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Sample records for monoamine oxidases mao

  1. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men

    National Research Council Canada - National Science Library

    Shumay, Elena; Logan, Jean; Volkow, Nora D; Fowler, Joanna S

    2012-01-01

    ...). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype...

  2. Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol

    Directory of Open Access Journals (Sweden)

    Fatma Pinar Turkmenoglu

    2015-04-01

    Full Text Available The inhibitory effects of flavonoids on monoamine oxidases (MAOs have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1, isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2]-β-D-glucopyranoside (2, isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2]-6''-O-acetyl-β-D-glucopyranoside (3 and salvigenin (4 were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4 was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1 appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1 has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1 and salvigenin (4 as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.

  3. Monoamine Oxidase Inhibitory Constituents of Propolis: Kinetics and Mechanism of Inhibition of Recombinant Human MAO-A and MAO-B

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    Narayan D. Chaurasiya

    2014-11-01

    Full Text Available Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant human monoamine oxidase (MAO-A and MAO-B. The dichloromethane extract of propolis showed potent inhibition of human MAO-A and MAO-B. Further fractionation identified the most active fractions as rich in flavonoids. Galangin and apigenin were identified as the principal MAO-inhibitory constituents. Inhibition of MAO-A by galangin was about 36 times more selective than MAO-B, while apigenin selectivity for MAO-A vs. MAO-B was about 1.7 fold. Apigenin inhibited MAO-B significantly more potently than galangin. Galangin and apigenin were further evaluated for kinetic characteristics and the mechanism for the enzymes’ inhibition. Binding of galangin and apigenin with MAO-A and -B was not time-dependent and was reversible, as suggested by enzyme-inhibitor binding and dissociation-dialysis assay. The inhibition kinetics studies suggested that galangin and apigenin inhibited MAO-A and -B by a competitive mechanism. Presence of prominent MAO inhibitory constituents in propolis products suggests their potential for eliciting pharmacological effects that might be useful in depression or other neurological disorders. The results may also have important implications in drug-dietary supplement interactions.

  4. Radiochemistry devoted to the production of monoamine oxidase (MAO-A and MAO-B) ligands for brain imaging with positron emission tomography.

    Science.gov (United States)

    Kersemans, Ken; Van Laeken, Nick; De Vos, Filip

    2013-01-01

    Monoamine oxidase (MAO) belongs to a family of flavin-containing integral enzymes that are present in the outer mitochondrial membrane in neurons and glial cells in the central nervous system. These enzymes catalyze the oxidative deamination of various neurotransmitters, biogenic amines, and xenobiotics, thereby influencing their availability and physiological activity in brain and body. Over the past decades, many potential positron emission tomography tracers have been put forward to visualize MAO in the brain with varying success, and recent publications on the topic illustrate the continuing interest in the field. The present review gives an overview of the compounds that have been put forward as possible MAO tracers in the brain and focuses on the radiochemical procedures that have been developed to produce them up till now. Relevant radioligands are grouped by the main radiochemical strategies that have been employed to synthesize them, and some interesting details and findings that are crucial to the radiosyntheses are provided.

  5. Predicting drunk driving: contribution of alcohol use and related problems, traffic behaviour, personality and platelet monoamine oxidase (MAO) activity.

    Science.gov (United States)

    Eensoo, Diva; Paaver, Marika; Harro, Maarike; Harro, Jaanus

    2005-01-01

    The aim of the study was to characterize the predictive value of socio-economic data, alcohol consumption measures, smoking, platelet monoamine oxidase (MAO) activity, traffic behaviour habits and impulsivity measures for actual drunk driving. Data were collected from 203 male drunk driving offenders and 211 control subjects using self-reported questionnaires, and blood samples were obtained from the two groups. We identified the combination of variables, which predicted correctly, approximately 80% of the subjects' belonging to the drunk driving and control groups. Significant independent discriminators in the final model were, among the health-behaviour measures, alcohol-related problems, frequency of using alcohol, the amount of alcohol consumed and smoking. Predictive traffic behaviour measures were seat belt use and paying for parking. Among the impulsivity measures, dysfunctional impulsivity was the best predictor; platelet MAO activity and age also had an independent predictive value. Our results support the notion that drunk driving is the result of a combination of various behavioural, biological and personality-related risk factors.

  6. The inhibition of monoamine oxidase by esomeprazole

    OpenAIRE

    2013-01-01

    Virtual screening of a library of drugs has suggested that esomeprazole, the S-enantiomer of omeprazole, may possess binding affinities for the active sites of the monoamine oxidase (MAO) A and B enzymes. Based on this finding, the current study examines the MAO inhibitory properties of esomeprazole. Using recombinant human MAO-A and MAO-B, IC50 values for the inhibition of these enzymes by esomeprazole were experimentally determined. To examine the reversibility of MAO inhibition by esomepra...

  7. Discovery of New Chemical Entities for Old Targets: Insights on the Lead Optimization of Chromone-Based Monoamine Oxidase B (MAO-B) Inhibitors.

    Science.gov (United States)

    Reis, Joana; Cagide, Fernando; Chavarria, Daniel; Silva, Tiago; Fernandes, Carlos; Gaspar, Alexandra; Uriarte, Eugenio; Remião, Fernando; Alcaro, Stefano; Ortuso, Francesco; Borges, Fernanda

    2016-06-23

    The discovery of new chemical entities endowed with potent, selective, and reversible monoamine oxidase B inhibitory activity is a clinically relevant subject. Therefore, a small library of chromone derivatives was synthesized and screened toward human monoamine oxidase isoforms (hMAO-A and hMAO-B). The structure-activity relationships studies strengthen the importance of the amide spacer and the direct linkage of carbonyl group to the γ-pyrone ring, along with the presence of meta and para substituents in the exocyclic ring. The most potent MAO-B inhibitors were N-(3'-chlorophenyl)-4-oxo-4H-chromene-3-carboxamide (20) (IC50 = 403 pM) and N-(3',4'-dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (27) (IC50 = 669 pM), acting as competitive and noncompetitive reversible inhibitors, respectively. Computational docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed selectivity and potency. Compound 27 stands out due to its favorable toxicological profile and physicochemical properties, which pointed toward blood-brain barrier permeability, thus being a valid candidate for subsequent animal studies.

  8. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  9. Leflunomide, a Reversible Monoamine Oxidase Inhibitor.

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    Petzer, Jacobus P; Petzer, Anél

    2016-01-01

    A screening study aimed at identifying inhibitors of the enzyme, monoamine oxidase (MAO), among clinically used drugs have indicated that the antirheumatic drug, leflunomide, is an inhibitor of both MAO isoforms. Leflunomide inhibits human MAO-A and MAO-B and exhibits IC50 values of 19.1 μM and 13.7 μM, respectively. The corresponding Ki values are 17.7 μM (MAO-A) and 10.1 μM (MAO-B). Dialyses of mixtures of the MAO enzymes and leflunomide show that inhibition of the MAOs by leflunomide is reversible. The principal metabolite of leflunomide, teriflunomide (A77 1726), in contrast is not an MAO inhibitor. This study concludes that, although leflunomide is only moderately potent as an MAO inhibitor, isoxazole derivatives may represent a general class of MAO inhibitors and this heterocycle may find application in MAO inhibitor design. In this respect, MAO inhibitors are used in the clinic for the treatment of depressive illness and Parkinson's disease, and are under investigation as therapy for certain types of cancer, Alzheimer's disease and age-related impairment of cardiac function.

  10. Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl

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    Schulz, D.; Schulz, D.; Mirrione, M.; Henn, F.A.

    2009-11-29

    Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n = 10), non-helpless (cNLH, n = 12) and wild type (WT, n = 8) Sprague Dawley rats. The animals were exposed to an open field for 10 min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs on the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n = 4-5 per group), chronic treatment with a high dose of the monoamineoxidase (MAO)-Binhibitordeprenyl (10 mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10 mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning.

  11. Dual functions of transcription factors, transforming growth factor-beta-inducible early gene (TIEG)2 and Sp3, are mediated by CACCC element and Sp1 sites of human monoamine oxidase (MAO) B gene.

    Science.gov (United States)

    Ou, Xiao-Ming; Chen, Kevin; Shih, Jean C

    2004-05-14

    Monoamine oxidases (MAO) A and B catalyze the oxidative deamination of many biogenic and dietary amines. Abnormal expression of MAO has been implicated in several psychiatric and neurodegenerative disorders. Human MAO B core promoter (-246 to -99 region) consists of CACCC element flanked by two clusters of overlapping Sp1 sites. Here, we show that cotransfection with transforming growth factor (TGF)-beta-inducible early gene (TIEG)2 increased MAO B gene expression at promoter, mRNA, protein, and catalytic activity levels in both SH-SY5Y and HepG2 cells. Mutation of the CACCC element increased the MAO B promoter activity, and cotransfection with TIEG2 further increased the promoter activity, suggesting that CACCC was a repressor element. This increase was reduced when the proximal Sp1 overlapping sites was mutated. Similar interactions were found with Sp3. These results showed that TIEG2 and Sp3 were repressors at the CACCC element but were activators at proximal Sp1 overlapping sites of MAO B. Gel-shift and chromatin immunoprecipitation assays showed that TIEG2 and Sp3 bound directly to CACCC element and the proximal Sp1 sites in both synthetic oligonucleotides and natural MAO B core promoter. TIEG2 had a higher affinity to Sp1 sites than CACCC element, whereas Sp3 had an equal affinity to both elements. Thus, TIEG2 was an activator, but Sp3 had no effect on MAO B gene expression. This study provides new insights into MAO B gene expression and illustrates the complexity of gene regulation.

  12. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

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    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  13. Nitrogen heterocycles as potential monoamine oxidase inhibitors: Synthetic aspects

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    Pravin O. Patil

    2014-12-01

    Full Text Available The present review highlights the synthetic methods of monoamine oxidase inhibitors (MAO belonging to a group of nitrogen heterocycles such as pyrazoline, indole, xanthine, oxadiazole, benzimidazole, pyrrole, quinoxaline, thiazole and other related compounds (1990–2012. Moreover, it emphasizes salient findings related to chemical structures and the bioactivities of these heterocycles as MAO inhibitors. The aim of this review is to find out different methods for the synthesis of nitrogen containing heterocycles and their bioactivity related aspects as MAO inhibitors.

  14. A novel fluorogenic probe for monoamine oxidase assays

    Institute of Scientific and Technical Information of China (English)

    You You Lu; Yu Guang Wang; Bin Dai; Yi Qi Dai; Zhao Wang; Zheng Wei Fu; Qing Zhu

    2008-01-01

    Monoamine oxidase is flavoenzymes, widely distributed in mammals. It is well recognized that MAOs serve an important role in metabolism that they have close relationship with health .Along with the discoveries between MAOs and neurotic disease, more and more studies have been jumped in .In this paper, we design a new probe for assaying the activities of MAOs. The results showed that the probe [7-(3-aminopropoxy)coumarin] is simple, effective and sensitive for MAOB.

  15. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors

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    Legoabe LJ

    2015-07-01

    Full Text Available Lesetja J Legoabe,1 Anél Petzer,1 Jacobus P Petzer1,21Centre of Excellence for Pharmaceutical Sciences, 2Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South AfricaAbstract: Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO inhibitors, a series of C5-substituted 2-acetylphenol analogs (15 and related compounds (two were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease.Keywords: monoamine oxidase, MAO, inhibition, 2-acetylphenol, structure–activity relationship

  16. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    Science.gov (United States)

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.

  17. Low platelet monoamine oxidase activity in pathological gambling

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    Carrasco, J.L. [Department of Psychiatry, Centro de Salud Mental, Parla Madrid (Spain); Saiz-Ruiz, J. [Department of Psychiatry and Haematology, Hospital Ramon y Cajal, Madrid (Spain); Hollander, E. [Department of Psychiatry, Mount Sinai School of Medicine, Queens Hospital Center, New York (United States); Cesar, J. [Department of Haematology, Hospital Ramon y Cajal, Madrid (Spain); Lopez-Ibor, J.J. Jr. [Department of Psychiatry, Hospital San Carlos, Complutense University, Madrid (Spain)

    1994-12-01

    Decreased platelet monoamine oxidase (MAO) activity has been reported in association with sensation-seeking personality type and in some mental disorders associated with a lack of impulse control. Pathological gambling itself has been related with both sensation-seeking and reduced impulse control. Platelet MAO activity was investigated in 15 DSM-III-R pathological gamblers from our outpatient clinic. Gamblers had a significantly lower platelet MAO activity than a group of 25 healthy controls. The range of MAO levels in gamblers was also significantly shorter than in controls. In controls, platelet MAO levels showed the previously described negative correlations with sensation-seeking scores but not in gamblers. The findings are consistent with previous studies showing an association of low platelet MAO activity with impulse control disorders and raise some interesting therapeutic alternatives for pathological gambling. (au) (40 refs.).

  18. Chromone-2- and -3-carboxylic acids inhibit differently monoamine oxidases A and B.

    Science.gov (United States)

    Alcaro, Stefano; Gaspar, Alexandra; Ortuso, Francesco; Milhazes, Nuno; Orallo, Francisco; Uriarte, Eugenio; Yáñez, Matilde; Borges, Fernanda

    2010-05-01

    Chromone carboxylic acids were evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. The biological data indicated that only chromone-3-carboxylic acid is a potent hMAO-B inhibitor, with a high degree of selectivity for hMAO-B compared to hMAO-A. Conversely the chromone-2-carboxylic acid resulted almost inactive against both MAO isoforms. Docking experiments were performed to elucidate the reasons of the different MAO IC(50) data and to explain the absence of activity versus selectivity, respectively. 2010 Elsevier Ltd. All rights reserved.

  19. Brain Monoamine Oxidase-A Activity Predicts Trait Aggression

    Science.gov (United States)

    Alia-Klein, Nelly; Goldstein, Rita Z.; Kriplani, Aarti; Logan, Jean; Tomasi, Dardo; Williams, Benjamin; Telang, Frank; Shumay, Elena; Biegon, Anat; Craig, Ian W.; Henn, Fritz; Wang, Gene-Jack; Volkow, Nora D.; Fowler, Joanna S.

