk of withdrawal symptoms after longstanding and intense abuse of gamma-hydroxybutyric acid. Case presentation A 23 year old Caucasian woman presented with gamma-hydroxybutyric addiction and withdrawal syndrome. The symptoms of gamma-hydroxybutyric withdrawal in this patient initially went unrecognized, upon which her situation deteriorated in such a way that she needed to be admitted to the Intensive Care Unit for airway protection and mechanical ventilation. Treatment with high doses of benzodiazepines led to liberation of the ventilator and further recovery. Conclusion Withdrawal symptoms of gamma-hydroxybutyric addiction are often not well recognized and the responsible physicians at Emergency Department, Intensive Care Unit and the Psychiatry ward need better understanding of diagnose and treatment. Gamma-hydroxybutyric acid withdrawal is potentially life threatening and its management may require a multidisciplinary approach. Early recognition of gamma-hydroxybutyric acid withdrawal may lead to better management of these patients. PMID:20181164

  1. Craving and nicotine withdrawal in a Spanish smoking cessation sample.

    PubMed

    Piñeiro, Bárbara; López-Durán, Ana; Fernández del Río, Elena; Martínez, Úrsula; Brandon, Thomas H; Becoña, Elisardo

    2014-01-01

    Craving and nicotine withdrawal syndrome (NWS) are components of the tobacco use disorder in DSM-5. They both appear after smoking cessation or an abrupt reduction in tobacco use, and they are associated with both short and long-term smoking-cessation outcomes. The aim of the present study was to examine the association of craving and withdrawal with smoking cessation at the end of the treatment and relapse at 3 months follow-up in a Spanish sample of smokers. The sample comprised 342 smokers (37.7% men; 62.3% women) receiving a cognitive-behavioral treatment for smoking cessation. The assessments of craving and withdrawal were conducted using the Minnesota Nicotine Withdrawal Scale. Abstainers at the end of the treatment, compared to non abstainers, showed significantly lower post-treatment withdrawal, and post-treatment craving. Furthermore, they had lower scores in pre-treatment nicotine dependence. Among abstainers, craving decreased significantly from pre-cessation levels, while in those participants who did not quit smoking it remained on the same levels. High nicotine dependence was a predictor of smoking at the end of the treatment, whereas high nicotine withdrawal predicted relapse at 3 months. Findings support the robust role of craving and NWS in smoking cessation and relapse, although they differ in their specific patterns of change over time. PMID:25314038

  2. Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

    PubMed

    Enrico, P; Migliore, M; Spiga, S; Mulas, G; Caboni, F; Diana, M

    2016-05-13

    Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal. PMID:26899424

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

    PubMed Central

    2010-01-01

    Background The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research. Methods A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization. Results Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured. Conclusions We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers. PMID:20492717

  4. Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal.

    PubMed

    Ren, Wenwei; Tao, Jingyan; Wei, Youdan; Su, Hang; Zhang, Jie; Xie, Ying; Guo, Jun; Zhang, Xiangyang; Zhang, Hailing; He, Jincai

    2016-02-01

    Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal.179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only).Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28  ±  490.69 vs 1241.27  ±  335.52  pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70  ±  580.59 vs 1621.41  ±  591.07  pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70  ±  580.59 vs 1241.27  ±  335.52  pg/mL; F = 2.29, P = 0.13).Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal. PMID:26844469

  5. Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal

    PubMed Central

    Ren, Wenwei; Tao, Jingyan; Wei, Youdan; Su, Hang; Zhang, Jie; Xie, Ying; Guo, Jun; Zhang, Xiangyang; Zhang, Hailing; He, Jincai

    2016-01-01

    Abstract Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal. 179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only). Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28 ± 490.69 vs 1241.27 ± 335.52 pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70 ± 580.59 vs 1621.41 ± 591.07 pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70 ± 580.59 vs 1241.27 ± 335.52 pg/mL; F = 2.29, P = 0.13). Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal. PMID:26844469

  6. Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers

    PubMed Central

    Cooper, Kim N.; Mahoney, James J.; Bordnick, Patrick S.; Salas, Ramiro; Kosten, Thomas R.; Dani, John A.; De La Garza, Richard

    2015-01-01

    Introduction: Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Methods: Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. Results: The data show that self-reported levels of “craving” (p < .01) and “thinking about cigarettes” (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). Conclusions: In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting. PMID:25475087

  7. Groundwater withdrawal impacts in a karst area

    NASA Astrophysics Data System (ADS)

    Destephen, R. A.; Benson, C. P.

