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Sample records for repeated alcohol administration

  1. Operant alcohol self-administration in dependent rats: focus on the vapor model.

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    Vendruscolo, Leandro F; Roberts, Amanda J

    2014-05-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be.

  2. Repeated administration of adenosine increases its cardiovascular effects in rats.

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    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  3. Kerusakan Hati Akibat Keracunan Alkohol Berulang pada Tikus Wistar (LIVER DAMAGE DUE TO ALCOHOL INTOXICATION REPEAT IN WISTAR RATS

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    Ni Made Suaniti

    2014-08-01

    Full Text Available The aims of this study was to determine the liver damage from alcohol intoxication in Wistar rats.The design used in this study was a randomized true experimental post test only control group design. Thestudy used 15 rats divided into 3 treatment groups each of which consists of 5 rats. The first group wasgiven distill water. The second group was given 5% alcohol, and the third group was given 20% alcohol. Ratswere treated with alcohol daily for six weeks. Biochemical markers were detected the levels of aldehydedehydrogenase (ALDH in serum and histological changes in liver tissue. ALDH is a biochemical markerof a sensitive and specific ethanol after chronic alcohol administration. Blood sample was collected at 6and 24 hours after the last peroral administration of repeated alcohol treatment, and serum levels ofALDH was tested by enzyme linked immunosorbent assay (ELISA. The results showed that the levels ofALDH in the blood of alcohol treated Wistar rats significantly higher as compared to those of control rats.ALDH levels increased by 83.11% after administration of 5% alcohol and 112.05% after administration of20% taken after 6 hours of alcohol for 6 weeks. On samples taken after 24 hours, ALDH levels by 95.11%after administration of 5% alcohol and 86.79% after administration of 20% alcohol. Oral treatment with20% alcohol chronically was led to changes in the microscopic structure (necrosis of liver tissue in Wistarrats. Liver tissue damage occured due to repeated use of alcohol is accompanied by increasing serum levelsof ALDH in Wistar rats.

  4. R(+-baclofen, but not S(--baclofen, alters alcohol self-administration in alcohol-preferring rats

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    Irene eLorrai

    2016-04-01

    Full Text Available Racemic baclofen [(±-baclofen] has repeatedly been reported to suppress several alcohol-motivated behaviors, including alcohol drinking and alcohol self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+-baclofen, suppressing alcohol intake and the less active enantiomer, S(--baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may extend also to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP rats were initially trained to lever-respond on a Fixed Ratio (FR 4 (FR4 schedule of reinforcement for alcohol (15%, v/v in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±-baclofen (3 mg/kg, R(+-baclofen (0.75, 1.5, and 3 mg/kg, and S(--baclofen (6, 12, and 24 mg/kg under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±-baclofen reduced the number of lever-responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+-baclofen was approximately twice as active as (±-baclofen: treatment with 1.5 mg/kg R(+-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±-baclofen. Conversely, treatment with all doses of S(--baclofen failed to affect alcohol self-administration. These results (a confirm that non-sedative doses of (±-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b apparently do not extend to operant alcohol self-administration in sP rats the capability of S(--baclofen to stimulate alcohol drinking in mice.

  5. Alcohol intake and colorectal cancer: a comparison of approaches for including repeated measures of alcohol consumption

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    Thygesen, Lau Caspar; Wu, Kana; Grønbaek, Morten

    2008-01-01

    BACKGROUND: In numerous studies, alcohol intake has been found to be positively associated with colorectal cancer risk. However, the majority of studies included only one exposure measurement, which may bias the results if long-term intake is relevant.METHODS: We compared different approaches...... for including repeated measures of alcohol intake among 47,432 US men enrolled in the Health Professionals Follow-up Study. Questionnaires including questions on alcohol intake had been completed in 1986, 1990, 1994, and 1998. The outcome was incident colorectal cancer during follow-up from 1986 to 2002.RESULTS......: During follow-up, 868 members of the cohort experienced colorectal cancer. Baseline, updated, and cumulative average alcohol intakes were positively associated with colorectal cancer, with only minor differences among the approaches. These results support moderately increased risk for intake >30 g...

  6. Safety of Moxifloxacin following repeated intramuscular administration in Wistar rats

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    K.A. Sadariya

    Full Text Available Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum of antibacterial activity. The study was conducted to evaluate the safety of Moxifloxacin (5.0 mg/kg after repeated intramuscular administration at 24 h interval for 14 days in male and female wistar rats. Hematological (Haemoglobin, RBC, WBC, MCV, MCH, MCHC, HCT and DLC, blood biochemical parameters (AST, ALT, ALP, Total Bilirubin, Total Serum Protein, Serum Albumin, Globulin, Serum Creatinine, Urea, Uric acid and Blood glucose and histopathological examination of various tissues were carried out in the present study. Male and female animals of any group did not reveal any clinical symptoms and mortality attributable to the 14 days intramuscular administration of Moxifloxacin. The data were compared by unpaired two tail `t` test using Graph Pad Prism (Version 4.00. All above hematological and blood biochemical parameters were found to fluctuate within normal range during treatment period and the mean values were not significantly differ (p < 0.05 from corresponding control values. Moreover, no gross or microscopic changes were found in the liver, kidney, heart, spleen, stomach, intestine and joint cartilages of the treated wistar rats. Results indicate that daily administration of Moxifloxacin for 14 days seems to be safe and well tolerated in rats. [Veterinary World 2010; 3(10.000: 449-452

  7. Safety of Ketoprofen in Cow calves following repeated intravenous administration

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    R. D. Singh

    2009-06-01

    Full Text Available Ketoprofen is a non steroidal anti-inflammatory drug (NSAID used for its anti-inflammatory,analgesic and antipyretic properties in Veterinary Medicine. The present study was planned to assess safety of ketoprofen (3 mg.kg-1 after repeated intravenous administration at 24 hours interval for five days in six crossbred cow calves (6-12 months age and weighing between 60-122 kg. Ketoprofen in calves was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC, blood biochemical (AKP, ACP, AST, ALT, LDH, Total bilirubin, Serum Creatinine, BUN, Serum total protein, Serum albumin and Blood glucose parameters. [Vet. World 2009; 2(3.000: 105-107

  8. Neurocognitive performance following acute mephedrone administration, with and without alcohol.

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    de Sousa Fernandes Perna, E B; Papaseit, E; Pérez-Mañá, C; Mateus, J; Theunissen, E L; Kuypers, Kpc; de la Torre, R; Farré, M; Ramaekers, J G

    2016-12-01

    Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The present study assessed the effect of mephedrone alone and after co-administration with alcohol on neurocognitive function. It was hypothesised that mephedrone would improve psychomotor performance but impair memory performance, when administered alone. Neurocognitive performance was expected to be impaired following mephedrone when combined with alcohol. Eleven participants received single doses of 200 mg mephedrone or placebo combined with 0.8 g/kg alcohol or placebo. Neurocognitive performance was assessed at baseline (T0), at one hour (T1) and four hours after (T2) mephedrone administration, by means of the Divided Attention Task (DAT), Critical Tracking Task (CTT), and the Spatial Memory Test (SMT). Mephedrone intoxication impaired short-term spatial memory at T1 and improved critical tracking performance at T2 Mephedrone alone did not affect divided attention, but did show an interaction with alcohol on reaction time at T2 Reaction time decreased when mephedrone was combined with alcohol as compared to alcohol alone. Alcohol intoxication impaired both short- and long-term spatial memory at T1 and divided attention at T1 and T2 Critical tracking performance was not affected by alcohol intoxication. The current findings support the hypothesis that mephedrone improves psychomotor performance, impairs spatial memory and does not affect divided attention performance. Stimulatory effects of mephedrone were not sufficient to compensate for the impairing effects of alcohol on most performance parameters.

  9. Temporal alcohol availability predicts first-time drunk driving, but not repeat offending.

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    Schofield, Timothy P; Denson, Thomas F

    2013-01-01

    Alcohol availability has been linked to drunk driving, but research has not examined whether this relationship is the same for first-time and repeat offenses. We examined the relationship between the business hours of alcohol outlets licensed to serve alcohol for on-premises consumption and misdemeanor-level (first offense) and felony-level drunk driving (repeat offense) charges in New York State in 2009. Longer outlet business hours were associated with more misdemeanor drunk driving charges, but were not associated with felony drunk driving charges. The per capita density of on-premises alcohol outlets did not affect misdemeanor or felony drunk driving charges. The results suggest that temporal alcohol availability may be an impelling factor for first-time drunk driving, but other factors likely influence repeat drunk driving behaviors.

  10. Temporal alcohol availability predicts first-time drunk driving, but not repeat offending.

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    Timothy P Schofield

    Full Text Available Alcohol availability has been linked to drunk driving, but research has not examined whether this relationship is the same for first-time and repeat offenses. We examined the relationship between the business hours of alcohol outlets licensed to serve alcohol for on-premises consumption and misdemeanor-level (first offense and felony-level drunk driving (repeat offense charges in New York State in 2009. Longer outlet business hours were associated with more misdemeanor drunk driving charges, but were not associated with felony drunk driving charges. The per capita density of on-premises alcohol outlets did not affect misdemeanor or felony drunk driving charges. The results suggest that temporal alcohol availability may be an impelling factor for first-time drunk driving, but other factors likely influence repeat drunk driving behaviors.

  11. A Multilevel Structural Equation Model of Within- and Between-Person Associations among Subjective Responses to Alcohol, Craving, and Laboratory Alcohol Self-Administration

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    Wardell, Jeffrey D.; Ramchandani, Vijay A.; Hendershot, Christian S.

    2017-01-01

    Subjective responses to alcohol are important determinants of drinking behavior and have been linked with risk for alcohol use disorders. However, few attempts have been made to examine proximal within-person associations among state changes in subjective responses and ongoing alcohol self-administration in the laboratory. This study disaggregated within- and between-person associations among subjective responses and alcohol self-administration, while also examining the mediating role of craving and the moderating role of trait impaired control over alcohol. Sixty young heavy drinkers (mean age=19.90, SD=0.86) completed self-report measures including the Impaired Control Scale, then participated in a 2-hour intravenous alcohol self-administration session using the Computer-Assisted Self-infusion of Ethanol (CASE) paradigm. Repeated assessments of subjective stimulation, subjective sedation, and craving were examined in relation to ongoing in-session self-administration, as indexed by breath alcohol concentration (BrAC) assessed 15 minutes later. Multilevel structural equation modeling was used to disentangle within-person and between-person associations. The results showed few significant associations at the between-person level, except for a direct negative association between sedation and BrAC. At the within-person level, state fluctuations in stimulation were positively associated with both craving and subsequent BrAC, whereas state changes in sedation were negatively associated with craving and positively associated with BrAC. Within-person indirect associations from subjective stimulation and sedation to subsequent BrAC mediated via craving were statistically significant. Also, participants higher on impaired control showed stronger within-person associations between craving and greater subsequent BrAC. The results suggest that subjective responses to alcohol and craving have proximal associations with self-administration behavior, the strength of which is

  12. Thiamin metabolism in the rat during long term alcohol administration.

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    Bitsch, R; Hansen, J; Hötzel, D

    1982-01-01

    In order to test the effect of a long term alcohol administration on the thiamin metabolism in blood, heart and liver under suboptimal supply, an experiment with rats was carried out over a period of 16 weeks. The suboptimal thiamin supply became visible mainly in the liver stores which were lowered during the whole test period. The unphosphorylated thiamin (T) of liver and heart was not detectable after 4 weeks up to the end of experiment. On the other hand the total thiamin concentration in the erythrocytes increased from the beginning due to an enhanced thiamin-diphosphate (TDP) and thiamintriphosphate (TTP) pool and T was lowered to undetectable amounts only after 16 weeks. In contrast, the alpha-TK in blood and liver was enhanced only after 2 and 4 weeks and tended to become normal by the end of the test period indicating an apoenzyme degeneration. Alcohol ingestion resulted in a general diminution of the total thiamin and the thiamin phosphates in blood, heart and liver and a reduced thiamin excretion in urine. An alcohol induced shift of the phosphorylation status could be observed only in the liver, but not in the heart and the erythrocytes, leading to a lowered concentration of T and TMP. The results demonstrate that the level of thiamin and thiamin phosphates in blood and organs under suboptimal thiamin supply seems to be more sensitive to chronic alcohol administration than the transketolase activity and the alpha-TK value.

  13. Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats.

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    Besheer, Joyce; Frisbee, Suzanne; Randall, Patrick A; Jaramillo, Anel A; Masciello, Maria

    2016-02-01

    Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations.

  14. Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

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    May, Christina E.; Haun, Harold L.; Griffin, William C.

    2015-01-01

    Introduction Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol) on conditioned taste aversion, ataxia and locomotor activity after repeated exposure. Methods Four groups of mice were exposed by oral gavage twice daily to vehicle, ethanol (4 g/kg), caffeine (15 mg/kg), or the ethanol/caffeine combination. Conditioned taste aversion to saccharin and ataxia in the parallel rod task were evaluated after 8 or 16 gavages, respectively, using ethanol (1–3 g/kg) or ethanol/caffeine (3mg/kg + 2 g/kg) challenges. In addition, locomotor activity was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. Results Repeated oral gavage of ethanol produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/ethanol combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated ethanol exposure, there was significant tolerance to ethanol in the conditioned taste aversion and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced ethanol-induced conditioned taste aversion. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/ethanol combination and appeared to reduce the ataxic response to high doses of ethanol. Conclusion The data support the general hypothesis that repeated exposure to caffeine influences the response to ethanol. Together with previously published work, these data indicate

  15. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

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    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...

  16. Motivation for alcohol becomes resistant to quinine adulteration after 3 to 4 months of intermittent alcohol self-administration.

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    Hopf, Frederic Woodward; Chang, Shao-Ju; Sparta, Dennis R; Bowers, Michael S; Bonci, Antonello

    2010-09-01

    Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (>8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose-response for quinine taste preference in IAA and continuous-access animals was determined. Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in

  17. An unusual case of homicide by use of repeated administration of organophosphate insecticides.

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    De Letter, E A; Cordonnier, J A C M; Piette, M H A

    2002-03-01

    We present an unusual murder case by use of repeated administration of organophosphate insecticides. A 49-year-old woman suffering from mental retardation, epileptic fits and acromegaly was poisoned by her husband. At first, her death was considered as a 'sudden and unexpected' natural death. Abdominal abscesses of pancreatic origin found at autopsy were compatible with repeated administration of pesticides with anticholinergic action. In her medical history at least one episode consistent with an organophosphate intoxication was retrieved. Thorough inquiry revealed that the victim had ingested phosphamidon and/or omethoate orally. Organophosphate intoxication should be considered when unexplained neurological symptoms are associated with pancreatic disturbances.

  18. Dose-dependent effects of intravenous alcohol administration on cerebral blood flow in young adults.

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    Strang, Nicole M; Claus, Eric D; Ramchandani, Vijay A; Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S

    2015-02-01

    Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge.

  19. Water metabolism in rats subjected to chronic alcohol administration

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    Parlesak, Alexandr; Pohl, C.; Bode, J.C.;

    2004-01-01

    AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion ...

  20. Video Teleconference Administration of the Repeatable Battery for the Assessment of Neuropsychological Status

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    Galusha-Glasscock, Jeanine M.; Horton, Daniel K.; Weiner, Myron F.; Cullum, C. Munro

    2016-01-01

    Teleneuropsychology applications are growing, but a limited number of assessment tools have been studied in this context. The present investigation was designed to determine the feasibility and reliability of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) administration by comparing video teleconference (VTC) with face-to-face (FF) test conditions. Eighteen adult subjects over age 55 with and without cognitive impairment were administered Forms A and B of the RBANS in VTC and FF settings in counterbalanced fashion. Similar RBANS scores were obtained in both test conditions, with generally high correlations between administration methods. Results support the feasibility and reliability of remote administration of the RBANS via VTC. PMID:26446834

  1. Intravenous ethanol infusions can mimic the time course of breath alcohol concentrations following oral alcohol administration in healthy volunteers.

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    Ramchandani, Vijay A; Plawecki, Martin; Li, Ting-Kai; O'Connor, Sean

    2009-05-01

    Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (C(max)), times of peak BrAC (T(max)), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean C

  2. Repeated administration of histamine improves memory retrieval of inhibitory avoidance by lithium in mice.

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    Zarrindast, Mohammad Reza; Parsaei, Leila; Ahmadi, Shamseddin

    2008-01-01

    The influence of repeated administration of histamine on lithium-induced state dependency has been investigated. A single-trial step-down inhibitory avoidance task was used to assess memory in adult male NMRI mice. Intraperitoneal (i.p.) administration of lithium (10 mg/kg), immediately after training (post-training), impaired inhibitory avoidance memory on the test day. Pre-test administration of lithium reversed amnesia induced by the drug given after training, with the maximum response at a dose of 10 mg/kg. Repeated intracerebroventricular (i.c.v.) administration of histamine (20 microg/mouse) for 3 consecutive days followed by 5 days of no drug treatment improved memory retrieval of inhibitory avoidance by a pre-test lower dose (5 mg/kg i.p.) of lithium. In contrast, 3 days of i.c.v. injections of both the histamine H1 receptor antagonist pyrilamine (40 microg/mouse) and the histamine H2 receptor antagonist ranitidine (6.25 and 12.5 microg/mouse) prevented the improving effect of pre-test lithium (10 mg/kg i.p.) on memory retrieval. The results suggest that the repeated administration of histaminergic agents may induce a sensitization which affects the memory impairment induced by lithium.

  3. Effects of caffeine on alcohol consumption and nicotine self-administration in rats.

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    Rezvani, Amir H; Sexton, Hannah G; Johnson, Joshua; Wells, Cori; Gordon, Karen; Levin, Edward D

    2013-09-01

    Caffeine, alcohol, and nicotine are 3 of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other's consumption. In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions. Copyright © 2013 by the Research Society on Alcoholism.

  4. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

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    Moreno-Rocha, Luis Alfonso; López-Muñoz, Francisco Javier; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam

    2016-11-01

    Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  5. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

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    Luis Alfonso Moreno-Rocha

    2016-11-01

    Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  6. Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults.

    Science.gov (United States)

    Hendershot, Christian S; Claus, Eric D; Ramchandani, Vijay A

    2016-01-01

    Human laboratory and animal models implicate variation in the μ-opioid receptor gene (OPRM1) as relevant for alcohol-related reward. OPRM1 is associated with alcohol self-administration in non-human primate studies, but the relevance of this finding to human models is unclear. This study used computer-assisted self-infusion of ethanol (CASE) to examine associations among OPRM1 A118G genotype, subjective responses to alcohol and intravenous alcohol self-administration in young heavy drinkers (n = 40, mean age = 19.95 years, SD = 0.82). Participants completed a 2-hour CASE session comprising a priming phase followed by ad libitum self-administration in a free-access paradigm. Participants achieved a mean peak breath alcohol concentration (BrAC) of 81.18 mg% (SD = 24.96). Those with the OPRM1 118G variant (GA or GG genotypes) achieved significantly higher peak BrAC (M = 94.90 mg%, SD = 16.56) than those with the AA genotype (M = 74.46 mg%, SD = 25.36), reflecting a significantly greater number of alcohol requests among GA/GG participants. Eighty percent of GA/GG participants surpassed a threshold defining a laboratory analog of heavy alcohol exposure (80 mg%) compared with 46 percent of AA participants. Results indicated significant associations between subjective measures of alcohol sensitivity and CASE outcomes, although the pattern of findings differed across self-report measures. Subjective responses did not differ by OPRM1 status. These results offer further support for the feasibility of the CASE paradigm and provide initial evidence for an association of OPRM1 with alcohol self-administration in a human laboratory context. © 2014 Society for the Study of Addiction.

  7. Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

    Science.gov (United States)

    Rezvani, Amir H.; Sexton, Hannah G.; Johnson, Joshua; Wells, Cori; Gordon, Karen; Levin, Edward D.

    2013-01-01

    Background Caffeine, alcohol and nicotine are three of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other’s consumption. Methods In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring P rats, caffeine (5, 10 and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of oral caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute oral administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute oral caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Results Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute oral caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute oral administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. Conclusions These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions. PMID:23895206

  8. Motivation for alcohol becomes resistant to quinine adulteration after 3-4 months of intermittent alcohol self-administration

    Science.gov (United States)

    Hopf, F. Woodward; Chang, Shao-Ju; Sparta, Dennis R.; Bowers, M. Scott; Bonci, Antonello

    2010-01-01

    Background Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (> 8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. Methods Outbred Wistar rats underwent 3-4 months or ∼1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/L) on the motivation of to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3-4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose-response for quinine taste preference in IAA and continuous-access animals was determined. Results Motivation for alcohol after 3-4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/L quinine. In contrast, after 3-4 month of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/L quinine. In addition, motivation for alcohol after only ∼1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/L quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/L) that significantly reduced alcohol drinking in animals

  9. Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study

    OpenAIRE

    Oosterhof, Chris A.; Mansari, Mostafa El; Bundgaard, Christoffer; Blier, Pierre

    2015-01-01

    Background: Brexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems. Methods: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons...

  10. Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells.

    Science.gov (United States)

    Globerson-Levin, Anat; Waks, Tova; Eshhar, Zelig

    2014-05-01

    Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

  11. Neurocognitive performance following acute mephedrone administration, with and without alcohol

    NARCIS (Netherlands)

    de Sousa Fernandes Perna, E B; Papaseit, E; Pérez-Mañá, C; Mateus, J; Theunissen, E L; Kuypers, K.P.C.; de la Torre, R; Farré, M; Ramaekers, J G

    2016-01-01

    Recreational use of mephedrone, alone and in combination with alcohol, has increased over the past years. Pharmacological properties of mephedrone share similarities with methylenedioxymethamphetamine (MDMA), but its effect on neurocognitive function has not been well established in humans. The pres

  12. Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats.

    Science.gov (United States)

    Albarellos, G A; Montoya, L; Landoni, M F

    2005-09-01

    The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.

  13. Resistance to change of alcohol self-administration: effects of alcohol-delivery rate on disruption by extinction and naltrexone.

    Science.gov (United States)

    Jimenez-Gomez, Corina; Shahan, Timothy A

    2007-03-01

    A common finding in resistance to change research with food-maintained operant behavior is that the persistence of behavior depends on the rate of reinforcement delivered in the context in which the behavior occurs. The present experiment evaluated the effects of rate of response-dependent alcohol delivery on the resistance to change of rats' alcohol self-administration in the face of disruption produced by extinction and a range of doses of naltrexone (1.0, 3.0, 10.0 mg/kg, subcutaneous). Rats responded for a 10% alcohol solution in a multiple schedule of reinforcement arranging a higher rate of alcohol delivery (variable interval 15 s) in the presence of one stimulus and a lower rate of alcohol delivery (variable interval 45 s) in the presence of another stimulus. Baseline response rates and resistance to extinction were higher in the presence of the stimulus associated with higher rates of alcohol delivery. This finding is consistent with studies of the resistance to change of food-maintained behavior. The rate of alcohol delivered in the components, however, did not systematically affect resistance to disruption by naltrexone. One interpretation of this finding from the perspective of behavioral momentum theory is that naltrexone may decrease the impact of alcohol-associated stimuli on the persistence of drinking by reducing sensitivity to the relative reinforcement conditions arranged in the presence of different stimuli.

  14. Comparison of the effect of the GABAB receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in three different lines of alcohol-preferring rats

    Science.gov (United States)

    Maccioni, Paola; Zaru, Alessandro; Loi, Barbara; Lobina, Carla; Carai, Mauro A.M.; Gessa, Gian Luigi; Capra, Alessandro; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Hyytiä, Petri; Lumeng, Lawrence; Colombo, Giancarlo

    2012-01-01

    Background Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator (PAM), GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. The present study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in three lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). Methods Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. Results The rank of order of the reinforcing and motivational properties of alcohol was: P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was: P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all three rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. Conclusions These results suggest that: (a) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (b) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (c) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats

  15. Effect of repeated oral administration on taurocholate on hepatic excretory function in the rat.

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1981-07-01

    The effect of repeated administration of taurocholate on bile acid pool size, biliary composition and biliary excretory capacity for bile acids and two xenobiotics was determined. The bile acid pool was increased 50 to 60% by oral administration of sodium taurocholate (300--900 mg/kg, 10 ml/kg) every 12 hr for 2 days to male Sprague-Dawley rats. Bile flow, biliary excretion of bile acids, cholesterol and phospholipid and the concentrations of phospholipid and bile acids in bile were increased in rats treated with 750 mg of taurocholate per kg. No effect was observed on Na+,K+ or Cl- levels. The biliary transport maximum for taurocholate was increased by 30% in rats treated with 750 mg/kg. In contrast, the plasma disappearance and biliary excretion of phenol-3,6-dibromphthalein and ouabain were not affected by taurocholate administration.

  16. Production of ethyl alcohol by a repeated batch fermentation method. Kurikaeshi kaibun hakkoho ni yoru arukoru no seizoho

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, T. (Tokyo (Japan)); Takagi, Y. (Chiba (Japan)); Shiba, M. (Kagoshima (Japan))

    1994-01-11

    This invention relates to a production method of ethyl alcohol from sugar and starch raw materials by a repeated batch fermentation method and aims to provide a method to produce ethyl alcohol efficiently by accurate repetition. Conventional batch fermentation methods require the experiences and skill to confirm an end point of the fermentation and have a problem in a control of repeated batch fermentation. This invention uses a gas flow meter of a velocity head measurement type and judges an end point of fermentation at a time when the amount of the exhaust gas flow from the fermentation is 0.35 to 0.1 m[sup 3] per hour and per 1 kl fermentation liquid or below and the next batch fermentation is started. By this invention, ethyl alcohol is produced efficiently from the raw materials with less damage of the yeast and efficient repeated batch fermentation is realized. 6 figs., 1 tab.

  17. Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats.

    Science.gov (United States)

    Macnamara, Claire L; Holmes, Nathan M; Westbrook, R Fred; Clemens, Kelly J

    2016-06-01

    Varenicline is a partial nicotine receptor agonist widely prescribed as a smoking cessation medication. Repeated (or long-term) use of varenicline has been proposed as a treatment option for tobacco addiction. However the effect of repeated varenicline use on motivation for nicotine is unknown. Here the intravenous nicotine self-administration paradigm in rats was used to model the consequences of varenicline treatment across repeated cycles of administration, extinction and reinstatement. Rats acquired nicotine self-administration across 20 days before undergoing 6 days of extinction, where each extinction session was preceded by a single injection of varenicline or saline. This was followed by a single varenicline-free nicotine-primed reinstatement test. All rats then reacquired nicotine self-administration for 10 days followed by a second cycle of extinction. Across this period, rats either received a second cycle of varenicline (VAR-VAR) or saline (SAL-SAL), or the alternative treatment (SAL-VAR, VAR-SAL), followed by a final reinstatement test. Treatment with varenicline increased responding across the first cycle of extinction, but did not affect responding in the reinstatement test. Across the second cycle, varenicline again increased responding across extinction, and critically, rats treated with varenicline across cycle 1 and saline across cycle 2 (Group VAR-SAL) exhibited more reinstatement than rats in any other group. The effect of VAR on nicotine seeking was not due to its effects on locomotor activity. Instead, the results suggest that a history of VAR can increase vulnerability to reinstatement/relapse when its treatment is discontinued. The possible mechanisms of this increased vulnerability are discussed.

  18. Effects of nicotine gum on repeated administration of the Stroop test.

    Science.gov (United States)

    Provost, S C; Woodward, R

    1991-01-01

    Using a double-blind procedure, 24 non-smoking subjects chewed either 2 mg nicorette gum or a placebo for 20 min, before completing a Stroop test on three occasions. Colour-word reading and simple colour naming times were consistent across repeats, and were unaffected by nicotine. However, the time taken to name the colour of incongruous colour word stimuli declined across trials. This increase in speed across repeats was significantly greater in those subjects who had received nicotine. These data are consistent with previous reports of a decreased Stroop effect following nicotine administration, but are not compatible with a simple model which assumes that nicotine alters the way in which information is filtered by selective attentional mechanisms. The present results can be explained by postulating that nicotine influences either the rate at which colour naming become more automatic, or changes the way in which resources are allocated to non-automatic processes.

  19. Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats.

    Science.gov (United States)

    Sun, Jinling; Tian, Lin; Cui, Ruisi; Li, Xinwang

    2017-04-01

    Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis.

  20. Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

    Science.gov (United States)

    Wabno, Joanna; Hess, Grzegorz

    2013-05-01

    Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach. In slices prepared 2 days after the last drug administration from animals receiving imipramine for 14 days (dose 10 mg/kg p.o., twice daily) the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from layer II/III pyramidal neurons was decreased, while the mean amplitude of sIPSCs was increased. These effects were absent in slices obtained from rats which received imipramine once. Application of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN 082), a selective mGluR7 allosteric agonist, to the slice incubation medium resulted in a decrease in the mean frequency of sIPSCs in preparations obtained from repeated imipramine-treated animals, in contrast to slices originating from control rats where no AMN 082-induced effects were observed. Repeated imipramine treatment reduced protein density levels of the three tested GABAA receptor subunits: α 1, β 2 and γ 2. These data indicate that repeated treatment of normal rats with imipramine results in a modification of the release mechanism of GABA from presynaptic terminals and its modulation by mGluR7 receptors as well as in an alteration in GABAA receptor subunit protein levels in the rat cerebral cortex.

  1. Serotonin-3 Receptors in the Posterior Ventral Tegmental Area Regulate Ethanol Self-Administration of Alcohol-Preferring (P) Rats

    Science.gov (United States)

    Rodd, Zachary A.; Bell, Richard L.; Oster, Scott M.; Toalston, Jamie E.; Pommer, Tylene J.; McBride, William J.; Murphy, James M.

    2015-01-01

    Several studies indicated the involvement of serotonin-3 (5-HT3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers were used to examine the effects of 7 consecutive bilateral micro-infusions of ICS205-930 (ICS), a 5-HT3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (v/v) ethanol self-administration. P rats readily acquired ethanol self-administration by the 4th session. The three highest doses (0.125, 0.25 and 1.25 ug) of ICS prevented acquisition of ethanol self-administration. During the acquisition post-injection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the 3 highest doses (0.75, 1.0 and 1.25 ug) of ICS significantly increased responding on the ethanol lever; following the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Micro-infusion of ICS into the posterior VTA did not alter the low responding on the water lever, and did not alter saccharin (0.0125% w/v) self-administration.. Micro-infusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration, and/or repeated treatments with a 5-HT3 receptor antagonist may alter neuronal circuitry within the posterior VTA. PMID:20682192

  2. Persistence and accumulation of micronucleated hepatocytes in liver of rats after repeated administration of diethylnitrosamine.

    Science.gov (United States)

    Narumi, Kazunori; Ashizawa, Koji; Fujiishi, Yohei; Tochinai, Ryota; Okada, Emiko; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Hamada, Shuichi; Kaneko, Kimiyuki; Ohyama, Wakako

    2013-08-15

    A repeat-dose micronucleus assay in adult rat liver was recently developed [Mutat. Res. 747 (2012) 234-239]. This assay demonstrated a high detectability of hepatocarcinogens at relatively low doses, as indicated by dose-dependent micronucleus induction. Because the adult rat liver is known to have a long life-span, this desirable property of the assay will be an advantage in detecting micronucleated hepatocytes (MNHEPs) that have persisted for long periods in the liver following repeated dosing. However, no data directly supporting the underlying mechanisms have been published to date. In the present study, we verified the mechanisms by means of pulse-labeling of micronucleated hepatocytes with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU). The rodent hepatocarcinogen diethylnitrosamine (DEN) was repeatedly administered orally to male Crl:CD (SD) rats (6 weeks old) for up to 2 weeks, and EdU was injected intraperitoneally on days 1, 7, or 14. Hepatocytes were isolated by use of a non-perfusion technique at 24h, 1 week, or 2 weeks after EdU injection and analyzed for EdU incorporation and micronucleus formation. The results of our study confirmed that MNHEPs labeled with EdU on the first day of DEN administration persisted until 2 weeks post-administration in the rat livers. However, the frequency of MHNEPs among EdU-labeled hepatocytes decreased over time. In addition, the number of terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL)-positive cells in the liver tissue increased, suggesting selective removal of micronucleated cells. Theoretical calculation of the cumulative MNHEP frequency on each of the days on which DEN was administered, taking into account the rate of loss, came out closer to the actual value observed in the liver micronucleus test. Taken together, these results indicate that although micronucleated cells induced in rat livers by administration of the genotoxic hepatocarcinogen DEN undergo selective removal, they

  3. Programming Community Resources; A Training Program For Alcohol Program Administrators.

    Science.gov (United States)

    National Center for Alcohol Education, Arlington, VA.

    This guide is designed to upgrade and/or develop the assessment and negotiation skills of management personnel who are involved in developing and coordinating resources among community agencies to provide comprehensive services for individuals with alcohol problems. This training program addresses the following topics: (1) community assessment;…

  4. Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration.

    Science.gov (United States)

    Kosiorek-Witek, Anna; Makulska-Nowak, Helena Elżbieta

    2016-01-01

    The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of μ-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY). Surprisingly, repeated administration of fluoxetine reduced morphine analgesia, with the weakening of opioid antinociceptive action comparable to the duration of serotonin reuptake inhibitor administration. It was also concluded that the antinociceptive action of morphine in female rats and the alteration of its efficacy as a result of fluoxetine premedication for several days depend on oestrus cycle phase. The highest sensitivity of female rats to morphine was reported in the dioestrus and oestrus phases; much lower values were reported for the metoestrus phase.

  5. Antinociceptive effects of tramadol in co-administration with metamizol after single and repeated administrations in rats.

    Science.gov (United States)

    Moreno-Rocha, Luis Alfonso; Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa; Bravo, Guadalupe; López-Muñoz, Francisco Javier

    2012-11-01

    Combinations of two analgesic drugs of the same or different class are widely used in clinical therapy to enhance its antinociceptive effects and reduce the side effects. In order to evaluate a possible antinociceptive synergistic interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and tramadol s.c., an atypical opioid (opioid receptor agonist), were administered alone or in combination. In the present study, the antinociceptive efficacy and the possible development of pharmacological tolerance produced by the combination tramadol plus metamizol during a 4-day treatment in rats using the plantar test was evaluated. Male Wistar rats were s.c. injected with tramadol (17.8 mg/kg), metamizol (177.8 mg/kg) or the combination tramadol plus metamizol three times a day for 4 days. Both metamizol and tramadol produced antinociceptive effects with a low rate trend towards tolerance development at the end of the treatment. The antinociceptive efficacy of tramadol and metamizol co-administration gradually decreased after the second injection. These data suggest that when the combination is given in a unique administration it results in an important potentiation of their individual antinociceptive effects. But, the repeated coadministration of tramadol plus metamizol results in a development of tolerance.

  6. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal... Justice Programs, Executive Office for Immigration Review, Executive Office for United States...

  7. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    Science.gov (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  8. Latent inhibition is disrupted by acute and repeated administration of corticosterone.

    Science.gov (United States)

    Shalev, U.; Feldon, J.; Weiner, I.

    1998-12-01

    Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

  9. Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2013-12-01

    Full Text Available Background/Aims: Bone marrow-derived cells (BMDCs reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT] and control (C groups (saline, IT. C and SIL groups were further randomized to receive BMDCs (2×106 cells or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype, apoptotic cells, the level of transforming growth factor (TGF-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

  10. Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits.

    Science.gov (United States)

    Khan, Adil Mehraj; Rampal, Satyavan; Sood, Naresh Kumar

    2016-03-09

    The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction (p meloxicam both alone and in combination with levofloxacin, whereas an increase (p meloxicam-alone treated group and inhibited (p meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p meloxicam both alone and in combination with levofloxacin (p meloxicam.

  11. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-01-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans. PMID:1637802

  12. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-06-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.

  13. Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration.

    Science.gov (United States)

    Coetzee, J F; Mosher, R A; Griffith, G R; Gehring, R; Anderson, D E; KuKanich, B; Miesner, M

    2015-12-01

    The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration.

  14. Analyzing repeated measures semi-continuous data, with application to an alcohol dependence study.

    Science.gov (United States)

    Liu, Lei; Strawderman, Robert L; Johnson, Bankole A; O'Quigley, John M

    2016-02-01

    Two-part random effects models (Olsen and Schafer,(1) Tooze et al.(2)) have been applied to repeated measures of semi-continuous data, characterized by a mixture of a substantial proportion of zero values and a skewed distribution of positive values. In the original formulation of this model, the natural logarithm of the positive values is assumed to follow a normal distribution with a constant variance parameter. In this article, we review and consider three extensions of this model, allowing the positive values to follow (a) a generalized gamma distribution, (b) a log-skew-normal distribution, and (c) a normal distribution after the Box-Cox transformation. We allow for the possibility of heteroscedasticity. Maximum likelihood estimation is shown to be conveniently implemented in SAS Proc NLMIXED. The performance of the methods is compared through applications to daily drinking records in a secondary data analysis from a randomized controlled trial of topiramate for alcohol dependence treatment. We find that all three models provide a significantly better fit than the log-normal model, and there exists strong evidence for heteroscedasticity. We also compare the three models by the likelihood ratio tests for non-nested hypotheses (Vuong(3)). The results suggest that the generalized gamma distribution provides the best fit, though no statistically significant differences are found in pairwise model comparisons.

  15. Evaluation of safety profile of black shilajit after 91 days repeated administration in rats

    Institute of Scientific and Technical Information of China (English)

    Velmurugan C; Vivek B; Wilson E; Bharathi T; Sundaram T

    2012-01-01

    Objective: To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. Methods: In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2500 and 5000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. Results: The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. Conclusions: The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia.

  16. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress

    Directory of Open Access Journals (Sweden)

    Muhammad Farhan

    2016-09-01

    Full Text Available Background: Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI, has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Methods: Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits. Results: Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg. Conclusion: The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.