    2008-01-01

    The genetic deletion of monoamine oxidase A (MAO A, an enzyme which breaks down the monoamine neurotransmitters norepinephrine, serotonin and dopamine) produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, MIM 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in-vivo in healthy non-smoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the Multidimensional Personality Questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than a third of the variability. Since trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression. PMID:18463263

  20. The inhibition of monoamine oxidase by phenformin and pentamidine.

    Science.gov (United States)

    Barkhuizen, M; Petzer, A; Petzer, J P

    2014-09-01

    A computational study has suggested that phenformin, an oral hypoglycaemic drug, may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The present study therefore investigates the MAO inhibitory properties of phenformin. Pentamidine, a structurally related diamidine compound, has previously been reported to be a MAO inhibitor and was included in this study as a reference compound. Using recombinant human MAO-A and MAO-B, this study finds that phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50 value of 41 µM. Pentamidine, on the other hand, potently inhibits both MAO-A and MAO-B with IC50 values of 0.61 μM and 0.22 μM, respectively. An examination of the recoveries of the enzymatic activities after dilution and dialysis of the enzyme-inhibitor complexes shows that both compounds interact reversibly with the MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive inhibitor with estimated Ki values of 0.41 μM and 0.22 μM for the inhibition of MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of MAO-A inhibition with an estimated Ki value of 65 µM. This study concludes that biguanide and amidine functional groups are most likely important structural features for the inhibition of the MAOs by phenformin and pentamidine, and compounds containing these and closely related functional groups should be considered as potential MAO inhibitors. Furthermore, the biguanide and amidine functional groups may act as useful moieties in the future design of MAO inhibitors.

  1. Selected C7-substituted chromone derivatives as monoamine oxidase inhibitors.

    Science.gov (United States)

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-12-01

    A series of C7-substituted chromone (1-benzopyran-4-one) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The chromones are structurally related to a series of C7-functionalized coumarin (1-benzopyran-2-one) derivatives which has been reported to act as potent MAO inhibitors. The results of the current study document that the chromones are highly potent reversible inhibitors of MAO-B with IC(50) values ranging from 0.008 to 0.370 μM. While the chromone derivatives also exhibit affinities for MAO-A, with IC(50) values ranging from 0.495 to 8.03 μM, they are selective for the MAO-B isoform. Structure-activity relationships (SAR) show that 7-benzyloxy substitution of chromone is suitable for MAO-B inhibition with tolerance for a variety of substituents and substitution patterns on the benzyloxy ring. It may be concluded that 7-benzyloxychromones are appropriate lead compounds for the design of reversible and selective MAO-B inhibitors. With the aid of modeling studies, potential binding orientations and interactions of selected chromone derivatives in the MAO-A and -B active sites are examined. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Adipogenesis-related increase of semicarbazide-sensitive amine oxidase and monoamine oxidase in human adipocytes.

    Science.gov (United States)

    Bour, Sandy; Daviaud, Danièle; Gres, Sandra; Lefort, Corinne; Prévot, Danielle; Zorzano, Antonio; Wabitsch, Martin; Saulnier-Blache, Jean-Sébastien; Valet, Philippe; Carpéné, Christian

    2007-08-01

    A strong induction of semicarbazide-sensitive amine oxidase (SSAO) has previously been reported during murine preadipocyte lineage differentiation but it remains unknown whether this emergence also occurs during adipogenesis in man. Our aim was to compare SSAO and monoamine oxidase (MAO) expression during in vitro differentiation of human preadipocytes and in adipose and stroma-vascular fractions of human fat depots. A human preadipocyte cell strain from a patient with Simpson-Golabi-Behmel syndrome was first used to follow amine oxidase expression during in vitro differentiation. Then, human preadipocytes isolated from subcutaneous adipose tissues were cultured under conditions promoting ex vivo adipose differentiation and tested for MAO and SSAO expression. Lastly, human adipose tissue was separated into mature adipocyte and stroma-vascular fractions for analyses of MAO and SSAO at mRNA, protein and activity levels. Both SSAO and MAO were increased from undifferentiated preadipocytes to lipid-laden cells in all the models: 3T3-F442A and 3T3-L1 murine lineages, human SGBS cell strain or human preadipocytes in primary culture. In human subcutaneous adipose tissue, the adipocyte-enriched fraction exhibited seven-fold higher amine oxidase activity and contained three- to seven-fold higher levels of mRNAs encoded by MAO-A, MAO-B, AOC3 and AOC2 genes than the stroma-vascular fraction. MAO-A and AOC3 genes accounted for the majority of their respective MAO and SSAO activities in human adipose tissue. Most of the SSAO and MAO found in adipose tissue originated from mature adipocytes. Although the mechanism and role of adipogenesis-related increase in amine oxidase expression remain to be established, the resulting elevated levels of amine oxidase activities found in human adipocytes may be of potential interest for therapeutic intervention in obesity.

  3. 3-Coumaranone derivatives as inhibitors of monoamine oxidase

    Directory of Open Access Journals (Sweden)

    Van Dyk AS

    2015-10-01

    Full Text Available Adriaan S Van Dyk,1,2 Jacobus P Petzer,1,2 Anél Petzer,1 Lesetja J Legoabe1 1Centre of Excellence for Pharmaceutical Sciences, 2Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa Abstract: The present study examines the monoamine oxidase (MAO inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform. 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50 values of 0.004–1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme–inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson’s disease and Alzheimer’s disease. Keywords: benzofuran-3(2H-one, MAO, inhibition, reversible, competitive, Parkinson’s disease 

  4. Selected chromone derivatives as inhibitors of monoamine oxidase.

    Science.gov (United States)

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-09-01

    A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy]chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC(50) values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC(50) values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

    Science.gov (United States)

    Obata, Toshio; Aomine, Masahiro

    The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

  6. Multifunctional coumarin derivatives: monoamine oxidase B (MAO-B) inhibition, anti-β-amyloid (Aβ) aggregation and metal chelation properties against Alzheimer's disease.

    Science.gov (United States)

    Huang, Ming; Xie, Sai-Sai; Jiang, Neng; Lan, Jin-Shuai; Kong, Ling-Yi; Wang, Xiao-Bing

    2015-02-01

    A series of coumarin derivatives were designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most of these compounds exhibited significant potency to inhibit hMAO-B selectively and self-induced Aβ1-42 aggregation. In particular, compound 13 presented the greatest potential to inhibit hMAO-B (IC50=0.081μM, SI >1234) and good inhibition of Aβ1-42 aggregation (52.9% at 20μM). Moreover, compound 13 could function as a metal-chelator, penetrate the blood-brain barrier (BBB) and show low cell toxicity in rat pheochromocytoma (PC12) and SH-SY5Y cells. Taken together, these results suggested that compound 13 might be a promising multifunctional agent for AD treatment.

  7. Lack of platelet monoamine oxidase activity in Cebus monkeys (Cebus albifrons).

    Science.gov (United States)

    Heintz, R; Richardson, M A; Perumal, A S; Casey, D E

    1989-01-01

    1. Recent evidence suggests that monoamine oxidase (MAO) plays an important role modulating the extrapyramidal syndromes produced by neuroleptic drugs in both human and nonhuman primates. 2. To evaluate the possibility of using peripheral blood platelet MAO-B levels as indices of central nervous system MAO-B effects, we measured platelet MAO-B levels in Cebus monkeys that were previously tested with neuroleptics (N = 36) or drug naive (N = 6). 3. No platelet MAO-B was consistently detectable in these blood samples. 4. Thus platelet measures of MAO-B do not reliably reflect brain MAO-B function in nonhuman primates and do not offer a useful model for studying blood-brain MAO-B relationships.

  8. High-throughput screening for monoamine oxidase-A and monoamine oxidase-B inhibitors using one-step fluorescence assay

    Institute of Scientific and Technical Information of China (English)

    Hong-mei GUANG; Guan-hua DU

    2006-01-01

    Aim: To develop high-throughput screening (HTS) assays for monoamine oxidase (MAO)-A and MAO-B inhibitors. Methods: A fluorescence probe based method measuring MAO-A and MAO-B activity was established and optimized, with its sensitivity, stability and specificity evaluated. Reaction conditions including enzyme sources, substrate concentrations, incubation volume and reaction time in 384-well format were optimized to achieve sensitive and low consumptive goal. Results: In optimized conditions, dynamic parameters of MAO-A and MAO-B were obtained. The Km value of serotonin to MAO-A was 1.66 μmol/L, while that of benzylamine to MAO-B was 0.80 umol/L. The IC50 value of clorgyline to MAO-A was 2.99 nmol/L, and that of deprenyl to MAO-B was 7.04 nmol/L, matching those obtained from traditional spectrometric assays. Among tested samples, one compound exerted an inhibitory effect on MAO-A activity with IC50 as 0.36 μmol/L, and three compounds had an inhibitory effect on MAO-B activity with IC50 as 0.13,0.19, and 0.13 μmol/L. The Z' factor was 0.71±0.03 and 0.75±0.03 in MAO-A-inhibitor and MAO-B-inhibitor HTS system, respectively. Conclusion: The established assays can be well applied to MAO-A and MAO-B inhibitor screening with high quality, precision and reproducibility.

  9. Evaluation of the Inhibitory Effects of Bavachinin and Bavachin on Human Monoamine Oxidases A and B

    Directory of Open Access Journals (Sweden)

    Najla O. Zarmouh

    2015-01-01

    Full Text Available Monoamine oxidase B inhibitors (MAO-BIs are used in the early management of Parkinson’s disease (PD. Long-term suspected side effects of MAO-B classical inhibitors established the need for safer alternative therapeutic agents. In our study, the flavanone bavachinin (BNN and its analog bavachin (BVN found in the seeds of Psoralea corylifolia L. ethanolic extract (PCSEE were investigated for their human MAO-A and MAO-B (hMAO-A and hMAO-B inhibition. Both PCSEE and BNN effectively reduced hMAO-B activity more than hMAO-A while BVN had activating effects. BNN showed selective hMAO-B inhibition (IC50 ~ 8.82 μM more than hMAO-A (IC502009;~ 189.28 μM. BNN in the crude extract was determined by HPLC, also validated by TLC showing a yield of 0.21% PCSEE dry weight. BNN competitively inhibited hMAO-A and hMAO-B, with a lower hMAO-B Ki than hMAO-A Ki by 10.33-fold, and reduced hMAO-B Km/Vmax efficiency ratio to be comparable to the standard selegiline. Molecular docking examination of BNN and BVN predicted an indirect role of BNN C7-methoxy group for its higher affinity, selectivity, and reversibility as an MAO-BI. These findings suggest that BNN, which is known to be a potent PPAR-γ agonist, is a selective and competitive hMAO-B inhibitor and could be used in the management of PD.

  10. Potential of Natural Products of Herbal Origin as Monoamine Oxidase Inhibitors.

    Science.gov (United States)

    Orhan, Ilkay Erdogan

    2016-01-01

    Monoamine oxidase (MAO, E.C. 1.4.3.4) is a flavin-adenine type of enzyme with two isoforms referred to MAO-A and MAO-B that function for oxidation of monoamines. While MAO-A inhibitors are effective as antidepressant and anxiolytic drugs (e.g. chlorgyline, moclobemide, and lazabemide), inhibitors of MAO-B (e.g. Ldeprenyl, pargyline, and rasagiline) are used against neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Considering the need for novel MAO inhibitors due to side effects of the current ones, natural products have become attractive targets for researchers. Up till now, many studies revealed strong MAO inhibitory activity of flavonoid, xanthone, alkaloid, and coumarin derivatives from herbal sources, which also become good models for the synthetic MAO inhibitors. For this purpose, the present review focuses on examples of in vitro and in vivo MAO-inhibiting natural compounds of plant origin from a wide variety of chemical classes isolated mainly between 2000 - 2015.

  11. Monoamine oxidase B inhibitors from the fruits of Opuntia ficus-indica var. saboten.

    Science.gov (United States)

    Han, Y N; Choo, Y; Lee, Y C; Moon, Y I; Kim, S D; Choi, J W

    2001-02-01

    Three varieties of methyl citrate and 1-methyl malate were isolated from the fruits of Opuntia ficus-indica var. saboten Makino through in vitro bioassay-guided isolation for the inhibition on monoamine oxidase(MAO). The IC50 values for MAO-B of 1-monomethyl citrate, 1,3-dimethyl citrate, trimethyl citrate and 1-methyl malate were 0.19, 0.23, 0.61 and 0.25 mM, respectively. However, on MAO-A, their inhibitions showed only marginal activity.

  12. Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression.

    Science.gov (United States)

    Ordway, G A; Farley, J T; Dilley, G E; Overholser, J C; Meltzer, H Y; Balraj, E K; Stockmeier, C A; Klimek, V

    1999-11-13

    An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; pdepression (r(2)=0.14; pdepression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.

  13. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice.

    Science.gov (United States)

    Singh, Chanpreet; Bortolato, Marco; Bali, Namrata; Godar, Sean C; Scott, Anna L; Chen, Kevin; Thompson, Richard F; Shih, Jean C

    2013-07-30

    The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.

  14. Iododerivative of pargyline: A potential tracer for the exploration of monoamine oxidase sites by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Lena, Isabelle; Ombetta, Jean-Edouard; Chalon, Sylvie; Dognon, Anne-Marie; Baulieu, Jean-Louis; Frangin, Yves; Garreau, Lucette; Besnard, Jean-Claude; Guilloteau, Denis

    1995-08-01

    Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [{sup 125}I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [{sup 125}I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [{sup 125}I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with {sup 123}I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

  15. [Substrate-inhibitory analysis of monoamine oxidase from hepatopancreas of the octopus Bathypolypus arcticus].

    Science.gov (United States)

    Basova, I N; Iagodina, O V

    2012-01-01

    Study of the substrate-inhibitory specificity of mitochondrial monoamine oxidase (MAO) of hepatopancreas of the octopus Bathypolypus arcticus revealed distinctive peculiarities of catalytic properties of this enzyme. The studied enzyme, on one hand, like the classic MAO of homoiothermal animals, is able to deaminate tyramine, serotonin, benzylamine, tryptamine, beta-phenylethylamine, while, on the other hand, deaminates histamine and does not deaminate putrescine--classic substrates of diamine oxidase (DAO). Results of the substrate-inhibitory analysis with use of chlorgiline and deprenyl are indirect proofs of the existence in the octopus hepatopancreas of one molecular MAO form. Semicarbazide and pyronine G turned out to be weak irreversible inhibitors, four derivatives of acridine--irreversible inhibitors of the intermediate effectiveness with respect to the octopus hepatopancreas MAO; specificity of action of inhibitors at deamination of different substrates was equal.

  16. Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion.

    Science.gov (United States)

    Feldman, J M; Chapman, B

    1975-12-01

    Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3, 4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35 +/- 8.7 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.

  17. In vitro evaluation of Bacopa monniera extract and individual constituents on human recombinant monoamine oxidase enzymes.