    1993-12-01

    During a 3000-gpm pump test on a groundwater supply well in Augusta County, Virginia, residential properties were impacted. The impacts included lowered farm pond water levels, development of a sinkhole, and water level decrease in residential wells. A study was performed to assess whether a lower design yield was possible with minimal impacts on adjacent property. This study included a 48-h 1500-gpm pump test that evaluated impacts due to: (1) sinkhole development and potential damage to homes, (2) loss of water in residential wells, and (3) water-quality degradation. Spring flows, residential well levels, survey monuments, and water quality were monitored. Groundwater and surface water testing included inorganic water-quality parameters and microbiological parameters. The latter included particulate analyses, Giardia cysts, and coliforms, which were used to evaluate the connection between groundwater and local surface waterbodies. Although results of the study indicated a low potential for structural damage due to future sinkhole activity, it showed that the water quality of some residential wells might be degraded. Because particulate analyses confirmed that groundwater into the supply well is under the direct influence of surface water, it was recommended that certain residents be placed on an alternate water supply prior to production pumping and that filtration be provided for the well in accordance with the Surface Water Treatment Rule. A mitigation plan was implemented. This plan included crack surveys, a long-term settlement station monitoring program, and limitation of the groundwater withdrawal rate to 1.0 million gallons per day (mgd) and maximum production rate to 1500 gpm.

  8. Treatment of Alcohol Withdrawal Syndrome with and without Dexmedetomidine

    PubMed Central

    Beg, Muna; Fisher, Sara; Siu, Dana; Rajan, Sudhir; Troxell, Lawrence; Liu, Vincent X

    2016-01-01

    Context: Studies suggest that dexmedetomidine—an intravenous central-acting α2-adrenergic agonist that effectively reduces anxiety among critically ill patients—is being used in patients with severe alcohol withdrawal. However, evidence supporting its use is limited, and it is not approved for this indication. Objective: To assess the effect of dexmedetomidine on severe alcohol withdrawal symptoms and to compare its use with benzodiazepines alone. Design: A retrospective, cohort study of 77 patients admitted to the adult medical intensive care unit with severe alcohol withdrawal between January 1, 2009, and October 31, 2013. Main Outcome Measures: The difference in lorazepam equivalents and Clinical Institute Withdrawal Assessment for Alcohol scores in the 24 hours before and after initiation of dexmedetomidine therapy. Results: The frequency of dexmedetomidine use increased dramatically between 2009 and 2013 (16.7% vs 82.4%; p = 0.01). Initiation of dexmedetomidine therapy was associated with significant improvements in Clinical Institute Withdrawal Assessment for Alcohol scores over corresponding 24-hour intervals (14.5 vs 8.5; p < 0.01). Benzodiazepine use also decreased, but the difference was not statistically significant at 24 hours (p = 0.10). Dexmedetomidine was well tolerated, requiring discontinuation of therapy in only 4 patients (10.5%). Dexmedetomidine use was also associated with significantly longer hospitalizations (p < 0.01). Conclusion: Dexmedetomidine initiation was associated with a reduction in short-term alcohol withdrawal symptoms in patients in the intensive care unit, with only a few patients experiencing adverse events. However, its use was also associated with longer hospitalizations. Further research is necessary to evaluate whether dexmedetomidine is efficacious or cost-effective in severe alcohol withdrawal. PMID:27168398

  9. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  10. Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

    PubMed Central

    Sharma, Hari S; Ali, Syed F; Patnaik, Ranjana; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Muresanu, Dafin F

    2011-01-01

    The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were developed by cessation of the drug administration on day 13th that were prominent on day 14th and continued up to day 15th (24 to 72 h periods). In a separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15th. In these animals, morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the withdrawal symptoms and neuronal damage. Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the HSP expression during this phase. Furthermore, cerebrolysin reduced the withdrawal symptoms on day 14th to 15th. Taken together these observations suggest that cellular stress plays an important role in morphine induced pain pathology and exogenous supplement of growth factors, i.e. cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier. PMID:21886595