  17. Repeated administration of dopaminergic agents in the dorsal hippocampus and morphine-induced place preference.

    Science.gov (United States)

    Zarrindast, M-R; Nasehi, M; Rostami, P; Rezayof, A; Fazli-Tabaei, S

    2005-03-01

    The aim of the present experiments was to investigate whether repeated intra-hippocampal CA1 (intra-CA1) administration of dopaminergic agents can affect morphine-induced conditioned place preference (CPP). Effects of repeated intra-CA1 injections of dopamine (DA) receptor agonists and antagonists on morphine-induced CPP in rats were investigated using an unbiased 3-day schedule of place conditioning. Animals receiving once-daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner: the maximum response was observed with 3 mg/kg morphine. Three days' intra-CA1 injections of apomorphine (0.25-1 microg/rat) followed by 5 days free of the drug, significantly decreased morphine CPP (1 and 3 mg/kg, s.c.). Moreover, pre-treatment with the highest dose of apomorphine (1 microg/rat) altered the effect of morphine to an aversive response. The morphine (1 and 3 mg/kg) CPP was also significantly decreased in animals that previously received three intra-CA1 injections of SKF 38393 (2-9 microg/rat), quinpirole (1-3 microg/rat) or sulpiride (1-3 microg/rat), and significantly increased in animals that had previously received three intra-CA1 injections of SCH 23390 (0.02 microg/rat). The 3-day pre-treatment with apomorphine, SKF 38393 or quinpirole reduced locomotor activity in the test session, while SCH 23390 and sulpiride did not have any influence on locomotor activity. It is concluded that repeated injections of DA receptor agents in the dorsal hippocampus, followed by 5 days free of the drugs, can affect morphine reward.

  18. The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

    Science.gov (United States)

    Job, Martin O; Shen, Li L; Kuhar, Michael J

    2013-08-29

    CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.

  19. Penetration of prulifloxacin into gynaecological tissues after single and repeated oral administrations.

    Science.gov (United States)

    Gorlero, Franco; Lorenzi, Paola; Rosignoli, Maria Teresa; Picollo, Rossella; Ruggieri, Alessandro; Barattè, Simona; Dionisio, Paolo

    2007-01-01

    This study aimed to evaluate the penetration into gynaecological tissues of ulifloxacin, the active metabolite of prulifloxacin, a once-daily fluoroquinolone administered once or in repeated doses. This was an open-label, randomised study that included 20 consenting female inpatients (age range 40-65 years) requiring total simple hysterectomy as a result of benign disease. Three groups of patients were enrolled: group A (four patients whose gynaecological tissue samples were used to set up the bioanalytical method); group B (eight patients treated 3 hours before surgery with one 600 mg tablet of prulifloxacin); group C (eight patients treated with prulifloxacin 600 mg once daily for 3 days and undergoing surgery 3 hours after the last dose). Patients to be treated with prulifloxacin were randomly allocated to group B or C. During surgery, samples of blood were collected jointly with healthy tissue removed from the endometrium, proximal fallopian tube, vaginal posterior fornix and portio vaginalis. Ulifloxacin concentrations in plasma and gynaecological tissues were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. An intrastudy assessment of the bioanalytical method performance was also conducted for plasma and tissues using calibration and quality control data (spiked samples). Ulifloxacin mean concentrations were always higher in group C than in group B patients, both in plasma (0.76 vs 0.53 microg/mL) and in gynaecological tissues, namely fallopian tube (1.38 vs 0.81 microg/g), posterior fornix (1.48 vs 1.05 microg/g), portio vaginalis (1.46 vs 1.45 microg/g) and endometrium (2.20 vs 1.39 microg/g), as expected after repeated drug administrations. Tissue concentrations observed after repeated administrations were generally higher than the ulifloxacin minimum inhibitory concentrations for pathogens more frequently involved in gynaecological bacterial infections. The mean tissue/plasma ratios ranged between 1.5 and

  20. Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients.

    Science.gov (United States)

    Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Dom, Geert; Cappelle, Delphine; Maudens, Kristof E; van Nuijs, Alexander L N; Covaci, Adrian; Neels, Hugo

    2015-02-01

    Ethyl glucuronide (EtG), a minor metabolite of alcohol, is used as a sensitive marker in hair to detect the retrospective consumption of alcohol. The proximal 0-3 cm hair segment is often used for analysis, providing information on alcohol consumption over the past 3 months. Using more distal segments would allow the detection of alcohol consumption over longer time periods, thereby addressing the chronicity of the consumption. In view of this, permanent coloring and bleaching were shown in vitro to alter EtG concentrations in hair, but no in vivo studies are available to prove or disprove this. To investigate the influence of repeated bleaching and permanent coloring on EtG concentrations in vivo and to assess the stability of EtG concentrations in distal compared to proximal hair segments. Hair samples from alcohol-dependent patients with uncolored/unbleached (N=4), permanent coloration (N=5) and bleached hair (N=5) were analyzed in two to six 3 cm long segments for EtG concentrations, and alcohol consumption and hair cosmetic treatments were assessed. We observed that hair bleaching and permanent coloring reduces EtG concentrations by 82±11% and 65±24%, respectively, with correlations between the number of cosmetic treatments and the decrease in EtG concentrations. EtG remained stable in untreated hair samples up to 18 cm. EtG is a sensitive marker to assess chronic alcohol consumption up to 18 months in alcohol-dependent patients with no cosmetic hair treatments. However, in alcohol-dependent patients who color or bleach their hair, care should be taken when interpreting EtG measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Enhanced alcohol self-administration and reinstatement in a highly impulsive, inattentive recombinant inbred mouse strain

    Directory of Open Access Journals (Sweden)

    Maarten eLoos

    2013-10-01

    Full Text Available Deficits in executive control have frequently been associated with alcohol use disorder. Here we investigated to what extent pre-existing genetically encoded levels of impulsive/inattentive behavior associate with motivation to take alcohol and vulnerability to cue-induced reinstatement of alcohol seeking in an operant self-administration paradigm. We took advantage of BXD16, a recombinant inbred strain previously shown to have enhanced impulsivity and poor attentional control. We compared BXD16 with C57BL/6J mice in a simple choice reaction time task (SCRTT and confirmed its impulsive/inattentive phenotype. BXD16 mice were less active in a novel open field, and were equally active in an automated home cage environment, showing that increased impulsive responding of BXD16 mice could not be explained by enhanced general activity compared to C57BL/6J mice. After training in a sucrose/alcohol fading self-administration procedure, BXD16 showed increased motivation to earn 10% alcohol solution, both under fixed ratio (FR1 and progressive ratio (PR2 schedules of reinforcement. Responding on the active lever readily decreased during extinction training with no apparent differences between strains. However, upon re-exposure to alcohol-associated cues, alcohol seeking was reinstated to a larger extent in BXD16 than in C57BL/6J mice. Although further studies are needed to determine whether impulsivity/inattention and alcohol seeking depend on common or separate genetic loci, these data show that in mice enhanced impulsivity coincides with increased motivation to take alcohol, as well as relapse vulnerability.

  2. Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

    2008-08-15

    Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

  3. [Repeated perioperative administration of fructose and sorbitol in a female patient with hereditary fructose intolerance [HFI)].

    Science.gov (United States)

    Sachs, M; Asskali, F; Förster, H; Encke, A

    1993-03-01

    The present paper reports on an adult female patient whose hereditary fructose intolerance (HFI) was at first not diagnosed and who, within the space of 2 years after repeated elective surgery and the perioperative administration of fructose and sorbitol, developed "hepatic and renal failure of unclear origin." At a later stage we were able to establish the diagnosis of HFI by means of a fructose tolerance test in both she and her brother, for whom intolerance to fruit and desserts had been known since early childhood. In addition, literature references to fatalities following the parenteral application of fructose and sorbitol were analyzed. During the course of fructose infusion in both the patient and her brother with HFI, the following metabolic changes were noted: hypoglycemia, elevated rise in the blood fructose concentration, hyperlactacidemia, elevated rise in the blood fructose concentration, hyperlactacidemia, and hyperammonemia. These metabolic changes proved to be reversible after discontinuing the fructose infusion. Analysis of the literature on the fatalities following parenteral fructose administration established that fruit and dessert intolerance was known for all collated patients with HFI, and that, clearly, no regular metabolic tests had been conducted.

  4. Fine structures and states of water in poly(vinyl alcohol) hydrogels prepared by repeated freezing and thawing

    OpenAIRE

    1997-01-01

    Investigations have been made into the relationship between structure and states of water in unfrozen poly (vinyl alcohol) (PVA) hydrogels prepared by repeated freezing and thawing of aqueous solution with various PVA concentrations. The states of water were investigated by using a pulsed nuclear magnetic resonance spectroscopy. Every unfrozen PVA hydrogel gave only one spin-lattice relaxation time (T-1) value. T-1 of all unfrozen hydrogels were smaller than that of free water and decreased w...

  5. Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress.

    Science.gov (United States)

    Traini, Chiara; Evangelista, Stefano; Girod, Vincent; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana

    2017-04-01

    Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L- and T-type Ca(2+) channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP-, NK1r-, nNOS-, VIP-, and S100β-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT-IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L-type Ca(2+) channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Pharmacokinetics of marbofloxacin in lactating cows after repeated intramuscular administrations and pharmacodynamics against mastitis isolated strains.

    Science.gov (United States)

    Schneider, M; Vallé, M; Woehrlé, F; Boisramé, B

    2004-01-01

    The plasma and milk pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial compound, were evaluated in dairy cows, as well as its pharmacodynamic characteristics against mastitis-isolated pathogens. Marbofloxacin was given intramuscularly as a 10% aqueous solution to dairy cows either at a single dose or at repeated doses of 2 mg/kg once daily for 3 d. Blood and milk samples were collected for the determination of the concentration of marbofloxacin and of its putative metabolites: N-desmethyl-marbofloxacin and N-oxide-marbofloxacin. Bacterial field isolates were from milk samples collected from dairy cows suspected of having an intramammary infection. After identification, the minimal inhibitory concentration (MIC) was determined against the isolated strains. The maximal marbofloxacin concentration (Cmax) observed in milk after the first administration was 1.024 microg/mL, and the area under the curve during the first dosing interval was 6.513 microg/h per milliliter. After the third administration, these parameters were slightly increased (about 20% at most). Both metabolites were detected in the milk, but their concentrations were below the limit of quantification. The MIC against 90% of the population (MIC90) of Escherichia coli was 0.016 microg/mL, and it was 0.229 microg/mL against Staphylococcus aureus. The following surrogate clinical outcome markers were obtained against E. coli strains: a Cmax/MIC ratio of 67 and an area under the curve/MIC ratio of 407 h. Hence, a possible efficacy of marbofloxacin in the treatment of E. coli-induced mastitis could be expected as the endpoints of 10 and 250 h, respectively, are reached.

  7. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    Science.gov (United States)

    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  8. Brain Activation Associated with Automatic Processing of Alcohol-Related Cues in Young Heavy Drinkers and Its Modulation by Alcohol Administration.

    Science.gov (United States)

    Kreusch, Fanny; Goffaux, Valerie; Siep, Nicolette; Houben, Katrijn; Quertemont, Etienne; Wiers, Reinout W

    2015-10-01

    While the automatic processing of alcohol-related cues by alcohol abusers is well established in experimental psychopathology approaches, the cerebral regions involved in this phenomenon and the influence of alcohol intake on this process remain unknown. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the neural mechanisms underlying the processing of task-irrelevant alcohol-related stimuli in young heavy drinkers and their modulation by alcohol administration. Twelve heavy drinking male participants were scanned on 2 separate days; once after a low dose of alcohol intake (0.4 g/kg), and once after a placebo intake, in balanced order. Images of alcoholic drinks, soft drinks, or neutral objects were shown while participants' neural activity was recorded through fMRI. Moreover, participants' attentional focus was manipulated using a task which required them to process the central images of interest (focus alcohol condition) or a center unattended task (focus not on alcohol condition). Results indicated that an explicit judgment on beverage-related cues increased activation in the prefrontal area compared with the judgment of neutral objects. By comparison with that of task-irrelevant neutral cues, the processing of task-irrelevant alcohol-related cues increased the activation in a large network of cerebral areas including visual and temporal regions, the bilateral anterior cingulate cortex, the posterior cingulate cortex, and the putamen. Moreover, in the condition with focus not on alcohol, the ventral tegmental area (VTA) was particularly activated by the presentation of (task-irrelevant) alcohol-related cues compared to task-irrelevant soft-drink-related cues. The VTA was especially involved in the automatic processing of alcohol-related cues in young heavy drinkers. Low dose of alcohol did not modulate the neural substrates involved in the processing of salient alcohol-related cues. Copyright © 2015 by the Research Society

  9. The effects of repeated opioid administration on locomotor activity: II. Unidirectional cross-sensitization to cocaine.

    Science.gov (United States)

    Smith, Mark A; Greene-Naples, Jennifer L; Felder, Jennifer N; Iordanou, Jordan C; Lyle, Megan A; Walker, Katherine L

    2009-08-01

    Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between drugs from different pharmacological classes and may play a role in the escalation of drug use in polydrug-abusing populations. The purpose of this study was to examine cross-sensitization between opioids and cocaine and to determine the extent to which cross-sensitization is mediated by an opioid's selectivity for mu, kappa, and delta receptors. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and the locomotor effects of cocaine were tested 8 days later. The mu agonists, morphine and buprenorphine, and the delta agonist, BW373U86 [(+/-)-4-[(R(*))-[(2S(*),5R(*))-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide hydrochloride], produced cross-sensitization to cocaine, such that repeated administration of these drugs over a 10-day period significantly enhanced cocaine's locomotor effects when tested later. Coadministration of the opioid antagonist naltrexone prevented morphine and buprenorphine from producing cross-sensitization. Coadministration of naltrexone, but not the delta antagonist naltrindole, also prevented BW373U86 from producing cross-sensitization. The kappa agonist spiradoline failed to produce cross-sensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the kappa antagonist nor-binaltorphimine. The mixed mu/kappa opioids butorphanol, nalbuphine, and nalorphine did not produce cross-sensitization under any condition examined. These data indicate that agonist activity at mu receptors positively modulates cross-sensitization between opioids and cocaine, whereas agonist activity at kappa receptors negatively modulates

  10. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration.

    Science.gov (United States)

    Freeman, Willard M; Vanguilder, Heather D; Guidone, Elizabeth; Krystal, John H; Grant, Kathleen A; Vrana, Kent E

    2011-08-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. Two-dimensional difference in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within-subject samples collected before exposure to ethanol and after 3 months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of serum amyloid A4 (SAA4), retinol-binding protein, inter-alpha inhibitor H4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption.

  11. Repeated oral administration of chitosan/DNA nanoparticles delivers functional FVIII with the absence of antibodies in hemophilia A mice.

    Science.gov (United States)

    Dhadwar, S S; Kiernan, J; Wen, J; Hortelano, G

    2010-12-01

    Current treatment of hemophilia A is expensive and involves regular infusions of factor (F)VIII concentrates. The supply of functional FVIII is further compromised by the generation of neutralizing antibodies. Thus, the development of an alternative safe, cost effective, non-invasive treatment that circumvents immune response induction is desirable. To evaluate the feasibility of oral administration of chitosan nanoparticles containing FVIII DNA to provide sustainable FVIII activity in hemophilia A mice. Nanoparticles were characterized for morphology, DNA protection and transfection efficiency. Oral administration of nanoparticles containing canine FVIII in C57Bl/6 FVIII(-/-) hemophilia A mice was evaluated for biodistribution, plasma FVIII activity and phenotypic correction. Sustainable FVIII expression was elucidated after repeated nanoparticle administration. Immune responses to repeated oral nanoparticle administration were also investigated. Chitosan nanoparticles had a particle size range of 200-400 nm and protected DNA from endonuclease and pH degradation. In addition, nanoparticles transfected HEK 293 cells resulted in expression of eGFP, luciferase and FVIII. Hemophilia A mice that ingested chitosan nanoparticles demonstrated transient canine FVIII expression reaching > 100 mU 1 day after treatment, together with partial phenotypic correction. The delivered FVIII plasmid DNA was detected in the intestine and, to a lesser extent, in the liver. Importantly, repeated weekly administrations restored FVIII activity. Furthermore, inhibitors and non-neutralizing FVIII antibodies were not detectable. Repeat oral administration of FVIII DNA formulated in chitosan nanoparticles resulted in sustained FVIII activity in hemophilic mice, and thus may provide a non-invasive alternative treatment for hemophilia A. © 2010 International Society on Thrombosis and Haemostasis.

  12. Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

    Science.gov (United States)

    Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

    2014-08-01

    Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

  13. Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers.

    Science.gov (United States)

    Sommer, Christian; Seipt, Christian; Spreer, Maik; Blümke, Toni; Markovic, Alexandra; Jünger, Elisabeth; Plawecki, Martin H; Zimmermann, Ulrich S

    2015-06-01

    While the utility of experimental free-access alcohol self-administration paradigms is well established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. Timeline Follow-back drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing 1 of 2 similar alcohol self-administration paradigms. In study 1, 18 social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a nonexposed age-matched control group of 42 (28 females, mean age 18.4 years) subjects. In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to prestudy levels (p alcohol-exposed participants reported 7.1% and non-alcohol-exposed controls 6.5% fewer drinking days at poststudy measurement (p alcohol self-administration experiments does not increase subsequent real-life drinking of young adults. Copyright © 2015 by the Research Society on Alcoholism.

  14. Use of an administrative data set to determine optimal scheduling of an alcohol intervention worker.

    Science.gov (United States)

    Peterson, Timothy A; Desmond, Jeffrey S; Cunningham, Rebecca

    2012-06-01

    Brief alcohol interventions are efficacious in reducing alcohol-related consequences among emergency department (ED) patients. Use of non-clinical staff may increase alcohol screening and intervention; however, optimal scheduling of an alcohol intervention worker (AIW) is unknown. Determine optimal scheduling of an AIW based on peak discharge time of alcohol-related ED visits. Discharge times for consecutive patients with an alcohol-related diagnosis were abstracted from an urban ED's administrative data set from September 2005 through August 2007. Queuing theory was used to identify optimal scheduling. Data for weekends and weekdays were analyzed separately. Stationary independent period-by-period analysis was performed for hourly periods. An M/M/s queuing model, for Markovian inter-arrival time/Markovian service time/and potentially more than one server, was developed for each hour assuming: 1) a single unlimited queue; 2) 75% of patients waited no longer than 30 min for intervention; 3) AIW spent an average 20 min/patient. Estimated average utilization/hour was calculated; if utilization/hour exceeded 25%, AIW staff was considered necessary. There were 2282 patient visits (mean age 38 years, range 11-84 years). Weekdays accounted for 45% of visits; weekends 55%. On weekdays, one AIW from 6:00 a.m.-9:00 a.m. (max utilization 42%/hour) would accommodate 28% of weekday alcohol-related patients. On weekends, 5:00 a.m.-11:00 a.m. (max utilization 50%), one AIW would cover 54% of all weekend alcohol-related visits. During other hours the utilization rate falls below 25%/hour. Evaluating 2 years of discharge data revealed that 30 h of dedicated AIW time--18 weekend hours (5:00 a.m.-11:00 a.m.), 12 weekday hours (6:00 a.m.-9:00 a.m.)--would allow maximal patient alcohol screening and intervention with minimal additional burden to clinical staff. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Science.gov (United States)

    Robins, Meridith T; Lu, Julie; van Rijn, Richard M

    2016-01-01

    The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  16. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Meridith T Robins

    Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  17. Altered performance in a rat gambling task after acute and repeated alcohol exposure

    NARCIS (Netherlands)

    Spoelder, Marcia; Lesscher, Heidi M B; Hesseling, Peter; Baars, Annemarie M; Lozeman-van T Klooster, José G; Mijnsbergen, Rob; Vanderschuren, Louk J M J

    2015-01-01

    RATIONALE: A bidirectional relationship between alcohol use disorder (AUD) and deficits in impulse control and decision making has been suggested. However, the mechanisms by which neurocognitive impairments predispose to, or result from AUD remain incompletely understood. OBJECTIVES: The aim of this

  18. Women's risk of repeat abortions is strongly associated with alcohol consumption: a longitudinal analysis of a Russian national panel study, 1994-2009.

    Directory of Open Access Journals (Sweden)

    Katherine Keenan

    Full Text Available Abortion rates in Russia, particularly repeat abortions, are among the highest in the world, and abortion complications make a substantial contribution to the country's high maternal mortality rate. Russia also has a very high rate of hazardous alcohol use. However, the association between alcohol use and abortion in Russia remains unexplored. We investigated the longitudinal predictors of first and repeat abortion, focussing on women's alcohol use as a risk factor. Follow-up data from 2,623 women of reproductive age (16-44 years was extracted from 14 waves of the Russian Longitudinal Monitoring Survey (RLMS, a nationally representative panel study covering the period 1994-2009. We used discrete time hazard models to estimate the probability of having a first and repeat abortion by social, demographic and health characteristics at the preceding study wave. Having a first abortion was associated with demographic factors such as age and parity, whereas repeat abortions were associated with low education and alcohol use. After adjustment for demographic and socioeconomic factors, the risk of having a repeat abortion increased significantly as women's drinking frequency increased (P<0.001, and binge drinking women were significantly more likely to have a repeat abortion than non-drinkers (OR 2.28, 95% CI 1.62-3.20. This association was not accounted for by contraceptive use or a higher risk of pregnancy. Therefore the determinants of first and repeat abortion in Russia between 1994-2009 were different. Women who had repeat abortions were distinguished by their heavier and more frequent alcohol use. The mechanism for the association is not well understood but could be explained by unmeasured personality factors, such as risk taking, or social non-conformity increasing the risk of unplanned pregnancy. Heavy or frequent drinkers constitute a particularly high risk group for repeat abortion, who could be targeted in prevention efforts.

  19. Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

    Science.gov (United States)

    Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

    2016-04-01

    It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

  20. Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Kloster; Mielke, Louise Vennegaard

    2016-01-01

    treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption...... not differ between the study phases (p > 0.05). CONCLUSIONS: These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should...... be advanced compared with preoperative administration....

  1. Effect of exogenous administration of Candida albicans autoregulatory alcohols in a murine model of hematogenously disseminated candidiasis.

    Science.gov (United States)

    Martins, Margarida; Lazzell, Anna L; Lopez-Ribot, Jose L; Henriques, Mariana; Oliveira, Rosário

    2012-08-01

    Candida albicans supernatants contain a mixture of autoregulatory alcohols. In vitro, when added individually or in combination, these alcohols inhibit the yeast to filamentous form conversion. Here we evaluate the in vivo effect of the exogenous administration of a Cocktail solution simulating the composition of alcohols present in a C. albicans culture supernatant (1 ml; 94 μmol l(-1) isoamyl alcohol, 70 μmol l(-1) 2-phenylethanol, 3.2 n mol l(-1) E -nerolidol, and 18 n mol l(-1) E,E -farnesol) using the well established murine model of hematogenously disseminated candidiasis. Mice injected intraperitoneally with the Cocktail solution demonstrated increased survival and decreased organ fungal burden compared to control mice. Histological observations suggest that the Cocktail, to some extent, has an inhibitory effect on cell filamentation within the kidney. These findings suggest that the exogenous administration of C. albicans autoregulatory alcohols displays a protective effect during disseminated candidiasis.

  2. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine.

    Science.gov (United States)

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa

    2007-07-30

    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  3. The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lasfargues, G.; Lardot, C.; Lauwerys, R.; Lison, D. [Catholic Univ. of Louvain (Belgium)] [and others

    1995-05-01

    Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture was greater compared to Co or WC alone. The present study compares the delayed lung response after intratracheal administration of Co or WC-Co particles. The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used as reference materials producing an acute toxic insult and progressive fibrogenic response, respectively. Cellular and biochemical parameters were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) were very modest, if any. Following repeated intratracheal instillations, increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4x1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4x0.06 mg/100 g body wt) or WC (4x1 mg/100 g body wt). The mechanism of the fibrotic reaction induced by WC-Co seems different from the progressive inflammatory reaction induced by crystalline silica. We suggest that it might result from a scarring reaction elicited by repeated acute insults as observed after repeated administration of arsenic trioxide. 34 refs., 10 figs., 3 tabs.

  4. Associations of repeated high alcohol use with unsafe driving behaviors, traffic offenses, and traffic crashes among young drivers: Findings from the New Zealand Drivers Study.

    Science.gov (United States)

    Begg, Dorothy; Brookland, Rebecca; Connor, Jennie

    2017-02-17

    The objective of this study was to describe self-reported high alcohol use at each of the 3 licensing stages of graduated driver licensing and its relationship to drink-driving behaviors, intentional risky driving, aggressive driving, alcohol traffic offenses, non-alcohol traffic offenses, and traffic crashes. The New Zealand Drivers Study (NZDS) is a multistage, prospective cohort study of newly licensed drivers interviewed at all 3 stages of the graduated driver licensing system: learner (baseline), restricted (intermediate), and full license. At each stage, alcohol use was self-reported using the Alcohol Use Disorders Identification Test (AUDIT-C), with high alcohol use defined as a score of ≥4 for males and ≥3 for females. Sociodemographic and personality data were obtained at the baseline interview. Alcohol-related, intentional risky, and aggressive driving behaviors were self-reported following each license stage. Traffic crashes and offenses were identified from police records. Crashes were also self-reported. Twenty-six percent (n = 397) reported no high alcohol use, 22% at one license stage, 30% at 2 stages, and 22% at 3 stages. Poisson regression results (unadjusted and adjusted) showed that the number of stages where high alcohol use was reported was significantly associated with each of the outcomes. For most outcomes, and especially the alcohol-involved outcomes, the relative risk increased with the number of stages of high alcohol use. We found that high alcohol use was common among young newly licensed drivers and those who repeatedly reported high alcohol use were at a significantly higher risk of unsafe driving behaviors. Recently introduced zero blood alcohol concentration (BAC) should help to address this problem, but other strategies are required to target persistent offenders.

  5. Repeated Administration of Mercury Intensifies Brain Damage in Multiple Sclerosis through Mitochondrial Dysfunction

    Science.gov (United States)

    Kahrizi, Farzad; Salimi, Ahmad; Noorbakhsh, Farshid; Faizi, Mehrdad; Mehri, Freshteh; Naserzadeh, Parvaneh; Naderi, Nima; Pourahmad, Jalal

    2016-01-01

    In this study we investigated the additive effect of mercury on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model. Experimental animals (female C57BL/6 mice) are divided into four groups (n = 8); control, Hg, EAE, EAE with Hg. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG). Neurobehavioral alterations are recorded and then mice were sacrificed at day 28 and brain mitochondria were isolated and mitochondrial toxicity parameters including mitochondrial swelling, reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were measured. Our results showed that repeated treatment of mercury following induction of EAE in mice significantly increased the neurobehavioral scores, as well as mitochondrial toxicity through ROS formation, mitochondrial swelling, collapse of MMP and cytochrome c release. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis.

  6. Evaluation of statistical tools used in short-term repeated dose administration toxicity studies with rodents.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Sakuratani, Yuki; Abe, Takemaru; Kamata, Eiichi; Hayashi, Makoto

    2008-02-01

    In order to know the different statistical tools used to analyze the data obtained from twenty-eight-day repeated dose oral toxicity studies with rodents and the impact of these statistical tools on interpretation of data obtained from the studies, study reports of 122 numbers of twenty-eight-day repeated dose oral toxicity studies conducted in rats were examined. It was found that both complex and easy routes of decision trees were followed for the analysis of the quantitative data. These tools include Scheffe's test, non-parametric type Dunnett's and Scheffe's tests with very low power. Few studies used the non-parametric Dunnett type test and Mann-Whitney's U test. Though Chi-square and Fisher's tests are widely used for analysis of qualitative data, their sensitivity to detect a treatment-related effect is questionable. Mann-Whitney's U test has better sensitivity to analyze qualitative data than the chi-square and Fisher's tests. We propose Dunnett's test for analysis of quantitative data obtained from twenty-eight-day repeated dose oral toxicity tests and for qualitative data, Mann-Whitney's U test. For both tests, one-sided test with p=0.05 may be applied.

  7. Repeated Intrathecal Triamcinolone Acetonide Administration in Progressive Multiple Sclerosis: A Review

    Directory of Open Access Journals (Sweden)

    Mazen Abu-Mugheisib

    2011-01-01

    Full Text Available At the present time, anti-inflammatory, immunomodulatory, or immunosuppressive treatments of multiple sclerosis (MS are mainly effective in the early phases of the disease but are of less advantage in progressive phases. Current therapeutic strategies of both primary and secondary progressive MS are rare. One alternative may be intrathecal application of triamcinolone acetonide (TCA. Number of papers deal with advantages and disadvantages of intrathecal administration in MS. Former trials lacked detailed selection of MS patients, with small sample sizes, low steroid dosages, and only a small number of intrathecal administration of short acting steroids. The present paper summarizes recent trials performed following a different treatment regime. They were conducted in patients with progressive MS suffering mainly from spinal symptoms and documented a significant improvement of EDSS and walking distance (WD. Intrathecal TCA administration is a proposal to take into account as one therapy option in patients with a progressive clinical course and predominantly spinal symptoms.

  8. Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents - current status

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan [University of Nis, Faculty of Medicine, Nis (Serbia); Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Center for Radiology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-05-15

    Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. (orig.)

  9. The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.

    Science.gov (United States)

    Korolenko, Tatyana A; Tuzikov, Fedor V; Johnston, Thomas P; Tuzikova, Natalia A; Kisarova, Yana A; Zhanaeva, Svetlana Ya; Alexeenko, Tatyana V; Zhukova, Natalia A; Brak, Ivan V; Spiridonov, Victor K; Filjushina, Elena E; Cherkanova, Marina S; Monoszon, Anna A

    2012-11-01

    The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL₁₋₃-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL₁₋₂-C and VLDL₃₋₅-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL₂-C and HDL₃-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases.

  10. Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo chlorpyrifos dosimetry and cholinesterase inhibition.

    Science.gov (United States)

    Lee, S; Poet, T S; Smith, J N; Hjerpe, A L; Gunawan, R; Timchalk, C

    2011-01-01

    Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 ± 13 and 66 ± 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no

  11. Alcohol

    Science.gov (United States)

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  12. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  13. The effects of repeated intravenous iohexol administration on renal function in healthy beagles – a preliminary report

    Directory of Open Access Journals (Sweden)

    Kirberger Robert M

    2012-08-01

    Full Text Available Abstract Background Contrast induced nephrotoxicity (CIN is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies. Methods This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6–8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR and a variety of laboratory assays. Results Only GFR showed a significant decrease (17% after the second injection but not to a clinically or pathologically significant level. Conclusions No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.

  14. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    Science.gov (United States)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  15. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

    Indian Academy of Sciences (India)

    Y-J Choi; J Y Kim; S B Yoo; J-H Lee; J W Jahng

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  16. Effect of Repeated Administration of hCG on Ovarian Response in PMSG-superovulated Ouled Djellal Ewes (Algeria

    Directory of Open Access Journals (Sweden)

    Lamraoui, R.

    2014-01-01

    Full Text Available The objective of this study was to evaluate the effect of repeated administration of hCG on ovarian response in PMSG-superovulated ewes. Intravaginal pessaries containing 40 mg fluorogestone acetate (FGA were inserted in all ewes (n=9 and remained in situ for 14 days. Two days prior to pessary removal, all ewes were treated with 1000 IU of PMSG. On the day of sponge removal (day 0, the females were randomly assigned to 2 treatments. The first group (n=3 did not receive any hCG, while the second group (n=6 treated inter-muscular with hCG (500 IU during days 0-2. On day 8, laparotomy was performed to assess numbers of corpora lutea (CL and anovulatory follicles (AF. Blood samples were collected for analysis of serum progesterone (P4 using radioimmunoassay (RIA method. The results obtained for first and second group was in number of CL (6.33±1.15 and 10.50±5.54, number of AF (2 ±3.46 and 4.16±5.70, then the levels of P4 (5.75± 4.45 and 13.22±6.80 ng/ml, respectively. These results indicate that the repeated administration of hCG post-sponge removal increases number of CL and improves luteal function in ewes after PMSG-superovulatory treatment.

  17. Effects of Oral Administration of Silymarin in a Juvenile Murine Model of Non-alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Veronica Marin

    2017-09-01

    Full Text Available The increasing prevalence of non-alcoholic fatty liver disease (NAFLD in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid profile, transaminases, HOMA-IR, steatosis, inflammation, fibrosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic life style changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a significant improvement in glycemia, visceral fat, lipid profile, and liver fibrosis. Moreover, it reduced (both in vitro and in vivo ALT, hepatic inflammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the beneficial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH.

  18. Liquid chromatographic determination and depletion profile of oxytetracycline in milk after repeated intramuscular administration in sheep.

    Science.gov (United States)

    Fletouris, Dimitrios J; Papapanagiotou, Elias P; Nakos, Dimitrios S

    2008-12-01

    A simple, rapid and specific ion-pair liquid chromatographic method for the routine determination of the marker residue of oxytetracycline in sheep milk, at levels as low as 20 microg/kg, has been developed. Milk samples were acidified and extracted with acetonitrile. The extracts were purified by treatment with ammonium sulphate and concentrated into diluted phosphoric acid. Separation was carried out isocratically on a Nucleosil C(18) column using a mobile phase that contained both positively and negatively charged pairing ions. The in-house validated method gave overall recoveries and overall relative standard deviations better than 86% and 4.6%, respectively. The method was successfully applied to study the depletion of oxytetracycline in sheep milk and to estimate the withdrawal period after intramuscular administration of a commercial oxytetracycline formulation.

  19. Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.

    Science.gov (United States)

    Cox, Brittney M; Shah, Mrudang M; Cichon, Teri; Tancer, Manuel E; Galloway, Matthew P; Thomas, David M; Perrine, Shane A

    2014-01-01

    Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior.

  20. Brain-derived neurotrophic factor mediates the suppression of alcohol self-administration by memantine.

    Science.gov (United States)

    Jeanblanc, Jérôme; Coune, Fabien; Botia, Béatrice; Naassila, Mickaël

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) within the striatum is part of a homeostatic pathway regulating alcohol consumption. Memantine, a non-competitive antagonist of N-methyl-D-aspartate receptors, induces expression of BDNF in several brain regions including the striatum. We hypothesized that memantine could decrease ethanol (EtOH) consumption via activation of the BNDF signalling pathway. Effects of memantine were evaluated in Long-Evans rats self-administering moderate or high amounts of EtOH 6, 30 and 54 hours after an acute injection (12.5 and 25 mg/kg). Motivation to consume alcohol was investigated through a progressive ratio paradigm. The possible role for BDNF in the memantine effect was tested by blockade of the TrkB receptor using the pharmacological agent K252a and by the BDNF scavenger TrkB-Fc. Candidate genes expression was also assessed by polymerase chain reaction array 4 and 28 hours after memantine injection. We found that memantine decreased EtOH self-administration and motivation to consume EtOH 6 and 30 hours post-injection. In addition, we found that inhibition or blockade of the BDNF signalling pathway prevented the early, but not the delayed decrease in EtOH consumption induced by memantine. Finally, Bdnf expression was differentially regulated between the early and delayed timepoints. These results demonstrate that an acute injection of memantine specifically reduces EtOH self-administration and motivation to consume EtOH for at least 30 hours. Moreover, we showed that BDNF was responsible for the early effect, but that the delayed effect was BDNF-independent.

  1. Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol following Repeated Exposure to Cycles of Ethanol Access and Deprivation

    OpenAIRE

    Rodd, Zachary A.; Bell, Richard L.; McQueen, Victoria K.; Davids, Michelle R.; Hsu, Cathleen C.; Murphy, James M.; Li, Ting-Kai; Lumeng, Lawrence; McBride, William J.

    2005-01-01

    The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of ...

  2. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  3. Tolerance in the anxiolytic profile following repeated administration of diazepam but not buspirone is associated with a decrease in the responsiveness of postsynaptic 5-HT-1A receptors.

    Science.gov (United States)

    Khan, Asma; Haleem, D J

    2007-12-01

    To understand the role of serotonin (5-hydroxytryptamine; 5-HT)-1A receptors in the treatment of anxiety and the development of tolerance to benzodiazepines the present study was designed to monitor the responsiveness of postsynaptic 5-HT-1A receptors following repeated administration of diazepam and buspirone. Results show that tolerance in the anxiolytic profile is produced following repeated administration (2 weeks) of diazepam (2 mg/kg) but not buspirone (0.5 mg/kg). The behavioral effects of 8-OH-DPAT at a dose of 0.25 mg/kg were monitored 3 days after repeated administration of saline or buspirone or diazepam. The results show that 8-OH-DPAT elicited forepaw treading was smaller in repeated diazepam but not repeated buspirone injected rats, while hyperlocomotive effects of 8-OH-DPAT were smaller in both repeated buspirone and repeated diazepam injected rats. The results suggest that postsynaptic 5-HT-1A receptor-dependent responses were attenuated following long-term administration of diazepam but not buspirone. Role of 5-HT-1A receptors in the development of tolerance to the anxiolytic effects of diazepam but not buspirone is discussed.

  4. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

    Science.gov (United States)

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.

  5. Effects of varenicline on operant self-administration of alcohol and/or nicotine in a rat model of co-abuse.

    Science.gov (United States)

    Funk, D; Lo, S; Coen, K; Lê, A D

    2016-01-01

    Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol.

  6. Repeated methamphetamine administration differentially alters fos expression in caudate-putamen patch and matrix compartments and nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Jakub P Jedynak

    Full Text Available BACKGROUND: The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase ("sensitization" in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatum--the so-called patch/striosome and matrix. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens. Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but not in the matrix or in the core or shell of the nucleus accumbens. CONCLUSIONS/SIGNIFICANCE: These data suggest that drug-induced alterations in the patch compartment of the dorsal caudate-putamen may preferentially contribute to some of the enduring changes in brain activity and behavior produced by repeated treatment with methamphetamine.

  7. Region-specific induction of deltaFosB by repeated administration of typical versus atypical antipsychotic drugs.

    Science.gov (United States)

    Atkins, J B; Chlan-Fourney, J; Nye, H E; Hiroi, N; Carlezon, W A; Nestler, E J

    1999-08-01

    Whereas acute administration of many types of stimuli induces c-Fos and related proteins in brain, recent work has shown that chronic perturbations cause the region-specific accumulation of novel Fos-like proteins of 35-37 kD. These proteins, termed chronic FRAs (Fos-related antigens), have recently been shown to be isoforms of DeltaFosB, which accumulate in brain due to their enhanced stability. In the present study, we sought to extend earlier findings that documented the effects of acute administration of antipsychotic drugs (APDs) on induction of Fos-like proteins by investigating the ability of typical and aytpical APDs, after chronic administration, to induce these DeltaFosB isoforms in several brain regions implicated in the clinical actions of these agents. By Western blotting we found that chronic administration of the typical APD, haloperidol, dramatically induces DeltaFosB in caudate-putamen (CP), a brain region associated with the extrapyramidal side effects of this drug. A smaller induction was seen in the nucleus accumbens (NAc) and prefrontal cortex (PFC), brain regions associated with the antipsychotic effects of the drug. In contrast, chronic administration of the prototype atypical APD clozapine failed to significantly increase levels of DeltaFosB in any of the three brain regions, and even tended to reduce DeltaFosB levels in the NAc. Two putative atypical APDs, risperidone and olanzapine, produced small but still significant increases in the levels of DeltaFosB in CP, but not NAc or PFC. Studies with selective receptor antagonists suggested that induction of DeltaFosB in CP and NAc is most dependent on antagonism of D2-D3 dopamine receptors, with antagonism of D1-like receptors most involved in the PFC. Immunohistochemical analysis confirmed the greater induction of DeltaFosB in CP by typical versus atypical APDs, with no significant induction seen in PFC with either class of APD. Together, these findings demonstrate that repeated administration

  8. Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

    Directory of Open Access Journals (Sweden)

    Mukae Takehiro

    2011-09-01

    Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

  9. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.