    Science.gov (United States)

    Singh, Rajbir; Ramakrishna, Rachumallu; Bhateria, Manisha; Bhatta, Rabi Sankar

    2014-09-01

    Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used worldwide for its nootropic action. Chemically standardized extract of B. monniera is now available as over the counter herbal remedy to enhance memory in children and adults. Considering the nootropic action of B. monniera, we evaluated the effect of clinically available B. monniera extract and six of B. monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C, bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO) enzymes. The effect of B. monniera extract and individual constituents on human recombinant MAO-A and MAO-B enzymes was evaluated using MAO-Glo(TM) assay kit (Promega Corporation, USA), following the instruction manual. IC50 and mode of inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture inhibited the MAO-A and MAO-B enzymes. Bacopaside I exhibited mixed mode of inhibition with IC50 and Ki values of 17.08 ± 1.64 and 42.5 ± 3.53 µg/mL, respectively, for MAO-A enzyme. Bacopaside I is the major constituent of B. monniera, which inhibited the MAO-A enzyme selectively.

  18. Inhibition of monoamine oxidase by selected C6-substituted chromone derivatives.

    Science.gov (United States)

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-03-01

    Chromone has been reported to be a useful scaffold for the design of monoamine oxidase (MAO) inhibitors. In an attempt to discover highly potent MAO inhibitors and to contribute to the known structure-activity relationships (SAR) of MAO inhibition by chromones, in the present study, we have synthesized a series of chromone derivatives substituted at C6 with a variety of alkyloxy substituents, and evaluated the resulting compounds as inhibitors of recombinant human MAO-A and -B. The results document that the C6-substituted chromones are potent reversible MAO-B inhibitors with IC(50) values in the low nM range (2-76 nM). The chromones were also found to bind reversibly to MAO-A, but with lower affinities compared to MAO-B. It may therefore be concluded that C6-substituted chromones are highly potent MAO-B selective inhibitors and promising lead compounds for the development of therapy for neurodegenerative disorders such as Parkinson's disease. The results of this study are discussed with reference to possible binding orientations of a selected C6-substituted chromone in the active site cavities of MAO-A and -B. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Process characterization of a monoamine oxidase

    DEFF Research Database (Denmark)

    Ramesh, Hemalata; Woodley, John

    2014-01-01

    .e, on biocatalyst development (e.g. improvement of expression levels), process development (e.g. improved oxygen supply, product removal strategies) or biocatalyst stabilization (e.g. through immobilization or directed evolution). This paper presents a systematic method to identify the bottleneck of a potential...... biocatalytic process using a monoamine oxidase to synthesise an intermediate in the manufacture of a drug for treating Hepatitis C (Telaprevir)....

  20. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Bradley J Robottom

    2011-01-01

    Full Text Available Bradley J RobottomDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Parkinson's disease (PD is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors.Keywords: monoamine oxidase inhibitors, rasagiline, selegiline, Parkinson's disease, efficacy, safety

  1. Desmodeleganine, a new alkaloid from the leaves of Desmodium elegans as a potential monoamine oxidase inhibitor.

    Science.gov (United States)

    Zhi, Kang-Kang; Yang, Zhong-Duo; Shi, Dan-Feng; Yao, Xiao-Jun; Wang, Ming-Gang

    2014-10-01

    Desmodeleganine (1), a new potential monoamine oxidase inhibitor, along with three known alkaloids, bufotenin (2), hydroxy-N, N-dimethyltryptamine N(12)-oxide (3), 2-(5-methoxy-1H-indol-3-yl)-N, and N-dimethylethylamine (4) were isolated from the leaves of Desmodium elegans. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. 1 showed strong monoamine oxidase inhibitory activity with IC50 value of 13.92 ± 1.5 μM, when the IC50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The molecular modeling was also performed to explore the binding mode of compounds 1, 2 at the active site of MAO-A and MAO-B.

  2. Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress-induced Neuronal Death in Huntington Disease.

    Science.gov (United States)

    Ooi, Jolene; Hayden, Michael R; Pouladi, Mahmoud A

    2015-12-01

    Monoamine oxidases (MAO) are important components of the homeostatic machinery that maintains the levels of monoamine neurotransmitters, including dopamine, in balance. Given the imbalance in dopamine levels observed in Huntington disease (HD), the aim of this study was to examine MAO activity in a mouse striatal cell model of HD and in human neural cells differentiated from control and HD patient-derived induced pluripotent stem cell (hiPSC) lines. We show that mouse striatal neural cells expressing mutant huntingtin (HTT) exhibit increased MAO expression and activity. We demonstrate using luciferase promoter assays that the increased MAO expression reflects enhanced epigenetic activation in striatal neural cells expressing mutant HTT. Using cellular stress paradigms, we further demonstrate that the increase in MAO activity in mutant striatal neural cells is accompanied by enhanced susceptibility to oxidative stress and impaired viability. Treatment of mutant striatal neural cells with MAO inhibitors ameliorated oxidative stress and improved cellular viability. Finally, we demonstrate that human HD neural cells exhibit increased MAO-A and MAO-B expression and activity. Altogether, this study demonstrates abnormal MAO expression and activity and suggests a potential use for MAO inhibitors in HD.

  3. Monoamine oxidase B layer-by-layer film fabrication and characterization toward dopamine detection

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Celina Massumi; Pereira, Tamyris Paschoal [Universidade Federal de São Carlos, UFSCar, CCTS, Sorocaba, São Paulo (Brazil); Mascagni, Daniela Branco Tavares [Universidade Estadual de São Paulo — UNESP, Sorocaba, São Paulo (Brazil); Leite de Moraes, Marli [Universidade Federal de São Paulo, Unifesp, São José dos Campos, São Paulo (Brazil); Ferreira, Marystela, E-mail: marystela@ufscar.br [Universidade Federal de São Carlos, UFSCar, CCTS, Sorocaba, São Paulo (Brazil)

    2016-01-01

    In this work nanostructured film composites of the monoamine oxidase B (MAO-B) enzyme, free or encapsulated in liposomes, were fabricated by the layer-by-layer (LbL) self-assembly technique, employing polyethylene imine (PEI) as polycation. Initially, the MAO-B enzyme was incorporated into liposomes in order to preserve its enzymatic structure ensuring their activity and catalytic stability. The LbL film growth was monitored by surface plasmon resonance (SPR) by gold resonance angle shift analysis after each bilayer deposition. Subsequently, the films were applied as amperometric biosensors for dopamine detection using Prussian Blue (PB) as the electron mediator. The biosensor fabricated by MAO-B incorporated into liposomes composed of DPPG:POPG in the ratio (1:4) (w/w) showed the best performance with a sensitivity of 0.86 (μA cm{sup −2})/(mmol L{sup −1}) and a detection limit of 0.33 mmol L{sup −1}. - Highlights: • Monoamine oxidase B incorporation in liposomes was proposed to preserve the enzyme. • Layer-by-layer films composed of MAO-B (free and in liposomes) were fabricated. • Amperometric response using ITO/Prussian Blue covered with the MAO-B films was studied. • Sensitivity, limit of detection and apparent Michaelis–Menten constant were compared.

  4. Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.

    1983-09-01

    Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.

  5. New insights into the biological properties of Crocus sativus L.: chemical modifications, human monoamine oxidases inhibition and molecular modeling studies.

    Science.gov (United States)

    De Monte, Celeste; Carradori, Simone; Chimenti, Paola; Secci, Daniela; Mannina, Luisa; Alcaro, Francesca; Petzer, Anél; N'Da, Clarina I; Gidaro, Maria Concetta; Costa, Giosuè; Alcaro, Stefano; Petzer, Jacobus P

    2014-07-23

    Although there are clinical trials and in vivo studies in literature regarding the anxiolytic and antidepressant activities of the components of Crocus sativus L., their effects on the human monoamine oxidases (hMAO-A and hMAO-B), enzymes which are involved in mental disorders and neurodegenerative diseases, have not yet been investigated. We have thus examined the hMAO inhibitory activities of crocin and safranal (the most important active principles in saffron) and, subsequently, designed a series of safranal derivatives to evaluate which chemical modifications confer enhanced inhibition of the hMAO isoforms. Docking simulations were performed in order to identify key molecular recognitions of these inhibitors with both isoforms of hMAO. In this regard, different mechanisms of action were revealed. This study concludes that safranal and crocin represent useful leads for the discovery of novel hMAO inhibitors for the clinical management of psychiatric and neurodegenerative disorders.

  6. Inhibitory effect of acetylcholine on monoamine oxidase A and B activity in different parts of rat brain.

    Science.gov (United States)

    Osman, Mohamed Y; Osman, Hassan M Y

    2008-01-01

    Acetylcholine (CAS 60-31-1, ACh), which is similar in its chemical structure to the carbamate aldicarb, was found to inhibit brain monoamine oxidase isoenzymes, namely MAO-A and B. The effect of ACh on both isoenzymes extracted from the whole brain of male albino rats and its different parts (frontal cortex, basal ganglia, cerebellum, pons and medulla oblongata) was studied. The results indicated that ACh inhibited MAO-A from the cerebellum and MAO-B from the basal ganglia more than MAO iso-enzymes from other brain parts. The inhibition was of the competitive type. It was also found that the enzyme inhibitor dissociation constants (Ki) and the affinity constants (Ki/Km) of MAO-A were higher than those of MAO-B.

  7. Inhibition of monoamine oxidase by furazolidone in the chicken and the influence of the alimentary flora thereon.

    OpenAIRE

    Ali, B. H.; Bartlet, A. L.

    1980-01-01

    1 The addition of furazolidone to the feed at the therapeutic level (0.04% w/w, 10 days) inhibited monoamine oxidase (MAO) activity by 47 to 72% in chicken duodenal mucosa, heart and brain, but in the liver the enzyme activity was unaffected by the treatment. 2 Furazolidone (200 mg/kg) administered by crop tube inhibited MAO activities in duodenal mucosa, liver, heart and brain. 3 Furazolidone (200 mg/kg) injected intramuscularly did not inhibit MAO activity in the chicken. 4 Pretreatment of ...

  8. Biosensor based on inhibition of monoamine oxidases A and B for detection of β-carbolines.

    Science.gov (United States)

    Radulescu, Maria-Cristina; Bucur, Madalina-Petruta; Bucur, Bogdan; Radu, Gabriel Lucian

    2015-05-01

    β-Carbolines are inhibitors of monoamine oxidases (MAO-A and MAO-B) and can be found in foods, hallucinogenic plant or various drugs. We have developed a fast analysis method for β-carbolines based on the inhibition of MAO. The enzymes were immobilized on screen-printed electrodes modified with a stabilized film of Prussian blue that contain also copper. We have used benzylamine as substrate for the enzymatic reaction and the hydrogen peroxide was measured amperometrically at -50 mV. The detection limits obtained were 5.0 µM for harmane and 2.5 µM for both harmaline and norharmane. The MAO-A is inhibited by all three tested β-carbolines (harmane, norharmane, and harmaline) while MAO-B is inhibited only by norharmane. The presence of norharmane in mixtures of β-carbolines can be identified based on the difference between the cumulative inhibition of MAO-A by all β-carbolines and MAO-B inhibition. The developed biosensors were used for food analysis.

  9. Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts

    Directory of Open Access Journals (Sweden)

    O. M. Duicu

    2016-01-01

    Full Text Available Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD and diabetes mellitus (DM. Recently, mitochondrial monoamine oxidases (MAOs have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1 Control (CTRL, valvular patients without CHD; (2 CHD, patients with confirmed CHD; and (3 CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2 emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

  10. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats.

  11. Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease.

    Science.gov (United States)

    Garcia-Miralles, Marta; Ooi, Jolene; Ferrari Bardile, Costanza; Tan, Liang Juin; George, Maya; Drum, Chester L; Lin, Rachel Yanping; Hayden, Michael R; Pouladi, Mahmoud A

    2016-04-01

    Abnormal monoamine oxidase A and B (MAO-A/B) activity and an imbalance in monoamine neurotransmitters have been suggested to underlie the pathobiology of depression, a major psychiatric symptom observed in patients with neurodegenerative diseases, such as Huntington disease (HD). Increased MAO-A/B activity has been observed in brain tissue from patients with HD and in human and rodent HD neural cells. Using the YAC128 mouse model of HD, we studied the effect of an irreversible MAO-A inhibitor, clorgyline, on the levels of select monoamine neurotransmitters associated with affective function. We observed a decrease in striatal levels of the MAO-A/B substrates, dopamine and norepinephrine, in YAC128 HD mice compared with wild-type mice, which was accompanied by increased anxiety- and depressive-like behaviour at five months of age. Treatment for 26 days with clorgyline restored dopamine, serotonin, and norepinephrine neurotransmitter levels in the striatum and reduced anxiety- and depressive-like behaviour in YAC128 HD mice. This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD.

  12. Natural Products Screening for the Identification of Selective Monoamine Oxidase-B Inhibitors

    Science.gov (United States)

    Zarmouh, Najla O.; Messeha, Samia S.; Elshami, Faisel M.; Soliman, Karam F. A.

    2016-01-01

    Aims Monoamine oxidase-B inhibitors (MAO-BIs) are used for the initial therapy of Parkinson’s disease. Also, MAO-BIs have shown to be effective neuroprotective agents in several neurodegenerative diseases. However, some concerns exist regarding the long-term use of these compounds. Meanwhile, natural compounds showed potential MAO-B selective inhibitions. To date, few selective natural MAO-BIs have been identified. Therefore, the current study is designed to identify plants with potent and specific MAO-B inhibition. Study Design In this work, we utilized high throughput screening to evaluate the different plants ethanolic extract for their effectiveness to inhibit recombinant human (h)MAO-A and hMAO-B and to determine the relative selectivity of the top MAO-BI. Methodology Recombinant human isozymes were verified by Western blotting, and the 155 plants were screened. A continuous fluorometric screening assay was performed followed by two separate hMAO-A and hMAO-B microtiter screenings and IC50 determinations for the top extracts. Results In the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of hMAO-B (RIB) and another 9% showed more than 1.5-fold relative inhibition of hMAO-A. The top extracts with the most potent RIBs were Psoralea corylifolia seeds, Phellodendron amurense bark, Glycyrrhiza uralensis roots, and Ferula assafoetida roots, with the highest RIB of 5.9-fold. Furthermore, extensive maceration of the promising extracts led to increase inhibitory effects with a preserved RIB as confirmed with luminescence assay. The top four extracts hMAO-BIs were equally potent (IC50= 1.3 to 3.8 μg/mL) with highly significant relative selectivities to inhibit hMAO-B (4.1- to 13.4-fold). Conclusion The obtained results indicate that Psoralea corylifolia seeds, Ferula assafoetida, Glycyrrhiza uralensis roots, and Phellodendron amurense ethanolic extracts have selective inhibitions for human MAO-B. Investigating these plant extracts as

  13. The monoamine oxidase inhibition properties of selected structural analogues of methylene blue.

    Science.gov (United States)

    Delport, Anzelle; Harvey, Brian H; Petzer, Anél; Petzer, Jacobus P

    2017-06-15

    The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC50=0.0037μM), Nile blue (IC50=0.0077μM) and 1,9-dimethyl methylene blue (IC50=0.018μM) exhibiting higher potency inhibition compared to MB (IC50=0.07μM). Nile blue also represents a potent MAO-B inhibitor with an IC50 value of 0.012μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Synthetic and Natural Monoamine Oxidase Inhibitors as Potential Lead Compounds for Effective Therapeutics.

