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Author Boeuf-Cazou, O.; Bongue, B.; Ansiau, D.; Marquie, J.-C.; Lapeyre-Mestre, M. file  url
  Title Impact of long-term benzodiazepine use on cognitive functioning in young adults: the VISAT cohort Type Journal Article
  Year 2011 Publication (up) European Journal of Clinical Pharmacology Abbreviated Journal Eur J Clin Pharmacol  
  Volume 67 Issue 10 Pages 1045-1052  
  Keywords Adult; Aptitude/drug effects; Benzodiazepines/*administration & dosage/adverse effects; Cognition/*drug effects; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Memory, Long-Term/drug effects; Mental Recall/drug effects; Middle Aged; Neuropsychological Tests; Prospective Studies; Questionnaires; Sex Factors  
  Abstract PURPOSE: Results from a number of studies have suggested a relationship between cognitive alteration and benzodiazepine use in the elderly. The aim of this study was to determine the impact of benzodiazepine use on cognitive functions in a young adult population. METHODS: This study included 1,019 French salaried workers from the VISAT (Aging, Health and Work) cohort whose objective was to determine the long-term impact of working conditions on health and aging. Data were collected during interviews by occupational physicians in 1996, 2001 and 2006. Cognitive function was assessed using five cognitive tests (immediate free recall test, delayed free recall test, recognition test, Digit Symbol Substitution Subtest and visual search speed test). Cognitive scores obtained after a 10-year follow-up were investigated among three categories of benzodiazepine users, namely, non-users, occasional users and long-term users, using analysis of covariance models adjusted for several potential confounders in men and women separately. RESULTS: In the course of the 10 year-follow-up, 3.9% of subjects were defined as occasional users of benzodiazepine and 7.5% as long-term users. The analysis revealed a significant alteration of long-term memory in women whereas there was no significant association in men. CONCLUSIONS: Long-term use of benzodiazepine leads to specific impairment in long-term memory only in women.  
  Call Number Serial 265  
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Author Lill, A.P.; Rodl, C.B.; Steinhilber, D.; Stark, H.; Hofmann, B. file  url
  Title Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy Type Journal Article
  Year 2015 Publication (up) European Journal of Medicinal Chemistry Abbreviated Journal Eur J Med Chem  
  Volume 89 Issue Pages 503-523  
  Keywords Arachidonate 5-Lipoxygenase/*metabolism; Dose-Response Relationship, Drug; Humans; Leukotriene Antagonists/chemical synthesis/chemistry/*pharmacology; Leukotrienes/*metabolism; Lipoxygenase Inhibitors/chemical synthesis/chemistry/*pharmacology; Molecular Structure; Structure-Activity Relationship; Thiazoles/chemical synthesis/chemistry/*pharmacology; 5-Lipoxygenase; Anti-leukotriene therapy; Hydroxythiazoles; Inflammation; Solubility; Structure-activity relationship  
  Abstract Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure-activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 muM) and cell-free assays (IC50 values 0.03 muM) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy.  
  Call Number Serial 1464  
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Author Hall, A.C.; Turcotte, C.M.; Betts, B.A.; Yeung, W.-Y.; Agyeman, A.S.; Burk, L.A. file  url
doi  openurl
  Title Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids Type Journal Article
  Year 2004 Publication (up) European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume 506 Issue 1 Pages 9-16  
  Keywords Animals; Dose-Response Relationship, Drug; Drug Synergism; Female; Gene Expression; Glycine/pharmacology; Humans; Membrane Potentials/drug effects; Menthol/chemistry/*pharmacology; Monoterpenes/*pharmacology; Oocytes/drug effects/physiology; Patch-Clamp Techniques; Receptors, GABA-A/genetics/*physiology; Receptors, Glycine/genetics/*physiology; Stereoisomerism; Xenopus; gamma-Aminobutyric Acid/pharmacology  
  Abstract Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine EC20 responses increased by 496+/-113% and 135+/-56%, respectively). (+)-Menthol, 100 microM, reduced EC50 values for GABA and glycine from 82.8+/-9.9 to 25.0+/-1.8 microM, and from 98.7+/-8.6 to 75.7+/-9.4 microM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels.  