    Science.gov (United States)

    Schiavon, Angélica Pupin; Bonato, Jéssica Mendes; Milani, Humberto; Guimarães, Francisco Silveira; Weffort de Oliveira, Rúbia Maria

    2016-01-04

    Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice.

  10. Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats.

    Science.gov (United States)

    Isogai, Yukihiro; Takao-Kawabata, Ryoko; Takakura, Aya; Sugimoto, Emika; Nakazono, Osamu; Ikegaki, Ichiro; Kuriyama, Hiroshi; Ishizuya, Toshinori

    2015-10-01

    Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats. The amount of serum osteocalcin, a bone formation marker, was transiently reduced after single TPTD administration, but increased thereafter, remaining increased for several days. In contrast, the amount of excreted urinary C-telopeptide, a bone resorption marker, increased transiently after single TPTD administration, and subsequently returned to control levels on the day after administration. Tissue histomorphometric analyses conducted 8 h after administration showed no changes in bone formation or bone resorption parameters. However, at 48 h, the bone formation parameters OS/BS and Ob.S/BS were increased, while the bone resorption parameter ES/BS was decreased. After repeated TPTD administration for 4 weeks, OS/BS, Ob.S/BS, and MS/BS increased, while Oc.S/BS decreased. Serum osteocalcin at 4 weeks after repeated administration was significantly correlated with OS/BS and Ob.S/BS. These present findings indicate that TPTD has dual, time-dependent effects on bone resorption and bone formation. Immediately after single administration, there was transient promotion of bone resorption and suppression of bone formation. However, sustained stimulation of bone formation occurred thereafter. Furthermore, these data suggest that this sustained bone formation led to anabolic effects with repeated TPTD administration.

  11. Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration.

    Science.gov (United States)

    Abu Lila, Amr S; Nawata, Kosuke; Shimizu, Taro; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2013-11-01

    The accelerated blood clearance (ABC) phenomenon accounts for the rapid systemic clearance of PEGylated nanocarriers upon repeated administrations. IgM production against the polyethylene glycol (PEG) coating in PEGylated liposomes is now known to be responsible for such unexpected pharmacokinetical alterations. The ABC phenomenon poses a remarkable clinical challenge by reducing the therapeutic efficacy of encapsulated drugs and causing harmful effects due to the altered tissue distribution pattern of the drugs. In this study, we investigated the in vivo performance of liposomes modified with polyglycerol (PG) upon repeated injection, and the in vivo therapeutic efficacy of such liposomes when they encapsulated a cytotoxic agent, doxorubicin (DXR). Repeated injection of PEG-coated liposomes in rats induced the ABC phenomenon, while repeated injection of PG-coated liposomes did not. In addition, DXR-containing PG-coated liposomes showed antitumor activity that was superior to that of free DXR and similar to that of DXR-containing PEG-coated liposomes upon repeated administration. These results indicate that polyglycerol (PG) might represent a promising alternative to PEG via enhancing the in vivo performance of liposomes by not eliciting the ABC phenomenon upon repeated administration.

  12. The effect of repeated nicotine administration on the performance of drug-naive rats in a five-choice serial reaction time task.

    Science.gov (United States)

    Blondel, A; Simon, H; Sanger, D J; Moser, P

    1999-11-01

    Nicotine improves cognitive performance both in animals and in humans, particularly in tests involving attentional processes. The five-choice serial reaction time task (5-CSRTT) is widely used as a model of attentional performance in rats, and previous studies have demonstrated effects of nicotine in this task on measures such as improved reaction time. Using a modified version of this task (in which rats were required to respond to the disappearance of one of five stimulus lights), we evaluated the effects of repeated nicotine administration (0.3 mg/kg, intraperitoneally, on three occasions over 7 days) in drug-naive rats. After the first administration, nicotine increased accuracy and reduced inappropriate responding (anticipatory responses and responses during time-out) compared to performance following vehicle administration on the preceding day. However, with repeated administration the improvement in accuracy disappeared, and other effects became apparent. Thus, after the third administration the main effects of nicotine were to increase inappropriate responding and to reduce reaction times. A fourth administration 1-2 weeks later produced similar results to the third administration, suggesting that the effects of nicotine were now constant. Despite the general increase in inappropriate responding, there was no impairment in accuracy. In contrast to the response to repeated nicotine, the performance of the rats on the 3 vehicle days remained constant. These data demonstrate that the administration of nicotine to drug-naive subjects improves performance in the 5-CSRTT but that with repeated administration this effect disappears and is replaced by a profile in which inappropriate and impulsive responding predominate.

  13. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse

    Energy Technology Data Exchange (ETDEWEB)

    Vanyukov, M.M.; Moss, H.B.; Tarter, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1995-04-24

    An association between the liability to early onset alcoholism/substance abuse and a recently discovered dinucleotide repeat length polymorphism at the MAOA gene (MAOCA-1) was examined using polymerase chain reaction (PCR). A significant correlation between the presence/absence of the disorder and the length of the MAOCA-1 repeat was found in males, but not females, with {open_quotes}long{close_quotes} alleles (repeat length above 115 bp) associated with both increased risk for the disorder and lower age of onset of substance abuse. These preliminary data suggest that further exploration of the relationship between the MAOA gene and behavioral traits in an expanded sample is warranted. 22 refs., 1 fig., 3 tabs.

  14. Paradoxical reaction of raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis.

    Science.gov (United States)

    Barreira, Rebeca Iglesias; García, Belén Bardán; López, Mónica Granero; Legazpi, Iria Rodríguez; Díaz, Hortensia Álvarez; Penín, Isaura Rodríguez

    2012-10-01

    To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

  15. Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase in rat hippocampus after repeated low-dose dexamethasone administration.

    Science.gov (United States)

    Drakulić, Dunja; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana; Veličković, Nataša; Guševac, Ivana; Mitrović, Nataša; Buzadžić, Ivana; Horvat, Anica

    2015-04-01

    Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

  16. Alcohol

    NARCIS (Netherlands)

    Hendriks, H.F.; Tol, A. van

    2005-01-01

    Alcohol consumption affects overall mortality. Light to moderate alcohol consumption reduces the risk of coronary heart disease; epidemiological, physiological and genetic data show a causal relationship. Light to moderate drinking is also associated with a reduced risk of other vascular diseases an

  17. Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of d-luciferin: effect on intensity, time kinetics and repeatability of photon emission

    Energy Technology Data Exchange (ETDEWEB)

    Keyaerts, Marleen; Vanhove, Chris; Caveliers, Vicky; Bossuyt, Axel; Lahoutte, Tony [Vrije Universiteit Brussel (VUB), In Vivo Cellular and Molecular Imaging (ICMI) Laboratory, Brussels (Belgium); University Hospital Brussels (UZ-Brussel), Department of Nuclear Medicine, Brussels (Belgium); Verschueren, Jacob [University of Antwerp, Bio-Imaging lab, Department of Biomedical Sciences, Antwerp (Belgium); Bos, Tomas J. [Vrije Universiteit Brussel (VUB), Department of Haematology and Immunology, Brussels (Belgium); Tchouate-Gainkam, Lea O.; Peleman, Cindy [Vrije Universiteit Brussel (VUB), In Vivo Cellular and Molecular Imaging (ICMI) Laboratory, Brussels (Belgium); Breckpot, Karine [Vrije Universiteit Brussel (VUB), Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Brussels (Belgium)

    2008-05-15

    In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. d-luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal. The aim of this study is to compare the repeatability of BLI measurement after IV versus IP administration of d-luciferin and assess the correlation between photon emission and histological cell count both in vitro and in vivo. Fluc-positive R1M cells were subcutaneously inoculated in nu/nu mice. Dynamic BLI was performed after IV or IP administration of d-luciferin. Maximal photon emission (PE{sub max}) was calculated. For repeatability assessment, every acquisition was repeated after 4 h and analysed using Bland-Altman method. A second group of animals was serially imaged, alternating IV and IP administration up to 21 days. When mice were killed, PE{sub max} after IV administration was correlated with histological cell number. The coefficients of repeatability were 80.2% (IV) versus 95.0% (IP). Time-to-peak is shorter, and its variance lower for IV (p < 0.0001). PE{sub max} was 5.6 times higher for IV. A trend was observed towards lower photon emission per cell in larger tumours. IV administration offers better repeatability and better sensitivity when compared to IP. In larger tumours, multiple factors may contribute to underestimation of tumour burden. It might, therefore, be beneficial to test novel therapeutics on small tumours to enable an accurate evaluation of tumour burden. (orig.)

  18. Repeated administration of D-amphetamine induces loss of [I-123]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    NARCIS (Netherlands)

    J. Booij; K. de Bruin; W.B. Gunning

    2006-01-01

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in arnphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of

  19. Alcohol

    Science.gov (United States)

    ... changes that come from drinking alcohol can make people do stupid or embarrassing things, like throwing up or peeing on themselves. Drinking also gives people bad breath, and no one enjoys a hangover. ...

  20. Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

    Science.gov (United States)

    Rejitha, S; Prathibha, P; Indira, M

    2012-10-01

    Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

  1. Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

    DEFF Research Database (Denmark)

    Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N;

    2009-01-01

    1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection......Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase...

  2. Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

    Science.gov (United States)

    Erb, Suzanne; McPhee, Matthew; Brown, Zenya J; Kupferschmidt, David A; Song, Lifang; Lovejoy, David A

    2014-08-01

    The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors.

  3. 78 FR 20890 - Polyvinyl Alcohol From Taiwan: Preliminary Results of Antidumping Duty Administrative Review...

    Science.gov (United States)

    2013-04-08

    ... Economy Unit, to Ronald K. Lorentzen, Acting Assistant Secretary for Import Administration, ``Decision... Duty Centralized Electronic Service System (``IA ACCESS''). Access to IA ACCESS is available to...

  4. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  5. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  6. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart.

    Directory of Open Access Journals (Sweden)

    Maren Weischer

    2014-03-01

    Full Text Available Cross-sectional studies have associated short telomere length with smoking, body weight, physical activity, and possibly alcohol intake; however, whether these associations are due to confounding is unknown. We tested these hypotheses in 4,576 individuals from the general population cross-sectionally, and with repeat measurement of relative telomere length 10 years apart. We also tested whether change in telomere length is associated with mortality and morbidity in the general population. Relative telomere length was measured with quantitative polymerase chain reaction. Cross-sectionally at the first examination, short telomere length was associated with increased age (P for trend across quartiles = 3 × 10(-77, current smoking (P = 8 × 10(-3, increased body mass index (P = 7 × 10(-14, physical inactivity (P = 4 × 10(-17, but not with increased alcohol intake (P = 0.10. At the second examination 10 years later, 56% of participants had lost and 44% gained telomere length with a mean loss of 193 basepairs. Change in leukocyte telomere length during 10 years was associated inversely with baseline telomere length (P<1 × 10(-300 and age at baseline (P = 1 × 10(-27, but not with baseline or 10-year inter-observational tobacco consumption, body weight, physical activity, or alcohol intake. Prospectively during a further 10 years follow-up after the second examination, quartiles of telomere length change did not associate with risk of all-cause mortality, cancer, chronic obstructive pulmonary disease, diabetes mellitus, ischemic cerebrovascular disease, or ischemic heart disease. In conclusion, smoking, increased body weight, and physical inactivity were associated with short telomere length cross-sectionally, but not with telomere length change during 10 years observation, and alcohol intake was associated with neither. Also, change in telomere length did not associate prospectively with mortality or morbidity in the general population.

  7. Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice

    Science.gov (United States)

    Johansson, Emily M.; García-Gutiérrez, María S.; Moscoso-Castro, María; Manzanares, Jorge; Valverde, Olga

    2015-01-01

    The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1β (IL-1β) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. PMID:26566284

  8. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    Directory of Open Access Journals (Sweden)

    Błażej Poźniak

    Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

  9. Effect of long-term, peroral administration of sugar alcohols on man.

    Science.gov (United States)

    Mäkinen, K K

    1984-01-01

    Certain sugar alcohols (polyols), notably mannitol, sorbitol and xylitol have gained use in food manufacturing for sweetening and technical purposes. These compounds are natural polyols that occur in small amounts in animals and plants. Some sugar alcohols, like xylitol, appear as normal intermediates in the carbohydrate metabolism. Exogenous mannitol, sorbitol and xylitol are metabolized in the human body along pre-existing, physiological pathways. Moderate doses of least xylitol and sorbitol are almost totally absorbed and metabolized, chiefly in the liver cells, thereby eventually contributing to the formation of glucose and liver glycogen. Various slowly absorbed carbohydrates, including sugar alcohols, when taken in orally in large quantities, can give rise to osmotic diarrhea. The available data indicate that the severity of such gastro-intestinal disturbances, induced by large doses of polyols, decrease in the following order: mannitol, sorbitol, xylitol. This osmotic diarrhea resembles that caused by lactose in subjects with restricted or frank lactose intolerance. The quantities of xylitol, for example, required to elicit diarrhea are so high that the consumption of xylitol for dental purposes does not cause any problems in children or adults. Long-term feeding trials and peroral loading experiments on human subjects have been unable to show any clinically significant differences between chronic users of xylitol and comparative human material in factors related to various metabolic functions of the body. These subjects have not shown any delayed or acute reactions which could be distinguished from those caused by the consumption of a sucrose diet. The available clinical data generally suggest that moderate consumption of the above polyols is not harmful to human metabolism.

  10. Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H;

    2010-01-01

    -induced phosphorylation of Erk2 in the prefrontal cortex occurs following acute, but not repeated administration. Our results demonstrate that repeated agonist administration increases the number of alpha7 nAChRs in the brain, and leads to coupling versus uncoupling of specific intracellular signaling....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n......-120596 and NS1738 do not increase [(125)I]-BTX binding. Furthermore, A-582941-induced increase in Arc and c-fos mRNA expression in the prefrontal cortex is enhanced and unaltered, respectively, after repeated administration, demonstrating that the alpha7 nAChRs remain responsive. Contrarily, A-582941...

  11. Long-term Administration of Alcohol in Rats: Effects on Glucagon and Insulin Levels in Sera During Pre-Pregnancy, Pregnancy and Lactation Periods

    OpenAIRE

    ZEYBEK, Birsen; TÜRKMEN, Gülhan

    2002-01-01

    The effects of long-term administration of ethyl alcohol on insulin and glucagon hormone levels during pregnancy and lactation periods of rats were investigated. Female wistar albinos, 200±20 g, were used in this study. The control group consisted of 15 rats, and the experimental group consist of 25 ethyl-alcohol-addicted rats. While 0.9% saline (with sucrose) was to the control group, a 5 g kg perday dose of 20% ethyl alcohol was given to the experimental group. Blood samples were taken fiv...

  12. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord.

    Science.gov (United States)

    Shi, L; Tang, G P; Gao, S J; Ma, Y X; Liu, B H; Li, Y; Zeng, J M; Ng, Y K; Leong, K W; Wang, S

    2003-07-01

    Gene delivery into the spinal cord provides a potential approach to the treatment of spinal cord traumatic injury, amyotrophic lateral sclerosis, and spinal muscular atrophy. These disorders progress over long periods of time, necessitating a stable expression of functional genes at therapeutic levels for months or years. We investigated in this study the feasibility of achieving prolonged transgene expression in the rat spinal cord through repeated intrathecal administration of plasmid DNA complexed with 25 kDa polyethylenimine (PEI) into the lumbar subarachnoid space. With a single injection, DNA/PEI complexes could provide transgene expression in the spinal cord 40-fold higher than naked plasmid DNA. The transgene expression at the initial level persisted for about 5 days, with a low-level expression being detectable for at least 8 weeks. When repeated dosing was tested, a 70% attenuation of gene expression was observed following reinjection at a 2-week interval. This attenuation was associated with apoptotic cell death and detected even using complexes containing a noncoding DNA that did not mediate any gene expression. When each component of the complexes, PEI polymer or naked DNA alone, were tested in the first dosing, no reduction was found. Using polyethylene glycol (PEG)-grafted PEI for DNA complexes, no attenuation of gene expression was detected after repeated intrathecal injections, even in those rats receiving three doses, administered 2 weeks apart. Lumbar puncture is a routine and relatively nontraumatic clinical procedure. Repeated administration of DNA complexed with PEG-grafted PEI through this less invasive route may prolong the time span of transgene expression when needed, providing a viable strategy for the gene therapy of spinal cord disorders.

  13. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  14. Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

    Science.gov (United States)

    Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

    2017-05-24

    COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABAB receptor. This study evaluated whether COR659 shared with previously tested GABAB PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABAB PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABAB receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABAB receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

  15. Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction.

    Science.gov (United States)

    Huang, He; Liu, Cun-Ming; Sun, Jie; Jin, Wen-Jie; Wu, Yu-Qing; Chen, Jing

    2017-09-15

    Sevoflurane is one of the most widely used inhalation anesthetics in pediatric anesthesia. A large number of studies have demonstrated that repeated treatment with high concentrations or long durations of sevoflurane anesthesia during the neonatal period can induce neuroapoptosis and long-term learning disability. In clinical practice, we observed that a subset of patients underwent minor surgery under sevoflurane anesthesia more than once from birth to adolescence. Therefore, this research was conducted to investigate whether a 2% concentration of sevoflurane (clinically relevant usage of sevoflurane) for 1 h (a short duration) can induce neuroapoptosis and neurocognitive dysfunction in adolescent rats that received sevoflurane (2% for 1 h) during the neonatal period. Group I: neonatal rats at postnatal day 7 (PND-7) were treated with oxygen under controlled conditions and then raised to PND-60. Group II: PND-7 rats were treated with 2% sevoflurane for 1 h and then raised to PND-60. Group III: the PND-60 rats were treated with 2% sevoflurane for 1 h and in group IV the PND-7 rats were treated with 2% sevoflurane for 1 h and then anesthetized with 2% sevoflurane for 1 h at PND-60 again. The expression of caspase-3, Bax and Bcl-2 in the hippocampal dentate gyrus (DG) were measured by Western blot analysis. Neuroapoptosis in the hippocampal DG was assessed using NeuN/caspase-3 double-immunofluorescence staining. Spatial reference memory was tested by the Morris water maze test. The present data showed that sevoflurane (2% for 1 h) did not induce obvious hippocampal neuroapoptosis in the PND-7 rats and PND-60 rats; their performance in hippocampal-dependent spatial memory was not significantly impaired; however, the rats in group IV showed poor performance in the Morris water maze test and the neuroapoptosis in group IV was significantly increased. Our findings suggested that sevoflurane can induce neuroapoptosis and cognitive dysfunction in

  16. Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.

    Science.gov (United States)

    Duke, Angela N; Kaminski, Barbara J; Weerts, Elise M

    2014-01-01

    Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.

  17. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice

    OpenAIRE

    ORIKASA, Shuzo; NABESHIMA, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (109 CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of ky...

  18. Biodistribution of BPA and BSH after single, repeated and simultaneous administrations for neutron-capture therapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)], E-mail: ichikawa@pharm.kobegakuin.ac.jp; Taniguchi, E. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fukumori, Y. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)

    2009-07-15

    The effect of administration mode of L-BPA and BSH on the biodistribution in the melanoma-bearing hamsters was investigated. In single intravenous (i.v.) administration, BSH (100 mg BSH/kg) showed no significant retention of {sup 10}B in all the tissues, including tumors, while long-term retention of {sup 10}B in the tumor, muscle and brain was observed with L-BPA (500 mg BPA/kg). The dose escalation of L-BPA and the simultaneous single administration of L-BPA and BSH were not so effective at increasing boron accumulation in tumor after bolus i.v. injection. The boron concentration in tumor was 41 {mu}g B/g after single bolus i.v. injection even at the dose of 1000 mg BPA/kg. In contrast, two sequential bolus i.v. injections of L-BPA with the dose of 500 mg BPA/kg each was found to be effective at increasing {sup 10}B accumulation in the tumor; the maximum {sup 10}B concentration in the tumor reached 52 {mu}g B/g at 3 h after the second i.v. injection.

  19. The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

    Science.gov (United States)

    Erfurt, L; Schandry, R; Rubenbauer, S; Braun, U

    2014-09-25

    The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

    Science.gov (United States)

    Orikasa, Shuzo; Nabeshima, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-Zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan. These results suggest the potential of BB536 for supplemental treatment of the symptoms of schizophrenia.

  1. Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters

    Directory of Open Access Journals (Sweden)

    Nostell Katarina EA

    2012-02-01

    Full Text Available Abstract Background The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise. Methods In a crossover design, after a glycogen depleting exercise, twelve Standardbred trotters received either repeated oral boluses of glucose, 1 g/kg body weight (BW at 0, 2 and 4 h with addition of leucine 0.1 g/kg BW at 0 and 4 h (GLU+LEU, or repeated boluses of water at 0, 2 and 4 h (CON. Blood samples for analysis of glucose, insulin and amino acid concentrations were collected prior to exercise and over a 6 h post-exercise period. A mixed model approach was used for the statistical analyses. Results Plasma leucine, isoleucine, valine, tyrosine and phenylalanine concentrations increased after exercise. Post-exercise serum glucose and plasma insulin response were significantly higher in the GLU+LEU treatment compared to the CON treatment. Plasma leucine concentrations increased after supplementation. During the post-exercise period isoleucine, valine and methionine concentrations decreased in both treatments but were significantly lower in the GLU+LEU treatment. There was no correlation between the insulin response and the response in plasma leucine, isoleucine, valine and methionine. Conclusions Repeated post-exercise administration with a mixture of leucine

  2. Loss of phenotype of parvalbumin interneurons in rat prefrontal cortex is involved in antidepressant- and propsychotic-like behaviors following acute and repeated ketamine administration.

    Science.gov (United States)

    Zhou, ZhiQiang; Zhang, GuangFen; Li, XiaoMin; Liu, XiaoYu; Wang, Nan; Qiu, LiLi; Liu, WenXue; Zuo, ZhiYi; Yang, JianJun

    2015-04-01

    Accumulating evidence has demonstrated that single subanesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant-like effects. Nevertheless, repeated subanesthetic doses of ketamine produce psychosis-like effects with dysfunction of parvalbumin (PV) interneurons. We hypothesized that PV interneurons play an important role in the antidepressant-like actions of ketamine, and different changes in PV interneurons occur with the antidepressant-like and propsychotic-like effects of ketamine. To test this hypothesis, ketamine's antidepressant-like effects were evaluated by the forced swimming test. Ketamine-induced stereotyped behaviors and hyperactivity actions and the function of PV interneurons were also assessed. We demonstrated that an acute dose of 10 mg/kg ketamine induced significant antidepressant-like effects and reduced the levels of PV and the gamma-aminobutyric acid (GABA)-producing enzyme GAD67 in the rat prefrontal cortex. Moreover, inhibition of ketamine-induced loss of PV by apocynin blocked these antidepressant-like effects. Repeated administration of 30 mg/kg ketamine elicited stereotyped behaviors and hyperactivity actions as well as a longer duration of PV and GAD67 loss, higher brain glutamate levels, and lower brain GABA levels than acute single dose of ketamine. Our results reveal that the loss of phenotype of PV interneurons in the prefrontal cortex contributes to the antidepressant-like actions and is also involved in the propsychotic-like behaviors following acute and repeated ketamine administration, which may be partially mediated by the disinhibition of glutamate signaling. The different degrees and durations of the actions on PV interneurons produced by the two regimens of ketamine may partly underline the behavioral variance between the antidepressant- and propsychotic-like effects.

  3. Hepatotoxicity assessment of Mn-doped ZnS quantum dots after repeated administration in mice

    Directory of Open Access Journals (Sweden)

    Yang YJ

    2015-09-01

    Full Text Available Yanjie Yang,1,2 Shuang-Yu Lv,2 Bianfei Yu,1 Shuang Xu,1 Jianmin Shen,3 Tong Zhao,1 Haixia Zhang1 1Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, 2School of Medicine, Henan University, Kaifeng, Henan, 3Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China Abstract: Doped ZnS quantum dots (QDs have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase, the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase, or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future. Keywords: liver, serum aminotransferases, antioxidant enzymes, ultrastructure

  4. Effects of Alcohol and Saccharin Deprivations on Concurrent Ethanol and Saccharin Operant Self-Administration by Alcohol-Preferring (P) Rats

    Science.gov (United States)

    Toalston, Jamie E.; Oster, Scott M.; Kuc, Kelly A.; Pommer, Tylene J.; Murphy, James M.; Lumeng, Lawrence; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2008-01-01

    Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of EtOH and saccharin (SACC) deprivations on operant oral self-administration. P rats were allowed to lever press concurrently self-administer EtOH (15% v/v) and SACC (0.0125% g/v) for 8 weeks. Rats were then maintained on daily operant access (non-deprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of EtOH daily, or deprived of EtOH and given 2 ml of SACC daily. All groups were then given two weeks of daily operant access to EtOH and SACC, followed by an identical second deprivation period. P rats responded more for EtOH than SACC. All deprived groups increased responding on the EtOH lever, but not on the SACC lever. Daily consumption of 2 ml EtOH decreased the duration of the ADE. Home cage access to 2 ml SACC also decreased the ADE but to a lesser extent than access to EtOH. A second deprivation period further increased and prolonged the expression of an ADE. These results show EtOH is a more salient reinforcer than SACC. With concurrent access to EtOH and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both EtOH and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between EtOH and SACC in their CNS reinforcing effects. PMID:18400451

  5. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Directory of Open Access Journals (Sweden)

    Mario Rivera-Meza

    2017-07-01

    Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

  6. Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

    Science.gov (United States)

    Gao, Wanxia; Zhao, Jie; Gao, Zhonghong

    2017-01-01

    It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction. PMID:28103293

  7. 76 FR 78014 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review...., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism, National Institutes...

  8. 78 FR 42529 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review....D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism,...

  9. 76 FR 26308 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Scientific Review Administrator, National Institutes On Alcohol Abuse & Alcoholism National, Institutes...

  10. 77 FR 22794 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-17

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism...

  11. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    Science.gov (United States)

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  12. Cellular Composition of the Spleen and Changes in Splenic Lysosomes in the Dynamics of Dyslipidemia in Mice Caused by Repeated Administration of Poloxamer 407.

    Science.gov (United States)

    Goncharova, N V; Shurlygina, A V; Mel'nikova, E V; Karmatskikh, O L; Avrorov, P A; Loktev, K V; Korolenko, T A

    2015-11-01

    We studied the effect of dyslipidemia induced by poloxamer 407 (300 mg/kg twice a week for 30 days) on cellular composition of the spleen and splenocyte lysosomes in mice. Changes in blood lipid profile included elevated concentrations of total cholesterol, aterogenic LDL, and triglycerides most pronounced in 24 h after the last poloxamer 407 injection; gradual normalization of lipid profile was observed in 4 days (except triglycerides) and 10 days. The most pronounced changes in the spleen (increase in organ weight and number of cells, inhibition in apoptosis, and reduced accumulation of vital dye acridine orange in lysosomes) were detected on day 4; on day 10, the indices returned to normal. Cathepsin D activity in the spleen also increased at these terms. The relationship between changes in the cellular composition of the spleen and dynamics of serum lipid profile in mice in dyslipidemia caused by repeated administrations of relatively low doses of poloxamer 407 is discussed.

  13. Repeated ketamine administration alters N-methyl-d-aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans

    Science.gov (United States)

    Lipsky, Robert H

    2015-01-01

    For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. PMID:25245072

  14. The Effect of Subchronic Administration of the Aqueous and Hydro-alcoholic Extracts of Crocus sativus from Estahbanat, Fars Province, on Mice

    Directory of Open Access Journals (Sweden)

    M Emamghoreishi

    2012-02-01

    Full Text Available Background & aim: In Iranian traditional medicine, Crocus sativus L. has been defined as an exultant plant. The present study was undertaken to determine the effect of subchronic administration of aqueous and hydro-alcoholic extracts of Crocus sativus on mice. Methods: The effect of subchronic i.p. administration of different doses of the aqueous extract (50, 100, 200, 400 mg/kg or water and the hydro-alcoholic extract (100, 200, 400, 800 mg/kg or water of Crocus sativus stigma on immobility, climbing, and swimming behaviors were evaluated in the forced swimming test in mice. Fluoxetine (20 mg/kg and imipramine (15 mg/kg were used as reference drugs. Additionally, the effect of both plant preparations on spontaneous activity was examined. The collected data was analyzed using One-way ANOVA. Results: The aqueous extract at doses of 50 and 100 mg/kg produced a significant reduction in immobility along with an increase in climbing behavior which is similar to those which have been observed with imipramine. The hydro-alcoholic extract did not show significant effects on immobility, climbing and swimming behaviors of all studied doses, compared to control group. The aqueous extract of all studied doses and the hydro-alcoholic extract at dose of 1600 mg/kg decreased spontaneous activity. Conclusion: The results of this study suggests that the aqueous, but not hydro-alcoholic, extract of Crocus sativus stigma from Estahbanat in Fars province, in subchronic administration possess an antidepressant-like activity which may be mediated through norepinephrine system.

  15. Comparison of Student Self-Reported and Administrative Data regarding Intercession into Alcohol Misuse among College Freshmen Dormitory Residents

    Science.gov (United States)

    Novik, Melinda G.; Boekeloo, Bradley O.

    2013-01-01

    Intercession into collegiate alcohol misuse by the Department of Resident Life (DRL) in freshmen dormitories at one large Mid-Atlantic, diverse, public university was examined. Freshmen dormitory resident drinkers (n = 357), 71% of whom reported alcohol misuse, were surveyed. Student self-report and DRL documentation, respectively, revealed that…

  16. Comparison of Student Self-Reported and Administrative Data regarding Intercession into Alcohol Misuse among College Freshmen Dormitory Residents

    Science.gov (United States)

    Novik, Melinda G.; Boekeloo, Bradley O.

    2013-01-01

    Intercession into collegiate alcohol misuse by the Department of Resident Life (DRL) in freshmen dormitories at one large Mid-Atlantic, diverse, public university was examined. Freshmen dormitory resident drinkers (n = 357), 71% of whom reported alcohol misuse, were surveyed. Student self-report and DRL documentation, respectively, revealed that…

  17. The acceptability of repeat Internet-based hybrid diet assessment of previous 24-h dietary intake: administration of the Oxford WebQ in UK Biobank.

    Science.gov (United States)

    Galante, Julieta; Adamska, Ligia; Young, Alan; Young, Heather; Littlejohns, Thomas J; Gallacher, John; Allen, Naomi

    2016-02-28

    Although dietary intake over a single 24-h period may be atypical of an individual's habitual pattern, multiple 24-h dietary assessments can be representative of habitual intake and help in assessing seasonal variation. Web-based questionnaires are convenient for the participant and result in automatic data capture for study investigators. This study reports on the acceptability of repeated web-based administration of the Oxford WebQ--a 24-h recall of frequency from a set food list suitable for self-completion from which energy and nutrient values can be automatically generated. As part of the UK Biobank study, four invitations to complete the Oxford WebQ were sent by email over a 16-month period. Overall, 176 012 (53% of those invited) participants completed the online version of the Oxford WebQ at least once and 66% completed it more than once, although only 16% completed it on all four occasions. The response rate for any one round of invitations varied between 34 and 26%. On most occasions, the Oxford WebQ was completed on the same day that they received the invitation, although this was less likely if sent on a weekend. Participants who completed the Oxford WebQ tended to be white, female, slightly older, less deprived and more educated, which is typical of health-conscious volunteer-based studies. These findings provide preliminary evidence to suggest that repeated 24-h dietary assessment via the Internet is acceptable to the public and a feasible strategy for large population-based studies.

  18. Enhanced self-administration of alcohol in muscarinic acetylcholine M4 receptor knockout mice

    DEFF Research Database (Denmark)

    de la Cour, Cecilie; Sørensen, Gunnar; Wörtwein, Gitta

    2015-01-01

    -established. Moreover, the M4-/- mice displayed a reduced capacity to extinguish their alcohol-seeking behavior. Taken together, alcohol consumption is elevated in M4-/- mice, indicating that the M4 receptor is involved in mediating the reinforcing effects of alcohol. The M4 receptor should be further explored......Modulation of cholinergic neurotransmission via nicotinic acetylcholine receptors is known to alter alcohol-drinking behavior. It is not known if muscarinic acetylcholine receptor subtypes have similar effects. The muscarinic M4 receptor is highly expressed in the brain reinforcement system...... and involved in regulation of cholinergic and dopaminergic transmission. Here we investigate, for the first time, the role of the M4 receptor in alcohol consumption using M4 knockout (M4-/-) and wild-type (M4+/+) mice. Experimentally naïve M4-/- and M4+/+ mice were trained to orally self-administer 5%, 8...

  19. Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

    Directory of Open Access Journals (Sweden)

    Malki Rana

    2008-04-01

    Full Text Available Abstract Background Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA. Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2, the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3, the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B, as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5 in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7th day for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes. Results The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions. Conclusion Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.

  20. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  1. The effect of repeated administrations of llama ovulation-inducing factor (OIF/NGF) during the peri-ovulatory period on corpus luteum development and function in llamas.

    Science.gov (United States)

    Fernández, A; Ulloa-Leal, C; Silva, M; Norambuena, C; Adams, G P; Guerra, M; Ratto, M H

    2014-10-01

    The objective of the study was to test the hypothesis that repeated administrations of OIF/NGF during the peri-ovulatory period (pre-ovulatory, ovulatory, early post-ovulatory), will enhance the luteotrophic effect in llamas. Female llamas were examined daily by transrectal ultrasonography in B- and Doppler-mode using a scanner equipped with a 7.5-MHz linear-array transducer to monitor ovarian follicle and luteal dynamics. When a growing follicle ≥7mm was detected, llamas were assigned randomly to one of the three groups and given 1mg of purified OIF/NGF im (intramuscular) (a) pre-ovulation (single dose; n=12), (b) pre-ovulation and at the time of ovulation (2 doses, n=10), or (c) pre-ovulation, at the time of ovulation, and 24h after ovulation (3 doses, n=10). The pre-ovulatory follicle diameter at the time of treatment, ovulation rate and the first day of CL detection did not differ (P=0.3) among groups. However, maximum CL diameter was greatest (P=0.003) in llamas in the 2-dose group, and smallest in the 3-dose group. Accordingly, the 2 dose-group had the largest day-to-day profile for CL diameter (Pllama seminal plasma is luteotrophic and the effect on CL size and function is affected by the number and timing of treatments during the peri-ovulatory period.

  2. An In Vivo Evaluation of the Effect of Repeated Administration and Clearance of Targeted Contrast Agents on Molecular Imaging Signal Enhancement

    Directory of Open Access Journals (Sweden)

    Jason E. Streeter, Paul A. Dayton

    2013-01-01

    Full Text Available Competitive inhibition diminishes ligand adhesion as receptor sites become occupied with competing ligands. It is unknown if this effect occurs in ultrasound molecular imaging studies where endothelial binding sites become occupied with adherent bubbles or bubble fragments. The goal of this pilot study was to assess the effect that repeated administration and clearance of targeted agents has on successive adhesion. Two groups of animals were imaged with 3-D ultrasonic molecular imaging. Injections and imaging were performed on Group 1 at time 0 and 60 minutes. Group 2 received injections of microbubbles at 0, 15, 30, 45 and 60 minutes with imaging at 0 and 60 minutes. At 60 minutes, Group 1 targeting relative to baseline was not significantly different from Group 2 (1.06±0.27 vs. 1.08±0.34, p=0.93. Data suggest that multiple injections of targeted microbubbles do not block sufficient binding sites to bias molecular imaging data in serial studies.

  3. 78 FR 21615 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-11

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial ] Review... Foster, Ph.D., Scientific Review Administrator, National Institutes on Alcohol Abuse &...

  4. Alcoholism and Alcohol Abuse

    Science.gov (United States)

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  5. Two different methods for repeated intrathecal administration in rats%大鼠鞘内反复给药两种方法的比较

    Institute of Scientific and Technical Information of China (English)

    任占杰; 于志军; 张增臻; 张成明; 张广学

    2009-01-01

    Objective To compare the feasibility of direct spinal puncture and reserving micro-catheter in spinal space during repeated intrathecal administration. Methods Forty Sprague-Dawley rats were randomly divided into 2 groups:direct spinal puncture (group puncture) and reserving micro-catheter in spinal space group (group reserve). The duration of operation were recorded. 5 days after operation, rata in both groups were intrathecally administerde morphine(10 μg/10μl) for 7 days and thermal withdrawal latency(TWL) were assessed. Results The operation in group reserve took shorter time than the group puncture, but micro-catheter were pulled out in 5 rats in group reserve. There is no difference of TWL between two groups. Conclusion Both methods are suitable for repeated intrathecal administration.%目的 比较大鼠蛛网膜下腔长期置管和反复蛛网膜下腔穿刺两种给药方法的难易程度及反复给药的可行性.方法 40只清洁级SD大鼠以随机数字表法分为置管组和穿刺组各20只.置管组通过蛛网膜下腔长期置管给药,穿刺组反复行蛛网膜下腔穿刺给药.记录每次进行操作所用的时间.2组均从实验第5天开始鞘内注射吗啡10 μg/1μl,连续给药7 d,用热辐射法测定大鼠热缩足潜伏期(TWL).对2组实验时间和TWL进行比较分析.结果 置管组操作时间较穿刺组短,差异有统计学意义(P<0.01).置管组5只大鼠导管脱出.鞘内给药后,置管组和穿刺组TWL测定值均较基础值增加,差异有统计学意义(P<0.01).2组间TWL测定值差异无统计学意义.结论 蛛网膜下腔长期置管和反复蛛网膜下腔穿刺均可作为鞘内多次给药方法,但在选择时应该考虑到操作难易程度、给药方式、反复给药并发症等因素的影响.

  6. The use of administrative data as a substitute for individual screening scores in observational studies related to problematic alcohol or drug use.