    Science.gov (United States)

    Pathak, Ashish; Srivastava, Amit K; Singour, Pradeep K; Gouda, Panchanan

    2016-01-01

    Monoamine oxidases A and B (MAO-A and B) play a critical role in the metabolism of intracellular neurotransmitters of the central nervous system. For decades, MAO inhibitors have proven their clinical efficacy as potential drug targets for several neurological and neurodegenerative diseases. Use of first generation non selective MAO inhibitors as neuropsychiatric drugs elicited several side effects like hypertensive crisis and cheese reaction. Therefore their use is now limited due to non-selectivity towards MAO isoforms and inhibition of metabolizing enzymes like cytochrome P450. Development of selective and specific MAO inhibitors like moclobemide, toloxatone improves their efficacy as disease-modifying effects in monotherapy as well as adjunctive therapy. Recently a lot of research has been done to elucidate the pharmacological potential of medicinal plants and their isolated bioactive constituents having MAO inhibitory activity. Herbs containing MAO inhibitors are extensively used for the development of potent synthetic drugs and as safe and effective alternatives to the available synthetic drugs in the treatment of neurodegenerative diseases such as depression, Parkinson and Alzheimer's. In several diseases like Parkinson natural MAO inhibitors prevented the neuron denaturalization by their dual action via enhancing neurotransmission of dopamine as well as lowering the generation of free radicals and toxins. Currently development of selective MAO inhibitors is still under study to achieve more effective therapies by using Computer Aided Drug Designing, Ligand-based models and structure-activity hypothesis. These approaches also facilitate understanding the interaction of newly designed molecule with MAO enzymes and the rationalization of probable mechanisms of action.

  15. Monoamine oxidase B layer-by-layer film fabrication and characterization toward dopamine detection.

    Science.gov (United States)

    Miyazaki, Celina Massumi; Pereira, Tamyris Paschoal; Mascagni, Daniela Branco Tavares; de Moraes, Marli Leite; Ferreira, Marystela

    2016-01-01

    In this work nanostructured film composites of the monoamine oxidase B (MAO-B) enzyme, free or encapsulated in liposomes, were fabricated by the layer-by-layer (LbL) self-assembly technique, employing polyethylene imine (PEI) as polycation. Initially, the MAO-B enzyme was incorporated into liposomes in order to preserve its enzymatic structure ensuring their activity and catalytic stability. The LbL film growth was monitored by surface plasmon resonance (SPR) by gold resonance angle shift analysis after each bilayer deposition. Subsequently, the films were applied as amperometric biosensors for dopamine detection using Prussian Blue (PB) as the electron mediator. The biosensor fabricated by MAO-B incorporated into liposomes composed of DPPG:POPG in the ratio (1:4) (w/w) showed the best performance with a sensitivity of 0.86 (μA cm(-2))/(mmol L(-1)) and a detection limit of 0.33 mmol L(-1).

  16. Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B.

    Science.gov (United States)

    Hagenow, S; Stasiak, A; Ramsay, R R; Stark, H

    2017-01-13

    Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer's disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.

  17. Effect of short-time exposures to nickel and lead on brain monoamine oxidase from Danio rerio and Poecilia reticulata.

    Science.gov (United States)

    Senatori, Ornella; Setini, Andrea; Scirocco, Annunziata; Nicotra, Antonietta

    2009-06-01

    The aim of this work was to verify, in two small size freshwater teleosts Danio rerio and Poecilia reticulata, the effects of short-time exposures (24 and 72 h) to a sublethal dose (500 microg/L) of nickel and lead, on brain monoamine oxidase (MAO), an important neural enzyme. The 24-h treatment using both metals caused a strong reduction of MAO activity in D. rerio brain, whereas causing a slight MAO activity stimulation in P. reticulata brain. The same treatment in both species did not affect the brain MAO mRNA production as showed by RT-PCR. Extending the duration of treatment as far as 72 h, partly (D. rerio) or completely (P. reticulata) reversed the metal effects on brain MAO activity suggesting that mechanisms to neutralize the metals had been activated.

  18. Development of new radiopharmaceuticals for imaging monoamine oxidase B

    Energy Technology Data Exchange (ETDEWEB)

    Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca; Sadovski, Oleg; Moran, Matthew D.; Parkes, Jun; Meyer, Jeffrey H.; Houle, Sylvain; Wilson, Alan A.

    2011-10-15

    Introduction: Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[{sup 18}F]-fluorohexyl)-N-methylpropargylamine ([{sup 18}F]FHMP; [{sup 18}F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[{sup 11}C]-methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([{sup 11}C]-2) and N-((1H-pyrrol-2-yl)methyl)-N-[{sup 11}C]-methyl-1-phenylmethanamine ([{sup 11}C]-3). Methods: Fluorine-18-labeled 1 was prepared via a tosyloxy precursor in 29%{+-}5% uncorrected radiochemical yield, relative to [{sup 18}F]-fluoride. Both carbon-11-labeled compounds were prepared with [{sup 11}C]CH{sub 3}I using the 'LOOP' method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [{sup 11}C]CO{sub 2}. All radiotracers had specific activities >37 GBq/{mu}mol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents. Results: A major radioactive metabolite in the rodent brain was observed following administration of [{sup 18}F]-1. While [{sup 11}C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [{sup 11}C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity. Conclusion: Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO

  19. Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives.

    Science.gov (United States)

    Mathew, Bijo; Mathew, Githa Elizabeth; Uçar, Gülberk; Baysal, Ipek; Suresh, Jerad; Mathew, Sincy; Haridas, Abitha; Jayaprakash, Venkatesan

    2016-08-01

    For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a Ki value of 0.33 ± 0.01 μm toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency.

  20. The new inhibitor of monoamine oxidase, M30, has a neuroprotective effect against dexamethasone-induced brain cell apoptosis

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    Shakevia Johnson

    2010-11-01

    Full Text Available Stress detrimentally affects the brain and body and can lead to or be accompanied by depression. Although stress and depression may contribute to each other, the exact molecular mechanism underlying the effects is unclear. However, there is a correlation between stress and an increase in glucocorticoid secretion which causes a subsequent increase in monoamine oxidase (MAO activity during stress. Consequently, MAO inhibitors have been used as traditional antidepressant drugs. Cellular treatment with the synthetic glucocorticoid, dexamethasone (a cellular stressor, has been reported to markedly increase both MAO A and MAO B catalytic activities, as well as apoptosis. This study compares the neuroprotective abilities of M30 (a new generation inhibitor of both MAO A and MAO B with rasagiline (Azilect®, another new MAO B inhibitor and selegiline (Deprenyl®, a traditional MAO B inhibitor in the prevention of dexamethasone-induced brain cell death and MAO activity in human neuroblastoma cells, SH-SY5Y. M30 demonstrated the highest inhibitory effect on MAO A; however, M30 showed the lowest inhibitory effect on MAO B enzymatic activity in comparison to rasagiline and selegiline. Although, M30 exhibited the greatest neuroprotective effect by decreasing cell death rates and apoptotic DNA damage compared to rasagiline and selegiline, these neuroprotective effects of M30 were, overall, similar to rasagiline. Summarily, M30 has a generally greater impact on neuroprotection than the MAO B inhibitors, selegiline and rasagiline. Our results suggest that M30 may have great potential in alleviating disorders involving increases in both MAO A and MAO B, such as stress-induced disorders.

  1. Development of radioiodinated ligands for exploration of brain monoamine oxidase by tomo-scintigraphy; Developpement de ligands radioactifs pour l'exploration des monoamines oxydases cerebrales en tomoscintigraphie

    Energy Technology Data Exchange (ETDEWEB)

    Rafii, H

    1996-07-01

    Monoamine oxidases, MAO, are important in the regulation of monoaminergic neuro-transmissions. The fluctuations in MAO activities has been observed in some psychiatric and neuro-degenerative diseases. Thus, quantification of cerebral MAO activity would be useful for diagnosis and the therapeutic follow-up of these disorders. With the object of doing an in vivo scintigraphic exploration of cerebral MAO by SPECT, we have undertaken to synthesize some radioiodinated MAO inhibitors. In the first part of this work, we have discussed the general properties of the monoamine oxidases and their inhibitors. In the second part we have described the scintigraphic methods. the ligands to be used for MAO exploration, and the radioiodination methods. At last in the third part, the development of three radioiodinated ligands has been presented: - [{sup 125}I]3-iodopargyline. In vivo results showed that, this radioligand blocked the cerebral MAO-B with moderate selectivity. However, complementary in vivo studies would be needed to define precisely its activity.- [{sup 125}I]Ro 16-6491. The cerebral fixation of this radioligand was in accordance with the MAO-B sites in the rat brains, but its fixation was too low for scintigraphic exploration in vivo with iodine-123. - [{sup 125}I]Ro 11-9900. In vivo studies of rat brains showed that the MAO-A sites were bound preferentially by this radioligand. The cerebral biodistribution of this ligand labelled with iodine-123 is considered for use in a model animal nearest to human pathology. (author)

  2. Psychological traits and platelet monoamine oxidase activity in eating disorder patients: their relationship and stability.

    Science.gov (United States)

    Podar, Iris; Jaanisk, Maiken; Allik, Jüri; Harro, Jaanus

    2007-01-30

    Self-reported behavior and attitudes towards eating [Eating Disorder Inventory-2; Garner DM (1991). Eating Disorder Inventory-2: Professional Manual. Odessa, Fl.: Psychological Assessment Resources; Estonian version Podar I, Hannus A, Allik J (1999). Personality and Affectivity Characteristics Associated With Eating Disorders: a Comparison of Eating Disordered, Weight-Preoccupied, and Normal Samples. J Pers Assess; 73(1), 133-147] and the activity of platelet monoamine oxidase (MAO) was studied in 11 patients with anorexia nervosa (AN), 43 patients with bulimia nervosa (BN) and a healthy control group (n=138). Nineteen patients filled in the EDI-2 questionnaire and donated blood samples three times with three month intervals in order to determine platelet MAO activity. Eating disordered (ED) patients scored higher on all EDI-2 subscales and had lower MAO activity compared to the control group. They also scored higher than the control group on the Neuroticism domain but lower on the Extraversion, Openness, and Conscientiousness domains of the NEO-PI-R questionnaire. The average stability of MAO on different occasions (r=.56) was slightly smaller than the stability of the EDI-2 scores (r=.70). The lack of correlations between personality dispositions and MAO activity indicates that they have independent influence on eating disorders. A possible relationship between neurochemical mechanisms and psychological symptoms of eating disordered behavior is discussed.

  3. Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors.

    Science.gov (United States)

    Gaspar, Alexandra; Silva, Tiago; Yáñez, Matilde; Vina, Dolores; Orallo, Franscisco; Ortuso, Francesco; Uriarte, Eugenio; Alcaro, Stefano; Borges, Fernanda

    2011-07-28

    Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of γ-pyrone nucleus act preferably as MAO-B inhibitors, with IC(50) values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical substitutions on position 2 of γ-pyrone nucleus result in complete loss of activity in both isoforms (chromones 2-12 except 3 and 5). Notably, chromone (19) exhibits an MAO-B IC(50) of 63 nM, greater than 1000-fold selectivity over MAO-A, and behaves as a quasi-reversible inhibitor. Docking experiments onto the MAO binding of the most active compound highlight different interaction patterns among the isoforms A and B. The differential analysis of the solvation effects among the chromone isomers gave additional insight about the superior outline of the 3-substituted chromone derivatives.

  4. Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy.

    Science.gov (United States)

    Menazza, Sara; Blaauw, Bert; Tiepolo, Tania; Toniolo, Luana; Braghetta, Paola; Spolaore, Barbara; Reggiani, Carlo; Di Lisa, Fabio; Bonaldo, Paolo; Canton, Marcella

    2010-11-01

    Several studies documented the key role of oxidative stress and abnormal production of reactive oxygen species (ROS) in the pathophysiology of muscular dystrophies (MDs). The sources of ROS, however, are still controversial as well as their major molecular targets. This study investigated whether ROS produced in mitochondria by monoamine oxidase (MAO) contributes to MD pathogenesis. Pargyline, an MAO inhibitor, reduced ROS accumulation along with a beneficial effect on the dystrophic phenotype of Col6a1(-/-) mice, a model of Bethlem myopathy and Ullrich congenital MD, and mdx mice, a model of Duchenne MD. Based on our previous observations on oxidative damage of myofibrillar proteins in heart failure, we hypothesized that MAO-dependent ROS might impair contractile function in dystrophic muscles. Indeed, oxidation of myofibrillar proteins, as probed by formation of disulphide cross-bridges in tropomyosin, was detected in both Col6a1(-/-) and mdx muscles. Notably, pargyline significantly reduced myofiber apoptosis and ameliorated muscle strength in Col6a1(-/-) mice. This study demonstrates a novel and determinant role of MAO in MDs, adding evidence of the pivotal role of mitochondria and suggesting a therapeutic potential for MAO inhibition.

  5. Monoamine Oxidases, Oxidative Stress, and Altered Mitochondrial Dynamics in Cardiac Ageing

    Directory of Open Access Journals (Sweden)

    Damien Maggiorani

    2017-01-01

    Full Text Available The advances in healthcare over the past several decades have resulted in populations now living longer. With this increase in longevity, a wider prevalence of cardiovascular diseases is more common and known to be a major factor in rising healthcare costs. A wealth of scientific evidence has implicated cell senescence as an important component in the etiology of these age-dependent pathologies. A number of studies indicate that an excess of reactive oxygen species (ROS contributes to trigger and accelerate the cardiac senescence processes, and a new role of monoamine oxidases, MAO-A and MAO-B, is emerging in this context. These mitochondrial enzymes regulate the level of catecholamines and serotonin by catalyzing their oxidative deamination in the heart. MAOs’ expression substantially increases with ageing (6-fold MAO-A in the heart and 4-fold MAO-B in neuronal tissue, and their involvement in cardiac diseases is supposedly related to the formation of ROS, via the hydrogen peroxide produced during the substrate degradation. Here, we will review the most recent advances in this field and describe why MAOs could be effective targets in order to prevent age-associated cardiovascular disease.