  11. Data withdrawal in randomized controlled trials: Defining the problem and proposing solutions: a commentary.

    PubMed

    Ye, Chenglin; Giangregorio, Lora; Holbrook, Anne; Pullenayegum, Eleanor; Goldsmith, Charlie H; Thabane, Lehana

    2011-05-01

    It is not uncommon for a participant to withdraw from a randomized controlled trial (RCT). The withdrawal of a participant results in missing data and the potential for withdrawal bias. Data withdrawal, or a request from a participant to withdraw all of their previously collected data from a study, is particularly problematic because it leaves little opportunity to characterize or statistically address those that have withdrawn to minimize withdrawal bias. The aim of this commentary is to (1) provide a synthesis of available information on the ethical and methodological issues related to data withdrawal in RCTs and (2) provide some suggestions on how to minimize the impact of data withdrawal during the execution or analysis phases of an RCT. We searched PubMed, EMBASE and JSTOR for published articles on data withdrawal. In addition, we used internet sources as an additional tool to identify content on data withdrawal from research ethics guidelines, legislation, research ethics boards, funding agencies, professional organizations and researchers. We did not find any definitive guidelines for dealing with data withdrawal. We propose recommendations for minimizing the occurrence of data withdrawal, including explicit and clear descriptions in consent forms of how data will be handled after participant withdrawal. We also suggest using imputation techniques to deal with the missing data during analysis. The current commentary can be used to minimize the impact of data withdrawal in RCTs. PMID:21300179

  12. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    PubMed

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  13. A dysphoric-like state during early withdrawal from extended access to methamphetamine self-administration in rats

    PubMed Central

    Jang, Choon-Gon; Whitfield, Timothy; Schulteis, Gery; Koob, George F.; Wee, Sunmee

    2012-01-01

    Rationale Negative emotional states during drug withdrawal may contribute to compulsive drug intake and seeking in humans. Studies suggest that extended access to methamphetamine induces compulsive drug intake in rats. Objective The present study tested the hypothesis that compulsive methamphetamine intake in rats with extended access is associated with negative emotional states during drug withdrawal. Methods Rats with short (1 h, ShA) and extended access (6 h, LgA) to methamphetamine self-administration (0.05 mg/kg/infusion) were tested for reward thresholds using intracranial self-stimulation (ICSS). Different groups of ShA and LgA rats were examined for depression-like and anxiety-like states in the novelty-suppressed feeding, open field, defensive burying, and forced swim tests. Results With extended access, ICSS thresholds gradually increased, which was correlated with the increase of drug intake. During drug withdrawal, the increased ICSS thresholds returned to levels observed before exposure to extended access to methamphetamine. Upon re-exposure to extended access to methamphetamine, ICSS thresholds showed a more rapid escalation than during the initial exposure. LgA rats showed a longer latency to approach chow in the center of a novel field and remained immobile longer in the forced swim test than ShA rats did during early withdrawal. In contrast, ShA rats actively buried an aversive shock probe whereas LgA rats remained immobile in the defensive burying test. Conclusion The data suggest that extended access to methamphetamine produces a more depressive-like state than anxiety-like state in rats during early withdrawal. PMID:23007601

  14. Water withdrawals, use, discharge, and trends in Florida, 2000

    USGS Publications Warehouse

    Marella, Richard L.

    2004-01-01

    In 2000, the estimated amount of water withdrawn in Florida was 20,148 million gallons per day (Mgal/d), of which 59 percent was saline and 41 percent was fresh. Ground water accounted for 62 percent of freshwater withdrawals and surface water accounted for the remaining 38 percent. Ninety-two percent of the 15.98 million people in Florida relied on ground water for their drinking water needs in 2000. Almost all of the saline water withdrawals (99.9 percent) were from surface water. Public supply accounted for 43 percent of ground water withdrawn in 2000, followed by agricultural self-supplied (39 percent), commercial-industrial self-supplied (including mining) (8.5 percent), recreational irrigation (4.5 percent), domestic self-supplied (4 percent), and power generation (1 percent). Agricultural self-supplied accounted for 62 percent of fresh surface water withdrawn in 2000, followed by power generation (20 percent), public supply (8 percent), recreational irrigation (6 percent), and commercial-industrial self-supplied (4 percent). Almost all of saline water withdrawn was used for power generation. The largest amount of freshwater was withdrawn in Palm Beach County and the largest amount of saline water was withdrawn in Hillsborough County. Significant withdrawals (more than 200 Mgal/d) of fresh ground water occurred in Miami-Dade, Polk, Orange, Palm Beach, Broward, and Collier Counties. Significant withdrawals (more than 200 Mgal/d) of fresh surface water occurred in Palm Beach, Hendry, and Escambia Counties. The South Florida Water Management District accounted for the largest amount of freshwater withdrawn (49 percent). About 62 percent of the total ground water withdrawn was from the Floridan aquifer system; 17 percent was from the Biscayne aquifer. Most of the surface water used in Florida was from managed and maintained canal systems or large water bodies. Major sources of fresh surface water include the Caloosahatchee River, Deer Point Lake, Hillsborough