    Science.gov (United States)

    Sears, Jeanne M; Krupski, Antoinette; Joesch, Jutta M; Estee, Sharon L; He, Lijian; Shah, Melissa Ford; Huber, Alice; Dunn, Chris; Ries, Richard; Roy-Byrne, Peter P

    2010-09-01

    Administrative data provide a rich resource for improving our understanding of individuals with substance use disorders. The validation of administrative proxies for moderate or high risk alcohol or drug (AOD) use could enhance the ability to carry out rigorous observational research (for example, for use in the construction of comparison groups). This study used receiver operating characteristic (ROC) curve techniques to assess how well AOD-related administrative indicators predicted self-reported AOD use obtained from AUDIT/DAST screening scores. An administrative AOD indicator, derived from a combination of medical encounter and billing data, arrest records, and publicly funded AOD-related services data, demonstrated discrimination in the acceptable range (AUC: 0.72-0.78) for identifying self-reported AOD use consistent with potential need for either (1) any AOD-related intervention, or (2) intensive AOD-related intervention or treatment. These findings held up in two distinct samples: a statewide Medicaid-only sample and a single-site mixed-payer sample that included the uninsured. Our findings suggest that indicators of AOD-related problems derived from administrative data can be useful for identifying moderate or high risk AOD use in a research context. The findings further suggest that proxies for substance use disorders, such as those evaluated here, can enhance future observational studies intended to improve health care for this population.

  7. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    Science.gov (United States)

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron

    2015-01-01

    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  8. Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 2nd communication: tissue levels and enzyme activity in rats after repeated administration, and placental and milk transfer after single administration.

    Science.gov (United States)

    Nakamura, A; Hirota, T; Sugihara, K; Watanabe, S; Tougou, K; Morino, A; Ezumi, Y; Takaichi, M

    1997-02-01

    The absorption, distribution and excretion of radioactivity in rats were studied during and after repeated oral administration of 30 mg/kg of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) once a day for 21 days. The plasma concentrations of radioactivity 24 h after each administration of 14C-NS-21 reached a steady state on the 5th day. 48 h after the 21st administration, the plasma concentrations of radioactivity were under the detection limit. The plasma concentrations of the radioactivity after the 7th oral administration of 14C-NS-21 was higher than that after the single administration, but similar to those after the 14th and 21st administrations. There were no marked differences in the elimination half-lives after each administration. The urinary and fecal excretion of the radioactivity was 21.5 and 81.3%, respectively, within 168 h after the 21st administration. In most tissues, no radioactivity was observed 336 h after the 21st administration. Repeated oral administration of 30 and 100 mg/kg of NS-21 once a day for 7 days had no effect on the cytochrome P-450 content, aniline hydroxylase and aminopyrine N-demethylase activity in rat liver. The transfer of radioactivity into fetuses and milk was investigated after single oral administration of 14C-NS-21 to female rats. In the 18th day pregnant rats, the radioactivity concentrations were lower in most fetal tissues than in the maternal plasma. After oral administration of 14C-NS-21 to lactating rats, the concentrations of radioactivity were higher in the milk than in the maternal plasma during an 8-h period. No radioactivity was observed in milk 48 h after administration.

  9. Binge-like ingestion of a combination of an energy drink and alcohol leads to cognitive deficits and motivational changes.

    Science.gov (United States)

    Takahashi, Tatiane T; Vendruscolo, Leandro F; Takahashi, Reinaldo N

    2015-09-01

    The combination of alcohol with an energy drink (ED) is believed to contribute to risky alcohol-drinking behaviors, such as binge drinking. However, the long-term effects on cognition and reward function that are caused by the repeated binge-like ingestion of alcohol and EDs are still poorly known. The present study examined the effects of a history of repeated exposure to alcohol and/or an ED on short-term memory and alcohol-seeking behavior. Male Wistar rats were given daily intragastric administration of alcohol (3.4g/kg) combined or not with an ED (10.71ml/kg) for 6 consecutive days. The rats were tested for locomotion 15min after the first intragastric treatment. Short-term memory was assessed in the novel object recognition and social discrimination tests 2-3days after the last intragastric administration. The rewarding effect of alcohol was tested 1-3weeks following the last intragastric administration in a conditioned place preference paradigm. The acute binge-like ingestion of alcohol decreased locomotor activity, whereas the combination of alcohol and an ED increased locomotion in the first minutes of assessment. Alcohol exposure produced cognitive deficits in both the object recognition and social discrimination tests, and adding the ED to the alcohol solution did not modify these effects. The combination of alcohol and the ED increased alcohol-induced conditioned place preference. Thus, a history of binge-like alcohol exposure combined with the ED caused subsequent cognitive deficits and increased alcohol seeking behavior, and such behavioral effects might contribute to the progression to alcohol abuse disorders.

  10. Repeated Superovulation via PMSG/hCG Administration Induces 2-Cys Peroxiredoxins Expression and Overoxidation in the Reproductive Tracts of Female Mice.

    Science.gov (United States)

    Park, Sun-Ji; Kim, Tae-Shin; Kim, Jin-Man; Chang, Kyu-Tae; Lee, Hyun-Shik; Lee, Dong-Seok

    2015-12-01

    Superovulation induced by exogenous gonadotropin treatment (PMSG/hCG) increases the number of available oocytes in humans and animals. However, Superovulatory PMSG/hCG treatment is known to affect maternal environment, and these effects may result from PMSG/hCG treatment-induced oxidative stress. 2-Cys peroxiredoxins (2-Cys Prxs) act as antioxidant enzymes that protect cells from oxidative stress induced by various exogenous stimuli. Therefore, the objective of this study was to test the hypothesis that repeated PMSG/hCG treatment induces 2-Cys Prx expression and overoxidation in the reproductive tracts of female mice. Immunohistochemistry and western blotting analyses further demonstrated that, after PMSG/hCG treatment, the protein expression levels of 2-Cys Prxs increased most significantly in the ovaries, while that of Prx1 was most affected by PMSG/hCG stimulation in all tissues of the female reproductive tract. Repeated PMSG/hCG treatment eventually leads to 2-Cys Prxs overoxidation in all reproductive organs of female mice, and the abundance of the 2-Cys Prxs-SO2/3 proteins reported here supports the hypothesis that repeated superovulation induces strong oxidative stress and damage to the female reproductive tract. Our data suggest that excessive oxidative stress caused by repeated PMSG/hCG stimulation increases 2-Cys Prxs expression and overoxidation in the female reproductive organs. Intracellular 2-Cys Prx therefore plays an important role in maintaining the reproductive organ environment of female mice upon exogenous gonadotropin treatment.

  11. Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys.

    Science.gov (United States)

    Destexhe, Eric; Grosdidier, Emilie; Baudson, Nathalie; Forster, Roy; Gerard, Catherine; Garçon, Nathalie; Segal, Lawrence

    2015-07-01

    The MAGE-A3 recombinant protein combined with AS15 immunostimulant (MAGE-A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE-A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE-A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post-injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3-month treatment-free period (2/5 per gender per group). Local and systemic reactions and MAGE-A3-specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post-mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post-injection), but returned to normal after 1-8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment-related macroscopic findings were recorded after the treatment-free period. MAGE-A3-specific antibody and T-cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE-A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys.

  12. Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

    Energy Technology Data Exchange (ETDEWEB)

    Offord, S.J.

    1986-01-01

    Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT/sub 1/ receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT/sub 1/ type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections of monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced /sup 3/H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT/sub 1/ type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors.

  13. Neuropeptide Y Administration into the Amygdala Suppresses Ethanol Drinking in Alcohol-Preferring (P) Rats Following Multiple Deprivations

    Science.gov (United States)

    Gilpin, Nicholas W.; Stewart, Robert B.; Badia-Elder, Nancy E.

    2008-01-01

    The present experiment examines the effects of NPY administered into the amygdala on ethanol drinking by alcohol-preferring P rats following long-term continuous ethanol access, with and without multiple periods of imposed ethanol abstinence. P rats had access to 15% (v/v) ethanol and water for 11 weeks followed by 2 weeks of ethanol abstinence, re-exposure to ethanol for 2 weeks, 2 more weeks of ethanol abstinence, and a final ethanol re-exposure. Immediately prior to the second ethanol re-exposure, 4 groups of rats received bilateral infusions NPY (0.25, 0.5, 1.0 μg) or artificial cerebrospinal fluid (aCSF) into the amygdala. Two additional groups were given uninterrupted ethanol access and were infused with a single NPY dose (1.0 μg) or aCSF. The highest NPY dose (1.0 μg) suppressed ethanol intake for 24 hrs in rats with a history of ethanol abstinence (i.e. deprivation) periods, but had no effect in rats with a history of continuous ethanol access. Water and food intakes were not altered. These results suggest that the amygdala mediates the suppressive effects of centrally administered NPY on ethanol drinking, and that NPY may block relapse-like drinking by opposing the anxiogenic effects of ethanol abstinence. PMID:18499241

  14. DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

    Science.gov (United States)

    Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

    2011-01-01

    Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in

  15. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice.

    Science.gov (United States)

    Rodríguez, Amaia; Moreno, Natalia R; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M; Frühbeck, Gema

    2015-07-10

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.

  16. Administrative Circulars

    CERN Multimedia

    Département des Ressources humaines

    2004-01-01

    Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

  17. Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania

    DEFF Research Database (Denmark)

    Braae, Uffe Christian; Magnussen, Pascal; Ndawi, Benedict

    This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with ‘track and treat’ of taeniosis cases on the prevalence of taeniosis. The study was conducted in 14 villages in Mbozi and Mbeya district, Tanzania. SAC recei...

  18. Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania

    DEFF Research Database (Denmark)

    Braae, Uffe Christian; Magnussen, Pascal; Ndawi, Benedict

    2017-01-01

    This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with ‘track and treat’ of taeniosis cases in the general population on the copro-antigen (Ag) prevalence of taeniosis. The study was conducted in 14 villages in ...

  19. Effects of single or repeated administration of a carbamate, propoxur, and an organophosphate, DDVP, on jejunal cholinergic activities and contractile responses in rats.

    Science.gov (United States)

    Kobayashi, H; Sato, I; Akatsu, Y; Fujii, S; Suzuki, T; Matsusaka, N; Yuyama, A

    1994-01-01

    Wistar rats were injected once or repeatedly for 10 days with dichlorvos (DDVP, 5 mg kg-1), propoxur (10 mg kg-1), oxotremorine (0.1 mg kg-1) or atropine (5 mg kg-1). Animals were killed 20 min or 24 h after single or consecutive injections, respectively, for determinations of cholinergic activities and contractile responses to acetylcholine (ACh) of the jejunum. Single treatments: while DDVP and propoxur decreased acetylcholinesterase (AChE) activity, oxotremorine and atropine did not. Although DDVP, propoxur and oxotremorine increased levels of ACh, atropine decreased them. Contractile responses to ACh were enhanced by DDVP and reduced by oxotremorine and atropine. The Bmax value of binding of [3H]quinuclidinyl benzylate (QNB) to muscarinic ACh receptors was decreased by atropine. Consecutive treatments: DDVP and oxotremorine decreased AChE activity markedly and slightly, respectively. Although DDVP and oxotremorine increased levels of ACh, propoxur decreased them. Without affecting the contractile responses, DDVP caused a reduction and propoxur and atropine caused an increase in the Bmax value for binding of [3H]QNB. Both the contractile responses and the value of Bmax for binding of [3H]-QNB were decreased by oxotremorine. In summary, propoxur and DDVP showed similar effects mainly through their anticholinesterase properties in the case of single injection, but DDVP had similar effects to those of oxotremorine and propoxur had similar effects to those of atropine in the case of repeated injection.

  20. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    Science.gov (United States)

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

  1. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

    Science.gov (United States)

    Mei, Lu; Tang, Youcai; Li, Ming; Yang, Pingchang; Liu, Zhiqiang; Yuan, Jieli; Zheng, Pengyuan

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal

  2. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

    Directory of Open Access Journals (Sweden)

    Lu Mei

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC together with cholesterol-lowering probiotics (P to improve high-fat diet (HFD-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1, low density lipoprotein receptor (LDL-R and farnesoid X receptor (FXR were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR was reduced. The expression of peroxisome proliferator activated receptor (PPAR-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1 were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the

  3. Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist

    OpenAIRE

    Tumati, Suneeta; Largent-Milnes, Tally M.; Keresztes, Attila; Ren, Jiyang; Roeske, William R.; Vanderah, Todd W; Varga, Eva V.

    2012-01-01

    Spinal glial activation has been implicated in sustained morphine-mediated paradoxical pain sensitization. Since activation of glial CB2 cannabinoid receptors attenuates spinal glial activation in neuropathies, we hypothesized that CB2 agonists may also attenuate sustained morphine–mediated spinal glial activation and pain sensitization. Our data indicate that co-administration of a CB2-selective agonist (AM 1241) attenuates morphine (intraperitoneal; twice daily; 6 days)-mediated thermal hyp...

  4. Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

    Institute of Scientific and Technical Information of China (English)

    Claudia PMS de Oliveira; Marcelo G de Oliveira; Fernanda I Simplicio; Vicência MR de Lima; Katia Yuahasi; Fabio P Lopasso; Ven(a)ncio AF Alves; Dulcinéia SP Abdalla; Flair J Carrilho; Francisco RM Laurindo

    2006-01-01

    AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model.METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg/day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg/d).Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution.LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 μg protein/mL) were incubated with CuCl2 (300 μmol/L) in the absence and presence of SNAC (300 μmol/L) for 15 h at 37 ℃. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 μmol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 μmol/L) at 37 ℃ in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 μmol/L) and monitored at 234 nm.RESULTS: Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates

  5. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex.

    Science.gov (United States)

    Egashira, Nobuaki; Iwasaki, Katsunori; Ishibashi, Ayumi; Hayakawa, Kazuhide; Okuno, Ryoko; Abe, Moe; Uchida, Naoki; Mishima, Kenichi; Takasaki, Kotaro; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro

    2008-08-01

    Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with Alzheimer's disease (AD) and other forms of senile dementia. BPSD have a serious impact on the quality of life of dementia patients, as well as their caregivers. However, an effective drug therapy for BPSD has not been established. Recently, the traditional Japanese medicine Yokukansan (YKS, Yi-gan san in Chinese) has been reported to improve BPSD in a randomized, single-blind, placebo-controlled study. Moreover, abnormalities of the serotonin (5-HT) system such as 5-HT2A receptors have been reported to be associated with BPSD of AD patients. In the present study, we investigated the effect of YKS on head-twitch response induced by 2,5-dimethoxy-4-iodoamphetamine (DOI, 5 mg/kg, i.p.) in mice, a behavioral response that is mediated, in part, by 5-HT2A receptors. Acute treatment with YKS (100 and 300 mg/kg, p.o.) had no effect on the DOI-induced head-twitch response, whilst 14 days repeated treatment with YKS (300 mg/kg, p.o.) significantly inhibited this response. Moreover, repeated treatment with YKS (300 mg/kg, p.o.) decreased expression of 5-HT2A receptors in the prefrontal cortex, which is part of the circuitry mediating the head-twitch response. These findings suggest that the inhibition of DOI-induced head-twitch response by YKS may be mediated, in part, by altered expression of 5-HT2A receptors in the prefrontal cortex, which suggests the involvement of the 5-HT system in psychopharmacological effects of YKS.

  6. Brain activation associated with automatic processing of alcohol‐related cues in young heavy drinkers and its modulation by alcohol administration

    NARCIS (Netherlands)

    F. Kreusch; V. Goffaux; N. Siep; K. Houben; E. Quertemont; R.W. Wiers

    2015-01-01

    Background: While the automatic processing of alcohol-related cues by alcohol abusers is well established in experimental psychopathology approaches, the cerebral regions involved in this phenomenon and the influence of alcohol intake on this process remain unknown. The aim of this functional magnet

  7. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  8. Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.

    Science.gov (United States)

    Qiu, Zhi-Kun; Zhang, Li-Ming; Zhao, Nan; Chen, Hong-Xia; Zhang, You-Zhi; Liu, Yan-Qin; Mi, Tian-Yue; Zhou, Wen-Wen; Li, Yang; Yang, Ri-Fang; Xu, Jiang-Ping; Li, Yun-Feng

    2013-08-01

    Post-traumatic stress disorder (PTSD) is a severely disabling anxiety disorder that may occur following exposure to a serious traumatic event. It is a psychiatric condition that can afflict anyone who has experienced a life-threatening or violent event. Previous studies have shown that changes in 18 kDa translocator protein (TSPO) expression (or function), a promising target for treating neurological disorders without benzodiazepine-like side effects, may correlate with PTSD. However, few studies have investigated the anti-PTSD effects of TSPO ligands. AC-5216, a ligand for TSPO, induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether AC-5216 ameliorates PTSD behavior in mice. Following the training session consisting of exposure to inescapable electric foot shocks, animals were administered AC-5216 daily during the behavioral assessments, i.e., situational reminders (SRs), the open field (OF) test, the elevated plus-maze (EPM) test, and the staircase test (ST). The results indicated that exposure to foot shocks induced long-term behavioral deficiencies in the mice, including freezing and anxiety-like behavior, which were significantly ameliorated by repeated treatment with AC-5216 but without any effect on spontaneous locomotor activity or body weight. In summary, this study demonstrated the anti-PTSD effects of AC-5216 treatment, suggesting that TSPO may represent a therapeutic target for anti-PTSD drug discovery and that TSPO ligands may be a promising new class of drugs for the future treatment of PTSD.

  9. Effectiveness of alcohol-based hand disinfectants in a public administration: Impact on health and work performance related to acute respiratory symptoms and diarrhoea

    Directory of Open Access Journals (Sweden)

    Hübner Nils-Olaf

    2010-08-01

    Full Text Available Abstract Background The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated. However, large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work, school and university each year. Hand disinfection is acknowledged as key element for infection control, but its effect in open, work place settings is unclear. Methods Our study involved a prospective, controlled, intervention-control group design to assess the epidemiological and economical impact of alcohol-based hand disinfectants use at work place. Volunteers in public administrations in the municipality of the city of Greifswald were randomized in two groups. Participants in the intervention group were provided with alcoholic hand disinfection, the control group was unchanged. Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly questionnaire over one year. On the whole, 1230 person months were evaluated. Results Hand disinfection reduced the number of episodes of illness for the majority of the registered symptoms. This effect became statistically significant for common cold (OR = 0.35 [0.17 - 0.71], p = 0.003, fever (OR = 0.38 [0.14-0.99], p = 0.035 and coughing (OR = 0.45 [0.22 - 0.91], p = 0.02. Participants in the intervention group reported less days ill for most symptoms assessed, e.g. colds (2.07 vs. 2.78%, p = 0.008, fever (0.25 vs. 0.31%, p = 0.037 and cough (1.85 vs. 2.00%, p = 0.024. For diarrhoea, the odds ratio for being absent became statistically significant too (0.11 (CI 0.01 - 0.93. Conclusion Hand disinfection can easily be introduced and maintained outside clinical settings as part of the daily hand hygiene. Therefore it appears as an interesting, cost-efficient method within the scope

  10. 75 FR 4900 - Drug Addiction and Alcoholism

    Science.gov (United States)

    2010-01-29

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Drug Addiction and Alcoholism AGENCY: Social Security Administration. ACTION: Request for Comments... persons whose drug addiction or alcoholism (DAA) may be a contributing factor material to...

  11. Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania.

    Science.gov (United States)

    Braae, Uffe Christian; Magnussen, Pascal; Ndawi, Benedict; Harrison, Wendy; Lekule, Faustin; Johansen, Maria Vang

    2017-01-01

    This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with 'track and treat' of taeniosis cases in the general population on the copro-antigen (Ag) prevalence of taeniosis. The study was conducted in 14 villages in Mbozi and Mbeya district, Tanzania. SAC made up 34% of the population and received MDA with praziquantel (40mg/kg) in 2012 (both districts) and in 2013 (Mbozi only). Three cross-sectional population-based surveys were performed in 2012 (R0), 2013 (R1), and 2014 (R2). In each survey approximately 3000 study subjects of all ages were tested for taeniosis using copro-Ag-ELISA. In total 9064 people were tested and copro-Ag-ELISA positive cases were offered treatment 6-8 months after sampling. The copro-Ag prevalence of taeniosis was significantly higher (Χ(2)-test, p=0.007) in Mbozi (3.0%) at R0 compared to Mbeya (1.5%). Twelve months after MDA in both districts (R1), the copro-Ag prevalence had dropped significantly in both Mbozi (2.0%, p=0.024) and in Mbeya (0.3%, p=0.004), but the significant difference between the districts persisted (Χ(2)-test, p<0.001). Ten months after the second round of MDA in Mbozi and 22 month after the first MDA (R2), the copro-Ag prevalence had dropped significantly again in Mbozi (0.8%, p<0.001), but had slightly increased in Mbeya (0.5%, p=0.051), with no difference between the two districts (Χ(2)-test, p=0.51). The taeniosis cases tracked and treated between round R0 and R2 represented 9% of the projected total number of taeniosis cases within the study area, based on the copro-Ag prevalence and village population data. Among SAC in Mbozi, infection significantly decreased at R1 (p=0.004, OR 0.12, CI: 0.02-0.41) and R2 (p=0.001, OR 0.24, CI: 0.09-0.53) when comparing to R0. In Mbeya infection significant decreased at R1 (p=0.013, OR 0.14, CI: 0.02-0.55), but no difference was found for R2 (p=0. 089), when comparing to R0 among SAC. This study

  12. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  13. Alcohol Alert

    Science.gov (United States)

    ... main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & ... on a single aspect of alcohol abuse and alcoholism. Please click on the desired publication for full ...

  14. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol.

    Science.gov (United States)

    Lopez, M F; Becker, H C; Chandler, L J

    2014-11-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol.

  15. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

    Directory of Open Access Journals (Sweden)

    Alfonso Díaz

    2016-01-01

    Full Text Available Energy drinks (EDs are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx and hippocampus (Hp of adult rats (90 days old. Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

  16. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

    Science.gov (United States)

    Díaz, Alfonso; Treviño, Samuel; Guevara, Jorge; Muñoz-Arenas, Guadalupe; Brambila, Eduardo; Espinosa, Blanca; Moreno-Rodríguez, Albino; Lopez-Lopez, Gustavo; Peña-Rosas, Ulises; Venegas, Berenice; Handal-Silva, Anabella; Morán-Perales, José Luis; Flores, Gonzalo; Aguilar-Alonso, Patricia

    2016-01-01

    Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats. PMID:27069534

  17. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

    Science.gov (United States)

    Diaz, Marvin R; Vollmer, Cyndel C; Zamudio-Bulcock, Paula A; Vollmer, William; Blomquist, Samantha L; Morton, Russell A; Everett, Julie C; Zurek, Agnieszka A; Yu, Jieying; Orser, Beverley A; Valenzuela, C Fernando

    2014-04-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats.

  18. Compound list: allyl alcohol [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available allyl alcohol AA 00010 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/allyl_alcohol....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/allyl_alcohol...dbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/allyl_alcohol.Rat.in_vivo.Liver.Repeat.zip ftp:/.../ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/allyl_alcohol.Rat.in_vivo.Kidney....Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/allyl_alcohol.Rat.in_vivo.Kidney.Repeat.zip ...

  19. Exposição repetida à cafeína aumenta a atividade locomotora induzida pelo femproporex em ratos adolescentes e adultos Repeated administration of caffeine increases femproporex-induced locomotor activity in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    Ana Helena Paro

    2008-09-01

    Full Text Available A cafeína e o femproporex são substâncias psicoestimulantes. O femproporex é muito utilizado no Brasil como anorexígeno enquanto a cafeína é amplamente consumida como constituinte regular da dieta. A administração repetida de psicoestimulantes induz sensibilização comportamental que se caracteriza pelo aumento progressivo dos seus efeitos locomotores. Pode ocorrer ainda sensibilização cruzada entre essas substâncias. Investigamos se a administração repetida de cafeína aumenta a locomoção induzida pelo femproporex em ratos adolescentes e adultos. Quarenta e oito ratos adolescentes (dia pós-natal 27 e 32 adultos (dia pós-natal 60 foram distribuídos em dois grupos que receberam injeção intra-peritoneal de 10,0 mg/kg de cafeína (CAF (adolescentes N = 24; adultos N = 16 ou salina (SAL (adolescentes N = 24; adultos N = 16 diariamente durante 10 dias. Três dias após a última injeção, cada grupo CAF ou SAL foi subdividido em dois subgrupos que receberam injeção i.p. de salina (SAL (1 mL/kg ou femproporex (FEM (2,0 mg/kg. Após as injeções, a atividade locomotora foi avaliada automaticamente em intervalos de 5 minutos durante 1 hora. Nossos resultados demonstraram que em ratos adolescentes e adultos o pré-tratamento com CAF aumenta a atividade locomotora induzida pela administração aguda de FEM, sugerindo que a cafeína causa sensibilização aos efeitos locomotores desse derivado anfetamínico.Caffeine and femproporex are psychostimulants drugs widely consumed in Brazil. Behavioral sensitization is defined as an augmentation in the behavioral effect of a psychostimulant upon re-administration. Repeated administration of a psychostimulant produces behavioral sensitization to that drug and cross-sensitization to other drugs. We investigated whether repeated administration of caffeine increases femproporex-induced locomotor activity in adolescent and adult rats. Forty-eight adolescent (postnatal day 27 and 32 adult

  20. Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.

    Science.gov (United States)

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

    2014-07-01

    Animal models are widely used to study antidepressant-like effect in rodents. However, it should be mentioned that pharmacological models do not always take into account the complexity of the disease process. In the present paper, we demonstrated that repeated but not acute treatment with a low dose of reserpine (0.2 mg/kg i.p.) led to a pharmacological model of depression which was based on its inhibitory effect on the vesicular monoamine transporter 2, and monoamines depleting action in the brain. In fact, we observed that chronic treatment with a low dose of reserpine induced a distinct depressive-like behavior in the forced swim test (FST), and additionally, it produced a significant decrease in the level of dopamine, noradrenaline, and serotonin in the brain structures. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its close methyl derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are exo/endogenous amines present naturally in the mammalian brain which demonstrated a significant antidepressant-like effect in the FST and the reserpine model of depression in the rat. Both compounds, TIQ and 1MeTIQ, administered chronically in a dose of 25 mg/kg (i.p.) together with reserpine completely antagonized reserpine-produced depression as assessed by the immobility time and swimming time. Biochemical data were in agreement with behavioral experiments and demonstrated that chronic treatment with a low dose of reserpine in contrast to acute administration produced a significant depression of monoamines in the brain structures and impaired their metabolism. These neurochemical effects obtained after repeated reserpine (0.2 mg/kg i.p.) in the brain structures were completely antagonized by joint TIQ or 1MeTIQ (25 mg/kg i.p.) administration with chronic reserpine. A possible molecular mechanism of action of TIQ and 1MeTIQ responsible for their antidepressant action is discussed. On the basis of the presented behavioral and biochemical studies, we suggest that both

  1. Alcohol Intolerance

    Science.gov (United States)

    ... beer-alcohol.aspx. Accessed Jan. 16, 2015. Alcohol angioedema and uticaria. American Academy of Allergy, Asthma & Immunology. http://www.aaaai.org/ask-the-expert/alcohol-angioedema-urticaria.aspx. Accessed Jan. 16, 2015. Alcohol and ...

  2. Disruption of long-term alcohol-related memory reconsolidation: Role of β-adrenoceptors and NMDA receptors

    Directory of Open Access Journals (Sweden)

    Jelte A Wouda

    2010-11-01

    Full Text Available Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol- related memories are prone to disruption by the β -adrenergicreceptor antagonist propranolol (10 mg/kg and the NMDA receptor antagonist MK801 (0.1 mg/kg following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were reexposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on 2 further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency towards reduced alcohol seeking (p=0.06. Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies.

  3. Alcohol and sex.

    Science.gov (United States)

    Vijayasenan, M E

    1981-01-14

    Diminished sexual functioning among individuals dependent upon alcohol has been assessed. Ninety-seven male patients entered the study, all inpatients as the unit for treatment of alcoholism and drug addiction (Villa 6) in Porirua Hospital, Porirua. The sexual ability of these patients before the development of alcoholism was also rated for the same items and this rating was used as a control. Of the 97 patients, 69 (71 percent) suffered from sexual dysfunction for a period more than 12 months prior to admission to hospital. The disturbances noted were diminished sexual desire (58 percent of patients), erectile impotence (16 percent), premature ejaculation (4 percent), ejaculatory in competence (22 percent). A high proportion of the alcoholics showed signs of sexual deviation-19 percent having performed sexual crimes and a further 28 percent having repeated thought of sexual crimes. The possible causes of alcohol induced sexual dysfunction are discussed.

  4. [Upgrade on alcohol abuse].

    Science.gov (United States)

    Bordini, L; Riboldi, L

    2010-01-01

    Problematic use of alcohol configures an element of interest in the context of preventive interventions aimed to ensuring the performance of any work in safety conditions. To contrast the acute alcohol abuse in the workplace the existing legislation provides alcoholimeters controls and prohibition of recruitment and administration of alcohol. Recent legislation (D.Lgs. 81/08) establishes health surveillance for alcohol dependence and appears still incomplete and difficult to apply. Clinical diagnostic tools available to the physician for alcohol dependence identification are well-defined and recently improved thanks to new laboratory markers with high sensitivity and specificity (CDT) and self-administered questionnaires. In this contest we are awaiting for legislative action to specify conditions and procedures for inspections in the workplace in order to face the problem of alcohol dependence without excessive bureaucracy and with more attention to preventive aspects.

  5. A New Animal Model of Depression Induced by Repeated Central Lipopolysaccharide Administration%一个中枢炎性免疫诱发长时程抑郁样行为的新模型

    Institute of Scientific and Technical Information of China (English)

    汤明明; 潘玉芹; 林文娟

    2014-01-01

    -like behavior at - and after- 24h post-LPS injection. In this study, single and triple central LPS administration were used to induce depressive-like behavior respectively. Sprague-Dawley rats were randomly divided into LPS group and control group. LPS (100ng/rat, one injection; or once every second day, total three times) or isotonic saline was administered by intracerebroventricular microinjection. The depressive-like behavior was measured by preference to saccharin, locomotor activity and immobility time of tail suspension. The result indicated that single central LPS injection induced partial depressive-like behaviors. There was significant difference in locomotor activity, but not in the preference of saccharin and immobility time of tail suspension. However, repeated central LPS administration induced significant depressive-like behaviors after 24h of the last LPS injection. The animals with triple central LPS administration consumed less saccharin solution, exhibited less locomotor activity in the open field, and maintained immobility time in tail suspension. The changes in locomotor activity and immobility time of tail suspension were even apparent until 72h after the last LPS injection. Our results demonstrate that a new effective model of depression can be established by means of repeated lateral ventricle LPS injections, and the induced depressive-like behavior has longer time duration than by the peripheral injection of LPS.

  6. Heavy drinking and alcohol-related injuries in college students.

    Science.gov (United States)

    Moure-Rodríguez, Lucía; Caamaño-Isorna, Francisco; Doallo, Sonia; Juan-Salvadores, Pablo; Corral, Montserrat; Rodríguez-Holguín, Socorro; Cadaveira, Fernando

    2014-01-01

    The main objective of this study is to evaluate the effect of heavy drinking on alcohol-related injuries. We carried out an open cohort study among university students in Spain (n=1,382). Heavy drinking and alcohol-related injuries were measured by administrating AUDIT questionnaires to every participant at the ages of 18, 20, 22 and 24. For data analysis we used a Multilevel Logistic Regression for repeated measures adjusting for consumption of alcohol and cannabis. The response rate at the beginning of the study was 99.6% (1,369 students). The incidence rate of alcohol-related injuries was 3.2 per 100 students year. After adjusting for alcohol consumption and cannabis use, the multivariate model revealed that a high frequency of heavy drinking was a risk factor for alcohol-related injuries (Odds Ratio=3.89 [95%CI: 2.16 - 6.99]). The proportion of alcohol-related injuries in exposed subjects attributable to heavy drinking was 59.78% [95%CI: 32.75 - 75.94] while the population attributable fraction was 45.48% [95%CI: 24.91 - 57.77]. We can conclude that heavy drinking leads to an increase of alcohol-related injuries. This shows a new dimension on the consequences of this public concern already related with a variety of health and social problems. Furthermore, our results allow us to suggest that about half of alcohol-related injuries could be avoided by removing this consumption pattern. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  7. 27 CFR 71.95 - Responsibilities of administrative law judges.

    Science.gov (United States)

    2010-04-01

    ... administrative law judges. 71.95 Section 71.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... PERMIT PROCEEDINGS Administrative Law Judges § 71.95 Responsibilities of administrative law judges. Administrative law judges shall be under the administrative control of the Administrator. They shall...

  8. αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior.

    Science.gov (United States)

    Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P; Treutlein, Jens; Cichon, Sven; Ridinger, Monika; Mattheisen, Peter; Herms, Stefan; Wodarz, Norbert; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Rietschel, Marcella

    2013-08-01

    The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.

  9. gamma-Hydroxybutyric acid (GHB) suppresses alcohol's motivational properties in alcohol-preferring rats.

    Science.gov (United States)

    Maccioni, Paola; Pes, Daniela; Fantini, Noemi; Carai, Mauro A M; Gessa, Gian Luigi; Colombo, Giancarlo

    2008-03-01

    gamma-Hydroxybutyric acid (GHB) reduces alcohol drinking, promotes abstinence from alcohol, suppresses craving for alcohol, and ameliorates alcohol withdrawal syndrome in alcoholics. At preclinical level, GHB suppresses alcohol withdrawal signs and alcohol intake in rats. The present study was designed to investigate whether GHB administration was capable of affecting alcohol's motivational properties (the possible animal correlate of human craving for alcohol) in selectively bred Sardinian alcohol-preferring rats. To this aim, rats were initially trained to lever press for alcohol (15%, vol/vol) under a procedure of operant, oral alcohol self-administration (fixed ratio 4 in 30-min daily sessions). Once responding for alcohol had stabilized, rats were divided into two groups and allocated to two independent experiments. Experiment 1 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on breakpoint for alcohol, defined as the lowest response requirement not achieved by each rat when exposed to a single-session progressive ratio schedule of reinforcement. Experiment 2 assessed the effect of GHB (0, 25, 50, and 100mg/kg, i.p.) on single-session extinction responding for alcohol (alcohol was absent and unreinforced responding was recorded). Breakpoint and extinction responding for alcohol are reliable indexes of alcohol's motivational strength. In Experiment 1, all doses of GHB reduced--by approximately 20% in comparison to saline-treated rats--breakpoint for alcohol. In Experiment 2, administration of 25, 50, and 100mg/kg GHB reduced--by approximately 25%, 40%, and 50%, respectively, in comparison to saline-treated rats--extinction responding for alcohol. Conversely, no dose of GHB altered breakpoint and extinction responding for sucrose (3%, wt/vol) in two independent subsets of Sardinian alcohol-preferring rats. Together, these data suggest that GHB administration specifically suppressed alcohol's motivational properties in Sardinian alcohol-preferring rats

  10. Study on absorption and accumulation of mercury in rats by repeated administration of Yuhong ointment%玉红膏重复给药大鼠体内汞的吸收及蓄积研究

    Institute of Scientific and Technical Information of China (English)

    邱恒; 孙新民; 黄雯; 胡小靖; 王旗; 牟稷征; 王丽霞

    2013-01-01

    Objective:To study in vivo mercury absorption and accumulation through repeated transdermal administration of Yuhong ointment containing calomel,in order to provide scientific evidences for clinical safe medication.Method:A total of 100 SD rats were randomly classified into five groups:the control group,the Yuhong ointment group,the double-concentration Yuhong Ointment group,the quadruple-concentration Yuhong ointment group and the 1.6% calomel group.The rats were treated with the dosage of 0.04 g · cm-2 by repeated transdermal administration for 2,4 weeks.After the drug discontinuance for 4 weeks,the levels of mercury in blood,urine,and tissues of heart,liver,brain and kidney were determined,respectively.Result:Compared with the control group,the blood mercury level of the Yuhong ointment group show no obvious change after treatment for 4 weeks.However,the levels of mercury in blood and urine of other experimental groups increased significantly with time and the increase in dosage,and so did the level of mercury in major organ.At 4 weeks,all experimental groups showed increase in the content of mercury,and kidneys displayed the highest level,whereas brain displayed the lowest level.After the drug discontinuance for 4 weeks,the mercury level in blood and urine of every dose group recovered to normal,with significant decline in the content of mercury in each organ.Conclusion:After transdermal administration in rats for 4 weeks,there was no obvious absorption of mercury in blood.Mercury was mainly accumulated in kidneys and excreted through urine.The results suggest that the patients' mercury content and kidney function indexes need to be monitored in long-term clinical use of Yuhong ointment.%目的:通过经皮重复给予大鼠不同浓度含轻粉玉红膏,考察体内汞的吸收及蓄积情况,为临床安全用药提供科学依据.方法:将100只SD大鼠随机分成5组:对照组、玉红膏组、2倍浓度玉红膏组、4倍浓度玉红膏组和1.6%

  11. Fibroblast Growth Factor 2 in the Dorsomedial Striatum Is a Novel Positive Regulator of Alcohol Consumption.

    Science.gov (United States)

    Even-Chen, Oren; Sadot-Sogrin, Yossi; Shaham, Ohad; Barak, Segev

    2017-09-06

    Repeated alcohol intake leads to mesostriatal neuroadaptations, resulting in drinking escalation and addiction phenotypes. Fibroblast growth factor 2 (FGF2) has been shown to interact with the mesostriatal dopaminergic system, and has been implicated in the actions of psychostimulants in the brain, and in several psychiatric disorders. Here, we report on a positive regulatory feedback loop of alcohol and FGF2 in rodent models. Specifically, we found that acute alcohol exposure (2.5 g/kg, i.p.) increased the mRNA expression of Fgf2 in the dorsal hippocampus, nucleus accumbens, and dorsal striatum. Longer alcohol exposure (7 d × 2.5 g/kg, i.p.) restricted these increases to the dorsal striatum, and the latter effect was blocked by the dopamine D2-like receptor antagonist haloperidol. Voluntary prolonged and excessive alcohol consumption in a 2-bottle choice procedure increased Fgf2 expression selectively in dorsomedial striatum (DMS) of both mice and rats. Importantly, we found that systemic administration of recombinant FGF2 (rFGF2) in mice, or rFGF2 infusion into the dorsal striatum or DMS of rats, increased alcohol consumption and preference, with no similar effects on saccharin or sucrose consumption. Finally, we found that inhibition of the endogenous FGF2 function in the DMS, by an anti-FGF2 neutralizing antibody, suppressed alcohol consumption and preference. Together, our results suggest that alcohol consumption increases the expression of Fgf2 in the DMS, and that striatal FGF2 promotes alcohol consumption, suggesting that FGF2 in the DMS is a positive regulator of alcohol drinking.SIGNIFICANCE STATEMENT Long-term alcohol intake may lead to neuroadaptations in the mesostriatal reward system, resulting in addiction phenotypes. Fibroblast growth factor 2 (FGF2) is crucial for the development and maintenance of the mesostriatal dopaminergic system. Here, we provide evidence for the involvement of FGF2 in alcohol-drinking behaviors. We show that alcohol

  12. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  13. National Institute on Alcohol Abuse and Alcoholism

    Science.gov (United States)

    Skip to main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use ...