  6. Cerebral monoamine oxidase A inhibition in tobacco smokers confirmed with PET and [{sup 11}C]Befloxatone

    Energy Technology Data Exchange (ETDEWEB)

    Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [INSERM U797, Research Unit ' Neuroimaging and Psychiatry' , Orsay (France); Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [CEA, ' Neuroimaging and Psychiatry, U797 Unit, Hospital Department Frederic Joliot and Neurospin (France); Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [Paris sud University - Paris Descartes University, UMR U797 (France); Berlin, I. [Service de Pharmacologie, Hopital Pitie-Salpetriere - Universite Paris6 - INSERM U677, Paris (France); Gregoire, M.C.; Bottlaender, M.; Roumenov, D.; Dolle, F.; Bourgeois, S. [CEA, DSV, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Artiges, E.; Trichard, Ch. [Psychiatry Department, Orsay Hospital, Orsay (France)

    2009-07-01

    The inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [{sup 11}C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [{sup 11}C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco. (authors)

  7. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

    OpenAIRE

    Petzer, Anél; Harvey, Brian H; Wegener, Gregers; Petzer, Jacobus P.

    2012-01-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displa...

  8. Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery

    Directory of Open Access Journals (Sweden)

    Oana M. Duicu

    2015-01-01

    Full Text Available Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

  9. The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer

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    Ping-Ho Chen

    2014-01-01

    Full Text Available Betel quid (BQ and areca nut (AN (major BQ ingredient are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO gene by inducing reactive oxygen species (ROS. The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

  10. The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer

    Science.gov (United States)

    Huang, Bin; Shieh, Tien-Yu; Wang, Yan-Hsiung; Chen, Yuk-Kwan; Wu, Ju-Hui; Huang, Jhen-Hao; Chen, Chun-Chia; Lee, Ka-Wo

    2014-01-01

    Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS. PMID:25389533

  11. Fluorescent Probes for Analysis and Imaging of Monoamine Oxidase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dokyoung; Jun, Yong Woong; Ahn, Kyo Han [POSTECH, Pohang (Korea, Republic of)

    2014-05-15

    Monoamine oxidases catalyze the oxidative deamination of dietary amines and amine neurotransmitters, and assist in maintaining the homeostasis of the amine neurotransmitters in the brain. Dysfunctions of these enzymes can cause neurological and behavioral disorders including Parkinson's and Alzheimer's diseases. To understand their physiological roles, efficient assay methods for monoamine oxidases are essential. Reviewed in this Perspective are the recent progress in the development of fluorescent probes for monoamine oxidases and their applications to enzyme assays in cells and tissues. It is evident that still there is strong need for a fluorescent probe with desirable substrate selectivity and photophysical properties to challenge the much unsolved issues associated with the enzymes and the diseases.

  12. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    Science.gov (United States)

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  13. Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

    Science.gov (United States)

    Lin, J S; Kitahama, K; Fort, P; Panula, P; Denney, R M; Jouvet, M

    1993-04-15

    It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t

  14. Causality pattern of the blood lead, monoamine oxidase A, and serotonin levels in brass home industry workers chronically exposed to lead

    Directory of Open Access Journals (Sweden)

    Aditya Marianti

    2016-04-01

    Full Text Available The present study aims to analyse the effects of lead (Pb chronic exposure on blood lead levels, Monoamine oxidase A enzyme (MAO A and serotonin levels of brass craftsmen in Pati, Central Java, Indonesia, and to examine the connections among these three variables. The brass home industry area was polluted by lead. Thus, it chronically exposes the workers to lead pollution. Therefore, their blood lead level increased and later raised the level of MAO A and reduced the level of serotonin. Path analysis results show that the path coefficient (ñ of lead effects in decreasing serotonin through MAO A pathway is -0.411. Furthermore, lead effects that directly affect serotonin level without passing through MAO A pathway is -0.391 with residual coefficient (e of 0.572. In conclusion, the increase of blood lead level causes an increase in level of MAO A and drop in the level of serotonin.

  15. Duration of hexobarbital-induced sleep and monoamine oxidase activities in rat brain: Focus on the behavioral activity and on the free-radical oxidation.

    Science.gov (United States)

    Tseilikman, Vadim E; Kozochkin, Denis A; Manukhina, Eugenia B; Downey, H Fred; Tseilikman, Olga B; Misharina, Maria E; Nikitina, Anna A; Komelkova, Maria V; Lapshin, Maxim S; Kondashevskaya, Marina V; Lazuko, Svetlana S; Kusina, Oxana V; Sahabutdinov, Marat V

    2016-04-01

    The present study is focused on the relationship between monoamine oxidase (MAO) activity and hepatic content of cytochrome P450 (CYP), which reflects the status of microsomal oxidation. For vital integrative evaluation of hepatic microsomal oxidation in rats, the hexobarbital sleep test was used, and content of CYP was measured in hepatic microsomes. Rats with short hexobarbital sleep time (SHST) had higher content of microsomal CYP than rats with long hexobarbital sleep time (LHST). Whole brain MAO-A and MAO-B activities, serotonin and carbonylated protein levels were higher in SHST than in LHST rats. MAO-A and MAO-B activities were higher in brain cortex of SHST rats; MAO-A activity was higher only in hypothalamus and medulla of LHST. The same brain regions of LHST rats had higher concentrations of carbonylated proteins and lipid peroxidation products than in SHST rats. MAO activity was correlated with microsomal oxidation phenotype. Rats with higher hepatic content of CYP had higher activities of MAO-A and MAO-B in the brain and higher plasma serotonin levels than rats with lower microsomal oxidation. In conclusion, data obtained in this study showed a correlation between MAO activity and microsomal oxidation phenotype.

  16. Inhibition of monoamine oxidase by furazolidone in the chicken and the influence of the alimentary flora thereon.

    Science.gov (United States)

    Ali, B H; Bartlet, A L

    1980-01-01

    1 The addition of furazolidone to the feed at the therapeutic level (0.04% w/w, 10 days) inhibited monoamine oxidase (MAO) activity by 47 to 72% in chicken duodenal mucosa, heart and brain, but in the liver the enzyme activity was unaffected by the treatment. 2 Furazolidone (200 mg/kg) administered by crop tube inhibited MAO activities in duodenal mucosa, liver, heart and brain. 3 Furazolidone (200 mg/kg) injected intramuscularly did not inhibit MAO activity in the chicken. 4 Pretreatment of the chickens with intramuscular neomycin did not antagonize the inhibition of MAO activity produced by furazolidone (200 mg/kg, crop tube). 5 Pretreatment with neomycin by crop tube to suppress the alimentary flora significantly reduced the effect of furazolidone on MAO activity, suggesting that the drug was transformed by the alimentary flora to an active metabolite which subsequently inhibited MAO activity in other organs. 6 Furazolidone in the feed (0.04% w/w, 10 days) or administered by crop tube (200 mg/kg) had no effect on the activity of aminopyrine demethylase in chicken liver. 7 The activity of aspartate transaminase in plasma was unaffected by the addition of furazolidone to the feed (0.04% w/w, 10 days).

  17. Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K.

    Science.gov (United States)

    Kim, Ji Ho; Son, Yeon Kyung; Kim, Gun Hee; Hwang, Keum Hee

    2013-05-30

    Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine β-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 μM, and 43.9 μM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 μM, and 42.5 μM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 μM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 μM and this value was higher than that of deprenyl (0.046 μM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 μM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

  18. The structure of monoamine oxidase from Aspergillus niger provides a molecular context for improvements in activity obtained by directed evolution.

    Science.gov (United States)

    Atkin, Kate E; Reiss, Renate; Koehler, Valentin; Bailey, Kevin R; Hart, Sam; Turkenburg, Johan P; Turner, Nicholas J; Brzozowski, A Marek; Grogan, Gideon

    2008-12-31

    Monoamine oxidase from Aspergillus niger (MAO-N) is a flavoenzyme that catalyses the oxidative deamination of primary amines. MAO-N has been used as the starting model for a series of directed evolution experiments, resulting in mutants of improved activity and broader substrate specificity, suitable for application in the preparative deracemisation of primary, secondary and tertiary amines when used as part of a chemoenzymatic oxidation-reduction cycle. The structures of a three-point mutant (Asn336Ser/Met348Lys/Ile246Met or MAO-N-D3) and a five-point mutant (Asn336Ser/Met348Lys/Ile246Met/Thr384Asn/Asp385Ser or MAO-N-D5) have been obtained using a multiple-wavelength anomalous diffraction experiment on a selenomethionine derivative of the truncated MAO-N-D5 enzyme. MAO-N exists as a homotetramer with a large channel at its centre and shares some structural features with human MAO B (MAO-B). A hydrophobic cavity extends from the protein surface to the active site, where a non-covalently bound flavin adenine dinucleotide (FAD) sits at the base of an 'aromatic cage,' the sides of which are formed by Trp430 and Phe466. A molecule of l-proline was observed near the FAD, and this ligand superimposed well with isatin, a reversible inhibitor of MAO-B, when the structures of MAO-N proline and MAO-B-isatin were overlaid. Of the mutations that confer the ability to catalyse the oxidation of secondary amines in MAO-N-D3, Asn336Ser reduces steric bulk behind Trp430 of the aromatic cage and Ile246Met confers greater flexibility within the substrate binding site. The two additional mutations, Thr384Asn and Asp385Ser, that occur in the MAO-N-D5 variant, which is able to oxidise tertiary amines, appear to influence the active-site environment remotely through changes in tertiary structure that perturb the side chain of Phe382, again altering the steric and electronic character of the active site near FAD. The possible implications of the change in steric and electronic environment

  19. Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?

    Science.gov (United States)

    Baler, Ruben D; Volkow, Nora D; Fowler, Joanna S; Benveniste, Helene

    2008-05-01

    Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development - but not during adult life - is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke-induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.

  20. Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan.

    Science.gov (United States)

    Ou, Xiao-Ming; Lu, Deyin; Johnson, Chandra; Chen, Kevin; Youdim, Moussa B H; Rajkowska, Grazyna; Shih, Jean C

    2009-08-01

    The inhibitors of monoamine oxidase B (MAO B) are effectively used as therapeutic drugs for neuropsychiatric and neurodegenerative diseases. However, their mechanism of action is not clear, since the neuroprotective effect of MAO B inhibitors is associated with the blockage of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-death cascade, rather than the inhibition of MAO B. Here, we provide evidence that GAPDH potentiates the ethanol-induced activity of MAO B and brain cell toxicity. The levels of nuclear GAPDH and MAO B activity are significantly increased in brain-derived cell lines upon 75 mM ethanol-induced cell death. Over-expression of GAPDH in cells enhances ethanol-induced cell death, and also increases the ethanol-induced activation of MAO B. In contrast, the MAO B inhibitors rasagiline and selegiline (0.25 nM) and the rasagiline metabolite, 1-R-aminoindan (1 muM) decreases the ethanol-induced MAO B, prevents nuclear translocation of GAPDH and reduces cell death. In addition, GAPDH interacts with transforming growth factor-beta-inducible early gene (TIEG2), a transcriptional activator for MAO B, and this interaction is increased in the nucleus by ethanol but reduced by MAO B inhibitors and 1-R-aminoindan. Furthermore, silencing TIEG2 using RNAi significantly reduces GAPDH-induced MAO B upregulation and neurotoxicity. In summary, ethanol-induced cell death, attenuated by MAO B inhibitors, may result from disrupting the movement of GAPDH with the transcriptional activator into the nucleus and secondly inhibit MAO B gene expression. Thus, the neuroprotective effects of rasagiline or 1-R-aminoindan on ethanol-induced cell death mediated by a novel GAPDH-MAO B pathway may provide a new insight in the treatment of neurobiological diseases including alcohol-use disorders.

  1. MAO inhibitors: risks, benefits, and lore.

    Science.gov (United States)

    Wimbiscus, Molly; Kostenko, Olga; Malone, Donald

    2010-12-01

    Monoamine oxidase (MAO) inhibitors were the first antidepressants introduced, but their use has dwindled because of their reported side effects, their food and drug interactions, and the introduction of other classes of agents. However, interest in MAO inhibitors is reviving. Here, we discuss their use, risks, and benefits in clinical medicine.

  2. Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030.

    Science.gov (United States)

    Costa, Jonas Henrique; da Costa, Bruna Zucoloto; de Angelis, Derlene Attili; Marsaioli, Anita Jocelyne

    2017-08-01

    High-throughput screening detected transaminases (TAs) and monoamine oxidases (MAOs) in fungi by applying a fluorogenic probe. Strains F026, F037, F041, F053, and F057 showed the highest enzymatic conversions (31, 60, 30, 40, and 32%, respectively) and where evaluated for their ability to transform piperidines. Strain F053 (Neopestalotiopsis sp. CBMAI 2030) revealed unusual enzymatic activity to deracemize 2-methyl-6-alkylpiperidines. Neopestalotiopsis sp. CBMAI 2030 was capable to convert 2-methyl-6-propylpiperidine, 2-methyl-6-butylpiperidine, and 2-methyl-6-pentylpiperidine in piperideine with 11, 14, and 24% conversion, respectively. The activity was enhanced by cultivating the fungus with 2-methyl-6-pentylpiperidine (38% conversion and 73% ee).

  3. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  4. Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Petzer, Anél, E-mail: 12264954@nwu.ac.za [Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Harvey, Brian H. [Division of Pharmacology, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Wegener, Gregers [Centre for Psychiatric Research, Aarhus University Hospital-Risskov, Skovagervej 2, 8240 Risskov (Denmark); Petzer, Jacobus P. [Division of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa)

    2012-02-01

    Methylene blue (MB) has been shown to act at multiple cellular and molecular targets and as a result possesses diverse medical applications. Among these is a high potency reversible inhibition of monoamine oxidase A (MAO-A) that may, at least in part, underlie its adverse effects but also its psycho- and neuromodulatory actions. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl species, is the major metabolite. Similar to MB, azure B also displays a variety of biological activities and may therefore contribute to the pharmacological profile of MB. Based on these observations, the present study examines the interactions of azure B with recombinant human MAO-A and -B. The results show that azure B is a potent MAO-A inhibitor (IC{sub 50} = 11 nM), approximately 6-fold more potent than is MB (IC{sub 50} = 70 nM) under identical conditions. Measurements of the time-dependency of inhibition suggest that the interaction of azure B with MAO-A is reversible. Azure B also reversibly inhibits the MAO-B isozyme with an IC{sub 50} value of 968 nM. These results suggest that azure B may be a hitherto under recognized contributor to the pharmacology and toxicology of MB by blocking central and peripheral MAO-A activity and as such needs to be considered during its use in humans and animals. Highlights: ► Methylene blue (MB) is a known potent MAO-A inhibitor. ► Azure B, the major metabolite of MB, is more potent as a MAO-A inhibitor. ► Azure B may be a contributor to the CNS pharmacology and toxicology of MB.

  5. Combination of polymorphic variants in serotonin transporter and monoamine oxidase-A genes may influence the risk for early-onset alcoholism.