  15. Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism: a model of motivation produced by opiate withdrawal?

    PubMed

    Mucha, R F; Fassos, F F; Perl, F M

    1995-07-01

    Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate withdrawal in the morphine-treated subject. Suggestions in the literature that these substances may activate directly some of the neural consequences of opiate and drug withdrawal prompted us to look for and examine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 10 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low doses of PTZ and VPA in the naive animal may activate processes activated by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produce writhes and ataxia (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ aversion was at a dose lower than that known to produce a PTZ cue. Implications were discussed for using withdrawal-like phenomena as a model in the non-treated organism of clinically-relevant withdrawal effects. PMID:7587968

  16. Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

    SciTech Connect

    Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki . E-mail: mikeda.emb@tmd.ac.jp

    2006-02-03

    The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16{sup INK4a}, a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.

  17. Diazepam withdrawal syndrome: its prolonged and changing nature.

    PubMed Central

    Mellor, C. S.; Jain, V. K.

    1982-01-01

    The diazepam withdrawal syndrome was studied in 10 patients who had abused the drug for 3 to 14 years. In the previous 6 months their consumption of diazepam had ranged from 60 to 120 mg daily; none had used other drugs during this period. The withdrawal period lasted about 6 weeks. The intensity of the symptoms and signs was high initially, fell during the first 2 weeks, then rose again in the third week, before finally declining. Three groups of symptoms and signs were identified. Group A symptoms occurred throughout withdrawal and included tremor, anorexia, insomnia and myoclonus. Group B symptoms and signs were largely confined to the first 10 days and were those of a toxic psychosis. Group C symptoms reached a peak in the third and fourth weeks of withdrawal and were characterized by sense perceptions that were either heightened or lowered. The symptom groups, the presence of tremor and myoclonus, and the relief of symptoms by a test dose permit diazepam withdrawal to be distinguished from anxiety. The biphasic course of the symptoms is probably related to the pharmacokinetics of diazepam. PMID:7139456

  18. Age-Related Changes in Demand-Withdraw Communication Behaviors.

    PubMed

    Holley, Sarah R; Haase, Claudia M; Levenson, Robert W

    2013-08-01

    Demand-withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands' and wives' demand-withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  19. Presumed Pseudotumor Cerebri Syndrome After Withdrawal of Inhaled Glucocorticoids.

    PubMed

    Kwon, Young Joon; Allen, Julian L; Liu, Grant T; McCormack, Shana E

    2016-06-01

    Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal brain parenchyma and cerebrospinal fluid constituents. PTCS after withdrawal of systemic corticosteroids also has been described in children. In contrast, to our knowledge, PTCS after withdrawal of inhaled glucocorticoids has not previously been described. Here we report the case of an 8-year and 6-month-old girl who developed signs and symptoms consistent with PTCS after withdrawal of inhaled glucocorticoids. The patient had excellent adherence to inhaled glucocorticoid therapy for ∼1 year before presentation, after which the therapy was stopped for concern related to poor growth. The withdrawal of inhaled glucocorticoids was associated with the development of severe headaches and diplopia, and further clinical examination led to the patient's diagnosis of likely PTCS. Although its occurrence is likely rare, clinicians caring for the many children receiving inhaled glucocorticoid therapy should be aware of the potential for PTCS after abrupt withdrawal of such treatment, and consider ophthalmology evaluation if patients report suggestive symptoms, such as headaches or vision changes in this context. PMID:27244842

  20. Age-Related Changes in Demand–Withdraw Communication Behaviors

    PubMed Central

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982