  14. El consumo de alcohol en personal administrativo y de servicios de una universidad del Ecuador O consumo de álcool em pessoal administrativo e de serviço de uma universidade do Equador Alcohol consumption in administrative and service personnel in an Ecuadorian university

    Directory of Open Access Journals (Sweden)

    Carmita María Bravo Ortiz

    2010-06-01

    .The aim of this descriptive study was to characterize the consumption of alcohol among workers in the administrative and service sectors at an Ecuadorian university and to determine differences in consumption between the two groups of workers. The Alcohol Use Disorders Identification Test (AUDIT was applied to 102 participants. The results showed that the service personnel consumed more alcohol than the administrative personnel with a mean total score of 7.26 against 1.84. The total prevalence of non-prejudicial consumption was 79.41%, prejudicial consumption 19.61% and dependency 0.98%. The total scores of 76.47% of the participants were within risk zone one; 18.63% risk zone two; 3.92% risk zone three; 0.98% risk zone four. In conclusion, due to the identification of hazardous consumption, it is necessary to implement a program of alcohol use prevention in the institution studied.

  15. Preoperative alcoholism and postoperative morbidity

    DEFF Research Database (Denmark)

    Tonnesen, H; Kehlet, H

    1999-01-01

    BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

  16. 经皮反复给予玉红膏对大鼠器官毒性的研究%Organ toxicity of Yuhong Ointment(玉红膏) after repeated transdermal administration in rats

    Institute of Scientific and Technical Information of China (English)

    胡小靖; 孙新民; 黄雯; 邱恒; 牟稷征; 王丽霞; 王旗

    2013-01-01

    Objective To observe the effects of Yuhong Ointment on rat's liver and kidney functions and histomorphology of heart,brain,liver,kidney and spleen after transdermal administration repeatedly,in order to provide experimental evidences for safe use of Yuhong Ointment in clinical practice.Methods A total of 100 SPF SD rats of equal number of both genders,weighting 200 g,were divided into 5 groups:matrix control group,1 time concentration of Yuhong Ointment group (containing 0.4% calomel),2 times concentration of Yuhong Ointment group (containing 0.8% calomel),4 times concentration of Yuhong Ointment group (containing 1.6% calomel) and calomel group (containing 1.6% calomel) by drawn lots randomly,each group comprised 20 rats.The model of rat's skin injury was prepared.Yuhong Ointment in different concentrations were applied on the skin-impaired once daily for 28 days.The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),blood urea nitrogen (BUN),creatinine (Cr) and N-acetyl beta-D glucosaminidase (NAG) of rats in different groups were measured before treatment,14 and 28 days after treatment,and 28 days after drug withdrawal,respectively.Ten rats in every group were sacrificed on 28 days after treatment and 28 days after drug withdrawal,respectively.The heart,brain,liver,kidney,and spleen of rats in different groups were taken and weighed up.The organ coefficients were calculated and the histomorphological changes of liver,kidney and spleen were examined.Results There were no statistically significant differences in levels of serum ALT、AST、BUN、Cr and NAG in rats among the different concentrations of Yuhong Ointment groups,1.6% calomel group and matrix control group (all P > 0.05).The level of serum Cr in rat of 1.6% calomel group was significantly higher than that of matrix control group 28 days after drug withdrawal (P < 0.05).The kidney coefficients of rats in 2 times and 4 times concentration of Yuhong Ointment group and

  17. Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse.

    Science.gov (United States)

    Carnicella, Sebastien; Ron, Dorit; Barak, Segev

    2014-05-01

    One of the major challenges in preclinical studies of alcohol abuse and dependence remains the development of paradigms that will elicit high ethanol intake and mimic the progressive transition from low or moderate social drinking to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of free-choice ethanol intake and withdrawal with the use of intermittent access to 20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a gradual escalation of voluntary ethanol intake and preference, eventually reaching ethanol consumption levels of 5-6 g/kg/24 h, and inducing pharmacologically relevant blood ethanol concentrations (BECs). This procedure has recently been gaining popularity due to its simplicity, high validity, and reliable outcomes. Here we review experimental and methodological data related to IA2BC, and discuss the usefulness and advantages of this procedure as a valuable pre-training method for initiating operant ethanol self-administration of high ethanol intake, as well as conditioned place preference (CPP). Despite some limitations, we provide evidence that IA2BC and related operant procedures provide the possibility to operationalize multiple aspects of alcohol abuse and addiction in a rat model, including transition from social-like drinking to excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be a useful and relevant procedure for preclinical evaluation of potential therapeutic approaches against alcohol abuse disorders.

  18. Comparative utilization of pharmacotherapy for alcohol use disorder and other psychiatric disorders among U.S. Veterans Health Administration patients with dual diagnoses.

    Science.gov (United States)

    Rubinsky, Anna D; Chen, Cheng; Batki, Steven L; Williams, Emily C; Harris, Alex H S

    2015-10-01

    Patients with alcohol use disorder (AUD) and another co-occurring psychiatric disorder are a vulnerable population with high symptom severity. Such patients may benefit from a full arsenal of treatment options including pharmacotherapy. Receipt of AUD pharmacotherapy is generally very low despite recommendations that it be made available to every patient with AUD, including those with co-occurring disorders. Little is known about pharmacotherapy rates for AUD compared to other psychiatric disorders among patients with dual diagnoses. This study compared rates of pharmacotherapy for AUD to those for non-substance use psychiatric disorders and tobacco use disorder among patients with dual diagnoses in the U.S. Veterans Affairs (VA) healthcare system. VA data were used to identify patients with AUD and another psychiatric disorder in fiscal year 2012, and to estimate the proportion receiving pharmacotherapy for AUD and for each comorbid condition. Among subsets of patients with AUD and co-occurring schizophrenic, bipolar, posttraumatic stress or major depressive disorder, receipt of medications for AUD ranged from 7% to 11%, whereas receipt of medications for the comorbid disorder ranged from 69% to 82%. Among patients with AUD and co-occurring tobacco use disorder, 6% received medication for their AUD and 34% for their tobacco use disorder. Among patients with dual diagnoses, rates of pharmacotherapy for AUD were far lower than those for the comorbid disorders and contrary to evidence that medications for AUD are effective. Additional system-wide implementation efforts to identify and address patient- and provider-level barriers are needed to increase AUD pharmacotherapy in this high-need population.

  19. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver

    Directory of Open Access Journals (Sweden)

    Naglaa Mohamed El-Lakkany

    2016-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF and N-acetylcysteine (NAC with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I, NAFLD-induced by feeding high-fat diet (HFD; II for 12 weeks, NAFLD switched to regular diet (RD; III, NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V, NAC in a dose of 500 mg/kg (VI, VII or MTF+NAC (VIII, IX respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05 serum alanine transaminase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma glutamyl transferase (g-GT, cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α, transforming growth factor (TGF-β1 and hepatic malondialdehyde (MDA compared with group I. Meanwhile, hepatic superoxide dismutase (SOD, glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05. These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH.

  20. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver.

    Science.gov (United States)

    El-Lakkany, Naglaa Mohamed; Seif El-Din, Sayed Hassan; Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; Ebeid, Fatma Abdel-Latif

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

  1. Cellulose acetate butyrate-pH/thermosensitive polymer microcapsules containing aminated poly(vinyl alcohol) microspheres for oral administration of DNA.

    Science.gov (United States)

    Fundueanu, Gheorghe; Constantin, Marieta; Bortolotti, Fabrizio; Cortesi, Rita; Ascenzi, Paolo; Menegatti, Enea

    2007-04-01

    The aim of this work is to safely transport bioadhesive microspheres loaded with DNA to intestine and to test their bioadhesive properties. Poly(vinyl alcohol) (PVA) microspheres were prepared by dispersion reticulation with glutaraldehyde and further aminated. These microspheres were firstly loaded with plasmid DNA by electrostatic interactions and then entrapped in cellulose acetate butyrate (CAB) microcapsules for gastric protection. The entrapped PVA microspheres do not have enough force by swelling to produce the rupture of CAB shell, therefore the resistance of microcapsules was weakened by incorporating different amount of the pH/thermosensitive polymer (SP) based on poly(N-isopropylacrylamide-co-methyl methacrylate-co-methacrylic acid) (NIPAAm-co-MM-co-MA). This polymer is insoluble in gastric juice at pH 1.2 and 37 degrees C, but quickly solubilized in intestinal fluids (pH 6.8 and pH 7.4). Therefore, DNA loaded PVA microspheres were not expelled in acidic media but were almost entirely discharged in small intestine or colon. The integrity of DNA after entrapment was tested by agarose gel electrophoresis indicating that no DNA degradation occurs during encapsulation. The percentage of adhered microspheres on the mucus surface of everted intestinal tissue was 65+/-18% for aminated PVA microspheres without DNA and almost 50+/-15% for those loaded with DNA. Non-aminated PVA microspheres display the lowest adhesive properties (33+/-12%). In conclusion DNA loaded microspheres were progressively discharged in intestine. The integrity of DNA was not modified after entrapment and release, as proved by agarose gel electrophoresis. Both loaded and un-loaded aminated microspheres display good bioadhesive properties.

  2. 21 CFR 184.1293 - Ethyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  3. 27 CFR 6.6 - Administrative provisions.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Administrative provisions. 6.6 Section 6.6 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., advertisements, promotions, and other activities pertaining to its business subject to the Act conducted by,...

  4. 27 CFR 10.6 - Administrative provisions.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Administrative provisions. 10.6 Section 10.6 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., advertisements, promotions, and other activities pertaining to its business subject to the Act conducted by,...

  5. 27 CFR 8.6 - Administrative provisions.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Administrative provisions. 8.6 Section 8.6 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., advertisements, promotions, and other activities pertaining to its business subject to the Act conducted by,...

  6. Alcohol Abuse

    Science.gov (United States)

    ... even small amounts of alcohol may hurt an unborn child)Drink alcohol while you are looking after ... shakes, being very suspicious), and can even include death. This is why you need your doctor’s care ...

  7. Alcohol Test

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The recent alcohol tax increase poses a challenge to China’s white spirits makers Alcohol, rather than wine, is an in-dispensable component to Chinese table culture. The financial crisis has failed to affect white spirits sales, but an alcohol tax increase might.

  8. Alcohol Poisoning

    Science.gov (United States)

    ... t be awakened is at risk of dying. Alcohol poisoning is an emergency If you suspect that someone has alcohol poisoning — even if you don't see the ... immediately. Never assume the person will sleep off alcohol poisoning. Be prepared to provide information. If you ...

  9. [Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide, adaptive mechanisms].

    Science.gov (United States)

    Miskevich, D A; Borodinskiĭ, A N; Petushok, N E; Konovalenko, O V; Lelevich, V V

    2006-01-01

    Alcohol administration can result in liver damage. Reactive oxygen species (ROS), nitric oxide (NO) and their interaction are crucial factors in this process. The aim of work was to investigate, free radical state and mechanisms of adaptation of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake. Repeated cycles of alcoholization caused an imbalance between production and utilization of various ROS. This imbalance was due to impairments in the system superoxide dismutase/catalase. Nevertheless, in most experimental groups there was clear reduction of lipid peroxidation (LPO) products evaluated by thiobarbituric acid reactive substances. This might be attributed to the antioxidant effect of NO. However, there was an increased level of transaminases in blood plasma. After 28 days of this experimental scheme all the parameters studied normalized.

  10. Facts about Alcohol and Alcoholism.

    Science.gov (United States)

    Hall, Leonard C.

    Recognition of alcoholism as a treatable illness is a result of public education based on scientific facts. This publication, a digest of a more detailed survey of research about drinking and alcoholism, presents information about alcohol and its effects on individuals and society. It provides facts about the short-term and long-term effects of…

  11. Alcoholic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Gonzalo; Guzzo-Merello; Marta; Cobo-Marcos; Maria; Gallego-Delgado; Pablo; Garcia-Pavia

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy(ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM.

  12. 21 CFR 177.1670 - Polyvinyl alcohol film.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyvinyl alcohol film. 177.1670 Section 177.1670... Components of Single and Repeated Use Food Contact Surfaces § 177.1670 Polyvinyl alcohol film. Polyvinyl alcohol film may be safely used in contact with food of the types identified in § 176.170(c) of...

  13. Naltrexone for Alcoholism

    Science.gov (United States)

    ... Prescription Medicines, Your Health ResourcesTags: alcohol abuse, alcohol addiction, alcohol dependence, alcoholism, craving, Depade, drunk, hepatoxicity, intoxication, naltrexone, narcotic antagonist, opiate ...

  14. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  15. Repeated administration of meta-chlorophenylpiperazine or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane produces tolerance to its stimulatory effect on adrenocorticotropin hormone but not prolactin or corticosterone secretion in rats.

    Science.gov (United States)

    Mazzola-Pomietto, P; Aulakh, C S; Huang, S J; Murphy, D L

    1996-11-01

    In an attempt to clarify whether m-chlorophenylpiperazine-(m-CPP) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-(DOI) induced increases in plasma adrenocorticotropin hormone, corticosterone and prolactin secretion are mediated by the same or different mechanisms, we studied the time course of development of tolerance to the neuroendocrine effects of m-CPP (2.5 mg/kg/day) and DOI (2.5 mg/kg/day) in rats and, furthermore, also evaluated possible cross-tolerance in responses to m-CPP and DOI. We observed the development of tolerance in adrenocorticotropin hormone responses after a single i.p. injection of m-CPP. However, there was no cross-tolerance to DOI when chronic (13 days) m-CPP-treated animals were challenged with DOI (2.5 mg/kg). Injections of DOI (2.5 mg/kg) for six days were required before tolerance developed to the effect of DOI on adrenocorticotropin hormone. Furthermore, cross-tolerance was observed when DOI-treated animals (2.5 mg/kg/day x 6) were challenged with m-CPP (2.5 mg/kg) on day 7. In contrast, daily administration of m-CPP and DOI for 13 days did not produce tolerance to their stimulating effects on corticosterone and prolactin secretion. Hypothalamic levels of 5-hydroxyindoleacetic acid but not 5-HT were significantly reduced after acute or subchronic administration of both m-CPP and DOI. Furthermore, no change in the approximate 50% reduction in 5-hydroxyindoleacetic acid after m-CPP was observed after subchronic administration of this drug. These findings suggest that separate mechanisms mediate m-CPP and DOI-induced adrenocorticotropin hormone secretion in rats.

  16. Demographic and Academic Trends in Drinking Patterns and Alcohol-Related Problems on Dry College Campuses

    Science.gov (United States)

    Taylor, Dexter M.; Johnson, Mark B.; Voas, Robert B.; Turrisi, Robert

    2006-01-01

    Restricting alcohol consumption on campus is a measure often used by college administrators to prevent alcohol abuse and-alcohol-related problems. The effect of dry campus policies on alcohol consumption and alcohol-related problems, however, remains poorly understood. This report will compare characteristics of two dry campuses with descriptions…

  17. Alcohol and pregnancy

    Science.gov (United States)

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

  18. Alcohol Energy Drinks

    Science.gov (United States)

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 28133 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are premixed ...

  19. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  20. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  1. NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION.

    Science.gov (United States)

    Matošić, Ana; Marušić, Srđan; Vidrih, Branka; Kovak-Mufić, Ana; Cicin-Šain, Lipa

    2016-03-01

    characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter amines, i.e. serotonin, adrenaline, noradrenaline and dopamine. Thus, this enzyme is the key factor for maintaining cytoplasmic concentration of various neurotransmitters and for regulation of the neurotransmitting synaptic activity. Taken this MAO function into consideration, MAO is the enzyme included in the etiology and pathogenesis of various neuropsychiatric and neurological disorders. The finding of the decreased platelet MAO activity in various psychiatric disorders has brought us to the assumption that this enzyme may be a constitutional/genetic indicator (trait marker) or an indicator of disease condition (state marker) in biologic psychiatry. There are only a few studies of alcohol addiction researching the connections of the MAO coding gene polymorphism and alcoholism; however, these studies are primarily related to the variable number of tandem repeats (VTNR) polymorphism in the regulatory gene region for MAO-A, considered to

  2. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  3. [Alcohol experience, alcohol knowledge, and alcohol expectancy in early adolescents].

    Science.gov (United States)

    Tak, Young-Ran; Yun, E-hwa; An, Ji-Yeon

    2007-02-01

    This study was to explore the prevalence of alcohol experiences and to identify the expectancy on the effects of alcohol and alcohol knowledge in early adolescents. The cross-sectional survey of 1854 students from seven middle schools in one district of Seoul was conducted by convenience sampling. Alcohol experience and early onset of alcohol use were measured by the Youth Risk Behavior Survey. Alcohol expectancy was measured by an Alcohol Effects Questionnaire. Over sixty five percent of adolescents reported that they had previous drinking experiences. The participants with no alcohol drinking experience had a lower level of alcohol knowledge than those with experience(t=2.73, p=.007). In expectancy on effects of alcohol, girls had a more positive alcohol expectation than boys(t=-2.54, p=.011). Alcohol knowledge negatively correlated with alcohol expectancy(r=-.40 p=.000). In regression of alcohol expectancy, gender and alcohol knowledge were significant predictors explaining 17%. The results support that alcohol expectancy is an important link with early drinking experiences and alcohol knowledge, focusing on the importance of gender differences. Therefore, an alcohol prevention program in early adolescence is needed and should be focused on multidimensionality of the alcohol expectancy with developmental and psychosocial factors for early adolescents.

  4. ConA 重复给药建立 ACLF 免疫状态动态转变的小鼠模型%Establishment of Model of Dynamic Change of Immune Status of ACLF Induced by ConA Repeated Administration in Mice

    Institute of Scientific and Technical Information of China (English)

    张楠楠; 杨淑殷; 陈柳莹; 尹珊; 王十锦; 刘三海; 王蓓蓓; 汪铮; 李海

    2016-01-01

    背景:慢加急性肝衰竭(ACLF)是我国常见的肝衰竭类型,目前尚缺乏能有效模拟 ACLF 免疫状态动态转变的动物模型。目的:通过刀豆球蛋白 A(ConA)重复给药,建立模拟 ACLF 免疫状态动态转变的动物模型。方法:小鼠随机分为对照组和 ConA 重复给药组,ConA 重复给药组小鼠给予球后内眦静脉丛注射 ConA 15 mg/ kg,每隔48 h 一次,共5次,对照组给予等体积0.9% NaCl 溶液。CBA 法检测外周血 IL-6、IL-10、IL-12、TNF-α、IFN-γ、MCP-1水平,并测定 IL-10/ TNF-α比值;流式细胞术检测外周血中单核细胞 HLA-DR 表达、CD4+ T 细胞数量及其比例以及 PD-1表达。结果:随着给药次数增加,ConA 重复给药组小鼠外周血细胞因子从促炎细胞因子为主转变成抗炎细胞因子为主。与对照组相比,ConA 重复给药组外周血中单核细胞 HLA-DR 表达下降(P <0.05);CD4+ T 细胞数量和比例下降(P <0.05),PD-1表达上调(P <0.05)。结论:本研究通过 ConA 重复刺激成功建立了模拟 ACLF 免疫状态从全身炎症反应综合征(SIRS)到代偿性抗炎反应综合征(CARS)动态转变的动物模型。%Background:Acute-on-chronic liver failure( ACLF)is a commonly seen liver failure in China,and lacking an animal model that can effectively simulate the dynamic change of immune status of ACLF. Aims:To establish an animal model that can simulate dynamic change of immune status of ACLF by repeated administration of concanavalin A(ConA). Methods:Mice were randomly divided into normal control group and ConA repeated administration group. Mice in ConA repeated administration group were injected with ConA 15 mg/ kg through retrobulbar angular vein every 48 hours for 5 times,and mice in control group were injected with same volume of 0. 9% NaCl solution. Serum levels of IL-6,IL-10,IL- 12,TNF-α,IFN-γ,MCP-1 in peripheral blood were assessed by CBA assay,and the

  5. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    Science.gov (United States)

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

  6. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  7. Alcohol industry sponsorship and alcohol-related harms in Australian university sportspeople/athletes.

    Science.gov (United States)

    O'Brien, Kerry S; Lynott, Dermot; Miller, Peter G

    2013-05-01

    Although there is evidence that alcohol sponsorship in sport is related to greater drinking, there is no empirical research on whether alcohol sponsorship is associated with alcohol-related harms. We examined whether there is an association between receipt of alcohol industry sponsorship, and attendance at alcohol sponsor's drinking establishments (e.g. bars), and alcohol-related aggression and antisocial behaviour in university students who play sport. University sportspeople (n = 652) completed surveys (response rate >80%) assessing receipt of alcohol industry sponsorship, attendance at sponsor's establishments and confounders [i.e. age, gender, sport type, location and alcohol consumption measured by Alcohol Use Disorders Identification Test--alcohol consumption (AUDIT-C) scores]. Participants also completed measures assessing displays and receipt of aggressive and antisocial behaviours (e.g. assaults, unwanted sexual advance, vandalism). Logistic regression models including confounders and reported attendance at alcohol sponsor's establishments showed that sportspeople receiving alcohol industry sponsorship were more likely to have been the victim of aggression (adjusted odds ratio 2.62, 95% confidence interval 1.22-5.64). Attending an alcohol sponsor's establishment was not associated with higher rates of other aggressive or antisocial behaviour. However, significant associations where found between AUDIT-C scores and having displayed and received aggression, and having damaged or had property damaged. Male sportspeople were more likely to have displayed and received aggressive and antisocial behaviour. Higher AUDIT-C scores, gender and receipt of alcohol industry sponsorship were associated with alcohol-related aggression/antisocial behaviours in university sportspeople. Sport administrators should consider action to reduce the harms associated with excessive alcohol consumption and alcohol industry sponsorship in sport. © 2012 Australasian Professional

  8. Alcohol withdrawal.

    Science.gov (United States)

    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.

  9. 21 CFR 573.880 - Normal propyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Normal propyl alcohol. 573.880 Section 573.880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additive Listing § 573.880 Normal propyl alcohol. Normal propyl alcohol may be safely used in feeds...

  10. 21 CFR 582.5580 - D-Pantothenyl alcohol.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false D-Pantothenyl alcohol. 582.5580 Section 582.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5580 D-Pantothenyl alcohol. (a) Product. D-Pantothenyl alcohol. (b) Conditions of...

  11. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  12. Hyperactivity, Learning Disabilities, and Alcohol.

    Science.gov (United States)

    Gold, Sandra; Sherry, Lee

    1984-01-01

    A review of research on the effects of alcohol consumption by pregnant women supports the U.S. Food and Drug Administration's warning about the possible negative effects (learning disabilities, hyperactivity, short attention span, and emotional liability) of children. (Author/CL)

  13. Predicting DUI recidivism: blood alcohol concentration and driver record factors.

    Science.gov (United States)

    Marowitz, L A

    1998-07-01

    This study examined the relationship between blood alcohol concentration (BAC) at arrest, driving history and other demographic factors, and the 1-year post-arrest probability of recidivism for drunk driving (DUI) convictees. Complex and simple prediction models were developed. All models found a statistically significant cubic relationship between BAC and recidivism, reflecting a relatively high rate of recidivism at a BAC of 0.00%, decreasing to a minimum at ca 0.09% BAC, then increasing to another relatively high rate at a BAC of ca 0.29%, followed by a decline in recidivism to BAC levels of 0.35% and beyond. High rates of recidivism at high BACs suggest alcohol dependency, while high rates at low BACs suggest the involvement of other impairing substances. The rate of DUI recidivism for offenders who refused alcohol testing was the same as for aggregated BAC-tested offenders who had prior DUIs at the time of the arrest. The probability of DUI recidivism predicted by a simple model using BAC, prior 2-year traffic convictions, and offender level (first or repeat offender) could be used along with other factors by presentence investigators, judges or in administrative settings to determine appropriate sanctions, treatment or other remedial measures. The findings support the notion that first offenders with high BAC levels and prior 2-year traffic convictions are at as high a risk of recidivating as many repeat offenders, and might therefore benefit from similar sanctions and/or remedial treatment. The findings also support viewing DUI arrestees with very low BACs as probable drug users with relatively high probabilities of recidivating.

  14. Monoamine oxidases and alcoholism. I. Studies in unrelated alcoholics and normal controls

    Energy Technology Data Exchange (ETDEWEB)

    Parsian, A.; Suarez, B.K.; Fisher, L. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1995-10-09

    Low platelet MAO activity has been associated with alcoholism. In order to evaluate the role of MAO genes in susceptibility to alcoholism, we have taken a biochemical and molecular genetic approach. The sample consisted of 133 alcoholic probands who were classified by subtypes of alcoholism and 92 normal controls. For those subjects typed for platelet MAO activity, alcoholics (N = 74) were found not to differ from the non-alcoholic controls (N = 34). Neither was there a significant difference between type I and type II alcoholics or between either subtype and normal controls. However, we do find significant differences between male and female alcoholics, but not between male and female controls. The allele frequency distribution for the MAO-A and MAO-B dinucleotide repeats is different between the alcoholic sample (N = 133) and the normal control sample (N = 92). In a two-way analysis of variance of MAO-B activity as a function of the allelic variation of each marker locus and diagnosis, there is no evidence for mean differences in activity levels for the different alleles. Our findings do not rule out a role for the MAO-B gene in controlling the enzyme activity because the dinucleotide repeats are located in introns. 52 refs., 1 figs., 4 tabs.

  15. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  16. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  17. Alcohol and Hepatitis

    Science.gov (United States)

    ... code here Enter ZIP code here Daily Living: Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one ... related to choices you make about your lifestyle . Alcohol and fibrosis Fibrosis is the medical term for ...

  18. Pharmacokinetics of metadoxine for injection after repeated doses in healthy volunteers

    Institute of Scientific and Technical Information of China (English)

    L(U) Yuan; KANG Zi-sheng; LIU Yan; LI Tian-yun; XIAO Yong-hong

    2007-01-01

    @@ Alcohol-induced liver disease is one of the main epidemic problems nowadays. Metadoxine is a pyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.1-3 The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.

  19. Administrating Solr

    CERN Document Server

    Mohan, Surendra

    2013-01-01

    A fast-paced, example-based guide to learning how to administrate, monitor, and optimize Apache Solr.""Administrating Solr"" is for developers and Solr administrators who have a basic knowledge of Solr and who are looking for ways to keep their Solr server healthy and well maintained. A basic working knowledge of Apache Lucene is recommended, but this is not mandatory.

  20. 短期重复使用几种精神药物对小鼠自主活动和脑单胺递质的影响%Effect of short-term repeated administration of several psychoactive drugs on locomotor activity and cerebral monamine transmitters in mice

    Institute of Scientific and Technical Information of China (English)

    詹皓; 唐桂香; 辛益妹

    2001-01-01

    目的观察短期重复使用几种精神药物对小鼠自主活动和脑单胺递质的影响,以评价药物作用的耐受性和副作用。方法雄性小鼠作为实验对象。中枢兴奋药实验分3组(每组n=6):①对照组;②咖啡因(Caf)组30 mg/kg;③右旋苯丙胺(Dex)组10 mg/kg。催眠药实验分4组(每组n=6):①对照组;②三唑仑(TZ)组0.04 mg/kg;③速可眠(Sec)组60 mg/kg;④褪黑素(Mel)组120 mg/kg。小鼠灌胃给药,1次/d,共7 d。于第1天和第7天称重和测定自主活动。Dex和TZ连续用药7 d后,用高效液相色谱法测定小鼠大脑皮层单胺递质及其代谢产物的变化。结果①对照组和用药组的体重差异无显著性意义;②连续用药7 d,Caf和Dex对自主活动的兴奋作用较第1天明显增强(P<0.05);③连续用药7 d,虽然催眠药对小鼠自主活动仍有显著的抑制作用,但作用强度较之第1天明显降低(P<0.05);④Dex和TZ连续用药7 d,小鼠大脑皮层单胺递质水平无明显改变,但Dex组的双羟基苯乙酸(DOPAC)和5-羟基吲哚乙酸(5-HIAA)及TZ组的5-HIAA明显降低(P<0.05)。结论①连续应用催眠药1周,其作用有一定的耐受性;②重复使用Dex和TZ 1周对鼠脑单胺递质的代谢可能产生不良影响。%Objective To observe the effect of short-term repeated administration of several psychoactive drugs on locomotor activity and cerebral monamine transmitters in mice and evaluate tolerance of drug action and their side-effects. Methods Male mice were used as subjects. The experiment of central stimulants was divided into 3 groups (n=6 each): ①control;②caffeine(Caf) 30 mg/kg; ③dexamphetamine(Dex) 10 mg/kg. The experiment of hypnotics included 4 groups: ①control; ②triazolam (TZ) 0.04 mg/kg;③seconal (Sec) 60 mg/kg; ④melatonin (Mel) 120 mg/kg. These drugs were given orally to the mice once daily for 7 days. Body weight and locomotor activity were determined on first

  1. Alcohol-flavoured tobacco products.

    Science.gov (United States)

    Jackler, Robert K; VanWinkle, Callie K; Bumanlag, Isabela M; Ramamurthi, Divya

    2017-06-07

    In 2009, the Food and Drug Administration (FDA) banned characterising flavours in cigarettes (except for menthol) due to their appeal to teen starter smokers. In August 2016, the agency deemed all tobacco products to be under its authority and a more comprehensive flavour ban is under consideration. To determine the scope and scale of alcohol-flavoured tobacco products among cigars & cigarillos, hookahs and electronic cigarettes (e-cigarettes). Alcohol-flavoured tobacco products were identified by online search of tobacco purveyors' product lines and via Google search cross-referencing the various tobacco product types versus a list of alcoholic beverage flavours (eg, wine, beer, appletini, margarita). 48 types of alcohol-flavoured tobacco products marketed by 409 tobacco brands were identified. Alcohol flavours included mixed drinks (n=25), spirits (11), liqueurs (7) and wine/beer (5). Sweet and fruity tropical mixed drink flavours were marketed by the most brands: piña colada (96), mojito (66) and margarita (50). Wine flavours were common with 104 brands. Among the tobacco product categories, brands offering alcohol-flavoured e-cigarettes (280) were most numerous, but alcohol-flavoured products were also marketed by cigars & cigarillos (88) and hookah brands (41). Brands by major tobacco companies (eg, Philip Morris, Imperial Tobacco) were well represented among alcohol-flavoured cigars & cigarillos with five companies offering a total of 17 brands. The widespread availability of alcohol-flavoured tobacco products illustrates the need to regulate characterising flavours on all tobacco products. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Fatal subacute liver failure after repeated administration of sevoflurane anaesthesia.

    Science.gov (United States)

    Zizek, David; Ribnikar, Marija; Zizek, Bogomir; Ferlan-Marolt, Vera

    2010-01-01

    Sevoflurane is a widely used halogenated inhalation anaesthetic. In comparison with other similar anaesthetics, it is not metabolized to potentially hepatotoxic trifluoroacetylated proteins. In this case report, we present a 66-year-old woman with breast carcinoma, who underwent sevoflurane general anaesthesia twice in 25 days. Soon after the second elective surgical procedure, jaundice and marked elevations in serum transaminases developed. The patient died 66 days thereafter. Autopsy results denied evidence of major cardiovascular abnormality, and histological examination confirmed massive liver cell necrosis with no feature of chronic liver injury. Sevoflurane anaesthesia was imputed as the cause after exclusion of other possible aetiological agents. Besides, coexistent malignant tumours found in the patient could have modulated the immunological response to the applied anaesthetic followed by fatal consequences.

  3. [Diagnosis of fetal alcohol spectrum disorders].

    Science.gov (United States)

    van Wieringen, Hester; Letteboer, Tom G W; Pereira, Rob Rodrigues; de Ruiter, Sanne; Balemans, Walter A F; Lindhout, Dick

    2010-01-01

    Prenatal alcohol exposure may cause decreased growth of the child, congenital abnormalities, specific facial characteristics, and, most importantly, mental retardation and behavioural disorders, all known as fetal alcohol spectrum disorders (FASD). A significant number of pregnant women in the Netherlands drink alcohol, but the prevalence of FASD in our country is unknown. Repeated and high peak blood alcohol concentrations, for example in the case of binge drinking by the mother, result in more severe abnormalities; a safe limit for alcohol consumption in pregnancy cannot be defined. In 2007 and 2008, Dutch paediatricians reported a total of 56 diagnosed cases of FASD, mostly adopted and foster children. Possibly the condition has not always been diagnosed. Use of international guidelines for diagnosis by the medical profession may improve detection. The guidelines of the Canadian Public Health Agency provide a useful and generally accepted classification, with strict cut-off points to avoid overdiagnosis; attention should always be paid to the broad differential diagnosis.

  4. Fragrance material review on benzyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Vitale, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Fragrance material review on anisyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of anisyl alcohol when used as a fragrance ingredient is presented. Anisyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for anisyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, skin sensitization, elicitation, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Fragrance material review on phenylethyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of phenylethyl alcohol when used as a fragrance ingredient is presented. Phenylethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenylethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Alcohol's actions on neuronal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Davis, Tiffany J; de Fiebre, Christopher M

    2006-01-01

    Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

  8. Joint Effect of Alcohol Consumption and Educational Level on Alcohol-related Medical Events

    DEFF Research Database (Denmark)

    Christensen, Helene Nordahl; Diderichsen, Finn; Hvidtfeldt, Ulla Arthur

    2017-01-01

    may also play a role. We investigated the joint effect of alcohol consumption and educational level on the rate of alcohol-related medical events. METHODS: We pooled seven prospective cohorts from Denmark that enrolled 74,278 men and women age 30-70 years (study period, 1981 to 2009). We measured...... alcohol consumption at baseline using self-administrated questionnaires. Information on highest attained education 1 year before study entry and hospital and mortality data on alcohol-related medical events were obtained through linkage to nationwide registries. We performed analyses using the Aalen...... additive hazards model. RESULTS: During follow-up (1,085,049 person-years), a total of 1718 alcohol-related events occurred. The joint effect of very high alcohol consumption (>21 [>28] drinks per week in women [men]) and low education on alcohol-related events exceeded the sum of their separate effects...

  9. Relationship between plasma concentration of β-hydroxybutyrate,acetoacetate, lactate and pyruvate and alcohol after oral or intravenous administration of alcohol to normal human subjects: a population pharmacodynamics (PD) analysis%口服及静注乙醇后血中乙醇与β-羟丁酸,乙酰乙酸,乳酸及丙酮酸浓度关系的探讨:一项群体药效动力学的研究

    Institute of Scientific and Technical Information of China (English)

    万捷; 李建国; HUI C ko; Tom LIONETTI; David T GEORGE; Susan E SHOAF

    2005-01-01

    目的:应用群体药理学方法探讨血浆中乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸(H/A)比值及乳酸/丙酮酸(L/P)比值变化的效应.方法:给14名健康成人口服剂量相当于1.02 g·L-1总身体水的乙醇.在另一项实验中,给8名健康成人静脉注射剂量相当于0.83 g·L-1总身体水的乙醇.在服用乙醇后380 min采取静脉血测定乙醇,β-羟丁酸,乙酰乙酸,乳酸及丙酮酸的血浆浓度.在静注乙醇后340min采血测定上述5种物质的血浆浓度.结果:在口服乙醇实验中,G0为66.6±8.1 mg·dl-1,显著低于102mg·dl-1,(t检验,P<0.001).清除相斜率β为0.229±0.05 mg·dl-1·min-1.在静注实验中,G0为75.6±10.9 mg·dl-1,与83 mg·dl-1比较无显著性差异,β为0.245±0.05mg·dl-1·min-1.在两项实验中,我们应用群体间接生理反应模型来拟合乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸比值及乳酸/丙酮酸比值变化的效应,并得出各项参数.同时,我们发现,当乙醇的清除相结束时,H/A比值尚未达最大值,说明在乙醇的零级代谢相时肝脏仍在产生NADH.乳酸和乙醇的关系曲线显示乳酸的变化呈现一种逆时钟方向的滞后.结论:血L/P比值不适合用作实时肝脏氧化状态的指标.本研究提供的参数将有益于将来研究乙醇对肝脏氧化状态的影响.%To investigate the relationship between plasma concentration of β-hydroxybutyrate, acetoacetate, lactate, pyruvate, β-hydroxybutyrate/acetoacetate (H/A ratio) and lactate/pyruvate (L/P ratio) and alcohol by population PD analysis after oral or intravenous administration of alcohol. METHODS: An oral dose of alcohol tered to 14 normal human subjects and an Ⅳ infusion (30 water was administered to 8 normal subjects. Venous blood was sampled for determination of alcohol (BAC),β-hydroxybutyrate, acetoacetate, lactate and pyruvate for 380 min after oral administration and for

  10. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  11. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  12. Evaluation of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in African Americans.

    Science.gov (United States)

    Marshall, Vanessa J; Ramchandani, Vijay A; Kalu, Nnenna; Kwagyan, John; Scott, Denise M; Ferguson, Clifford L; Taylor, Robert E

    2014-01-01

    The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers. The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates. Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p alcohol sessions compared with placebo sessions (p alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day. Copyright © 2013 by the

  13. Cognitive biases for social alcohol-related pictures and alcohol use in specific social settings: An event-level study

    NARCIS (Netherlands)

    Groefsema, M.M.; Engels, R.C.M.E.; Kuntsche, E.N.; Smit, K.; Luijten, M.

    2016-01-01

    Background: Alcohol use occurs mainly among friends, in social contexts, and for social reasons. Moreover, cognitive biases, such as attentional and approach biases, have repeatedly been associated with alcohol use. This study aimed to test whether nondependent drinkers display cognitive biases for

  14. What happened to alcohol consumption and problems in the Nordic countries when alcohol taxes were decreased and borders opened?

    DEFF Research Database (Denmark)

    Room, Robin; Bloomfield, Kim; Gmel, Gerhard

    2013-01-01

    , and the abolition of quantitative quotas on alcohol import for personal use from other European Union countries made cheaper alcohol more available in Denmark, Finland, and Sweden. Method: Analyses of routine statistical register data and summaries of results from longitudinal and repeated cross...

  15. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    Science.gov (United States)

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  16. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting...