    Science.gov (United States)

    Bordukalo-Niksic, Tatjana; Stefulj, Jasminka; Matosic, Ana; Mokrovic, Gordana; Cicin-Sain, Lipa

    2012-12-30

    The combinatory effect of polymorphisms in serotonin transporter and monoamine oxidase-A genes on the aetiopathogenesis of alcoholism was investigated in a sample of 714 individuals. Increased frequency of subjects having three 'suspected' genotypes (5-HTTLPR-LL, STin2-1010 and MAO-A 3-repeat allele) was found among type-2 alcoholic patients (P=0.0189). Results highlight serotonergic/genetic contribution to early-onset alcoholism.

  6. Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells.

    Science.gov (United States)

    Goldstein, David S; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J; Sharabi, Yehonatan

    2016-02-01

    According to the catecholaldehyde hypothesis, the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) contributes to the loss of nigrostriatal dopaminergic neurons in Parkinson's disease. Monoamine oxidase-A (MAO-A) catalyzes the conversion of intraneuronal dopamine to DOPAL and may serve as a therapeutic target. The "cheese effect"-paroxysmal hypertension evoked by tyramine-containing foodstuffs-limits clinical use of irreversible MAO-A inhibitors. Combined MAO-A/B inhibition decreases DOPAL production in rat pheochromocytoma PC12 cells, but whether reversible MAO-A inhibitors or MAO-B inhibitors decrease endogenous DOPAL production is unknown. We compared the potencies of MAO inhibitors in attenuating DOPAL production and examined possible secondary effects on dopamine storage, constitutive release, synthesis, and auto-oxidation. Catechol concentrations were measured in cells and medium after incubation with the irreversible MAO-A inhibitor clorgyline, three reversible MAO-A inhibitors, or the MAO-B inhibitors selegiline or rasagiline for 180 minutes. Reversible MAO-A inhibitors were generally ineffective, whereas clorgyline (1 nM), rasagiline (500 nM), and selegiline (500 nM) decreased DOPAL levels in the cells and medium. All three drugs also increased dopamine and norepinephrine, decreased 3,4-dihydroxyphenylalanine, and increased cysteinyl-dopamine concentrations in the medium, suggesting increased vesicular uptake and constitutive release, decreased dopamine synthesis, and increased dopamine spontaneous oxidation. In conclusion, clorgyline, rasagiline, and selegiline decrease production of endogenous DOPAL. At relatively high concentrations, the latter drugs probably lose their selectivity for MAO-B. Possibly offsetting increased formation of potentially toxic oxidation products and decreased formation of DOPAL might account for the failure of large clinical trials of MAO-B inhibitors to demonstrate slowing of neurodegeneration in Parkinson

  7. Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology

    Directory of Open Access Journals (Sweden)

    Li XinMin

    2007-09-01

    Full Text Available Abstract Background Calcium (Ca2+ has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A, a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca2+ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD. Results Incubation with Ca2+ selectively increases MAO-A enzymatic activity in protein extracts from mouse hippocampal HT-22 cell cultures. Treatment of HT-22 cultures with the Ca2+ ionophore A23187 also increases MAO-A activity, whereas overexpression of calbindin-D28K (CB-28K, a Ca2+-binding protein in brain that is greatly reduced in AD, decreases MAO-A activity. The effects of A23187 and CB-28K are both independent of any change in MAO-A protein or gene expression. The toxicity (via production of peroxyradicals and/or chromatin condensation associated with either A23187 or the AD-related β-amyloid peptide, which also increases free intracellular Ca2+, is attenuated by MAO-A inhibition in HT-22 cells as well as in primary hippocampal cultures. Conclusion These data suggest that increases in intracellular Ca2+ availability could contribute to a MAO-A-mediated mechanism with a role in AD-related oxidative stress.

  8. Hydralazine is involved in tele-methylhistamine metabolism by inhibiting monoamine oxidase B in pregnancy-associated hypertensive mice.

    Science.gov (United States)

    Kawasaki, Shohei; Kako, Koichiro; Nagashima, Yusuke; Kanou, Akihiko; Ishida, Junji; Fukamizu, Akiyoshi

    2017-01-07

    Hypertensive disorders of pregnancy globally affect 6-8% of gestation and remain a major cause of both foetal and maternal morbidity and mortality. However, the antihypertensive medications for the patients of this disease are strictly limited due to the teratogenic potentials. Here, we found that tele-methylhistamine (tMH) increased in response to the administration of hydralazine (Hdz), a vasodilative agent, in the pregnancy-associated hypertensive (PAH) mice. Hdz abrogated the degradation of tMH catalyzed by monoamine oxidase B (MAO-B) in vitro These results suggested that Hdz inhibited the MAO-B activity and consequently tMH increased in the maternal circulation of PAH mice.

  9. Synthesis and characterization of [{sup 125}I]N-(2-aminoethyl)-4-iodobenzamide as a selective monoamine oxidase B inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Rafii, Hamid; Chalon, Sylvie; Ombetta, Jean-Edouard; Frangin, Yves; Garreau, Lucette; Dognon, Anne-Marie; Lena, Isabelle; Bodard, Sylvie; Vilar, Marie-Paule; Besnard, Jean-Claude; Guilloteau, Denis

    1995-07-01

    We described the radiosynthesis of an analog of Ro 16-6491, [{sup 125}I]N-(2-aminoethyl)-4-iodobenzamide, for SPECT exploration of the monoamine oxidase B (MAO-B) in human brain. The radiolabelling was carried out by nucleophilic exchange of the brominated precursor at solid-state phase in presence of ammonium sulphate. The radiochemical purity of radioiodinated product was higher than 95%. In comparison with Ro 16-6491, the in vitro studies showed a good selectivity of stable N-(2-aminoethyl)-4-iodobenzamide for MAO-B but a slightly lower affinity. Biodistribution studies in the rat showed a high and selective uptake of this compound in the pineal gland 1 h after i.v. injection. The cerebral uptake was low, but the coupling of [{sup 125}I]N-(2-aminoethyl)-4-iodobenzamide with a lipophilic radical to enhance the passage through the blood-brain barrier can be envisaged.

  10. Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin.

    Science.gov (United States)

    Keung, W M

    2001-01-30

    Daidzin, a major active principle of an ancient herbal treatment for 'alcohol addiction', was first shown to suppress ethanol intake in Syrian golden hamsters. Since then this activity has been confirmed in Wistar rats, Fawn hooded rats, genetically bred alcohol preferring P rats and African green moneys under various experimental conditions, including two-level operant, two-bottle free-choice, limited access, and alcohol-deprivation paradigms. In vitro, daidzin is a potent and selective inhibitor of mitochondrial aldehyde dehydrogenase (ALDH-2). However, in vivo, it does not affect overall acetaldehyde metabolism in golden hamsters. Using isolated hamster liver mitochondria and 5-hydroxytryptamine (5-HT) and dopamine (DA) as the substrates, we demonstrated that daidzin inhibits the second but not the first step of the MAO/ALDH-2 pathway, the major pathway that catalyzes monoamine metabolism in mitochondria. Correlation studies using structural analogs of daidzin led to the hypothesis that the mitochondrial MAO/ALDH-2 pathway may be the site of action of daidzin and that one or more biogenic aldehydes such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or DOPAL derived from the action of monoamine oxidase (MAO) may be mediators of its antidipsotropic action.

  11. Simultaneous determination of cadaverine and putrescine using a disposable monoamine oxidase based biosensor.

    Science.gov (United States)

    Henao-Escobar, Wilder; Domínguez-Renedo, Olga; Asunción Alonso-Lomillo, M; Julia Arcos-Martínez, M

    2013-12-15

    The selective and simultaneous amperometric determination of putrescine (Put) and cadaverine (Cad) has been carried out using a novel design of screen-printed carbon electrode (SPCE) with two working electrodes connected in array mode. A mixture of 3% of tetrathiafulvalene (TTF), as mediator, and carbon ink was used for the construction of the screen-printed working electrode. The employment of different amounts of monoamine oxidase (MAO) enzyme on these modified TTF/SPCEs and the use of gold nanoparticles (AuNPs) allowed performing the simultaneous determination of both analytes. The amperometric detection has been performed by measuring the oxidation current of the mediator at a potential of+250 mV vs. screen-printed Ag/AgCl reference electrode. A linear response in the Cad concentration range from 19.6 till 107.1 µM and from 9.9 till 74.1 μM for Put was obtained at the MAO/AuNPs/TTF/SPCE biosensor. This device showed a capability of detection of 9.9 and 19.9±0.9 µM (n=4 α=β=0.05) and a precision of 4.9% and 10.3% in terms of relative standard deviation for Put and Cad, respectively. The developed biosensor was successfully applied to the simultaneous determination of Put and Cad in octopus samples.

  12. Elevated Monoamine Oxidase-A Distribution Volume in Borderline Personality Disorder Is Associated With Severity Across Mood Symptoms, Suicidality, and Cognition.

    Science.gov (United States)

    Kolla, Nathan J; Chiuccariello, Lina; Wilson, Alan A; Houle, Sylvain; Links, Paul; Bagby, R Michael; McMain, Shelley; Kellow, Charis; Patel, Jalpa; Rekkas, Paraskevi V; Pasricha, Suvercha; Meyer, Jeffrey H

    2016-01-15

    Monoamine oxidase-A (MAO-A) is a treatment target in neurodegenerative illness and mood disorders that increases oxidative stress and predisposition toward apoptosis. Increased MAO-A levels in prefrontal cortex (PFC) and anterior cingulate cortex (ACC) occur in rodent models of depressive behavior and human studies of depressed moods. Extreme dysphoria is common in borderline personality disorder (BPD), especially when severe, and the molecular underpinnings of severe BPD are largely unknown. We hypothesized that MAO-A levels in PFC and ACC would be highest in severe BPD and would correlate with symptom magnitude. [(11)C] Harmine positron emission tomography measured MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in severe BPD subjects (n = 14), moderate BPD subjects (n = 14), subjects with a major depressive episode (MDE) only (n = 14), and healthy control subjects (n = 14). All subjects were female. Severe BPD was associated with greater PFC and ACC MAO-A VT compared with moderate BPD, MDE, and healthy control subjects (multivariate analysis of variance group effect: F6,102 = 5.6, p multiple indicators of BPD severity, including BPD symptomatology, mood symptoms, suicidality, and neurocognitive impairment. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Reichmann Heinz

    2011-09-01

    Full Text Available Abstract Background Early initiation of pharmacotherapy in Parkinson's disease (PD is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. Discussion In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. Summary MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

  14. The use of multiscale molecular simulations in understanding a relationship between the structure and function of biological systems of the brain: the application to monoamine oxidase enzymes

    Directory of Open Access Journals (Sweden)

    Robert Vianello

    2016-07-01

    Full Text Available Aging society and therewith associated neurodegenerative and neuropsychiatric diseases, including depression, Alzheimer’s disease, obsessive disorders, and Parkinson’s disease, urgently require novel drug candidates. Targets include monoamine oxidases A and B (MAOs, acetylcholinesterase (AChE and butyrylcholinesterase (BChE, and various receptors and transporters. For rational drug design it is particularly important to combine experimental synthetic, kinetic, toxicological and pharmacological information with structural and computational work. This paper describes the application of various modern computational biochemistry methods in order to improve the understanding of a relationship between the structure and function of large biological systems including ion channels, transporters, receptors and metabolic enzymes. The methods covered stem from classical molecular dynamics simulations to understand the physical basis and the time evolution of the structures, to combined QM and QM/MM approaches to probe the chemical mechanisms of enzymatic activities and their inhibition. As an illustrative example, the later will focus on the monoamine oxidase family of enzymes, which catalyze the degradation of amine neurotransmitters in various parts of the brain, the imbalance of which is associated with the development and progression of a range of neurodegenerative disorders. Inhibitors that act mainly on MAO A are used in the treatment of depression, due to their ability to raise serotonin concentrations, while MAO B inhibitors decrease dopamine degradation and improve motor control in patients with Parkinson disease. Our results give strong support that both MAO isoforms, A and B, operate through the hydride transfer mechanism. Relevance of MAO catalyzed reactions and MAO inhibition in the context of neurodegeneration will be discussed.

  15. On-line radiochemical assay for monoamine oxidase utilizing high-performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Nissinen, E.; Linko-Loeppoenen SMae; Maennistoe P4

    1984-12-01

    A fast and sensitive assay for the determination of monoamine oxidase activity was developed. The method is based on the separation and quantitation of /sup 14/C-labeled assay products by high-performance liquid chromatography, which is interfaced directly into a flow-through radioactivity detector. This allows on-line quantitation of the radioactive compounds with picomole sensitivity. The method makes possible the complete separation and detection of the deaminated products of monoamine oxidase A and B substrates benzylamine and 5-hydroxytryptamine, respectively. This assay has been applied to the measurement of monoamine oxidase A and B activities in rat brain.

  16. Monoamine oxidase B single-photon emission tomography with [{sup 123}I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Buck, A. [Division of Nuclear Medicine, University Hospital Zurich (Switzerland); Frey, L.D. [Department of Nuclear Medicine, Kantonsspital Aarau (Switzerland); Blaeuenstein, P.; Schubiger, P. [Paul Scherrer Institut, Radiopharmacy Division, Villigen (Switzerland); Kraemer, G. [Swiss Epilepsy Clinic, Zurich (Switzerland); Siegel, A.; Weber, B.; Wieser, H.G. [Department of Neurology, University Hospital Zurich (Switzerland)

    1998-05-01

    Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [{sup 123}I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [{sup 123}I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology. (orig.) With 3 figs., 3 tabs., 28 refs.

  17. Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

    Science.gov (United States)

    Halberstadt, Adam L

    2016-04-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by

  18. Behavioral and Pharmacokinetic Interactions Between Monoamine Oxidase Inhibitors and the Hallucinogen 5-Methoxy-N,N-dimethyltryptamine

    Science.gov (United States)

    Halberstadt, Adam L.

    2016-01-01

    Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography–electrospray ionization–selective reaction monitoring–tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI

  19. Synthesis and biological assessment of novel 2-thiazolylhydrazones and computational analysis of their recognition by monoamine oxidase B.