  Call Number Serial 505  
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Author Hall, A.C.; Griffith, T.N.; Tsikolia, M.; Kotey, F.O.; Gill, N.; Humbert, D.J.; Watt, E.E.; Yermolina, Y.A.; Goel, S.; El-Ghendy, B.; Hall, C.D. file  url
doi  openurl
  Title Cyclohexanol analogues are positive modulators of GABA(A) receptor currents and act as general anaesthetics in vivo Type Journal Article
  Year 2011 Publication (up) European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume 667 Issue 1-3 Pages 175-181  
  Keywords Anesthetics, General/*pharmacology; Animals; Cyclohexanols/*chemistry/*pharmacology; *Electric Conductivity; Electrophysiological Processes/drug effects; Humans; Larva/drug effects/metabolism/physiology; Oocytes/metabolism; Receptors, GABA-A/genetics/*metabolism; Xenopus laevis/genetics  
  Abstract GABA(A) receptors meet all the pharmacological criteria required to be considered important general anaesthetic targets. In the following study, the modulatory effects of various commercially available and novel cyclohexanols were investigated on recombinant human gamma-aminobutyric acid (GABA(A), alpha(1)beta(2)gamma(2s)) receptors expressed in Xenopus oocytes, and compared to the modulatory effects on GABA currents observed with exposures to the intravenous anaesthetic agent, propofol. Submaximal EC(20) GABA currents were typically enhanced by co-applications of 3-300 muM cyclohexanols. For instance, at 30 muM 2,6-diisopropylcyclohexanol (a novel compound) GABA responses were increased ~3-fold (although similar enhancements were achieved at 3 muM propofol). As regards rank order for modulation by the cyclohexanol analogues at 30 muM, the % enhancements for 2,6-dimethylcyclohexanol~2,6-diethylcyclohexanol~2,6-diisopropylcyclohexanol~2,6- di-sec-butylcyclohexanol >>2,6-di-tert-butylcyclohexanol~4-tert-butylcyclohexanol>cyclohexanol~cyclopentan ol~2-methylcyclohexanol. We further tested the potencies of the cyclohexanol analogues as general anaesthetics using a tadpole in vivo assay. Both 2,6-diisopropylcyclohexanol and 2,6-dimethylcyclohexanol were effective as anaesthetics with EC(50)s of 14.0 muM and 13.1 muM respectively, while other cyclohexanols with bulkier side chains were less potent. In conclusion, our data indicate that cyclohexanols are both positive modulators of GABA(A) receptors currents and anaesthetics. The positioning and size of the alkyl groups at the 2 and 6 positions on the cyclohexanol ring were critical determinants of activity.  
  Call Number Serial 509  
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Author Chen, X.; Qian, Y.; Yan, F.; Tu, J.; Yang, X.; Xing, Y.; Chen, Z. file  url
  Title 5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells Type Journal Article
  Year 2013 Publication (up) European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume 721 Issue 1-3 Pages 86-95  
  Keywords Base Sequence; DEAD-box RNA Helicases/*metabolism; DNA Replication/genetics; Hep G2 Cells; Hepatitis B Antigens/genetics/metabolism; Hepatitis B virus/*genetics/*physiology; Humans; Immunity, Innate; Interferon Type I/*biosynthesis/genetics; Polyphosphates/*chemistry; RNA Interference; RNA, Messenger/genetics; RNA, Small Interfering/chemistry/*genetics; Transcription, Genetic/genetics; Virus Replication/*genetics; 3-(4,5)-dimethylthiahiazol-2-y1)-2,5-diphenytetrazolium bromide; 3p-siRNA; 5â²-Triphosphated siRNA; 5â²-triphosphated siRNA; BF-siRNA; Ciap; Elisa; Hbv; HBV e antigen; HBV s antigen; HBeAg; HBsAg; Hcc; HepG2.2.15 cells; Hepatitis B virus; Ifn; Ifnî±/β; Mtt; NC-siRNA; Od; Prr; Rig-I; RNA interference; RNAi; Rt-Pcr; Tlr; bifunctional siRNA; calf intestine alkaline phosphatase; double strand DNA; double strand RNA; dsDNA; dsRNA; enzyme-linked immunosorbent assay; hepatitis B virus; hepatocellular carcinoma; interferon; negative control siRNA; optical density; pathogen-recognition receptor; retinoic acid-inducible gene I; reverse transcription PCR; siRNA; single strand RNA; small interfering RNA; ssRNA; toll-like receptor  
  Abstract Hepatitis B virus (HBV) infection often results in acute or chronic viral hepatitis and other liver diseases including cirrhosis and hepatocellular carcinoma. Current therapies for HBV usually have severe side effects and can cause development of drug-resistant mutants. An alternative and safe immunotherapeutic approach for HBV infection is urgently needed for effective anti-HBV therapy. In this study, we propose a new strategy for anti-HBV therapy that activates type-I interferon (IFN) antiviral innate immunity through stimulating pattern-recognition receptors with RNA interference (RNAi) using a 5'-end triphosphate-modified small interfering RNA (3p-siRNA). We designed and generated a 3p-siRNA targeting overlapping region of S gene and P gene of the HBV genome at the 5'-end of pregenomic HBV RNA. Our results demonstrated that 3p-siRNA induced a RIG-I-dependent antiviral type-I IFN response when transfected into HepG2.2.15 cells that support HBV replication. The 3p-siRNA significantly inhibited HBsAg and HBeAg secretion from HepG2.2.15 cells in a RIG-I-dependent manner, and the antiviral effect of 3p-siRNA was superior to that of siRNA. Furthermore, 3p-siRNA had more pronounced inhibition effects on the replication of HBV DNA and the transcription of mRNA than that of siRNA. Finally, 3p-siRNA displayed antiviral activity with long-term suppression of HBV replication. In conclusion, our findings suggest that 3p-siRNA could act as a powerful bifunctional antiviral molecule with potential for developing a promising therapeutic against chronic HBV infection.  