  17. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with lamotrigine.

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Gorska, Dorota; Andrzejczak, Dariusz; Dyr, Wanda; Bieńkowski, Przemysław

    2015-02-01

    Several recent studies have indicated that lamotrigine, similarly to other antiepileptic drugs, may be useful in the therapy of alcohol dependence. The rationale for using lamotrigine in the treatment of alcohol addiction is based on its multiple mechanisms of action which include inhibition of voltage-sensitive sodium channels, modulation voltage-gated calcium currents and transient potassium outward current. However, the known mechanism of lamotrigine does not fully explain its efficacy in alcohol addiction therapy. For this reason we have decided to examine the effect of lamotrigine on the opioid system. Our previous studies showed that topiramate and levetiracetam (antiepileptic drugs) as well as the most effective drugs in alcohol addiction therapy i.e. naltrexone and acamprosate, when given repeatedly, all increased plasma beta endorphin (an endogenous opioid peptide) level, despite operating through different pharmacological mechanisms. It is known that low beta-endorphin level is often associated with alcohol addiction and also that alcohol consumption elevates the level of this peptide. This study aims to assess the effect of repeated treatment with lamotrigine on voluntary alcohol intake and beta-endorphin plasma level in alcohol preferring rats (Warsaw high preferring (WHP) rats). We observed a decrease in alcohol consumption in rats treated with lamotrigine. However we didn't observe significant changes in beta-endorphin level during withdrawal of alcohol, which may indicate that the drug does not affect the opioid system. We suppose that lamotrigine may be useful in alcohol dependence therapy and presents a potential area for further study.

  18. Electrical amygdala kindling in alcohol-withdrawal kindled rats.

    Science.gov (United States)

    Ulrichsen, J; Woldbye, D P; Madsen, T M; Clemmesen, L; Haugbøl, S; Olsen, C H; Laursen, H; Bolwig, T G; Hemmingsen, R

    1998-01-01

    Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

  19. Pavlovian sign-tracking model of alcohol abuse.

    Science.gov (United States)

    Tomie, Arthur; Sharma, Nikyta

    2013-09-01

    While poorly controlled alcohol drinking is a prominent symptom of alcohol abuse, its environmental determinants remain poorly understood. The Sign-Tracking Model (STM), developed by Tomie and his associates, postulates that poorly controlled alcohol drinking is due to the development of signal-directed behaviors induced by Pavlovian sign-tracking procedures. In laboratory studies of animal learning, presentation of the lever (conditioned stimulus, CS) followed by the presentation of the food (unconditioned stimulus, US) induces sign-tracking conditioned response (CR) performance, wherein rats approach and contact, then express consummatory-like responses (i.e., licking, gnawing, and chewing) directed at the lever CS. The Pavlovian sign-tracking CR is an involuntary acquired reflexive response. It is poorly controlled and elicited by the presentation of the CS. STM proposes that poorly controlled alcohol drinking in humans may be due to repeated pairings of the alcohol sipper (e.g., cocktail glass) CS with alcohol's rewarding effects US, resulting in sign-tracking CR performance. The cocktail glass CS will elicit Pavlovian sign-tracking CR performance of reflexive and involuntary alcohol intake. This paper reviews evidence in the Pavlovian conditioning literature that in animals the positive contingency between the alcohol sipper CS and alcohol US induces sign-tracking of alcohol drinking. Also reviewed is evidence that in human beings alcohol drinking is a direct function of the positive contingency between a particular alcohol glassware CS and alcohol US. Implications of these findings for the Sign-Tracking Model (STM) are discussed.

  20. Assessment of Alcohol Use Disorders among Court-Mandated DWI Offenders

    Science.gov (United States)

    Stasiewicz, Paul R.; Nochajski, Thomas H.; Homish, D. Lynn

    2007-01-01

    Convicted DWI offenders (N = 549) were assessed for alcohol use disorders. Repeat offenders had twice the rate of both lifetime and current alcohol use disorders compared with 1st-time offenders. Guidelines for determining alcohol problems in DWI offenders are recommended.

  1. Administrative Ecology

    Science.gov (United States)

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  2. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  3. Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.

    Science.gov (United States)

    Griffenhagen, Gregg M; Rezende, Marlis L; Gustafson, Daniel L; Hansen, Ryan J; Lunghofer, Paul J; Mama, Khursheed R

    2015-09-01

    To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. Prospective experimental study. Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1)  minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  4. Nicotine's effects on attentional efficiency in alcoholics.

    Science.gov (United States)

    Nixon, Sara Jo; Lawton-Craddock, Andrea; Tivis, Rick; Ceballos, Natalie

    2007-12-01

    Historically, the concomitant use of nicotine among alcoholics has not been methodologically accounted for. Given the observed cognitive enhancing effects of acute nicotine on attentional processes, it is important that the potentially positive effects of nicotine be disentangled from the negative effects of chronic alcohol dependence. The current study was conducted to address this question and to test the hypothesis that alcoholics who are regular smokers are more sensitive to the effects of nicotine on cognition as compared to regular smoking community controls. A 2 [drug group; alcoholics (n = 28), community controls (n = 27)] X 2 nicotine dose level [low (7 mg dose) vs. high (14 or 21 mg dose)] double-blind design was used to assess the differential effects of nicotine dose on a battery of neurocognitive tests focusing on attentional efficiency. As expected, the alcoholic group performed more poorly than did the control group. However, of greater interest to the current study was the finding that alcoholic participants differentially benefited from nicotine administration, as demonstrated in the differential dose effect. The concomitant use of nicotine may serve to "mask" or "overcome" some of the negative effects of chronic alcohol dependence in newly recovering alcoholics. This potential effect has significant implications for treatment development and further understanding of the process of recovery of function in chronic alcoholics.

  5. 枳子、葛根花和苦参混合药物对小鼠急性酒精中毒的防治作用%Prevention and Cure of Acute Alcohol Intoxica-tion in Mice by Administration of Compound of Japanese Raisintree Fruit, Lobed Kudzuvine Flower Bud and Lightyellow Sophora Root

    Institute of Scientific and Technical Information of China (English)

    孔玲; 李杰; 张秀珍

    2014-01-01

    Objective We aimed to investigate the preventive and therapeutical effect of compound of traditional Chinese drugs (Japanese raisintree fruit, lobed kudzuvine flower bud and lightyel ow sophora root) on acute alcohol intoxication in mice. [Method] Acute alcohol intoxication was induced by administering alcohol to mice. Three different doses (low, middle and high) of compound of traditional Chinese drugs were administered to mice before and after administering alcohol respectively to investigate the preventive and therapeutical effect of drugs on acute alcohol intox-ication through doing statistical analysis about drunk mice and their sleeping time. The concentration of malondialdehyde (MDA), reduced glutathione (GSH) and triglyc-erides (TG) in liver was also determined to investigate the protective effect of drugs on liver. [Result] The efficacy of compound of traditional Chinese drugs on acute al-cohol intoxication was dose-dependent. High-dose administration decreased the number of drunk mice significantly compared with control group; middle- and high-dose administration reduced the sleeping time of drunk mice and the concentration of MDA and TG in liver tissue; three doses al increased the concentration of GSH. [Conclusion] The compound of Japanese raisintree fruit, lobed kudzuvine flower bud and lightyel ow sophora root had preventive and therapeutical effect on hangover, and it also had certain preventive and therapeutical effect on liver damage caused by alcohol.%[目的]探讨中药枳子、葛根花和苦参混合药物对小鼠急性酒精中毒的防治作用。[方法]采用酒精灌胃法建立小鼠急性酒精中毒模型,灌喂低、中、高3种剂量的药物,进行先药后酒的预防醉酒和先酒后药的治疗醉酒试验,统计醉酒小鼠数目和小鼠睡眠时间,并通过检测小鼠肝组织中的丙二醛( MDA)、还原型谷胱甘肽(GSH)及血清甘油三酯(TG)的含量,研究药物对小鼠肝的保护作用

  6. Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate.

    Science.gov (United States)

    Umhau, John C; Schwandt, Melanie L; Usala, Julie; Geyer, Christopher; Singley, Erick; George, David T; Heilig, Markus

    2011-05-01

    Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α(2)-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses.

  7. Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

    Directory of Open Access Journals (Sweden)

    Alfredo Ghezzi

    Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

  8. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  9. Breath alcohol test

    Science.gov (United States)

    Alcohol test - breath ... There are various brands of breath alcohol tests. Each one uses a different method to test the level of alcohol in the breath. The machine may be electronic or manual. One ...

  10. Weight loss and alcohol

    Science.gov (United States)

    ... 19548203 . National Institute on Alcohol Abuse and Alcoholism. Rethinking Drinking: Alcohol and Your Health. rethinkingdrinking.niaaa.nih. ... about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  11. Behind the Label "Alcoholic."

    Science.gov (United States)

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  12. Offentlig administration

    DEFF Research Database (Denmark)

    Nielsen, Elof Nellemann; Rehr, Preben René

    En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer.......En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer....

  13. Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers.

    Science.gov (United States)

    Soo-ampon, Sompop; Wongwitdecha, Noppamars; Plasen, Surin; Hindmarch, Ian; Boyle, Julia

    2004-11-01

    Free recall of words has been extensively used in psychopharmacology to assess the effects of CNS-active drugs on memory functions. However, there is a relative lack of information on the impact of word frequency on the subsequent recall of words following the administration of psychoactive drugs. The present double-blind, placebo-controlled, repeated-measures experiment used lorazepam and alcohol to test the effects of word frequency on immediate and delayed word recall in 24 healthy volunteers. One half of the words contained in the lists had a high frequency (HF) of occurrence and the remainder were of low frequency (LF). The results showed that LF words were more sensitive to memory impairment than HF words. However, the more accurate recall of HF words (with respect to LF words) was eliminated when a combination of lorazepam with alcohol was administered. These findings indicate that word frequency has a significant impact on memory and, as such, is a factor to be taken into account when using memory recall tasks to assess the effects of psychoactive drugs on memory.

  14. A preliminary case study of androgen receptor gene polymorphism association with impulsivity in women with alcoholism

    Directory of Open Access Journals (Sweden)

    Mettman DJ

    2014-03-01

    Full Text Available Daniel J Mettman, Merlin G Butler, Albert B Poje, Elizabeth C Penick, Ann M Manzardo Departments of Psychiatry and Behavioral Sciences and Pediatrics, MS 4015, Kansas University Medical Center, Kansas City, KS, USA Objective: The androgen receptor (AR gene, located on the X chromosome, contains a common polymorphism involving cytosine-adenine-guanine (CAG repeats, which impacts disease and could contribute to the unequal sex ratio in alcoholism. CAG repeats in the AR gene are known to correlate with impulsivity in males. We report the first preliminary study examining the association between the number of CAG repeats and measures of impulsivity in females with chronic alcoholism. Methods: A total of 35 women and 85 men with chronic alcoholism were previously recruited for a nutritional clinical trial, and 26 well-characterized females (19 African–American and seven Caucasian with alcoholism agreed to participate for genetic testing. Genomic deoxyribonucleic acid (DNA was isolated from peripheral blood and CAG repeats determined by analyzing polymerase chain reaction (PCR-amplified products, using the polymorphic AR gene assay. CAG repeat length was correlated with raw scores from the Barratt Impulsivity Scale, version 11 and the Alcoholism Severity Scale. Results: CAG repeat lengths were significantly longer in Caucasian alcoholic women compared with African–Americans, and the average number of CAG repeats were significantly, positively correlated (P<0.05 with impulsivity scores. Women with average CAG repeat length (CAGave ≥18, representing the upper quartile of the repeat range, showed significantly greater mean raw impulsivity scores. CAG repeat length appeared to have less effect in African–American compared with Caucasian women, possibly due to a shorter average repeat length. Conclusion: We found an association between the number of CAG repeats and impulsivity in females with chronic alcoholism, specifically in women with CAGave

  15. ALCOHOL AND ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2014-01-01

    Full Text Available The article considers the questions of the relationship between the amount of the consumed alcohol, the type of alcoholic beverage, pattern of alcohol consumption and the blood pressure level. The article presents data on the positive effect of alcohol intake restrictions and recommendations for permissible limits of alcohol consumption. New possibilities of drug therapy aimed at limiting alcohol consumption are being reported.

  16. Genetics and alcoholism

    OpenAIRE

    Edenberg, Howard J; Foroud, Tatiana

    2013-01-01

    Alcohol is widely consumed, but excessive use creates serious physical, psychological and social problems and contributes to many diseases. Alcoholism (alcohol dependence, alcohol use disorders) is a maladaptive pattern of excessive drinking leading to serious problems. Abundant evidence indicates that alcoholism is a complex genetic disease, with variations in a large number of genes affecting risk. Some of these genes have been identified, including two genes of alcohol me...

  17. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren

    2008-01-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may...... be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking...... and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men...

  18. Alcohol withdrawal syndrome--an auto-immune disease? A neuroimmunologic model for pathogenesis of alcohol withdrawal symptoms.

    Science.gov (United States)

    Schubert, S

    1990-08-01

    A neuroimmunologic model of alcohol withdrawal symptoms is developed according to which these may be considered as an idiopathic auto-immune disease. During the alcohol abuse period of non-addicts, homeostasis may alter pathologically by gradual adaptation of the organism: auto-sensitisation develops and finally leads to the breakdown of auto-immune tolerance of the structural modifications set by alcohol withdrawal. The immunosystem regards the existing assimilation of alcohol as self, the withdrawal of alcohol as non-self. Alcohol withdrawal may be considered as an acknowledged physical stressor, and physical stressors as potential triggers of auto-immune diseases. Some so-called alcohol-induced diseases may originate in the pathogenic effects of preceding auto-immune responses to repeated alcohol withdrawals. Neuroimmunologic preconditions of potential auto-immune diseases exactly fit the alcohol withdrawal situation. Neuroimmunologic diseases themselves show close analogies respectively to alcohol withdrawal symptoms as well as to some alcohol-induced diseases. The myelin basis protein is assumed to be a potential auto-allergen. Finally withdrawal symptoms being the expression of physical dependence on alcohol, the model may highlight the very nature of physical dependence.

  19. Estimation of the Accuracy of Method for Quantitative Determination of Volatile Compounds in Alcohol Products

    CERN Document Server

    Charepitsa, S V; Zadreyko, Y V; Sytova, S N

    2016-01-01

    Results of the estimation of the precision for determination volatile compounds in alcohol-containing products by gas chromatography: acetaldehyde, methyl acetate, ethyl acetate, methanol, isopropyl alcohol, propyl alcohol, isobutyl alcohol, butyl alcohol, isoamyl alcohol are presented. To determine the accuracy, measurements were planned in accordance with ISO 5725 and held at the gas chromatograph Crystal-5000. Standard deviation of repeatability, intermediate precision and their limits are derived from obtained experimental data. The uncertainty of the measurements was calculated on the base of an "empirical" method. The obtained values of accuracy indicate that the developed method allows measurement uncertainty extended from 2 to 20% depending on the analyzed compound and measured concentration.

  20. Health risks of alcohol use

    Science.gov (United States)

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  1. Interrelations between Pain and Alcohol: An Integrative Review

    Science.gov (United States)

    Zale, Emily L.; Maisto, Stephen A.; Ditre, Joseph W.

    2015-01-01

    Pain and alcohol use are both highly prevalent in the general population, and pain-alcohol interrelations are of increasing empirical interest. Previous research has identified associations between pain and alcohol dependence, and the current review provides novel contributions to this emerging domain by incorporating studies that have tested relations between pain and low-to-moderate alcohol consumption, and by identifying potential psychosocial mechanisms of action. Specifically, we sought to integrate evidence of pain-alcohol relations derived from two directions of empirical inquiry (i.e., effects of alcohol on pain and effects of pain on alcohol use) across psychological, social, and biological literatures. We observed converging evidence that associations between alcohol consumption and pain may be curvilinear in nature. Whereas moderate alcohol use was observed to be associated with positive pain-related outcomes (e.g., greater quality of life), excessive drinking and alcohol use disorder appear to be associated with deleterious pain-related outcomes (e.g., greater pain severity). We also observed evidence that alcohol administration confers acute pain-inhibitory effects, and that situational pain may motivate alcohol consumption (e.g., drinking for pain-coping). Future research can inform theoretical and clinical applications through examination of temporal relations between pain and alcohol consumption, tests of hypothesized mechanisms, and the development of novel interventions. PMID:25766100

  2. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white...... men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence......, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1...

  3. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  4. Implicit Alcohol-Related Expectancies and the Effect of Context.

    Science.gov (United States)

    Monk, Rebecca L; Pennington, Charlotte R; Campbell, Claire; Price, Alan; Heim, Derek

    2016-09-01

    The current study examined the impact of varying pictorial cues and testing contexts on implicit alcohol-related expectancies. Seventy-six participants were assigned randomly to complete an Implicit Relational Assessment Procedure (IRAP) in either a pub or lecture context. The IRAP exposed participants to pictorial cues that depicted an alcoholic beverage in the foreground of a pub (alcohol-congruent stimuli) or university lecture theater (alcohol-incongruent stimuli), and participants were required to match both positive and negative alcohol-related outcome expectancies to these stimuli. Corresponding to a 4 × 2 design, IRAP trial types were included in the analysis as repeated-measure variables, whereas testing environment was input as a between-participants variable. Participants more readily endorsed that drinking alcohol was related to positive expectancies when responding to alcohol-congruent stimuli, and this was strengthened when participants completed the task in a pub. Moreover, they more readily confirmed that alcohol was related to negative expectancies when responding to alcohol-incongruent stimuli. These findings suggest that alcohol-related cues and environmental contexts may be a significant driver of positive alcohol-related cognitions, which may have implications for the design of interventions. They emphasize further the importance of examining implicit cognitions in ecologically valid testing contexts.

  5. Database Administrator

    Science.gov (United States)

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  6. Database Administrator

    Science.gov (United States)

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  7. [Representations of alcoholism in a former alcoholics' association: Alcoholics Anonymous].

    Science.gov (United States)

    Campos, Edemilson Antunes de

    2004-01-01

    This article is designed to review the representations of alcoholism provided by members of an association of former alcoholics, namely Alcoholics Anonymous (AA), based on partial results from a qualitative survey conducted in the Sapopemba group of AA in a neighborhood on the outskirts of the city of Sao Paulo, Brazil. The article thus analyzes alcoholism from an emic perspective, i.e., how it is conceived and managed by those who acknowledge themselves as being "sick as alcoholics", how they explain the sickness, how they experience it, and how they endeavor to overcome it. The purpose is to present AA and its treatment strategy and to highlight the link made by the association by conceiving of alcoholism as a physical, moral, and spiritual illness.

  8. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  9. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  10. 27 CFR 22.20 - Delegations of the Administrator.

    Science.gov (United States)

    2010-04-01

    ... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Administrative Provisions Authorities § 22.20 Delegations of the Administrator. The regulatory authorities of the... in TTB Order 1135.22, Delegation of the Administrator's Authorities in 27 CFR Part 22,...

  11. 31 CFR 8.62 - Administrative Law Judge.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Administrative Law Judge. 8.62... BUREAU OF ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.62 Administrative Law Judge. (a) Appointment. An Administrative Law Judge, appointed as provided by 5 U.S.C. 3105, shall conduct...

  12. Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

    Science.gov (United States)

    Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

    2014-07-01

    In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Effect of oral alcohol on left ventricular ejection fraction, volumes, and segmental wall motion in normals and in patients with recent myocardial infarction.

    Science.gov (United States)

    Gould, L; Gopalaswamy, C; Yang, D; Patel, D; Kim, B S; Patel, C; Becker, W H

    1985-11-01

    A first-pass nuclear angiogram and a multiple-gated acquisition study were obtained in 10 normal physicians and in 10 patients with a 7-to-10 day old transmural myocardial infarction. After the scan the subjects drank 2 oz. of whiskey. After 60 minutes, the multiple-gated acquisition study was repeated. In the normal group the left ventricular ejection fraction was 68% before and 72% after alcohol. The left ventricular end-diastolic volume increased from 89 to 97 ml while the left ventricular end-systolic volume decreased from 29 to 27 ml. The stroke volume rose from 61 to 70 ml/beat (p less than 0.05). The cardiac output increased from 4.0 to 5.0 l/min (p less than 0.05). In the infarction group, the left ventricular ejection fraction was 58% before and 56% after alcohol administration. The left ventricular end-diastolic volume fell from 111 to 96 ml, while the left ventricular end-systolic volume declined from 50 to 44 ml. The stroke volume fell from 61 to 52 ml/beat, while the cardiac output fell from 4.5 to 3.8 l/min. In the left ventricular infarction zones, alcohol produced in 9 of the 10 cardiac patients a decline in the left ventricular regional ejection fraction. In the normal group, alcohol produced no significant changes in the regional ejection fraction. The normal and the postinfarction patients responded differently to alcohol.

  14. Alcohol and Breastfeeding

    DEFF Research Database (Denmark)

    Haastrup, Maija Bruun; Pottegård, Anton; Damkier, Per

    2014-01-01

    While the harmful effects of alcohol during pregnancy are well-established, the consequences of alcohol intake during lactation have been far less examined. We reviewed available data on the prevalence of alcohol intake during lactation, the influence of alcohol on breastfeeding......, the pharmacokinetics of alcohol in lactating women and nursing infants and the effects of alcohol intake on nursing infants. A systematic search was performed in PubMed from origin to May 2013, and 41 publications were included in the review. Approximately half of all lactating women in Western countries consume...... alcohol while breastfeeding. Alcohol intake inhibits the milk ejection reflex, causing a temporary decrease in milk yield. The alcohol concentrations in breast milk closely resemble those in maternal blood. The amount of alcohol presented to nursing infants through breast milk is approximately 5...

  15. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  16. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  17. Alcohol and Group Formation: A Multimodal Investigation of the Effects of Alcohol on Emotion and Social Bonding

    OpenAIRE

    Sayette, Michael A.; Creswell, Kasey G.; Dimoff, John D.; Fairbairn, Catharine E.; Cohn, Jeffrey F.; Heckman, Bryan W.; Kirchner, Thomas R.; Levine, John M.; Moreland, Richard L.

    2012-01-01

    We integrated research on emotion and on small groups to address a fundamental and enduring question facing alcohol researchers: What are the specific mechanisms that underlie the reinforcing effects of drinking? In one of the largest alcohol-administration studies yet conducted, we employed a novel group-formation paradigm to evaluate the socioemotional effects of alcohol. Seven hundred twenty social drinkers (360 male, 360 female) were assembled into groups of 3 unacquainted persons each an...

  18. Effects of Alcohol Cues and Alcohol Intoxication on Drug Use Expectancies Among Men Who Have Sex With Men

    OpenAIRE

    2013-01-01

    Although alcohol and drug use have been identified as HIV-risk factors for men who have sex with men (MSM), little is known about how they interact. An alcohol administration paradigm was used to examine alcohol’s cue and pharmacological effects on perceived drug use benefits and consequences in 117 MSM. Planned contrasts indicated that those in the alcohol cue (i.e., placebo) condition reported lower perceived drug consequences compared to controls. No cue effects were found for drug benefit...

  19. A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kokubo Takeshi

    2013-02-01

    Full Text Available Abstract Background Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. Methods This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA, and a profile of mood states (POMS and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase. In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. Results There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. Conclusions Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the

  20. 78 FR 37991 - Alcohol and Controlled Substances Testing

    Science.gov (United States)

    2013-06-25

    ... approaches that maximize net benefits (including potential economic, environmental, public health and safety... Federal Transit Administration 49 CFR Part 655 RIN 2132-AB09 Alcohol and Controlled Substances Testing... to revise sections of the Alcohol and Controlled Substances (D&A) Testing regulation to...

  1. 21 CFR 862.3050 - Breath-alcohol test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath-alcohol test system. 862.3050 Section 862.3050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... diagnosis of alcohol intoxication. (b) Classification. Class I....

  2. 32 CFR 634.34 - Blood alcohol concentration standards.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Blood alcohol concentration standards. 634.34 Section 634.34 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... alcohol concentration standards. (a) Administrative revocation of driving privileges and other enforcement...

  3. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  4. Ivermectin reduces alcohol intake and preference in mice

    Science.gov (United States)

    Yardley, Megan; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah A.; Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.

    2012-01-01

    The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs. PMID:22465817

  5. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes.

    Science.gov (United States)

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten

    2008-06-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

  6. Deciding to quit drinking alcohol

    Science.gov (United States)

    ... quitting drinking; Quitting drinking; Quitting alcohol; Alcoholism - deciding to quit ... drinking problem when your body depends on alcohol to function and your drinking is causing problems with ...

  7. Administrative contracts

    Directory of Open Access Journals (Sweden)

    Vukićević-Petković Milica

    2015-01-01

    Full Text Available Administrative contracts are a special type of contract where usually one of the contracting parties is a public law body and which is concluded for the performance of public service and the realization of a public interest. They go a long way since its inception to its eventual final acceptance of all the legal systems. One of the enduring characteristics of this type of contract is their disquised or unnoticed existence. This is why only monitoring their development may lead to a complete understanding of the importance and essence of this institution as well as the need for its complete legal regulation.

  8. Alcohol Dependence and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Karl Mann

    2015-01-01

    Full Text Available Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of alcoholic liver disease (ALD is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE has significantly improved the early diagnosis of alcoholic liver cirrhosis (ALC. As demonstrated in the literature, inflammation-associated liver stiffness (LS rapidly decreases during alcohol detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of nalmefene in reducing alcohol consumption. Patients with a high or very high drinking risk level (DRL at baseline and randomisation show a clinically significant effect from nalmefene treatment, which is generally well tolerated. Moreover, reduced alcohol consumption supported by nalmefene in combination with psychosocial support may indeed help to reduce the alcohol-related burden and the large treatment gap.

  9. Postoperative repeated respiratory insufficiency and thyrotoxicosis in molar pregnancy.

    Science.gov (United States)

    Cekic, B; Geze, S; Ulusoy, H; Coskun, I; Erturk, E

    2012-06-01

    Following the removal of a hydatiform mole in a 34-year-old, 14-week pregnant patient, thyrotoxicosis and respiratory insufficiency attacks were twice unexpectedly repeated. The symptoms were resolved with the administration of plasmapheresis, antithyroid and β-blocker drugs and non-invasive mechanical ventilation; however, she was again operated due to prolonged elevated β-hCG.

  10. Interpersonal Violence and Alcohol and Other Drug Use. Infofacts/Resources

    Science.gov (United States)

    Higher Education Center for Alcohol and Other Drug Abuse and Violence Prevention, 2008

    2008-01-01

    Because alcohol and other drugs are involved in most acts of violence on campus, college and university administrators are under increasing pressure to acknowledge this connection and reduce alcohol consumption on campus. But because alcohol alone does not cause violence, campuses must also address other contributing factors. Since research has…

  11. 14 CFR 120.223 - Alcohol misuse information, training, and substance abuse professionals.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Alcohol misuse information, training, and substance abuse professionals. 120.223 Section 120.223 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... AND OPERATIONS DRUG AND ALCOHOL TESTING PROGRAM Alcohol Testing Program Requirements § 120.223...

  12. Consumo de alcohol alcoholismo

    OpenAIRE

    Rodríguez Páez, Pablo E.; Fundación Valle de Lili

    1999-01-01

    ¿Qué es el alcohol?/¿Cómo actual el alcohol en el organismo?/¿Qué efectos causa?/Efectos por el consumo crónico/¿El consumo de alcohol durante el embarazo afecta el embrión?/¿Qué otras consecuencias tiene el consumo de alcohol?/¿Cuándo se considera que una persona tiene problemas con su consumo de alcohol?/¿Cuándo se debe sospechar que alguien tiene problemas con el consumo de alcohol?/Características del saber beber adecuadamente?/¿Cuales son las alternativas de tratamiento para este problem...

  13. Stadium Alcohol Management: A Best Practices Approach

    Directory of Open Access Journals (Sweden)

    Richard Filce

    2016-03-01

    Full Text Available Sport managers have expressed the concern that the largest threat to fan safety emanates from alcohol overuse. A Turnkey Sports & Entertainment (2009 study asked 1,100 senior sport executives in the United States to rank various threats to fan safety. Alcohol abuse by unruly fans was listed by 62% of respondents, easily outpacing the next highest response of terrorism (18.73%. Previous studies have also identified an increase in violence and criminal activity relating to alcohol consumption at sporting events (Erickson et al., 2011; Menaker & Chaney, 2014. Intoxicated fans have been the source of numerous documented tort claims against vendors and facility owners (Bearman, 1983; Verni, 2006. Despite the known tort liability risk, administrators continue to make decisions without real evidence due to a lack of literature on alcohol policies at sporting events (Oster-Aaland & Neighbors, 2007. This paper will document the problems associated with alcohol consumption at sporting events, review current alcohol policies and barriers to the implementation of stricter policies, and conclude with research-based suggestions for best practices in stadium alcohol management relative to: policy and training, sales and marketing, tailgating, and detection and enforcement.

  14. Reducing impaired driving through the identification of Repeat Target Vehicles: A case study.

    Science.gov (United States)

    Stewart, James

    2012-02-01

    One of the most persistent groups of impaired drivers that are seemingly unaffected by social pressure, moral appeals, and the fear of arrest is that of the repeat impaired driver. This smaller group accounts for a disproportionate number of all impaired driving trips, often with high blood alcohol contents. New approaches are needed to identify and deal with the repeat impaired driver. We propose a method based on the discovery that almost 10% of all impaired driving calls for service involve repeat vehicles. Using the number of times a vehicle appears in our data, the average time to repeat, and the personality characteristics of the repeat impaired driver, we are able to create a comprehensive and predictive description of a Repeat Target Vehicle (RTV). Our method provides an opportunity to explore new and innovative crime reduction strategies that were never before possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  16. The Administration Proposal for Head Start Reauthorization. Joint Hearing on Examining Head Start and the Administration's Plans for Expanding and Improving It, before the Subcommittee on Children, Family, Drugs, and Alcoholism of the Committee on Labor and Human Resources, United States Senate and the Subcommittee on Human Resources of the Committee on Education and Labor. House of Representatives, One Hundred Third Congress, Second Session.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    These hearing transcripts present testimony concerning the Clinton Administration's plans to expand and improve Project Head Start. Testimony was heard from Senators Christopher J. Dodd, Dan Coats, Nancy Landon Kassebaum, Strom Thurmond, James M. Jeffords, and Harris Wofford, as well as Representatives Matthew G. Martinez and Susan Molinari, and…

  17. Evaluation of the CASPAR alcohol education curriculum.

    Science.gov (United States)

    DiCicco, L; Biron, R; Carifio, J; Deutsch, C; Mills, D J; Orenstein, A; Re, A; Unterberger, H; White, R E

    1984-03-01

    The CASPAR education-prevention program was initiated when experimental results indicated that a 5-hr alcohol education curriculum at a Catholic high school was able to reduce frequent intoxication among teenagers. Attempts to institutionalize such a program in the public schools shows that (1) alcohol education can generate widespread community and school support; (2) workshops can successfully train teachers to adopt a decision-making approach, though close supervision is needed to ensure that this approach is adhered to in classroom teaching; (3) the CASPAR model of alcohol education produces classroom situations conducive to many children feeling free to express alcohol-related concerns; (4) trained teachers can serve as intermediaries between students with alcohol-related concerns and community resources, in particular those resources that are designed to help children from families with alcoholism; (5) the CASPAR curriculum, implemented by trained teachers, produces statistically significant knowledge and attitude gains, whereas alternate programs such as a special-events approach produce smaller knowledge gains and little attitude change; and (6) to a considerable extent, knowledge and attitude gains persist over time, although retention is greater on knowledge items and among older students. The results suggest that there may be a behavioral impact of instruction in the form of reduced alcohol misuse among teenagers, although if there is, it requires intensive and repeated exposure and can be demonstrated in these data only among younger students while they remain in junior high school. Although such results may be viewed as less supportive than the original experiment with which this work began, they do suggest that alcohol education remains an effective prevention strategy.

  18. Alcohol homograph priming in alcohol-dependent inpatients

    NARCIS (Netherlands)

    Woud, M.L.; Salemink, E.; Gladwin, T.E.; Wiers, R.W.H.J.; Becker, E.S.; Lindenmeyer, J.; Rinck, M.

    2016-01-01

    Aim: Alcohol dependency is characterized by alcohol-related interpretation biases (IBs): Individuals with high levels of alcohol consumption generate more alcohol-related than alcohol-unrelated interpretations in response to ambiguous alcohol-related cues. However, a response bias could be an altern

  19. Alcohol Use and Older Adults

    Science.gov (United States)

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  20. ADMINISTRATIVE CIRCULARS

    CERN Multimedia

    Division des ressources humaines

    2000-01-01

    N° 2 (Rev. 1) - March 2000Guidelines and procedures concerning recruitment and probation period of staff membersN° 9 (Rev. 2) - March 2000Staff members contractsN° 16 (Rev. 2) - January 2000TrainingN° 30 (Rev. 1) - January 2000Indemnities and reimbursements upon taking up appointment and termination of contractN° 32 - February 2000Principles and procedures governing complaints of harassmentThese circular have been amended (No 2, N° 9, N° 16 and N° 30) or drawn up (N° 32).Copies are available in the Divisional Secretariats.Note:\tAdministrative and operational circulars, as well as the lists of those in force, are available for consultation in the server SRV4_Home in the Appletalk zone NOVELL (as GUEST or using your Novell username and password), volume PE Division Data Disk.The Word files are available in the folder COM, folder Public, folder ADM.CIRC.docHuman Resources DivisionTel. 74128

  1. Safety evaluation of SMMU-16, a biosimilar of HUMIRA, in Cynomolgus monkeys following a 4-week repeated administration%阿达木单抗类似药SMMU-16皮下注射对食蟹猴的重复给药毒性研究

    Institute of Scientific and Technical Information of China (English)

    谷晓蕾; 马秀娟; 弓雪莲; 张晓芳; 袁伯俊; 陆国才

    2015-01-01

    Objective To evaluate the toxicity of SMMU-16, a biosimilar of HUMIRA, in Cynomolgus monkeys following repeated subcutaneous administration. Methods According to the body weight, thirty healthy Cynomol-gus monkeys were randomly divided into 5 groups with 6 animals (half male and half female) in each group. Animals were subcutaneously treated once a week for 4 weeks with SMMU-16 (10 ,33 or 200 mg/kg), HUMIRA (33 mg/kg) or vehicle solution following a recovery period of 4 weeks. The injection volume was 4.0 ml/kg in all groups. Toxicological indexes were recorded during the testing. Results Compared with d0 (before administration) in the same group, RBC, Hb, HCT decreased significantly in SMMU-16 33, 200 mg/kg group and HUMIRA 33 mg/kg group, and the proportion of reticulo-cyte increased significantly in SMMU-16 33, 200 mg/kg group (P<0.05). Mild hyperplasia of bone marrow red cells were also found in these groups. Histopathological examination indicated thymic and splenic atrophy in SMMU -16 33, 200 mg/kg group and HUMIRA 33 mg/kg group at the end of the treatment. The above changes were reversible at the end of recovery period. The other indexes were not affected by the drug administration. Conclusion The main toxic target organs of SMMU-16 are immune system (thymus and spleen) and hematological system (erythrocyte series), and all the toxic effects are reversible. The NOAEL of SMMU-16 with continuous subcutaneous injection (4 weeks, once a week) is 10 mg/kg. The toxicities of SMMU-16 are comparable to those of HUMIRA at the same dose.%目的:探讨阿达木单抗类似药SMMU-16重复皮下注射对食蟹猴的安全性。方法30只健康食蟹猴按体重随机分为溶媒对照组,阳性对照组,SMMU-16低、中、高剂量组,其中SMMU-16低、中、高剂量组分别给予SMMU-1610、33、200 mg/kg,每组6只,雌雄各半。阳性对照组给予33.0 mg/kg 阿达木单抗,溶媒对照组给予SM-MU-16空白溶液。给药体积均为4.0 ml

  2. Alcohol and Cancer Risk

    Science.gov (United States)

    ... is through the activity of an enzyme called alcohol dehydrogenase, or ADH. Many individuals of Chinese, Korean, and ... Abstract] Yokoyama A, Omori T. Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck ...

  3. Alcohol Facts and Statistics

    Science.gov (United States)

    ... Standard Drink? Drinking Levels Defined Alcohol Facts and Statistics Print version Alcohol Use in the United States: ... 1245, 2004. PMID: 15010446 11 National Center for Statistics and Analysis. 2014 Crash Data Key Findings (Traffic ...

  4. Alcohol in moderation

    DEFF Research Database (Denmark)

    Mueller, Simone; Lockshin, Larry; Louviere, Jordan J.

    2011-01-01

    Purpose: The study examines the market potential for low and very low alcohol wine products under two different tax regimes. The penetration and market share of low alcohol wine are estimated under both tax conditions. Consumers’ alcoholic beverage purchase portfolios are analysed and those...... products identified, which are jointly purchased with low alcohol wines. The effect of a tax increase on substitution patterns between alcoholic beverages is examined. Methodology: In a discrete choice experiment, based on their last purchase, consumers select one or several different alcoholic beverages...... volume is estimated under the current tax regime. Between six to eight percent of consumers are expected to adopt low alcohol wine alternatives as part of their alcoholic beverage portfolio. Consumers of cask wine and light beer are more likely and consumers of medium-full strength beer and spirits...

  5. Benzyl Alcohol Topical

    Science.gov (United States)

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  6. Alcohol Use Screening

    Science.gov (United States)

    ... Centers Diseases + Condition Centers Mental Health Medical Library Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  7. Women and Alcohol

    Science.gov (United States)

    ... turn JavaScript on. Feature: Rethinking Drinking Women and Alcohol Past Issues / Spring 2014 Table of Contents Women react differently than men to alcohol and face higher risks from it. Pound for ...

  8. Children of alcoholics

    Directory of Open Access Journals (Sweden)

    Robert Oravecz

    2002-09-01

    Full Text Available The author briefly interprets the research – results, referring to the phenomenon of children of alcoholics, especially the psychological and psychopathological characteristics of children of alcoholics in adolescence and young adulthood. The author presents a screening study of adolescents. The sample contains 200 high school students at age 18. The aim of the survey was to discover the relationship between alcohol consumption of parents, PTSD - related psychopathological symptoms and reported life quality of their children. The study confirmed the hypothesis about a substantial correlation between high alcohol consumption of parents, higher psychopathological symptom - expression and lower reported life quality score of their children. Higher PTSD-related symptomatology in children of alcoholics is probably resulted by home violence, which is very often present in family of alcoholics. The article also evaluated the results regarding suicide ideation of children of alcoholics, which is definitely more frequent and more intense than in their peers living in non alcohol – dependent families.