    Science.gov (United States)

    Distinto, Simona; Yáñez, Matilde; Alcaro, Stefano; Cardia, M Cristina; Gaspari, Marco; Sanna, M Luisa; Meleddu, Rita; Ortuso, Francesco; Kirchmair, Johannes; Markt, Patrick; Bolasco, Adriana; Wolber, Gerhard; Secci, Daniela; Maccioni, Elias

    2012-02-01

    Monoamine oxidase B (MAO-B) is a promising target for the treatment of neurodegenerative disorders. We report the synthesis and the biological evaluation of halogenated derivatives of 1-aryliden-2-(4-phenylthiazol-2-yl)hydrazines. The fluorinated series shows interesting activity and great selectivity toward the human recombinant MAO-B isoform expressed in baculovirus infected BTI insect cells. The multiple crystal structures alignment of the enzyme highlighted pronounced induced fit (IF) adaptations with respect to bound ligands. Therefore, IF docking (IFD) experiments and molecular dynamic (MD) simulations were carried out to reveal the putative binding mode and to explain the experimentally observed differences in the activity of 1-(aryliden-2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazines. The importance of water molecules within the binding site was also investigated. These are known to play an important role in the binding site cavity and to mediate protein-ligand interactions. Detailed analyses of the trajectories provide insights on the chemical features required for the activity of this scaffold. In particular it was highlighted the importance of fluorine atom interacting with the water close to the cofactor and the influence of steric bulkiness of substituents in the arylidene moiety. Free energy perturbation (FEP) analysis confirmed experimental data. The information we deduced will help to develop novel high-affinity MAO-B inhibitors.

  20. Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition.

    Science.gov (United States)

    Cattaneo, Carlo; Caccia, Carla; Marzo, Antonio; Maj, Roberto; Fariello, Ruggero G

    2003-01-01

    Safinamide is a novel neuroprotectant combining sodium and calcium channel blocking properties with selective, reversible monoamine oxidase type B (MAO B) inhibition. Phase 1 studies have demonstrated that in healthy volunteers, the ED50 (a dose that inhibits enzyme activity by 50% in 50% of treated subjects) for MAO B inhibition is 87.5 microg/kg/day orally, and that no MAO A inhibition occurs after 10-mg/kg oral dosing. To assess the risk of inducing the "cheese effect," the effect of safinamide and placebo on the pressor response to tyramine was investigated in a group of healthy male volunteers. The study was an open, single-dose placebo-controlled trial with the 2 treatments in sequence. An increase of 30 mm Hg systolic blood pressure was obtained by intravenous tyramine administered by 0.5-mg incremental boluses injected at 15-minute intervals. The amount of tyramine necessary to achieve such a blood pressure increase was the same after the safinamide 2-mg/kg oral load compared with placebo. These results suggest that dietary restrictions for food with high tyramine content should not be required under safinamide treatment.

  1. Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion. Role of renal monoamine-oxidase.

    Science.gov (United States)

    de Luca Sarobe, Verónica; Di Ciano, Luis; Carranza, Andrea M; Levin, Gloria; Arrizurieta, Elvira E; Ibarra, Fernando R

    2010-01-01

    Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (UDAV) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of UDAV during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats UDAV (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 +/- 1.20 to 21.8 +/- 3.10 (p diuresis and natriuresis over controls. BNZ abolished the early UDAV peak to 3.2+/-0.72 (p diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

  2. Kinetics of Inhibition of Monoamine Oxidase Using Cymbopogon martinii (Roxb.) Wats.: A Potential Antidepressant Herbal Ingredient with Antioxidant Activity.

    Science.gov (United States)

    Gacche, R N; Shaikh, R U; Chapole, S M; Jadhav, A D; Jadhav, S G

    2011-07-01

    The study was designed to evaluate the antioxidant activity and effect of Cymbopogon martinii (Roxb.) Wats. (Poaceae) leaves on the activity of monoamine oxidase and kinetics of enzyme inhibition. Ethanol extract of C. martinii and rat brain mitochondrial monoamine oxidase preparation ware used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver-Burk plot. The DPPH was used as a source of free radical to evaluate antioxidant potential. It is observed that, the ethanolic extract of C. martinii inhibits the monoamine oxidase activity with competitive mode of inhibition. The V(max) (0.01 mM/min) remained constant while, K(m) varied from 21.00 ± 1.1, 43.33 ± 1.5 and 83.33 ± 1.4 mM for 100-500 μg/ml concentration of C. martinii. The K(i) values were calculated to be 90.00 ± 0.87, 75.00 ± 0.69, 68.18 ± 0.68 μg for 100-500 μg/ml concentration of C. martini. It also shows a significant DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging (IC(50) = 0.34 ± 0.05 mg/ml) and reducing activity (IC(50) = 0.70 ± 0.22 mg/ml). The C. martini can be considered as a possible source of MAO inhibitor used in the treatment of depression and other neurological disorders.

  3. 1-[2-(4-Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease.

    Science.gov (United States)

    Chung, Jin Yong; Lee, Ji Won; Ryu, Choon Ho; Min, Hye Kyung; Yoon, Yeo Jin; Lim, Mi Jung; Park, Cheol Hyoung

    2015-08-01

    Monoamine oxidase B (MAO-B) is well known as a therapeutic target for Parkinson's disease (PD). MAO-B inhibitors retain antiparkinsonism abilities to improve motor function and prevent neuronal loss by decreasing dopamine metabolism and oxidative stress in the brain. From the study to find novel antiparkinsonism drugs that can inhibit MAO-B activity, neuronal loss, and behavioral deficits in the mouse model of PD, we identified that 1-[2-(4-benzyloxyphenoxy)ethyl]imidazole (BPEI) or safinamide strongly and selectively inhibited MAO-B activities in a dose-dependent manner (IC50 of BPEI and safinamide for MAO-B were 0.016 and 0.0021 µM and for MAO-A were 70.0 and 370 µM, respectively). In ex vivo studies after an administration (30 mg/kg, i.p.) of BPEI or safinamide to normal mice, the MAO-B activity in the brain was reduced by up to 90.6% or 82.4% at 1.0 hr. BPEI (20 mg/kg, i.p.) or safinamide (20 mg/kg, i.p.) significantly reversed the behavioral impairments, dopamine levels in the striatum, and neuronal loss in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared with the MPTP-alone-treated group. In the 6-hydroxydopamine-induced PD rat model, behavioral improvement by levodopa sparing activity was observed in the BPEI- or safinamide-treated (20 mg/kg, i.p.) rats. Moreover, BPEI revealed additional curative activities for nonmotor symptoms of PD such as pain, anxiety, epilepsy, and depression in rodent disease models. Therefore, BPEI has broad therapeutic potential for treating motor symptoms via strong and selective inhibitory effects on MAO-B, with additional benefits for comorbid symptoms in PD. © 2015 Wiley Periodicals, Inc.

  4. The Use of Multiscale Molecular Simulations in Understanding a Relationship between the Structure and Function of Biological Systems of the Brain: The Application to Monoamine Oxidase Enzymes.

    Science.gov (United States)

    Vianello, Robert; Domene, Carmen; Mavri, Janez

    2016-01-01

    HIGHLIGHTS Computational techniques provide accurate descriptions of the structure and dynamics of biological systems, contributing to their understanding at an atomic level.Classical MD simulations are a precious computational tool for the processes where no chemical reactions take place.QM calculations provide valuable information about the enzyme activity, being able to distinguish among several mechanistic pathways, provided a carefully selected cluster model of the enzyme is considered.Multiscale QM/MM simulation is the method of choice for the computational treatment of enzyme reactions offering quantitative agreement with experimentally determined reaction parameters.Molecular simulation provide insight into the mechanism of both the catalytic activity and inhibition of monoamine oxidases, thus aiding in the rational design of their inhibitors that are all employed and antidepressants and antiparkinsonian drugs. Aging society and therewith associated neurodegenerative and neuropsychiatric diseases, including depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease, urgently require novel drug candidates. Targets include monoamine oxidases A and B (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and various receptors and transporters. For rational drug design it is particularly important to combine experimental synthetic, kinetic, toxicological, and pharmacological information with structural and computational work. This paper describes the application of various modern computational biochemistry methods in order to improve the understanding of a relationship between the structure and function of large biological systems including ion channels, transporters, receptors, and metabolic enzymes. The methods covered stem from classical molecular dynamics simulations to understand the physical basis and the time evolution of the structures, to combined QM, and QM/MM approaches to probe the chemical mechanisms of enzymatic

  5. Comparison of the Inhibition of Monoamine Oxidase and Butyrylcholinesterase Activities by Infusions from Green Tea and Some Citrus Peels

    Directory of Open Access Journals (Sweden)

    Ayokunle O. Ademosun

    2014-01-01

    Full Text Available This study sought to investigate the effect of infusions from green tea (Camellia sinensis and some citrus peels [shaddock (Citrus maxima, grapefruit (Citrus paradisi, and orange (Citrus sinensis] on key enzymes relevant to the management of neurodegenerative conditions [monoamine oxidase (MAO and butyrylcholinesterase (BChE]. The total phenol contents and antioxidant activities as typified by their 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS radicals scavenging abilities, ferric reducing antioxidant properties, and Fe2+ chelating abilities were also investigated. Green tea had the highest total phenol (43.3 mg/g and total flavonoid (16.4 mg/g contents, when compared to orange [total phenol (19.6 mg/g, total flavonoid (6.5 mg/g], shaddock [total phenol (16.3 mg/g, total flavonoid (5.2 mg/g], and grapefruit [total phenol (17.7 mg/g, total flavonoid (5.9 mg/g]. Orange (EC50 = 1.78 mg/mL had the highest MAO inhibitory ability, while green tea had the least MAO inhibitory ability (EC50 = 2.56 mg/mL. Similarly, green tea had the least BChE inhibitory ability (EC50 = 5.43 mg/mL when compared to the citrus peels’ infusions. However, green tea infusions had the strongest highest ABTS radical scavenging ability, reducing power, and Fe2+ chelating ability. The inhibition of MAO and BChE activities by the green tea and citrus peels infusions could make them good dietary means for the prevention/management of neurodegenerative conditions.

  6. Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5-aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide derivatives.

    Science.gov (United States)

    Koç, G Ş; Tan, O U; Uçar, G; Yildirim, E; Erol, K; Palaska, E

    2014-11-01

    28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The derivatives substituted by halogen on the fifth position of pyrazole ring, inhibited MAO-A enzyme with a high selectivity index. On the other hand, compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate selectivity index. Docking studies were done to highlight the interactions of the most active derivative with the active site of MAO-A. In addition, in vivo antidepressant and anxiolytic activities of the compounds having selective MAO-A inhibitory effects, were investigated by using Porsolt forced swimming and elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.

  7. No changes in lymphocyte muscarinic receptors and platelet monoamine oxidase-B examined as surrogate central nervous system biomarkers in a Faroese children cohort prenatally exposed to methylmercury and polychlorinated biphenyls

    DEFF Research Database (Denmark)

    Coccini, Teresa; Manzo, Luigi; Debes, Frodi

    2009-01-01

    Experimental evidence suggests that monoamine oxidase B (MAO-B) and muscarinic cholinergic receptors (mAChRs) are involved in the pathogenesis of neurotoxicity caused by methylmercury and polychlorinated biphenyls (PCBs). Blood samples from 7-year-old exposed children were analyzed for platelet M....../or PCB exposure, whereas these markers are significantly altered in sustained exposure scenarios, as shown by clinical studies in drug addicts or patients treated with psychopharmacological agents....

  8. Discovery of highly selective and potent monoamine oxidase B inhibitors: Contribution of additional phenyl rings introduced into 2-aryl-1,3,4-oxadiazin-5(6H)-one.

    Science.gov (United States)

    Lee, Jungeun; Lee, Yeongcheol; Park, So Jung; Lee, Joohee; Kim, Yeong Shik; Suh, Young-Ger; Lee, Jeeyeon

    2017-03-01

    Monoamine oxidase B (MAO-B) is a flavin adenine dinucleotide (FAD)-containing enzyme that plays a major role in the oxidative deamination of biogenic amines and neurotransmitters. Inhibiting MAO-B activity is a promising approach in the treatment of neurological disorders. Here, we report a series of 2-aryl-1,3,4-oxadiazin-5(6H)-one derivatives as highly selective and potent MAO-B inhibitors. Analysis of the binding sites of hMAO-A and hMAO-B led to design of linear analogs of 2-aryl-1,3,4-oxadiazin-5(6H)-one with an additional phenyl ring. Biological evaluation of the 26 new derivatives resulted in the identification of highly potent and selective inhibitors with optimal physicochemical properties to potentially cross the blood-brain barrier (BBB). Compounds 18a, 18b, 18e and 25b potently inhibited MAO-B, with IC50 values of 4-25 nM and excellent SI over MAO-A (18a > 25000, 18b > 8333 and 18e > 4000 and 25b > 4545). Docking results suggest that an optimal linker between two aromatic rings on the 2-aryl-1,3,4-oxadiazin-5(6H)-one scaffold is a key element in the binding and inhibition of MAO-B.

  9. The effects of monoamine oxidase inhibitors on the ejaculatory response induced by 5-methoxy-N,N-dimethyltryptamine in the rat.

    Science.gov (United States)

    Rényi, L.

    1986-01-01

    The ejaculatory response and other components of the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1, i.p.) were studied following single and repeated treatment of rats with eight different monoamine oxidase (MAO) inhibitors. Single and repeated treatment with the 5-HT agonist 5-MeODMT, and with low doses of the potent releaser of 5-HT, p-chloroamphetamine (PCA) were also included in the study. Repeated but not single treatment with 5-MeODMT reduced strongly but reversibly the ejaculatory response and the behavioural responses. Repeated but not single treatment with the nonselective and irreversible MAO inhibitors nialamide and pargyline reduced markedly the ejaculatory response but only slightly the 5-HT behavioural responses. Repeated treatment with the irreversible MAO-B inhibitor (-)-deprenyl, with the irreversible MAO-A inhibitor, clorgyline, with the reversible MAO-A inhibitor moclobemide, and with low doses of PCA did not affect either of the responses. Repeated but not single combined treatment with clorgyline plus PCA caused an almost complete blockade of all the four responses. The selective and reversible MAO-A inhibitors (as well as 5-HT releasers) amiflamine, alpha-ethyltryptamine, and alpha-methyltryptamine reduced markedly the ejaculatory response after both single and repeated treatments. The behavioural responses were blocked only after repeated treatment. It is concluded that single and repeated treatments of rats with different MAO inhibitors do not produce a common alteration in 5-HT2 receptor functions. Repeated treatment with 5-MeODMT caused a blockade of 75-95% of the ejaculatory response and 5-HT behavioural responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3091132

  10. Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation.