  Call Number Serial 1013  
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Author Fredriksen, M.; Halmoy, A.; Faraone, S.V.; Haavik, J. file  url
doi  openurl
  Title Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: a review of controlled and naturalistic studies Type Journal Article
  Year 2013 Publication (up) European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology Abbreviated Journal Eur Neuropsychopharmacol  
  Volume 23 Issue 6 Pages 508-527  
  Keywords Adrenergic Uptake Inhibitors/adverse effects/*therapeutic use; Adult; Amphetamine/adverse effects/therapeutic use; Attention Deficit Disorder with Hyperactivity/*drug therapy; Central Nervous System Stimulants/adverse effects/*therapeutic use; Cross-Sectional Studies; Humans; Longitudinal Studies; Methylphenidate/adverse effects/therapeutic use; Propylamines/adverse effects/*therapeutic use; Randomized Controlled Trials as Topic  
  Abstract Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood that often persists into adulthood. Although stimulant medications are recommended as the first-line treatment for ADHD because of their documented short-term effects in children and adults, less is known about their effects on long-term outcome in adults. Here we review the long-term efficacy and safety of the stimulant drugs methylphenidate and amphetamine, as well as the related compound atomoxetine. We performed a systematic review to identify direct and indirect effects of stimulant therapy on long-term outcome in adults. Five randomized controlled trials (RCTs), and 10 open-label extension studies of initial short-term RCTs, with total follow-up of at least 24weeks, were identified. All these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies showed that this favorable effect of medication was maintained during the open-label follow-up period. However, since the maximum duration of these pharmacological trials was 4years, we also reviewed 18 defined naturalistic longitudinal and cross-sectional studies, to provide more information about longer term functional outcomes, side effects and complications. These observational studies also showed positive correlations between early recognition of the disorder, stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients. In conclusion, stimulant therapy of ADHD has long-term beneficial effects and is well tolerated. However, more longitudinal studies of long duration should be performed. In addition, the ethical issues involved in performing double blind RCTs of many years duration should be further explored.  
  Call Number Serial 1092  
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Author Waismel-Manor, I.; Ifergane, G.; Cohen, H. file  url
  Title When endocrinology and democracy collide: emotions, cortisol and voting at national elections Type Journal Article
  Year 2011 Publication (up) European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology Abbreviated Journal Eur Neuropsychopharmacol  
  Volume 21 Issue 11 Pages 789-795  
  Keywords Adult; Aged; Aged, 80 and over; Decision Making; *Democracy; *Emotions; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrocortisone/*metabolism; Israel; Male; Middle Aged; *Politics; Psychiatric Status Rating Scales; Saliva/metabolism; Stress, Psychological/*psychology; Surveys and Questionnaires; Time; Young Adult  
  Abstract Faced with stressful experiences, such as uncertainty or novelty, the adrenal glands secrete glucocorticoid hormones to help us cope with stress. Since many decision-making situations are stressful, there is reason to believe that voting is a stressful event. In this study, we asked voters in Israel's national election (N=113) to report on their general affective state immediately before entering the polling place using the Positive Affect Negative Affect Schedule (PANAS) and to provide us with a saliva sample through which we could evaluate their cortisol levels. Compared to a second sample of voters who reported their affective state on election night (N=70), we found that voters at the ballot box had higher positive and negative affect. Moreover, our voters at the polling place exhibited cortisol levels that were significantly higher than their own normal levels obtained on a similar day, and significantly higher than those of a second control group sampled the day after the elections (N=6). Our data demonstrate that elections are exciting, yet stressful events, and it is this stress, among other factors, that elevates the cortisol levels of voters. Since elevated cortisol has been found to affect memory consolidation, impair memory retrieval and lead to risk-seeking behavior, we discuss how these outcomes of elevated cortisol levels may affect voting in general and the field of electoral studies in particular.  