  9. Sodium oxybate in maintaining alcohol abstinence in alcoholic patients with and without psychiatric comorbidity.

    Science.gov (United States)

    Caputo, Fabio; Francini, Sara; Brambilla, Romeo; Vigna-Taglianti, Federica; Stoppo, Michela; Del Re, Arfedele; Leggio, Lorenzo; Addolorato, Giovanni; Zoli, Giorgio; Bernardi, Mauro

    2011-06-01

    Sodium oxybate (SMO) is a GABA-ergic drug currently used for the treatment of alcohol-dependence in some European countries. In particular, clinical studies have shown a role of SMO in promoting alcohol abstinence, as well as in relieving withdrawal symptoms. The aim of this study was to describe alcohol abstinence and the onset of craving for and abuse of SMO in alcohol-dependent subjects with and without psychiatric co-morbidity. Forty-eight patients were enrolled and classified into two groups: group A (20 alcoholics without any psychiatric co-morbidity) and group B (28 alcoholics with a psychiatric co-morbidity). All patients were treated with oral SMO (50 mg/kg of body weight t.i.d.) for 12 weeks. Alcohol abstinence as well as alcohol drinking during the 12 weeks of treatment did not differ between the two groups at the end of treatment (p=0.9). In addition, a reduction of alcohol intake in both groups has been observed (pcraving for SMO was significantly more frequent in group B than group A (p=0.001). Cases of SMO abuse were observed in almost 10% of group B patients. In conclusion, alcohol abstinence achieved through SMO administration does not differ in patients with and without psychiatric co-morbidity. However, alcoholics with co-morbid borderline disorders appear to be at high risk of developing craving for and abuse of the drug; therefore, SMO may not be indicated in these patients. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Functional significance of subjective response to alcohol across levels of alcohol exposure.

    Science.gov (United States)

    Bujarski, Spencer; Hutchison, Kent E; Prause, Nicole; Ray, Lara A

    2017-01-01

    Pre-clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol-dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non-treatment-seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light-to-moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post-alcohol administration. However, stimulation was dose-dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose-dependently associated with and preceded craving among non-dependent HD.

  11. Alcohol and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Gao Yinglan; Song Jingyu; Jin Junshuo; Zhong Xiuhong; Ren Xiangshan; Liu Shuangping

    2005-01-01

    Objectives To study the relationship between alcohol and atherosclerosis (AS).Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS.Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis,which could lead to AS.

  12. Cardiovascular Responses and Differential Changes in Mitogen-Activated Protein Kinases Following Repeated Episodes of Binge Drinking

    Science.gov (United States)

    Gu, Lianzhi; Fink, Anne M.; Chowdhury, Shamim A.K.; Geenen, David L.; Piano, Mariann R.

    2013-01-01

    Aims: Excessive alcohol use in the form of binge drinking is associated with many adverse medical outcomes. Using an animal model, the primary objective of this study was to determine the effects of repeated episodes of binge drinking on myocardial structure, blood pressure (BP) and activation of mitogen-activated protein kinases (MAPKs). The effects of carvedilol, a beta-adrenergic blocker, were also examined in this animal model of binge drinking. Methods: Rats were randomized into three groups: control, binge and binge + carvedilol (20 mg/kg). Animals received intragastric administration of 5 g ethanol/kg in the morning × 4 days (Monday–Thursday) followed by no ethanol on Friday–Sunday. Animals were maintained on the protocol for 5 weeks. BP was measured using radiotelemetry methods. Animals underwent echocardiography at baseline, 2.5 and 5 weeks. Myocardial MAPKs were analyzed at 5 weeks using western blot techniques. Results: Over the course of 5 weeks, binge drinking was associated with significant transient increases in BP that were greater at 4 and 5 weeks compared with earlier time points. Carvedilol treatment significantly attenuated the binge-induced transient increases in BP at 4 and 5 weeks. No significant changes were found in echocardiographic parameters at any time period; however, binge drinking was associated with increased phosphorylation of p38 MAPK, which was blocked by carvedilol treatment. Conclusion: Repeated episodes of binge drinking result in progressive and transient increases in BP, no change in myocardial structure and differential regulation of MAPK activation. PMID:22878590

  13. Fetal Alcohol Exposure

    Science.gov (United States)

    ... her child’s genetic make-up, and changes in gene activity caused by prenatal alcohol exposure. NIH . . . Turning Discovery Into Health ® National Institute on Alcohol Abuse and Alcoholism www. niaaa. nih. gov • 301.443.3860 Interventions ...

  14. Hispanic Alcoholic Treatment Considerations.

    Science.gov (United States)

    Costello, Raymond M.

    1987-01-01

    A path analytic model for Hispanic alcoholics relating socioclinical prognostic variables to outcome following treatment in a therapeutic community differs markedly from that fitted to Anglo alcoholics. The differential relationship of education to alcoholism severity and outcome was noted specifically as reflecting different racial-ethnic paths…

  15. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  16. Alcoholism and Lesbians

    Science.gov (United States)

    Gedro, Julie

    2014-01-01

    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  17. Television: Alcohol's Vast Adland.

    Science.gov (United States)

    2002

    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  18. Alcohol and plasma triglycerides.

    Science.gov (United States)

    Klop, Boudewijn; do Rego, Ana Torres; Cabezas, Manuel Castro

    2013-08-01

    This study reviews recent developments concerning the effects of alcohol on plasma triglycerides. The focus will be on population, intervention and metabolic studies with respect to alcohol and plasma triglycerides. Alcohol consumption and fat ingestion are closely associated and stimulated by each other via hypothalamic signals and by an elevated cephalic response. A J-shaped relationship between alcohol intake and plasma triglycerides has been described. A normal body weight, polyphenols in red wine and specific polymorphisms of the apolipoprotein A-V and apolipoprotein C-III genes may protect against alcohol-associated hypertriglyceridemia. In contrast, obesity exaggerates alcohol-associated hypertriglyceridemia and therefore the risk of pancreatitis. High alcohol intake remains harmful since it is associated with elevated plasma triglycerides, but also with cardiovascular disease, alcoholic fatty liver disease and the development of pancreatitis. Alcohol-induced hypertriglyceridemia is due to increased very-low-density lipoprotein secretion, impaired lipolysis and increased free fatty acid fluxes from adipose tissue to the liver. However, light to moderate alcohol consumption may be associated with decreased plasma triglycerides, probably determined by the type of alcoholic beverage consumed, genetic polymorphisms and lifestyle factors. Nevertheless, patients should be advised to reduce or stop alcohol consumption in case of hypertriglyceridemia.

  19. Alcohol and Minority Youth.

    Science.gov (United States)

    Wright, Roosevelt, Jr.; Watts, Thomas D.

    1991-01-01

    Maintains that minority youth who use (or abuse) alcohol in American society deal with using alcohol, being minority, and being young, three dimensions viewed by society with mixed, sometimes hostile and/or fearful reactions. Suggests that examining alcoholism among minority youth involves coming to grips with poverty, education, income, and life…

  20. 75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

    Science.gov (United States)

    2010-01-12

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... percent for drugs and 0.15 percent for alcohol. Because the industry-wide random drug testing positive... (Administrator) has determined that the minimum annual random drug testing rate for the period January 1, 2010...

  1. Preventing alcohol use with a universal school-based intervention: results from an effectiveness study.

    Science.gov (United States)

    Strøm, Henriette Kyrrestad; Adolfsen, Frode; Handegård, Bjørn Helge; Natvig, Henrik; Eisemann, Martin; Martinussen, Monica; Koposov, Roman

    2015-04-09

    The effectiveness of the universal school-based alcohol prevention program "Unge & Rus" [Youth & Alcohol] was tested by an independent research group. The program aims to prevent alcohol use and to change adolescents' alcohol-related attitudes. The main outcome measure was frequency of monthly alcohol use, favorable alcohol attitudes, perceived behavioral control (PBC), positive alcohol expectancy and alcohol-related knowledge. Junior high school students (N = 2,020) with a mean age of 13.5 years participated in this longitudinal pre, post and one-year follow-up study with a quasi-experimental design, involving an intervention group and a comparison group recruited from 41 junior high schools in Norway. Multilevel analysis was used to account for the repeated observations (level 1) nested within students (level 2) who in turn were clustered within school classes (level 3). Results showed an increased level of alcohol-related knowledge in the intervention group (p alcohol use, alcohol-related attitudes, PBC or alcohol expectancy at one-year follow-up. This study offers adequate data on the effectiveness of a school-based alcohol prevention program widely implemented in Norway. Under its current method of implementation, use of the program cannot be supported over the use of standard alcohol curriculum within schools.

  2. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    Science.gov (United States)

    2008-01-01

    animals that died, respiratory arrest was the cause. The acute i.p. LD(50) for 15 ml/kg of Brucine base was 62.0 mg/kg, with central nervous system depression prior to the onset of convulsions, just as with oral Brucine. The acute intravenous (i.v.) LD(50) was 12.0 mg/kg. Brucine was nonmutagenic in an Ames assay at levels up to 6666 mu g/plate, with and without metabolic activation. In a repeat-insult patch test, for a hair care product containing 47% SD Alcohol 40 (95%), it was reported that Brucine Sulfate may be considered a nonprimary irritant and a nonprimary sensitizer. Three different sunscreen products (35% SD Alcohol 40-B, 72.4% SD Alcohol 40, and 74.5% SD Alcohol 40) did not show any signs of photoallergy in human subjects. Also, these three formulas did not exhibit any evidence of phototoxicity in humans. Denatonium Benzoate is a bitter substance detectable at a concentration of 10 ppb, discernibly bitter at 50 ppb, and unpleasantly bitter at 10 ppm. The distribution of topically applied lidocaine, a topical anesthetic chemically related to Denatonium Benzoate demonstrated that virtually no lidocaine appears in the plasma, suggesting that the larger Denatonium Benzoate molecule also would have little or no systemic exposure. Denatonium Benzoate (0.1%) did not show adverse effects in 10 rats in an acute inhalation toxicity test and 0.005% to 0.05% was nonirritating to ocular mucosa in 6 albino rabbits. The acute oral LD(50) for the male rats was 640 mg/kg and for females, 584 mg/kg. The LD(50) for the male rabbits was 508 mg/kg and for the female rabbits, 640 mg/kg. In two chronic toxicity studies, Denatonium Benzoate was administered (by gavage) at 1.6, 8, and 16 mg/kg/day, one using cynomologus monkeys and the other rats, resulted in no compound-related toxicity. The toxicity of SD Alcohols has also been tested, with implications for the particular denaturant used. An irritation test of 55.65% SD Alcohol 40-B denatured with Denatonium Benzoate using rabbits

  3. Impulsivity moderates the association between racial discrimination and alcohol problems.

    Science.gov (United States)

    Latzman, Robert D; Chan, Wing Yi; Shishido, Yuri

    2013-12-01

    Alcohol use among university students is a serious public health concern, particularly among minority students who may use alcohol to cope with experiences of racial discrimination. Although the impact of racial discrimination on alcohol use has been well-established, individual differences in factors that may act to either attenuate or exacerbate the negative effects of racial discrimination are largely unknown. One potentially fruitful individual differences trait that has repeatedly been found to predict alcohol problems is the multidimensional personality trait of impulsivity. Nonetheless, the ways in which various aspects of impulsivity interact with racial discrimination is yet unknown. The current study, therefore, examined the joint and interactive contribution of racial discrimination and impulsivity in the prediction of alcohol consumption among racial minority university students. Participants included 336 Black/African-American and Asian/Asian-American university students. Results revealed both racial discrimination and impulsivity to be significantly associated with alcohol problems. Further, individuals' responses to racial discrimination were not uniform. Specifically, the association between racial discrimination and alcohol problems was moderated by lack of Premeditation; racial discrimination was most strongly predictive of alcohol problems for those who reported low level of premeditation. Findings from the present study highlight the importance of investigating risk factors for alcohol problems across multiple levels of the ecology as individual personality traits appear to relate to how one might respond to the experience of racial discrimination. © 2013.

  4. Fragrance material review on β-methylphenethyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of β-methylphenethyl alcohol when used as a fragrance ingredient is presented. β-Methylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for β-methylphenethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Fragrance material review on α-isobutylphenethyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of α-isobutylphenethyl alcohol when used as a fragrance ingredient is presented. α-Isobutylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-isobutylphenethyl alcohol were evaluated then summarized and includes physical properties, skin sensitization, and repeated dose data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Fragrance material review on α-methylbenzyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of α-methylbenzyl alcohol when used as a fragrance ingredient is presented. α-Methylbenzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α-methylbenzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Fragrance material review on α,α-dimethylphenethyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of α,α-dimethylphenethyl alcohol when used as a fragrance ingredient is presented. α,α-Dimethylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for α,α-dimethylphenethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, and repeated dose data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al., 2012 for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Acute effects of nicotine on alcohol cue-reactivity in nondependent and dependent smokers.

    Science.gov (United States)

    McGrath, Daniel S; Peloquin, Marcel P; Ferdinand, Justin C; Barrett, Sean P

    2015-02-01

    Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  9. Geosat Exact Repeat Mission Waveform Data Records (WDR) (NODC Accession 0061150)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains waveform data records (WDRs) from the US Navy Geodetic Satellite (GEOSAT) Exact Repeat Mission (ERM) for the time period of November 08,...

  10. Genetics and alcoholism.

    Science.gov (United States)

    Edenberg, Howard J; Foroud, Tatiana

    2013-08-01

    Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

  11. The role of neuroimmune signaling in alcoholism.

    Science.gov (United States)

    Crews, Fulton T; Lawrimore, Colleen J; Walter, T Jordan; Coleman, Leon G

    2017-08-01

    Alcohol consumption and stress increase brain levels of known innate immune signaling molecules. Microglia, the innate immune cells of the brain, and neurons respond to alcohol, signaling through Toll-like receptors (TLRs), high-mobility group box 1 (HMGB1), miRNAs, pro-inflammatory cytokines and their associated receptors involved in signaling between microglia, other glia and neurons. Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders. Studies employing anti-oxidant, anti-inflammatory, anti-depressant, and innate immune antagonists further link innate immune gene expression to addiction-like behaviors. Innate immune molecules are novel targets for addiction and affective disorders therapies. This article is part of the Special Issue entitled "Alcoholism". Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. [Physical diseases in alcoholism].

    Science.gov (United States)

    Takase, Kojiro

    2015-09-01

    Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life.

  13. Alcohol and atherosclerosis

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Grønbaek, Morten

    2007-01-01

    (CHD). The cardioprotective effect of alcohol seems to be larger among middle-aged and elderly adults than among young adults, who do not have a net beneficial effect of a light to moderate alcohol intake in terms of reduced all-cause mortality. The levels of alcohol at which the risk of CHD is lowest......Light to moderate alcohol intake is known to have cardioprotective properties; however, the magnitude of protection depends on other factors and may be confined to some subsets of the population. This review focuses on factors that modify the relationship between alcohol and coronary heart disease...... and the levels of alcohol at which the risk of CHD exceeds the risk among abstainers are lower for women than for men. The pattern of drinking seems important for the apparent cardioprotective effect of alcohol, and the risk of CHD is generally lower for steady versus binge drinking. Finally, there is some...

  14. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  15. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  16. Alcohol disrupts sleep homeostasis.

    Science.gov (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  17. Changes in the Influence of Alcohol-Paired Stimuli on Alcohol Seeking across Extended Training

    Science.gov (United States)

    Corbit, Laura H.; Janak, Patricia H.

    2016-01-01

    Previous work has demonstrated that goal-directed control of alcohol-seeking and other drug-related behaviors is reduced following extended self-administration and drug exposure. Here, we examined how the magnitude of stimulus influences on responding changes across similar training and drug exposure. Rats self-administered alcohol or sucrose for 2 or 8 weeks. Previous work has shown that 8 weeks, but not 2 weeks of self-administration produces habitual alcohol seeking. Next, all animals received equivalent Pavlovian conditioning sessions where a discrete stimulus predicted the delivery of alcohol or sucrose. Finally, the impact of the stimuli on ongoing instrumental responding was examined in a Pavlovian–instrumental transfer (PIT) test. While a significant PIT effect was observed following 2 weeks of either alcohol or sucrose self-administration, the magnitude of this effect was greater following 8 weeks of training. The specificity of the PIT effect appeared unchanged by extended training. While it is well established that evaluation of the outcome of responding contributes less to behavioral control following extended training and/or drug exposure, our data indicate that reward–predictive stimuli have a stronger contribution to responding after extended training. Together, these findings provide insight into the factors that control behavior after extended drug use, which will be important for developing effective methods for controlling and ideally reducing these behaviors. PMID:27777560

  18. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

    Science.gov (United States)

    Fritz, Brandon M; Boehm, Stephen L

    2014-12-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance.

  19. The current situation of treatment systems for alcoholism in Korea.

    Science.gov (United States)

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun

    2013-02-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

  20. Alcohol and pregnancy

    Directory of Open Access Journals (Sweden)

    Anna Maria Paoletti

    2013-06-01

    Full Text Available Alcohol exerts teratogenic effects in all the gestation times, with peculiar features in relationship to the trimester of pregnancy in which alcohol is assumed. Alcohol itself and its metabolites modify DNA synthesis, cellular division, cellular migration and the fetal development. The characteristic facies of feto-alcoholic syndrome (FAS-affected baby depends on the alcohol impact on skull facial development during the first trimester of pregnancy. In association there are cerebral damages with a strong defect of brain development up to the life incompatibility. Serious consequences on fetal health also depends on dangerous effects of alcohol exposure in the organogenesis of the heart, the bone, the kidney, sensorial organs, et al. It has been demonstrated that maternal binge drinking is a high factor risk of mental retardation and of delinquent behaviour. Unfortunately, a lower alcohol intake also exerts deleterious effects on fetal health. In several countries of the world there is a high alcohol use, and this habit is increased in the women. Therefore, correct information has to be given to avoid alcohol use by women in the preconceptional time and during the pregnancy. Preliminary results of a study performed by the authors show that over 80% of pregnant and puerperal women are not unaware that more than 2 glasses of alcohol/week ingested during pregnancy can create neurological abnormalities in the fetus. However, after the information provided on alcoholic fetopathy, all women are conscious of the damage caused by the use of alcohol to the fetus during pregnancy. This study confirms the need to provide detailed information on the negative effects of alcohol on fetal health. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  1. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  2. Alcohol Expectancies in Young Adult Sons of Alcoholics and Controls.

    Science.gov (United States)

    Brown, Sandra A.; And Others

    Adolescent offspring of alcoholics have been found to have higher alcohol reinforcement expectancies than do teenagers from nonalcoholic families. In particular, those with a positive family history of alcoholism expect more cognitive and motor enhancement with alcohol consumption. This study examined the alcohol expectancies of 58 matched pairs…

  3. Human health risk assessment of long chain alcohols (LCOH)

    DEFF Research Database (Denmark)

    Veenstra, Gauke; Sanderson, Hans; Webb, Catherine

    2009-01-01

    Representative chemicals from the long chain alcohols category have been extensively tested to define their toxicological hazard properties. These chemicals show low acute and repeat dose toxicity with high-dose effects (if any) related to minimal liver toxicity. These chemicals do not show evide...... of human health are documented for the uses of these chemicals. © 2008....

  4. Dihydrocodeine / Agonists for Alcohol Dependents

    Directory of Open Access Journals (Sweden)

    Albrecht eUlmer

    2012-03-01

    Full Text Available Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients.Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC to 102 heavily alcohol addict-ed patients, later, also Buprenorphine, Clomethiazole (>6 weeks, Baclofen and in one case Amphetamine, each on individual indication. This paper focuses on the data with DH, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC-treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-step scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details.Conclusions: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around ¼ of the patients already. Many further

  5. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    Science.gov (United States)

    Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

    2012-06-01

    Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol.

  6. Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats.

    Science.gov (United States)

    Bowen, Michael T; Carson, Dean S; Spiro, Adena; Arnold, Jonathon C; McGregor, Iain S

    2011-01-01

    Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33-42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A "booster" shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems.

  7. [Alcohol and nutrition].

    Science.gov (United States)

    Maillot, F; Farad, S; Lamisse, F

    2001-11-01

    Alcoholism and alcohol-associated organ injury is one of the major health problems worldwide. Alcohol may lead to an alteration in intermediary metabolism and the relation between alcohol intake and body weight is a paradox. The effect of alcohol intake on resting metabolic rate, assessed by indirect calorimetry, and lipid oxidation, is still controversial. Small quantities of ethanol seem to have no effect on body weight. Ingestion of moderate amounts may lead to an increase in body weight, via a lipid-oxidizing suppressive effect. Chronic intake of excessive amounts in alcoholics leads to a decrease in body weight, probably via increased lipid oxidation and energy expenditure. Chronic ethanol abuse alters lipid-soluble (vitamins A, D and E) and water-soluble (B-complex vitamins, vitamin C) vitamins status, and some trace elements status such as magnesium, selenium or zinc.

  8. Alcohol, aggression, and violence

    Directory of Open Access Journals (Sweden)

    Darja Škrila

    2005-09-01

    Full Text Available Background: The association between alcohol and aggression has long been recognized, but the systematic research to understand the causal basis for this relationship and the processes that underlie it has only been undertaken in the past 25 years. In the article the most important mechanisms, by which alcohol affects behavior, are explained. Aggression in persons with alcohol dependence and the connection between antisocial (dissocial personality disorder, alcohol and aggression are described. In addition different forms of aggression or violence, that have been committed under the influence of alcohol, such as inter-partner violence, sexual assault, child abuse, crime and traffic accidents are described.Conclusions: The research findings can be used in the prevention and treatment of alcohol-related aggression.

  9. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Murilo Foppa

    2001-02-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  10. Administration of Anesthesia

    Science.gov (United States)

    ... a Surgeon What We Do Administration of Anesthesia Administration of Anesthesia Oral and maxillofacial surgeons are extensively ... Injury Wisdom Teeth Management Procedures Administration of Anesthesia Administration of Anesthesia Oral and maxillofacial surgeons are extensively ...

  11. Alcohol-induced oxidative stress in rat liver microsomes: Protective effect of Emblica officinalis.

    Science.gov (United States)

    Reddy, Vaddi Damodara; Padmavathi, Pannuru; Hymavathi, Reddyvari; Maturu, Paramahamsa; Varadacharyulu, N Ch

    2014-06-01

    The protective effect of Emblica officinalis fruit extract (EFE) against alcohol-induced oxidative damage in liver microsomes was investigated in rats. EFE (250mg/kg b.wt/day) and alcohol (5g/kg b.wt/day, 20%, w/v) were administered orally to animals for 60 days. Alcohol administration significantly increased lipid peroxidation, protein carbonyls with decreased sulfhydryl groups in microsomes, which were significantly restored to normal levels in EFE and alcohol co-administered rats. Alcohol administration also markedly decreased the levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in the liver microsomes, which were prevented with EFE administration. Further, alcohol administration significantly increased the activities of cytochrome P-450, Na(+)/K(+) and Mg(2+) ATPases and also membrane fluidity. But, administration of EFE along with alcohol restored the all above enzyme activities and membrane fluidity to normal level. Thus, EFE showed protective effects against alcohol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and restoring the various membrane bound and antioxidant enzyme activities to normal levels, and also by protecting the membrane integrity in rat liver microsomes. In conclusion, the polyphenolic compounds including flavonoid and tannoid compounds present in EFE might be playing a major role against alcohol-induced oxidative stress in rats.

  12. Alcohol use and menopause.

    Science.gov (United States)

    Wilsnack, Richard W; Wilsnack, Sharon C

    2016-04-01

    Clinicians should periodically assess their menopausal patients' alcohol use. Specific health hazards from excessive alcohol consumption, as well as potential benefits of low-level consumption (for cardiovascular disease, bone health, and type 2 diabetes), should be discussed with their patients who drink. The information in this Practice Pearl can help clinicians provide evidence-based guidance about alcohol consumption and its relationship to common health concerns.

  13. Alcoholism and Diabetes Mellitus

    OpenAIRE

    Soo-Jeong Kim; Dai-Jin Kim

    2012-01-01

    Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect i...

  14. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  15. Affordability of alcohol and alcohol-related mortality in Belarus.

    Science.gov (United States)

    Razvodovsky, Yury E

    2013-01-01

    Alcohol abuse has numerous adverse health and social consequences. The consumer response to changes in alcohol affordability is an important issue on alcohol policy debates. Studies from many countries have shown an inverse relationship between alcohol prices and alcohol consumption in the population. There are, however, suggestions that increasing the price of alcohol by rising taxes may have limited effect on alcohol-related problems, associated with long-term heavy drinking. The aim of the present study was to evaluate the relationship between alcohol affordability and alcohol-related mortality rates in post-Soviet Belarus. For this purpose trends in alcohol-related mortality rates (mortality from liver cirrhosis, pancreatitis, alcoholism and alcohol psychoses) and affordability of vodka between 1990 and 2010 were compared. The time series analysis revealed that 1% increase in vodka affordability is associated with an increase in liver cirrhosis mortality of 0,77%, an increase in pancreatitis mortality of 0.53%, an increase in mortality from alcoholism and alcohol psychoses of 0,70%. The major conclusion emerging from this study is that affordability of alcohol is one of the most important predictor of alcohol-related problems in a population. These findings provide additional evidence that decreasing in affordability of alcohol is an effective strategy for reducing alcohol consumption and alcohol-related harm.

  16. Administrative Law: The Hidden Comparative Law Course.

    Science.gov (United States)

    Strauss, Peter L.

    1996-01-01

    Argues that the main contribution of the Administrative Law course to law students is that it presents problems which contrast with those of the standard court-centered curriculum and can illuminate other areas of law, repeatedly confronting students with doctrinal differences. Offers several examples from civil procedure, constitutional law, and…

  17. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  18. Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with levetiracetam: a preliminary study.

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga; Bajer, Bartosz; Czarnecka, Elżbieta; Dyr, Wanda; Gorska, Dorota

    2011-03-28

    Many recent researches have confirmed the effectiveness of antiepileptic drugs in preventing alcohol dependency, whereas our previous study showed that repeated treatment with topiramate, a new antiepileptic drug, was effective in increasing the plasma levels of beta-endorphin (an endogenous opioid peptide) in rats. It is well documented that in humans a genetic deficit of beta-endorphin is often associated with alcohol addiction as alcohol consumption elevates the level of this peptide. The aim of the present study is multifaceted: to investigate the effect of repeated treatment of levetiracetam (50 or 100mg/kg b.w., twice daily) on voluntary alcohol intake in alcohol preferring rats (Warsaw High Preferring; WHP) and to assess changes in plasma beta-endorphin levels while alcohol is available and when it is not available for an extended period of time. We observed a noticeable increase in the levels of beta-endorphin in rats with free access to alcohol whether in a prolonged levetiracetam-treated or vehicle-treated group. However, in the levetiracetam group, a voluntary intake of alcohol diminished in comparison with both the pretreatment period and in comparison with the vehicle-treated rats. A similar increase in the plasma beta-endorphin levels was observed in levetiracetam-treated rats that did not have access to ethanol. This finding lets us to believe that levetiracetam may be a promising medication in treatment of alcohol dependency as its application leads to the increase in the beta-endorphin concentration and ultimately results in reducing deficiency of this peptide.

  19. A comparison of the anticipated and pharmacological effects of alcohol on cognitive bias, executive function, craving and ad-lib drinking.

    Science.gov (United States)

    Christiansen, Paul; Rose, Abigail K; Cole, Jon C; Field, Matt

    2013-01-01

    Acute alcohol administration alters automatic processing of alcohol-related cues, impairs executive functions and increases alcohol seeking. Few studies have investigated the effects of expecting to receive alcohol on these measures. Thirty-one social drinkers completed three experimental sessions receiving either 0.65 g/kg alcohol, a placebo and a control beverage (which they knew was not alcoholic) before reporting craving and completing a test battery including a measure of automatic alcohol-approach tendencies (stimulus response compatibility task), a measure of executive function (Controlled Oral Word Association Task (COWAT)) and a taste test assessing ad-lib drinking. Results indicated that alcohol administration impaired performance on the COWAT and increased ad-lib drinking; however, there were no significant differences on these measures after administration of placebo versus control beverages. Craving was increased after alcohol and (to a lesser extent) after placebo. Automatic alcohol-approach tendencies were pronounced after both alcohol and placebo compared to the control beverage, with no difference between alcohol and placebo. Results suggest craving is sensitive to the anticipated and pharmacological effects of alcohol, alcohol-approach tendencies are particularly sensitive to the anticipated effects of alcohol, and measures of executive function and ad-lib drinking are affected by the pharmacological, but not the anticipated, effects of alcohol.

  20. Measurement-based quantum repeaters

    CERN Document Server

    Zwerger, M; Briegel, H J

    2012-01-01

    We introduce measurement-based quantum repeaters, where small-scale measurement-based quantum processors are used to perform entanglement purification and entanglement swapping in a long-range quantum communication protocol. In the scheme, pre-prepared entangled states stored at intermediate repeater stations are coupled with incoming photons by simple Bell-measurements, without the need of performing additional quantum gates or measurements. We show how to construct the required resource states, and how to minimize their size. We analyze the performance of the scheme under noise and imperfections, with focus on small-scale implementations involving entangled states of few qubits. We find measurement-based purification protocols with significantly improved noise thresholds. Furthermore we show that already resource states of small size suffice to significantly increase the maximal communication distance. We also discuss possible advantages of our scheme for different set-ups.

  1. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  2. Initial subjective reward: Single-exposure conditioned place preference to alcohol in mice

    Directory of Open Access Journals (Sweden)

    Judith E. Grisel

    2014-11-01

    Full Text Available Most adults consume alcohol with relative impunity, but about 10-20% of users persist (or progress in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug’s reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction.

  3. Initial subjective reward: single-exposure conditioned place preference to alcohol in mice.

    Science.gov (United States)

    Grisel, Judith E; Beasley, John B; Bertram, Emma C; Decker, Brooke E; Duan, Chunyu A; Etuma, Mahder; Hand, Annie; Locklear, Mallory N; Whitmire, Matthew P

    2014-01-01

    Most adults consume alcohol with relative impunity, but about 10-20% of users persist (or progress) in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug's reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5 g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction.

  4. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  5. Alcohol Response and Consumption in Adolescent Rhesus Macaques: Life History and Genetic Influences

    Science.gov (United States)

    Schwandt, Melanie L.; Lindell, Stephen G.; Chen, Scott; Higley, J. Dee; Suomi, Stephen J.; Heilig, Markus; Barr, Christina S.

    2009-01-01

    The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Due to their extended period of adolescence, rhesus macaques are especially well-suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence. PMID:20113875

  6. Anticipatory 50 kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats.

    Science.gov (United States)

    Buck, Cara L; Malavar, Jordan C; George, Olivier; Koob, George F; Vendruscolo, Leandro F

    2014-09-01

    Rats emit 50kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol's stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50kHz USVs may be an indicator of context-elicited negative reinforcement learning.

  7. Alcohol: A Women's Health Issue

    Science.gov (United States)

    ... to drink than their peers. Staying Away From Alcohol. Young women under age 21 should not drink alcohol. ... talk frankly with their daughters about not drinking alcohol. Women in Young and Middle Adulthood Young women in their twenties ...

  8. Restraint stress enhances alcohol intake in adolescent female rats but reduces alcohol intake in adolescent male and adult female rats.

    Science.gov (United States)

    Wille-Bille, Aranza; Ferreyra, Ana; Sciangula, Martina; Chiner, Florencia; Nizhnikov, Michael E; Pautassi, Ricardo Marcos

    2017-08-14

    Adolescents may be more sensitive to stress-induced alcohol drinking than adults, which would explain the higher prevalence of alcohol abuse and dependence in late adolescence than in adulthood. The present study analyzed the impact of restraint stress on the initiation of alcohol intake across 2 weeks of intermittent, two-bottle choice intake in male and female adolescent rats and adult female rats. Restraint stress significantly increased alcohol intake and preference in female adolescent rats but decreased alcohol intake and preference in male adolescent and female adult rats. The effects of restraint stress on alcohol intake were mitigated in adolescent females following administration of the κ opioid receptor antagonist norbinaltorphimine. Adolescent but not adult female rats that were subjected to restraint stress spent more time on the open arms of the elevated plus maze. Female adolescents exposed to stress also exhibited greater risk-taking behaviors in a concentric square field test compared with non-stressed controls. These results indicate age- and sex-related differences in the sensitivity to alcohol-stress interactions that may facilitate the initiation of alcohol use in female adolescents. The facilitatory effect of stress on alcohol intake was related to greater exploratory and risk-taking behaviors in young females after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Alcohol and marijuana effects on ocular tracking.

    Science.gov (United States)

    Flom, M C; Brown, B; Adams, A J; Jones, R T

    1976-12-01

    Experienced alcohol and marijuana users were instructed to track with their eyes a small spot that moved horizontally back and forth in pendular (sinusoidal) motion across a 7.5-degree field. The frequency of spot oscillation was gradually increased from 0.5 to 3.0 Hz in 40 sec. Eye movement recordings showed the frequency at which smooth tracking and, soon thereafter, saccadic tracking broke down. These smooth and saccadic cutoff frequencies were reduced after administration of alcohol, but not after marijuana or placebo. For low alcohol doses, smooth tracking was impaired and saccadic tracking was unaffected, much like an effect previously reported for barbiturates. Alcohol seems to affect smooth tracking by increasing the central processing time required to generate the appropriate eye movement. It affects saccadic tracking by slightly decreasing saccadic velocity and to a greater extent by increasing latency time, part of which may be devoted to central processing. The site of action of alcohol appears to be central to both the paramedian pontine reticular formation and the flocculus of the cerebellum.

  10. Alcohol and atherosclerosis

    Directory of Open Access Journals (Sweden)

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  11. Leisure and Alcohol Expectancies.

    Science.gov (United States)

    Carruthers, Cynthia P.

    1993-01-01

    Presents the results of a study that investigated the ways individuals expected drinking to affect their leisure experiences, and the relationship of those expectancies to alcohol consumption patterns. Data from a sample of 144 adults indicated they expected alcohol to positively affect their leisure experiences. (SM)

  12. Pellagra In An Alcoholic

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available Pellagra is a nutritional disorder that occurs due to niacin deficiency. In the present day context, in western world, pellagra is confined to individuals who have improper food intake, such as psychiatry patients, alcoholics and recluses. Here with we report a case of pellagra occurring in a 60 year old male who was a chronic alcoholic.

  13. Alcohol and atherosclerosis

    DEFF Research Database (Denmark)

    Tolstrup, Janne; Grønbaek, Morten

    2007-01-01

    Light to moderate alcohol intake is known to have cardioprotective properties; however, the magnitude of protection depends on other factors and may be confined to some subsets of the population. This review focuses on factors that modify the relationship between alcohol and coronary heart diseas...

  14. Alcoholism and diabetes mellitus.

    Science.gov (United States)

    Kim, Soo-Jeong; Kim, Dai-Jin

    2012-04-01

    Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  15. Alcoholism and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Soo-Jeong Kim

    2012-04-01

    Full Text Available Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM, which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  16. Molecular basis of alcoholism.

    Science.gov (United States)

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.

  17. Children of Alcoholics

    Science.gov (United States)

    ... 11) • Abuse of drugs or alcohol; or • Aggression towards other children • Risk taking behaviors • Depression or suicidal thoughts or behavior Some children of alcoholics may cope by taking the role of responsible "parents" within the family and among friends. They may ...

  18. Alcohol, Medicines and Aging

    Science.gov (United States)

    ... declines with age, older people reach higher blood alcohol concentrations after each drink than younger people. Meanwhile, as we age we become more sensitive to some of the impairments alcohol produces. On tests that require ... younger adults after a few drinks. Similarly, balance, concentration, ...

  19. Alcohol Use and Cancer

    Science.gov (United States)

    ... a chemical that has been shown to cause cancer in lab animals. Alcohol and its byproducts can also damage the liver, leading to inflammation and scarring. As liver cells try to repair the ... to cancer. Effects on other harmful chemicals Alcohol may help ...

  20. Adolescents' Perceptions of Alcohol

    Science.gov (United States)

    Roy, Amit; Ikonen, Risto; Keinonen, Tuula; Kumar, Kuldeep

    2017-01-01

    Purpose: Rising trends in alcohol consumption and early drinking initiation pose serious health risks especially for adolescents. Learner's prior knowledge about alcohol gained from the social surroundings and the media are important sources that can impact the learning outcomes in health education. The purpose of this paper is to map adolescents'…

  1. Fetal Alcohol Spectrum Disorder

    Science.gov (United States)

    Caley, Linda M.; Kramer, Charlotte; Robinson, Luther K.

    2005-01-01

    Fetal alcohol spectrum disorder (FASD) is a serious and widespread problem in this country. Positioned within the community with links to children, families, and healthcare systems, school nurses are a critical element in the prevention and treatment of those affected by fetal alcohol spectrum disorder. Although most school nurses are familiar…

  2. Sulpiride Psychopharmacotherapy in Patients with Alcohol Addiction and Depression Comorbidity

    OpenAIRE

    2003-01-01

    Depression is quite common in the early stage of treatment for alcohol addiction. The patient's awareness of his difficult situation may be one of the reasons for depression. Furthermore, depression can develop as the result of depressive disorders that are primarily or secondarily associated with alcohol addiction. Antidepressive therapy is usually initiated after a two-week detoxification procedure. Only exceptionally it may start earlier in case of severe depressive disorder. The administr...

  3. Senior Administrators Should Have Administrative Contracts.

    Science.gov (United States)

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  4. Origin and fate of repeats in bacteria.

    Science.gov (United States)

    Achaz, G; Rocha, E P C; Netter, P; Coissac, E

    2002-07-01

    We investigated 53 complete bacterial chromosomes for intrachromosomal repeats. In previous studies on eukaryote chromosomes, we proposed a model for the dynamics of repeats based on the continuous genesis of tandem repeats, followed by an active process of high deletion rate, counteracted by rearrangement events that may prevent the repeats from being deleted. The present study of long repeats in the genomes of Bacteria and Archaea suggests that our model of interspersed repeats dynamics may apply to them. Thus the duplication process might be a consequence of very ancient mechanisms shared by all three domains. Moreover, we show that there is a strong negative correlation between nucleotide composition bias and the repeat density of genomes. We hypothesise that in highly biased genomes, non-duplicated small repeats arise more frequently by random effects and are used as primers for duplication mechanisms, leading to a higher density of large repeats.