  Call Number Serial 1720  
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Author Kim, E.J.; Namkoong, K.; Ku, T.; Kim, S.J. file  url
  Title The relationship between online game addiction and aggression, self-control and narcissistic personality traits Type Journal Article
  Year 2008 Publication (up) European Psychiatry : the Journal of the Association of European Psychiatrists Abbreviated Journal Eur Psychiatry  
  Volume 23 Issue 3 Pages 212-218  
  Keywords Adolescent; Adult; Aggression/*psychology; Behavior, Addictive/*diagnosis/epidemiology/psychology; Cross-Sectional Studies; Female; Health Surveys; Humans; *Internal-External Control; *Internet; Korea; Male; Personality Disorders/*diagnosis/epidemiology/psychology; Surveys and Questionnaires; *Video Games  
  Abstract OBJECTIVES: This study aimed to explore the relationship between online game addiction and aggression, self-control, and narcissistic personality traits, which are known as the psychological characteristics linked to “at-risk” populations for online game addiction. METHOD: A total of 1471 online game users (males 82.7%, females 17.3%, mean age 21.30+/-4.96) participated in this study and were asked to complete several self-report measures using an online response method. Questionnaires included demographic information and game use-related characteristics of the samples, the online game addiction scale (modified from Young's Internet addiction scale), the Buss-Perry aggression questionnaire, a self-control scale, and the narcissistic personality disorder scale. RESULTS: Our results indicated that aggression and narcissistic personality traits are positively correlated with online game addiction, whereas self-control is negatively correlated with online game addiction (p<0.001). In addition, a multiple regression analysis revealed that the extent of online game addiction could be predicted based on the person's narcissistic personality traits, aggression, self-control, interpersonal relationship, and occupation. However, only 20% of the variance in behavioral consequences was explained with the model. CONCLUSION: An interesting profile has emerged from the results of this study, suggesting that certain psychological characteristics such as aggression, self-control, and narcissistic personality traits may predispose some individuals to become addicted to online games. This result will deepen our understanding of the “at-risk” population for online game addiction and provide basic information that can contribute to developing a prevention program for people who are addicted to online games.  
  Call Number Serial 1491  
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Author Wagner, P.D. file  url
  Title New ideas on limitations to VO2max Type Journal Article
  Year 2000 Publication (up) Exercise and Sport Sciences Reviews Abbreviated Journal Exerc Sport Sci Rev  
  Volume 28 Issue 1 Pages 10-14  
  Keywords Altitude; *Cardiac Output; Exercise/*physiology; Humans; Muscle, Skeletal/*physiology; *Oxygen Consumption; Physical Endurance/physiology; *Pulmonary Diffusing Capacity  
  Abstract VO2max indicates maximal oxidative metabolic capacity (unfit subjects) or maximal O2 supply (athletes). The latter reflects integration of all transport steps from air to cytochromes. Every step contributes something; the importance of each contribution varies with conditions. Cardiac output seems most important at sea level; at higher altitudes, lung/muscle diffusion are more critical.  
  Call Number Serial 446  
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Author Thongthae, N.; Payungporn, S.; Poovorawan, Y.; T-Thienprasert, N.P. file  url
  Title A rational study for identification of highly effective siRNAs against hepatitis B virus Type Journal Article
  Year 2014 Publication (up) Experimental and Molecular Pathology Abbreviated Journal Exp Mol Pathol  
  Volume 97 Issue 1 Pages 120-127  
  Keywords 2',5'-Oligoadenylate Synthetase/genetics; Algorithms; Base Sequence; Gene Expression Regulation; Hep G2 Cells/virology; Hepatitis B virus/*genetics; Humans; Luciferases/genetics/metabolism; Molecular Sequence Data; NF-kappa B/genetics; Promoter Regions, Genetic; RNA, Small Interfering/chemistry/*genetics; Regulatory Sequences, Nucleic Acid; STAT1 Transcription Factor/genetics; Thermodynamics; Effective siRNAs; Hbv Pre; Hepatitis B virus; RNA interference; siRNA predicting program  
  Abstract RNA interference (RNAi) is a powerful gene knockdown technique used for study gene function. It also potentially provides effective agents for inhibiting infectious and genetic diseases. Most of RNAi studies employ a single siRNA designing program and then require large-scale screening experiments to identify functional siRNAs. In this study, we demonstrate that an assembly of results generated from different siRNA designing programs could provide clusters of predicting sites that aided selection of potent siRNAs. Based on the clusters, three siRNA target sites were selected on a conserved RNA region of hepatitis B virus (HBV), known as HBV post-transcriptional regulatory element (HBV PRE) at nucleotide positions 1317-1337, 1357-1377 and 1644-1664. All three chosen siRNAs driven by H1 promoter were highly effective and could drastically decrease expression of HBV transcripts (core, surface and X) and surface protein without induction of interferon response and cell cytotoxicity in liver cancer cell line (HepG2). Based on prediction of secondary structures, the silencing effects of siRNAs were less effective against a loop sequence of the mRNA target with hairpin structure. In summary, we demonstrate an effectual approach for identification of functional siRNAs. Moreover, highly potent siRNAs identified here may serve as novel agents for development of nucleic acid-based HBV therapy.  
  Call Number Serial 1012  
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