  5. Alcoholic hallucinosis: case report

    Directory of Open Access Journals (Sweden)

    Bárbara Werner Griciunas

    2017-03-01

    Full Text Available Case report of patient who has been an alcoholic for 40 years and, after reducing alcohol intake, developed auditory and visual hallucinations, which caused behavior change. Neurological issues, electrolyte disturbances and other organ dysfunctions were excluded as cause of said change. After intake of haloperidol and risperidone, the patient had regression of symptoms and denied having presented hallucinatory symptoms. The Manual Diagnóstico e Estatístico de Transtornos Mentais – 5ª edição (DSM-V includes alcoholic hallucinosis in the Substance-Induced Psychotic Disorder (alcohol, beginning during abstinence; however, the document is not yet very well accepted among the medical community. The difficulty of the team to confirm the diagnosis of alcoholic hallucinosis lies in the differential diagnosis, as Delirium tremens and severe withdrawal syndrome with psychotic symptoms. Thus, psychopathological differentiation is important, as well as continuity of research and collaboration of other clinical teams in the evaluation.

  6. Alcohol consumption in adolescents

    Directory of Open Access Journals (Sweden)

    Ilona Plevová

    2016-03-01

    Full Text Available Aim: To determine the level of alcohol consumption in a selected group of adolescents. Design: A descriptive cross-sectional study. Methods: The data were obtained using a part of the standardized ESPAD questionnaire for assessing consumption of alcoholic beverages. The sample comprised 422 students from seven secondary schools of different types in the city of Ostrava. For statistical analysis, the chi-squared test and Fisher's exact test (for n ≤ 5 were used. The data were processed using Stata v. 10. Results: More than half of respondents first tried alcohol before the age of 15. The most frequent alcohol-related problems were unprotected sex, decreased school performance and problems with parents or friends. Incomplete families were found to be an important factor in adolescents preferring and more frequently drinking beer. Conclusion: The study confirmed results reported by the Europe-wide survey ESPAD, namely that adolescents start to drink alcohol as early as before they turn fifteen.

  7. Homocysteine and alcoholism.

    Science.gov (United States)

    Bleich, S; Degner, D; Javaheripour, K; Kurth, C; Kornhuber, J

    2000-01-01

    Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

  8. Development and validation of a scale of attitudes towards alcohol, alcoholism and alcoholics.

    Science.gov (United States)

    Vargas, Divane de; Luis, Margarita Antonia Villar

    2008-01-01

    The objective of this study was the construction and validation of a scale that would measure the attitudes towards alcohol, alcoholism and the alcoholic, called the Scale of Attitudes Towards Alcohol, Alcoholism and the Alcoholic. The face and content validations, as well as the factor analysis of the data obtained in a preliminary test with 144 nursing students resulted in a scale consisting of 96 items, divided into 5 factors: Attitudes towards the alcoholic person: care and interpersonal relations; Etiology; Disease; Repercussions deriving from alcohol use/abuse; Alcoholic beverages. The general scale presented a consistency level of 0.90. The resulting instrument is concluded to be a reliable tool to evaluate attitudes towards alcohol, alcoholism and alcohol addicts.

  9. Suppression by gamma-hydroxybutyric acid of alcohol deprivation effect in rats: Preclinical evidence of its anti-relapse properties

    Directory of Open Access Journals (Sweden)

    Giancarlo eColombo

    2012-11-01

    Full Text Available Gamma-hydroxybutyric acid (GHB reduces (a alcohol intake and alcohol motivational properties in alcohol-preferring rats and (b alcohol drinking and craving for alcohol in human alcoholics. The present study was designed to extend to relapse-like drinking the capacity of GHB to suppress different alcohol-related behaviors in alcohol-preferring rats. The alcohol deprivation effect, defined as the temporary increase in alcohol intake occurring in laboratory animals after a period of alcohol deprivation, was used as model of alcohol relapse. Acute administration of non-sedative doses of GHB (0, 100, 200, and 300 mg/kg, i.p. resulted in the complete suppression of the extra-amount of alcohol consumed by Sardinian alcohol-preferring (sP rats during the first hour of re-access to alcohol after a 14-day period of deprivation. These data demonstrate that GHB suppressed relapse-like drinking in a rat model of excessive alcohol consumption.

  10. Malnutrition and hospital prognosis in the alcoholic patient.

    Science.gov (United States)

    Bienia, R; Ratcliff, S; Barbour, G L; Kummer, M

    1982-01-01

    The nutritional status of 65 alcoholic patients admitted to the Medical Service of a Veterans Administration Hospital was evaluated and compared to that 87 nonalcoholic patients admitted during the same period of time. There was no statistical difference in the prevalence of malnutrition in the alcoholic population (36.9%) when compared to the nonalcoholic population (43.7%). The death rate and incidence of infection were similar in both populations as was the prevalence of anemia, depressed total lymphocyte count, and skin test anergy. Malnutrition, however, correlated with an increased death rate and incidence of infection, regardless of whether the patient was an alcoholic or not.

  11. 75 FR 57473 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-21

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse and Alcoholism, Office of Extramural Activities,...

  12. 78 FR 42530 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2013-07-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Initial Review..., Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism,...

  13. 75 FR 10808 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-09

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Officer, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, 5635...

  14. 75 FR 24961 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings

    Science.gov (United States)

    2010-05-06

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis... Extramural Activities, National Institutes of Health, National Institute on Alcohol Abuse & Alcoholism,...

  15. 75 FR 63494 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-15

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis..., Extramural Project Review Branch, EPRB, National Institute on Alcohol Abuse and Alcoholism,...

  16. Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice

    Science.gov (United States)

    Satishchandran, Abhishek; Iracheta-Vellve, Arvin; Ambade, Aditya; Kodys, Karen; Catalano, Donna; Ward, Doyle V.; Szabo, Gyongyi

    2017-01-01

    Background Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology. Materials and methods Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated. Results Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfα), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST). Conclusions Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an

  17. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  18. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  19. Alcohol industry self-regulation: who is it really protecting?

    Science.gov (United States)

    Noel, Jonathan; Lazzarini, Zita; Robaina, Katherine; Vendrame, Alan

    2017-01-01

    Self-regulation has been promoted by the alcohol industry as a sufficient means of regulating alcohol marketing activities. However, evidence suggests that the guidelines of self-regulated alcohol marketing codes are violated routinely, resulting in excessive alcohol marketing exposure to youth and the use of content that is potentially harmful to youth and other vulnerable populations. If the alcohol industry does not adhere to its own regulations the purpose and design of these codes should be questioned. Indeed, implementation of alcohol marketing self-regulation in Brazil, the United Kingdom and the United States was likely to delay statutory regulation rather than to promote public health. Moreover, current self-regulation codes suffer from vague language that may allow the industry to circumvent the guidelines, loopholes that may obstruct the implementation of the codes, lax exposure guidelines that can allow excessive youth exposure, even if properly followed, and a standard of review that may be inappropriate for protecting vulnerable populations. Greater public health benefits may be realized if legislative restrictions were applied to alcohol marketing, and strict statutory alcohol marketing regulations have been implemented and defended successfully in the European Union, with European courts declaring that restrictions on alcohol marketing are proportional to the benefits to public health. In contrast, attempts to restrict alcohol marketing activities in the United States have occurred through private litigation and have been unsuccessful. None the less, repeated violations of industry codes may provide legislators with sufficient justification to pass new legislation and for such legislation to withstand constitutional review in the United States and elsewhere. © 2016 Society for the Study of Addiction.

  20. Alcohol Alert: Alcohol's Damaging Effects on the Brain

    Science.gov (United States)

    ... 44). Markers such as the P3 can help identify people who may be at greatest risk for developing problems with alcohol. END OF SIDEBAR ... Meta–analysis of P300 amplitude from males at risk for alcoholism. Psychological Bulletin 115:55–73, ... appeared in the journal Alcohol Research & Health, “Alcoholic Brain Damage” (Vol. 27, ...

  1. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  2. Alcoholism: genes and mechanisms.

    Science.gov (United States)

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  3. Fuel Class Higher Alcohols

    KAUST Repository

    Sarathy, Mani

    2016-08-17

    This chapter focuses on the production and combustion of alcohol fuels with four or more carbon atoms, which we classify as higher alcohols. It assesses the feasibility of utilizing various C4-C8 alcohols as fuels for internal combustion engines. Utilizing higher-molecular-weight alcohols as fuels requires careful analysis of their fuel properties. ASTM standards provide fuel property requirements for spark-ignition (SI) and compression-ignition (CI) engines such as the stability, lubricity, viscosity, and cold filter plugging point (CFPP) properties of blends of higher alcohols. Important combustion properties that are studied include laminar and turbulent flame speeds, flame blowout/extinction limits, ignition delay under various mixing conditions, and gas-phase and particulate emissions. The chapter focuses on the combustion of higher alcohols in reciprocating SI and CI engines and discusses higher alcohol performance in SI and CI engines. Finally, the chapter identifies the sources, production pathways, and technologies currently being pursued for production of some fuels, including n-butanol, iso-butanol, and n-octanol.

  4. Veterans Health Administration

    Science.gov (United States)

    ... code here VA » Veterans Health Administration Veterans Health Administration Robotic Brace for Veterans of Spinal Cord Injury ... Read more » VA Medical Centers The Veterans Health Administration is home to the United States’ largest integrated ...

  5. [Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol...... degradation drank approximately 30% more alcohol per week and had a higher risk of everyday and heavy drinking, and of alcoholism. Individuals with ADH1C slow versus fast alcohol degradation had a higher risk of heavy drinking Udgivelsesdato: 2008/8/25...

  6. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  7. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  8. Expanded complexity of unstable repeat diseases

    OpenAIRE

    Polak, Urszula; McIvor, Elizabeth; Dent, Sharon Y.R.; Wells, Robert D.; Napierala, Marek.

    2012-01-01

    Unstable Repeat Diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly expansion, of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequen...

  9. 76 FR 80781 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2012

    Science.gov (United States)

    2011-12-27

    ... Federal Railroad Administration 49 CFR Part 219 RIN 2130-AA81 Alcohol and Drug Testing: Determination of... random drug testing ] positive rate has remained below 1.0 percent for the last two years. The Federal Railroad Administrator (Administrator) has therefore determined that the minimum annual random drug testing...

  10. EPA Administrative Enforcement Dockets

    Data.gov (United States)

    U.S. Environmental Protection Agency — The EPA Administrative Enforcement Dockets database contains the electronic dockets for administrative penalty cases filed by EPA Regions and Headquarters. Visitors...

  11. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  12. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  13. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  14. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  15. ALCOHOL AND HEART RHYTHM DISORDERS

    Directory of Open Access Journals (Sweden)

    A. O. Yusupova

    2015-01-01

    Full Text Available Alcohol abuse and particularly extension of alcohol consumption in alcohol diseas increases the risk of cardiac arrhythmias development and aggravates existing arrhythmias. Patients do not always receive the necessary specific treatment due to lack of detection of the ethanol genesis of these arrhythmias. Management of patients with alcohol abuse and alcohol dependence, including its cardiac complications among other cardiac arrhythmias should use both antiarrhythmic and anti-alcohol drugs and antidepressants. Such issues as diagnosis and management of patients with alcohol-induced cardiac arrhythmias are presented.

  16. Repeat workers' compensation claims: risk factors, costs and work disability

    Directory of Open Access Journals (Sweden)

    Collie Alex

    2011-06-01

    Full Text Available Abstract Background The objective of our study was to describe factors associated with repeat workers' compensation claims and to compare the work disability arising in workers with single and multiple compensation claims. Methods All initial injury claims lodged by persons of working age during a five year period (1996 to 2000 and any repeat claims were extracted from workers' compensation administrative data in the state of Victoria, Australia. Groups of workers with single and multiple claims were identified. Descriptive analysis of claims by affliction, bodily location, industry segment, occupation, employer and workplace was undertaken. Survival analysis determined the impact of these variables on the time between the claims. The economic impact and duration of work incapacity associated with initial and repeat claims was compared between groups. Results 37% of persons with an initial claim lodged a second claim. This group contained a significantly greater proportion of males, were younger and more likely to be employed in manual occupations and high-risk industries than those with single claims. 78% of repeat claims were for a second injury. Duration between the claims was shortest when the working conditions had not changed. The initial claims of repeat claimants resulted in significantly (p lower costs and work disability than the repeat claims. Conclusions A substantial proportion of injured workers experience a second occupational injury or disease. These workers pose a greater economic burden than those with single claims, and also experience a substantially greater cumulative period of work disability. There is potential to reduce the social, health and economic burden of workplace injury by enacting prevention programs targeted at these workers.

  17. Pentatricopeptide repeat proteins in plants.

    Science.gov (United States)

    Barkan, Alice; Small, Ian

    2014-01-01

    Pentatricopeptide repeat (PPR) proteins constitute one of the largest protein families in land plants, with more than 400 members in most species. Over the past decade, much has been learned about the molecular functions of these proteins, where they act in the cell, and what physiological roles they play during plant growth and development. A typical PPR protein is targeted to mitochondria or chloroplasts, binds one or several organellar transcripts, and influences their expression by altering RNA sequence, turnover, processing, or translation. Their combined action has profound effects on organelle biogenesis and function and, consequently, on photosynthesis, respiration, plant development, and environmental responses. Recent breakthroughs in understanding how PPR proteins recognize RNA sequences through modular base-specific contacts will help match proteins to potential binding sites and provide a pathway toward designing synthetic RNA-binding proteins aimed at desired targets.

  18. Two-dimensional quantum repeaters

    Science.gov (United States)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  19. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  20. Hungarian repeat station survey, 2010

    Directory of Open Access Journals (Sweden)

    Péter Kovács

    2013-03-01

    Full Text Available The last Hungarian repeat station survey was completed between October 2010 and February 2011. Declination, inclination and the total field were observed using one-axial DMI fluxgate magnetometer mounted on Zeiss20A theodolite and GSM 19 Overhauser magnetometer. The magnetic elements of the sites were reduced to the epoch of 2010.5 on the basis of the continuous recordings of Tihany Geophysical Observatory. In stations located far from the reference observatory, the observations were carried out in the morning and afternoon in order to decrease the effect of the distant temporal correction. To further increase the accuracy, on-site dIdD variometer has also been installed near the Aggtelek station, in the Baradla cave, during the survey of the easternmost sites. The paper presents the technical details and the results of our last campaign. The improvement of the accuracy of the temporal reduction by the use of the local variometer is also reported.

  1. Adolescent alcohol exposure: Burden of epigenetic reprogramming, synaptic remodeling, and adult psychopathology

    Directory of Open Access Journals (Sweden)

    Evan J Kyzar

    2016-05-01

    Full Text Available Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can delay these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood.

  2. Alcohol Use and Sexual Risk Behaviors in a Migrant Worker Community.

    Science.gov (United States)

    McCoy, H Virginia; Shehadeh, Nancy; Rubens, Muni

    2016-06-01

    There are not many studies exploring the association between alcohol use and risky sexual behaviors among migrant workers. This study analyzed how changes in alcohol use was associated with changes in risky sexual behavior and psychosocial variables. Data for this study was drawn from an HIV risk reduction project. Repeated measures ANOVA and Linear mixed model statistical method was conducted to find changes and association between alcohol use, sexual risk and psychosocial variables over time. The sample (n = 203) was composed of African Americans (33.0 %) and Hispanics (77.0 %) men. Both groups, over time, showed reduction in sexual risk in accordance with reduction in alcohol use. Changes in alcohol use and psychosocial variables showed significant association with sexual risk changes over time. Psychological strategies like building social support should be considered for HIV risk reduction intervention directed towards high alcohol consuming migrant workers.

  3. DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

    Directory of Open Access Journals (Sweden)

    Kasey G Creswell

    Full Text Available Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition ×2 (genotype design (N = 422 to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

  4. DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

    Science.gov (United States)

    Creswell, Kasey G; Sayette, Michael A; Manuck, Stephen B; Ferrell, Robert E; Hill, Shirley Y; Dimoff, John D

    2012-01-01

    Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

  5. Alcohol use disorder

    Science.gov (United States)

    ... be a combination of a person's: Genes Environment Psychology, such as being impulsive or having low self- ... Examine you Ask about your medical and family history Ask about your alcohol use, and if you ...

  6. When alcohol acts

    DEFF Research Database (Denmark)

    Demant, Jakob

    2009-01-01

      Sociological studies into alcohol use seem to find it difficult to deal with the substance itself. Alcohol tends to be reduced to a symbol of a social process and in this way the sociological research loses sight of effects beyond the social. This paper suggests a new theoretical approach...... to the study of alcohol and teenagers' (romantic) relationships, inspired by actor-network theory (ANT). The central feature of ANT is to search for relationships, or rather networks, between all things relevant to the phenomenon. All material and semantic structures, things, persons, discourses, etc....... that influence a given situation are described as actants and are entered into the analysis. The aim of this paper is to propose a way of including materiality in sociological analyses of alcohol and to explore ways of using focus group interview material in ANT-inspired analysis. By analyzing a girl...

  7. an Unrecorded Alcohol Beverage

    African Journals Online (AJOL)

    NICO

    alcohol consumption, including malnutrition, selfneglect, poor hygiene, pale skin, weight .... Table 2 Analytical performance parameters of the GC-FID for the stan- dards (n = 3). .... Kluwer Academic Plenum Publishers,. New York, 1999, pp.

  8. Pentoxifylline for alcoholic hepatitis

    DEFF Research Database (Denmark)

    Whitfield, Kate; Rambaldi, Andrea; Wetterslev, Jørn

    2009-01-01

    -cause mortality and mortality due to hepatorenal syndrome, and conversely, an increase in serious and non-serious adverse events. However, the evidence is not firm; no conclusions can be drawn regarding whether pentoxifylline has a positive, negative, or neutral effect on participants with alcoholic hepatitis....... analysis did not support this result. Data from one trial suggests that pentoxifylline may increase the occurrence of serious and non-serious adverse events compared to control. AUTHORS' CONCLUSIONS: The current available data may indicate a possible positive intervention effect of pentoxifylline on all......BACKGROUND: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects...

  9. Antidepressants and Alcohol

    Science.gov (United States)

    ... Medication-FAQ/Can-I-drink-alcohol-while-taking-antidepressants. Accessed May 2, 2017. Back SE, et al. Treatment of co-occurring substance use disorder and anxiety-related disorders in adults. https://www.uptodate.com/ ...

  10. Alcohol en snelverkeer.

    NARCIS (Netherlands)

    Esser, P.H.

    1968-01-01

    Dr Esser voert diverse redenen aan om zo snel mogelijk te starten met ademanalyse op tijden en plaatsen dat bestuurders, die alcohol gebruikt hebben, verwacht kunnen worden. Hij wijst op de preventieve waarde hiervan. Zie ook A 1469.

  11. Alcohol advertising and youth.

    Science.gov (United States)

    Martin, Susan E; Snyder, Leslie B; Hamilton, Mark; Fleming-Milici, Fran; Slater, Michael D; Stacy, Alan; Chen, Meng-Jinn; Grube, Joel W

    2002-06-01

    This article presents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The symposium was organized and chaired by Joel W. Grube. The presentations and presenters were (1) Introduction and background, by Susan E. Martin; (2) The effect of alcohol ads on youth 15-26 years old, by Leslie Snyder, Mark Hamilton, Fran Fleming-Milici, and Michael D. Slater; (3) A comparison of exposure to alcohol advertising and drinking behavior in elementary versus middle school children, by Phyllis L. Ellickson and Rebecca L. Collins; (4) USC health and advertising project: assessment study on alcohol advertisement memory and exposure, by Alan Stacy; and (5) TV beer and soft drink advertising: what young people like and what effects? by Meng-Jinn Chen and Joel W. Grube.

  12. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  13. Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice.

    Science.gov (United States)

    Kishore, Kamal; Singh, Manjeet

    2005-07-01

    To investigate the effect of bacosides (alcoholic extract of brahmi) on scopolamine (3 mg kg(-1), ip), sodium nitrite (75 mg kg(-1), ip) and BN52021 (15 mg kg(-1), ip) induced experimental amnesia in mice, using Morris water maze test, all the agents were administered 30 min before the acquisition trials on each day and repeated for 4 consecutive days, and on 5th day during the retrieval trials. Bacosides on anterograde administration (before training) in mice, significantly decreased the escape latency time (ELT) during the acquisition trials for 4 consecutive days and increased the time spent (TS) in target quadrant during the retrieval trials on 5th day, and on retrograde administration (after training) bacosides were found not to affect TS significantly. Bacosides also significantly decreased the ELT and increased the TS in mice treated anterogradely with scopolamine and sodium nitrite. Bacosides did not exhibit any significant effect on TS of mice treated retrogradely with sodium nitrite. On the other hand, bacosides significantly increased the TS of mice treated retrogradely with BN52021. On the basis of the present results it can be concluded that bacosides facilitate anterograde memory and attenuate anterograde experimental amnesia induced by scopolamine and sodium nitrite possibly by improving acetylcholine level and hypoxic conditions, respectively. Beside this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level.

  14. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  15. Alcohol: Pleasures and Problems.

    Science.gov (United States)

    Finn, Peter; Lawson, Jane

    This student booklet is to be used in conjunction with the Teacher Manual and films of the DIAL A-L-C-O-H-O-L series. It presents facts and illustrations on the use of alcohol, and is intended to aid young people in deciding whether or not to drink. This booklet is divided into the following parts: (1) Introduction; (2) The Enjoyment of Drinking;…

  16. Consumo de alcohol

    OpenAIRE

    Luís Gustavo del Sol Padrón; Orestes Álvarez Fernández; Juan De Dios Rivero Berovides

    2010-01-01

    En este artículo se emite una definición clasificatoria de los individuos que consumen alcohol, según supuestos establecidos por Manconi. Se estratifican las personas atendiendo a los diferentes riesgos para este consumo. Se describen las afectaciones a la salud que produce el consumo de alcohol, y además se plantean las medidas estratégicas para propiciar una conducta efectiva antialcohólica. Por último, se presenta un flujograma para la inter...

  17. Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis.

    Science.gov (United States)

    Alén, Francisco; Mouret, Aurélie; Viveros, Maria-Paz; Llorente, Ricardo; Lepousez, Gabriel; Lledo, Pierre-Marie; López-Moreno, José Antonio

    2010-03-01

    Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system. Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse. Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis. Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration. WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol. These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.

  18. Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder.

    Science.gov (United States)

    Koob, George F

    2013-01-01

    Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state

  19. Alcohol-attributable and alcohol-preventable mortality in Denmark

    DEFF Research Database (Denmark)

    Eliasen, Marie; Becker, Ulrik; Grønbæk, Morten

    2014-01-01

    The aim of the study was to quantify alcohol-attributable and -preventable mortality, totally and stratified on alcohol consumption in Denmark 2010, and to estimate alcohol-related mortality assuming different scenarios of changes in alcohol distribution in the population. We estimated alcohol......-attributable and -preventable fractions based on relative risks of conditions causally associated with alcohol from meta-analyses and information on alcohol consumption in Denmark obtained from 14,458 participants in the Danish National Health Survey 2010 and corrected for adult per capita consumption. Cause-specific mortality...... data were obtained from the Danish Register of Causes of Death. In total, 1,373 deaths among women (5.0 % of all deaths) and 2,522 deaths among men (9.5 % of all deaths) were attributable to alcohol, while an estimated number of 765 (2.8 %) and 583 (2.2 %) deaths were prevented by alcohol...

  20. Alcohol drinking pattern and risk of alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette Skalshøi

    2015-01-01

    BACKGROUND & AIMS: Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS: We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993......-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS......: We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50...

  1. Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

    Science.gov (United States)

    Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

    2014-01-01

    Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.

  2. 75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

    Science.gov (United States)

    2010-12-20

    ... Federal Railroad Administration 49 CFR Part 219 Alcohol and Drug Testing: Determination of Minimum Random... rail industry random testing positive rates were .037 percent for drugs and .014 percent for alcohol. Because the industry-wide random drug testing positive rate has remained below 1.0 percent for the last...

  3. DIGLUCOSYLATION OF SALICYL ALCOHOL BY CELL SUSPENSION CULTURES OF SOLANUM LACINIATUM

    Institute of Scientific and Technical Information of China (English)

    ACHMAD SYAHRANI; FRANSISCA HARTUTI; GUNAWAN INDRAYANTO; ALISTAIR L.WILKINS

    2001-01-01

    A new biotransformation product, salicyl alcohol-7-O-β-D-(β-l,6-D-glucopyranosyl)-gluco pyranoside was isolated from cell suspension cultures of Solanum laciniatum, following administration of salicyl alcohol, and its structure was elucidated using a combination of one and two-dimensional 1H and 13C-NMR data, and positive and negative ion ESMS data.

  4. 20 CFR 416.544 - Paying benefits in installments: Drug addiction or alcoholism.

    Science.gov (United States)

    2010-04-01

    ... addiction or alcoholism. 416.544 Section 416.544 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... Underpayments § 416.544 Paying benefits in installments: Drug addiction or alcoholism. (a) General. For disabled recipients who receive benefit payments through a representative payee because drug addiction or...

  5. 20 CFR 404.480 - Paying benefits in installments: Drug addiction or alcoholism.

    Science.gov (United States)

    2010-04-01

    ... addiction or alcoholism. 404.480 Section 404.480 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL... Benefits § 404.480 Paying benefits in installments: Drug addiction or alcoholism. (a) General. For disabled beneficiaries who receive benefit payments through a representative payee because drug addiction or...

  6. Harry Potter and the Underage Drinkers: Can We Use This to Talk to Teens about Alcohol?

    Science.gov (United States)

    Welsh, Christopher

    2007-01-01

    Underage drinking continues to be a major problem in America. Approximately 20% of all alcohol consumed in the United States is consumed by minors with 44% of 8th graders and 77% of 12th graders reporting that they have tried alcohol at least once. The National Highway Traffic Safety Administration reported that, in 2003, as many as 3,657 drivers,…

  7. Harry Potter and the Underage Drinkers: Can We Use This to Talk to Teens about Alcohol?

    Science.gov (United States)

    Welsh, Christopher

    2007-01-01

    Underage drinking continues to be a major problem in America. Approximately 20% of all alcohol consumed in the United States is consumed by minors with 44% of 8th graders and 77% of 12th graders reporting that they have tried alcohol at least once. The National Highway Traffic Safety Administration reported that, in 2003, as many as 3,657 drivers,…

  8. Comparing Alcohol Marketing and Alcohol Warning Message Policies Across Canada.

    Science.gov (United States)

    Wettlaufer, Ashley; Cukier, Samantha N; Giesbrecht, Norman

    2017-08-24

    In order to reduce harms from alcohol, evidence-based policies are to be introduced and sustained. To facilitate the dissemination of policies that reduce alcohol-related harms by documenting, comparing, and sharing information on effective alcohol polices related to restrictions on alcohol marketing and alcohol warning messaging in 10 Canadian provinces. Team members developed measurable indicators to assess policies on (a) restrictions on alcohol marketing, and (b) alcohol warning messaging. Indicators were peer-reviewed by three alcohol policy experts, refined, and data were collected, submitted for validation by provincial experts, and scored independently by two team members. The national average score was 52% for restrictions on marketing policies and 18% for alcohol warning message policies. Most provinces had marketing regulations that went beyond the federal guidelines with penalties for violating marketing regulations. The provincial liquor boards' web pages focused on product promotion, and there were few restrictions on sponsorship activities. No province has implemented alcohol warning labels, and Ontario was the sole province to have legislated warning signs at all points-of-sale. Most provinces provided a variety of warning signs to be displayed voluntarily at points-of-sale; however, the quality of messages varied. Conclusions/Importance: There is extensive alcohol marketing with comparatively few messages focused on the potential harms associated with alcohol. It is recommended that governments collaborate with multiple stakeholders to maximize the preventive impact of restrictions on alcohol marketing and advertising, and a broader implementation of alcohol warning messages.

  9. Effects of a natural community intervention intensifying alcohol law enforcement combined with a restrictive alcohol policy on adolescent alcohol use.

    Science.gov (United States)

    Schelleman-Offermans, Karen; Knibbe, Ronald A; Kuntsche, Emmanuel; Casswell, Sally

    2012-12-01

    Determining whether intensified inspections on alcohol retailers, combined with a policy withdrawing liquor licenses if retailers are fined twice per annum, is effective in reducing adolescents' odds to initiate weekly drinking and drunkenness. Causal pathways by which the intervention was assumed to work were tested. A longitudinal (2008, 2009, and 2010) quasi-experimental comparison group design including two Dutch communities, one intervention and one comparison, was used. Outcomes were assessed by following a cohort of 1,327 adolescents (aged 13-15 years at baseline). The intervention resulted in increased retail inspections but only seven sanctions and no repeated sanctions in 1 year. The intervention did not reduce adolescents' odds to initiate weekly drinking. Weekly drinking adolescents in the intervention community were at reduced risk to initiate drunkenness. This effect was not mediated by smaller increases in the frequency of adolescents' alcohol purchases or their perceived ease of purchasing alcohol. Intensified enforcement was effective in preventing adolescent drunkenness. No mediating causal pathways were detected. Effectiveness of enforcement could be increased by adopting enforcement methods with a high likelihood of apprehension, increasing social support for restrictive measures, and mobilizing the community to be more outspoken against adolescent (heavy) drinking. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  10. 27 CFR 17.136 - Compliance with Food and Drug Administration requirements.

    Science.gov (United States)

    2010-04-01

    ... products manufactured solely for export or for uses other than internal human consumption (e.g. tobacco... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Compliance with Food and Drug Administration requirements. 17.136 Section 17.136 Alcohol, Tobacco Products and Firearms...

  11. Genes and Alcohol Consumption: Studies with Mutant Mice

    Science.gov (United States)

    Mayfield, Jody; Arends, Michael A.; Harris, R. Adron; Blednov, Yuri A.

    2017-01-01

    In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test. PMID:27055617

  12. Genes and Alcohol Consumption: Studies with Mutant Mice.

    Science.gov (United States)

    Mayfield, J; Arends, M A; Harris, R A; Blednov, Y A

    2016-01-01

    In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test.

  13. Mulberry Fruit Mitigates Alcohol Neurotoxicity and Memory Impairment Induced by Chronic Alcohol Intake

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2012-01-01

    Full Text Available Problem statement: To date, the therapeutic strategy efficacy against memory impairment induced by alcohol intoxication is still limited. The novel therapeutic strategy which is easy to approach, less toxic and less cost is required. Based on the role of oxidative stress in memory impairment induced by alcohol, the neuroprotective effect of substance possessing antioxidant has gained much attention. Therefore, we aimed to determine the effect of Morus alba fruits, substance possessing antioxidant, on spatial memory and brain damage in hippocampus. Approach: Male Wistar rats were induced alcoholism by increasing the alcohol concentration in drinking water gradually increased to 30% within 15-week period. Then, the alcoholic rats were orally given mulberry fruits powder at doses of 2, 10 and 50 mg kg-1 BW at a period of 14 days. The memory was assessed using Morris water maze after single administration and every 7 days until the end of the experimental period and at the end of experiment, hippocampus was isolated and determined the neuron density. In addition, the evaluation of Acetylcholinesterase (AChE activity and Malondialdehyde (MDA level were also performed. Results: Our results showed that all doses of mulberry fruits enhanced spatial memory and neurons density in hippocampus. The suppression of both AChE activity and MDA level were also observed. These results suggested that the neuroprotection of mulberry fruits might occur partly via the decreased oxidative stress damage while the cognitive enhancing effect might occur partly via the increased hippocampal neuron density and the suppression of AChE activity. Conclusion: Mulberry fruits can protect against brain damage and memory impairment induced by alcoholism. Therefore, mulberry fruits may be served as natural resource for developing food supplement against alcoholism. However, further researches about possible active ingredient and pharmacokinetic are required before moving forward

  14. Review of survey and experimental research that examines the relationship between alcohol consumption and men's sexual aggression perpetration.

    Science.gov (United States)

    Abbey, Antonia; Wegner, Rhiana; Woerner, Jacqueline; Pegram, Sheri E; Pierce, Jennifer

    2014-10-01

    This article systematically reviews empirical studies that examine associations between alcohol consumption and men's sexual aggression with the goal of identifying major findings; gaps in current knowledge; and directions for future research, practice, and policy. We identified 25 cross-sectional surveys, 6 prospective studies, and 12 alcohol administration experiments published between 1993 and August 2013 with male college students and young adult (nonincarcerated) samples. Many cross-sectional surveys have demonstrated that distal and proximal measures of men's alcohol consumption are positively associated with sexual assault perpetration, although very few of these studies evaluated how alcohol interacts with other risk and protective factors to exacerbate or inhibit sexual aggression. There are surprisingly few surveys that examine alcohol's effects at the event level and over short-time intervals to identify how changes in alcohol consumption are associated with changes in perpetration status. Alcohol administration studies suggest some important mechanisms that warrant additional investigation. © The Author(s) 2014.

  15. Repeater Effects on Score Equating for a Graduate Admissions Exam. Research Report. ETS RR-11-17

    Science.gov (United States)

    Yang, Wen-Ling; Bontya, Andrea M.; Moses, Tim P.

    2011-01-01

    Using self-reported but empirically verified repeater groups, we analyzed vast amounts of real test data across a wide range of administrations from a graduate admissions examination that was administered in a non-English language to investigate repeater effects on score equating using the nonequivalent groups with anchor test (NEAT) design. Both…

  16. Case of administrative dispute

    Directory of Open Access Journals (Sweden)

    Xhemazie Ibraimi

    2015-11-01

    Full Text Available The activity of administrative bodies includes big numbers of various acts and actions, through which the will of public administration is formed. The will of public administration bodies, expressed in administrative individual and normative acts, in administrative contracts and real acts, finds its reflection in the Constitution, laws and other provisions of legal character. All this activity is not inerrant and therefore, it is not uncontrollable. The supervision of executive activity is subject to political control of administrative acts through authorities designated for this purpose, as well as internal control and the judicial control. The institution of judicial control of administrative acts and actions appears as very important and widely treated in the legal doctrine. The protection of constitutional and legal rights of private persons is accomplished by subjecting administrative activity both to internal administrative control, as well as to the judicial control in accordance with legal provisions. The judicial control of administrative acts represents a constitutional guarantee for citizens to protect their rights through public and fair trial by an independent and impartial court. In this way, the Constitution empowers the common administrative court that invalidates an action or administrative act, but not all administrative acts may be subject to administrative dispute, with the exception of cases against which the administrative conflict cannot be carried out (negative enumeration.

  17. Histamine H3 receptor antagonist decreases cue-induced alcohol reinstatement in mice.

    Science.gov (United States)

    Nuutinen, Saara; Mäki, Tiia; Rozov, Stanislav; Bäckström, Pia; Hyytiä, Petri; Piepponen, Petteri; Panula, Pertti

    2016-07-01

    We have earlier found that the histamine H3 receptor (H3R) antagonism diminishes motivational aspects of alcohol reinforcement in mice. Here we studied the role of H3Rs in cue-induced reinstatement of alcohol seeking in C57BL/6J mice using two different H3R antagonists. Systemic administration of H3R antagonists attenuated cue-induced alcohol seeking suggesting that H3R antagonists may reduce alcohol craving. To understand how alcohol affects dopamine and histamine release, a microdialysis study was performed on C57BL/6J mice and the levels of histamine, dopamine and dopamine metabolites were measured in the nucleus accumbens. Alcohol administration was combined with an H3R antagonist pretreatment to reveal whether modulation of H3R affects the effects of alcohol on neurotransmitter release. Alcohol significantly increased the release of dopamine in the nucleus accumbens but did not affect histamine release. Pretreatment with H3R antagonist ciproxifan did not modify the effect of alcohol on dopamine release. However, histamine release was markedly increased with ciproxifan. In conclusion, our findings demonstrate that H3R antagonism attenuates cue-induced reinstatement of alcohol seeking in mice. Alcohol alone does not affect histamine release in the nucleus accumbens but H3R antagonist instead increases histamine release significantly suggesting that the mechanism by which H3R antagonist inhibits alcohol seeking found in the present study and the decreased alcohol reinforcement, reward and consumption found earlier might include alterations in the histaminergic neurotransmission in the nucleus accumbens. These findings imply that selective antagonists of H3Rs could be a therapeutic strategy to prevent relapse and possibly diminish craving to alcohol use. This article is part of the Special Issue entitled 'Histamine Receptors'.

  18. Verbal reasoning deficits in alcoholics.

    Science.gov (United States)

    Yohman, J R; Parsons, O A

    1987-04-01

    The Conceptual Level Analogies Test (CLAT), a well-constructed test of analogical reasoning, was given to groups of middle-aged male alcoholics and control subjects in two separate studies. As predicted, the alcoholics had lower CLAT scores than nonalcoholics in both studies. These results support the generalized-diffuse model of the neuropsychological effects of alcoholism. Contrary to prediction, alcoholics differed from control subjects as much on the easy analogies as they did on the hard analogies, which suggested that alcoholics differ both qualitatively and quantitatively from nonalcoholics in cognitive impairment. Finally, in two of three studies in our laboratory, familial alcoholics had significantly lower CLAT scores than nonfamilial alcoholics. These findings emphasize the importance of considering familial history of alcoholism when studying the neuropsychological functioning of alcoholics.

  19. Alcohol-impregnated wipes as an alternative in hand hygiene.

    Science.gov (United States)

    Butz, A M; Laughon, B E; Gullette, D L; Larson, E L

    1990-04-01

    The antimicrobial effectiveness of four hand-wash products for health care personnel included three liquid soaps that contained 4% chlorhexidine gluconate, 1% triclosan, or no antiseptic ingredient, respectively, and a 30% w/w ethyl alcohol-impregnated hand wipe. These products were evaluated for reduction in bacterial counts on hands after extended use of 15 handwashes per day for 5 consecutive days. The order of greatest to least log reduction among products at the end of the 5-day test period was chlorhexidine gluconate (2.01), triclosan (1.52), alcohol wipe (0.04), and control soap (0.03). Skin condition before and after handwash was assessed for each treatment group. Subjects reported less skin irritation with alcohol wipes than with the two antiseptic products. Repeated washing with alcohol wipes results in reductions in bacterial colony counts comparable with nonmedicated soap, sufficient to prevent transmission of pathogens by the hands in most situations that arise in nonacute health care settings. This evidence, in addition to increased user acceptability reported by the subjects who used alcohol wipes, suggests that alcohol wipes are an acceptable alternative to soap-and-water handwashing in nonacute health care settings.

  20. Relaxin-3 receptor (RXFP3 signalling mediates stress-related alcohol preference in mice.

    Directory of Open Access Journals (Sweden)

    Andrew W Walker

    Full Text Available Stressful life events are causally linked with alcohol use disorders (AUDs, providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3 prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT and Rxfp3 knockout (KO (C57/B6JRXFP3TM1/DGen littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.