    Science.gov (United States)

    Youdim, Moussa B H; Weinstock, Marta

    2004-01-01

    The major side effect with the use of first generation of non selective monoamine oxidase (MAO) inhibitors as neuropsychiatric drugs was what became known as the "cheese reaction". Namely, potentiation of sympathomimetic activity of ingested tyramine present in cheese and other food stuff, resulting from its ability to release noradrenaline, when prevented from metabolism by MAO. The identification of two forms of MAO, termed types A and B and their selective irreversible inhibitors resolved some of this problems. However irreversible MAO-A inhibitors continue to induce a cheese reaction, whereas MAO-B inhibitors at their selective dosage did not and led to introduction of L-deprenyl (selegiline) as an anti-Parkinson drug, since dopamine is equally well metabolized by both enzyme forms. The cheese reaction is a consequence of inhibition of MAO-A, the enzyme responsible for metabolism of noradrenaline and serotonin, located in peripheral adrenergic neurons. The consequence of these findings were the development of reversible MAO-A inhibitors (RIMA), moclobemide and brofaromin, as antidepressants and possible anti-Parkinson activity, with limited tyramine potentiation, since the amine can displace the inhibitor from its binding site on the enzyme. It has always been deemed a greater pharmacological advantage to inhibit both forms of the enzymes to get the full functional activities of the amine neurotransmitters, and without inducing a "cheese reaction". This was not possible until recently, with the development of the novel cholinesterase-brain selective MAO-AB inhibitor, TV3326 (N-propargyl-(3R)-aminoidnan-5-yl-ethyl methylcarbamate hemitartiate), a carbamate derivative of the irreversible MAO-B inhibitor anti-Parkinson drug, rasagiline. This drug is a brain selective MAO-A and B inhibitor, with little inhibition of liver and small intestine enzymes. Pharmacologically it has limited tyramine potentiation, very similar to moclobemide and being a MAO-AB inhibitor it

  11. Scale Alpha and Beta of Quantitative Convergence and Chemical Reactivity Analysis in Dual Cholinesterase/Monoamine Oxidase Inhibitors for the Alzheimer Disease Treatment Using Density Functional Theory (DFT

    Directory of Open Access Journals (Sweden)

    Alejandro Morales-Bayuelo

    2013-01-01

    Full Text Available Molecular quantum similarity descriptors and Density Functional Theory (DFT based reactivity descriptors were studied for a series of cholinesterase/monoamine oxidase inhibitors used for the Alzheimer's disease treatment (AD. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these molecules with acetylcholinesterase (AChE and butyrylcholinesterase (BuChE, as well as with monoamine oxidase (MAO A and B. The Topogeometrical Superposition Algorithm to handle flexible molecules (TGSA-Flex alignment method was used to solve the problem of the relative orientation in the quantum similarity (QS field. Using the molecular quantum similarity (MQS field and reactivity descriptors supported in the DFT was possible the quantification of the steric and electrostatic effects through of the Coulomb and Overlap quantitative convergence scales (alpha and beta. In addition, an analysis of reactivity indexes is development, using global and local descriptors, identifying the binding sites and selectivity in the (cholinesterase/monoamine oxidase inhibitors, understanding the retrodonor process, and showing new insight for drugs design in a disease of difficult control as Alzheimer.

  12. Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma.

    Science.gov (United States)

    Li, Pei Chuan; Siddiqi, Imran N; Mottok, Anja; Loo, Eric Y; Wu, Chieh Hsi; Cozen, Wendy; Steidl, Christian; Shih, Jean Chen

    2017-10-01

    Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2 . It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed, paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray-zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (p Hodgkin-lymphoma-derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. A survey of prescribing practices for monoamine oxidase inhibitors.

    Science.gov (United States)

    Balon, R; Mufti, R; Arfken, C L

    1999-07-01

    A survey examined prescribing practices for monoamine oxidase inhibitors (MAOIs) and explored reasons for the widely noted decline in their use. A one-page questionnaire was sent in 1997 to 1,129 members of the Michigan Psychiatric Association. A total of 717 responses were received, for a response rate of 64 percent. Only data from the 573 psychiatrists who were currently practicing were used. Twelve percent of the respondents never prescribed MAOIs, 27 percent had not prescribed them for at least three years, and 17 percent had prescribed them from one to three years ago. Thirty percent of the respondents had prescribed an MAOI within the past three months, and 14 percent between three and 12 months ago. The most frequent reasons for not prescribing the drugs were side effects and interactions with other medications (46 percent), preference for other medications (30 percent), and dietary restrictions necessary for patients taking MAOIs (19 percent). Ninety-two percent of respondents believed that MAOIs were useful for atypical depression, 64 percent for major depression, 54 percent for melancholic depression, 56 percent for panic disorder, 44 percent for social phobia, 27 percent for dysthymia, 12 percent for obsessive-compulsive disorder, and 19 percent for posttraumatic stress disorder. However, only 2 percent said they would use MAOIs as their first-line treatment in atypical depression, and only 3 percent would use them a first-line treatment in social phobia. The results document the commonly held view that practicing psychiatrists believe MAOIs are efficacious but use them infrequently, primarily due to concerns about side effects and drug interactions.

  14. Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [(11)C] Harmine Positron Emission Tomography Study.

    Science.gov (United States)

    Kolla, Nathan J; Matthews, Brittany; Wilson, Alan A; Houle, Sylvain; Bagby, R Michael; Links, Paul; Simpson, Alexander I; Hussain, Amina; Meyer, Jeffrey H

    2015-10-01

    Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [(11)C] harmine PET to measure MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=-0.50 to -0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity.

  15. Lower Monoamine Oxidase-A Total Distribution Volume in Impulsive and Violent Male Offenders with Antisocial Personality Disorder and High Psychopathic Traits: An [11C] Harmine Positron Emission Tomography Study

    Science.gov (United States)

    Kolla, Nathan J; Matthews, Brittany; Wilson, Alan A; Houle, Sylvain; Michael Bagby, R; Links, Paul; Simpson, Alexander I; Hussain, Amina; Meyer, Jeffrey H

    2015-01-01

    Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These include MAO-A knockout models in rodents evidencing impulsive aggression and positron emission tomography (PET) studies of healthy subjects reporting associations between low brain MAO-A levels and greater impulsivity or aggression. However, a fundamental gap in the literature is that it is unknown whether brain MAO-A levels are low in more severe, clinical disorders of impulsivity, such as ASPD. To address this issue, we applied [11C] harmine PET to measure MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in 18 male ASPD participants and 18 age- and sex-matched controls. OFC and VS MAO-A VT were lower in ASPD compared with controls (multivariate analysis of variance (MANOVA): F2,33=6.8, P=0.003; OFC and VS MAO-A VT each lower by 19%). Similar effects were observed in other brain regions: prefrontal cortex, anterior cingulate cortex, dorsal putamen, thalamus, hippocampus, and midbrain (MANOVA: F7,28=2.7, P=0.029). In ASPD, VS MAO-A VT was consistently negatively correlated with self-report and behavioral measures of impulsivity (r=−0.50 to −0.52, all P-values<0.05). This study is the first to demonstrate lower brain MAO-A levels in ASPD. Our results support an important extension of preclinical models of impulsive aggression into a human disorder marked by pathological aggression and impulsivity. PMID:26081301

  16. Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease.

    Science.gov (United States)

    Al-Baghdadi, Osamah B; Prater, Natalie I; Van der Schyf, Cornelis J; Geldenhuys, Werner J

    2012-12-01

    A series of compounds related to piperine and antiepilepsirine was screened in a monoamine oxidase A and B assay. Piperine is an alkaloid from the source plant of both black and white pepper grains, Piper nigrum. Piperine has been shown to have a wide range of activity, including MAO inhibitory activity. The z-factor for the screening assay was found to be greater than 0.8 for both assays. Notably, the compounds tested were selective towards MAO-B, with the most potent compound having an IC(50) of 498 nM. To estimate blood-brain barrier (BBB) permeability, we used a PAMPA assay, which suggested that the compounds are likely to penetrate the BBB. A fluorescent bovine serum albumin (BSA) high-throughput screening (HTS) binding assay showed an affinity of 8 μM for piperine, with more modest binding for other test compounds. Taken together, the data described here may be useful in gaining insight towards the design of selective MAO-B inhibitory compounds devoid of MAO-A activity.

  17. Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.

    Science.gov (United States)

    Halberstadt, Adam L; Buell, Mahalah R; Masten, Virginia L; Risbrough, Victoria B; Geyer, Mark A

    2008-11-01

    The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg) and the 5-HT(2A) antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAO(A) inhibitor clorgyline, whereas the selective MAO(B) inhibitor (-)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAO(A). Furthermore, 5-HT(2A) receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAO(A) inhibitors.

  18. Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Nunes, S.F.; Figueiredo, I.V. [Laboratório de Farmacologia, Faculdade de Farmácia, Universidade de Coimbra, Coimbra (Portugal); Pereira, J.S. [Instituto Português de Oncologia de Coimbra, Coimbra (Portugal); Lopes, M.C.; Caramona, M.M. [Laboratório de Farmacologia, Faculdade de Farmácia, Universidade de Coimbra, Coimbra (Portugal)

    2011-11-25

    The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: K{sub m} (r = 0.612, P = 0.034) and V{sub max} (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: K{sub m} (r = -0.625, P = 0.029) and V{sub max} (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

  19. Reducing the Burden of Difficult-to-Treat Major Depressive Disorder: Revisiting Monoamine Oxidase Inhibitor Therapy

    OpenAIRE

    Culpepper, Larry

    2013-01-01

    Objective: Difficult-to-treat depression (eg, depression with atypical or anxious symptoms, treatment-resistant depression, or depression with frequent recurrence) is a challenging real-world health issue. This critical review of the literature focuses on monoamine oxidase inhibitor (MAOI) therapy and difficult-to-treat forms of depression.

  20. Monoamine Oxidase a Promoter Gene Associated with Problem Behavior in Adults with Intellectual/Developmental Disabilities

    Science.gov (United States)

    May, Michael E.; Srour, Ali; Hedges, Lora K.; Lightfoot, David A.; Phillips, John A., III; Blakely, Randy D.; Kennedy, Craig H.

    2009-01-01

    A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a…

  1. The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line.

    Science.gov (United States)

    Satram-Maharaj, Tamara; Nyarko, Jennifer N K; Kuski, Kelly; Fehr, Kelsey; Pennington, Paul R; Truitt, Luke; Freywald, Andrew; Lukong, Kiven Erique; Anderson, Deborah H; Mousseau, Darrell D

    2014-12-01

    Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-A protein and levels of serotonin, a substrate of MAO-A implicated in depression, are paradoxically increased in malignancies, including breast cancer. The effect of clorgyline (CLG), a selective inhibitor of MAO-A, on malignant behaviour, expression of transitional markers, and biochemical correlates was examined in two human breast carcinoma cell lines, i.e. the epithelial, oestrogen receptor (ER)-positive MCF-7 cell line and the post-EMT (mesenchymal), ER-negative MDA-MB-231 cell line. CLG exerted little effect on malignant behaviour in MCF-7 cells, but inhibited proliferation and anchorage-independent growth, and increased invasiveness and active migration of MDA-MB-231 cells. CLG induced the expression of the mesenchymal marker vimentin in MCF-7 cells, but not in MDA-MB-231 cells. In contrast, CLG induced the epithelial protein marker E-cadherin in both cell lines, with a more robust effect in MDA-MB-231 cells (where a nuclear E-cadherin signal was also detected). This effect appears to be independent of any canonical Snai1-mediated regulation of E-cadherin mRNA expression. CLG interfered with the β-catenin/[phospho]GSK-3β complex as well as the E-cadherin/β-catenin complex in both cell lines cells, but, again, the effect was more robust in MDA-MB-231 cells. Parallel studies revealed a general lack of effect of CLG on the ER-negative, epithelial Au565 breast cancer cell line. Thus, any effect of CLG on metastatic behaviours appears to rely on the cell's EMT status rather than on the cell's ER status. These data suggest that inactivation of MAO-A triggers a mesenchymal-to-epithelial transition in MDA-MB-231 cells via a non-canonical mechanism

  2. MicroRNA-142 reduces monoamine oxidase A expression and activity in neuronal cells by downregulating SIRT1.

    Directory of Open Access Journals (Sweden)

    Amrita Datta Chaudhuri

    Full Text Available Aberrant expression of microRNAs (miRs has been implicated in the pathogenesis of several neurodegenerative disorders. In HIV-associated neurocognitive disorders (HAND, miR-142 was found to be upregulated in neurons and myeloid cells in the brain. We investigated the downstream effects of chronic miR-142 upregulation in neuronal cells by comparing gene expression in stable clones of the human neuroblastoma cell line BE(2M17 expressing miR-142 to controls. Microarray analysis revealed that miR-142 expression led to a reduction in monoamine oxidase (MAO A mRNA, which was validated by qRT-PCR. In addition to the mRNA, the MAOA protein level and enzyme activity were also reduced. Examination of primary human neurons revealed that miR-142 expression indeed resulted in a downregulation of MAOA protein level. Although MAOA is not a direct target of miR-142, SIRT1, a key transcriptional upregulator of MAOA is, thus miR-142 downregulation of MAOA expression is indirect. MiR-142 induced decrease in MAOA expression and activity may contribute to the changes in dopaminergic neurotransmission reported in HAND.

  3. Association of ventral striatum monoamine oxidase-A binding and functional connectivity in antisocial personality disorder with high impulsivity: A positron emission tomography and functional magnetic resonance imaging study.

    Science.gov (United States)

    Kolla, Nathan J; Dunlop, Katharine; Downar, Jonathan; Links, Paul; Bagby, R Michael; Wilson, Alan A; Houle, Sylvain; Rasquinha, Fawn; Simpson, Alexander I; Meyer, Jeffrey H

    2016-04-01

    Impulsivity is a core feature of antisocial personality disorder (ASPD) associated with abnormal brain function and neurochemical alterations. The ventral striatum (VS) is a key region of the neural circuitry mediating impulsive behavior, and low monoamine oxidase-A (MAO-A) level in the VS has shown a specific relationship to the impulsivity of ASPD. Because it is currently unknown whether phenotypic MAO-A markers can influence brain function in ASPD, we investigated VS MAO-A level and the functional connectivity (FC) of two seed regions, superior and inferior VS (VSs, VSi). Nineteen impulsive ASPD males underwent [(11)C] harmine positron emission tomography scanning to measure VS MAO-A VT, an index of MAO-A density, and resting-state functional magnetic resonance imaging that assessed the FC of bilateral seed regions in the VSi and VSs. Subjects also completed self-report impulsivity measures. Results revealed functional coupling of the VSs with bilateral dorsomedial prefrontal cortex (DMPFC) that was correlated with VS MAO-A VT (r=0.47, p=0.04), and functional coupling of the VSi with right hippocampus that was anti-correlated with VS MAO-A VT (r=-0.55, p=0.01). Additionally, VSs-DMPFC FC was negatively correlated with NEO Personality Inventory-Revised impulsivity (r=-0.49, p=0.03), as was VSi-hippocampus FC with Barratt Impulsiveness Scale-11 motor impulsiveness (r=-0.50, p=0.03). These preliminary results highlight an association of VS MAO-A level with the FC of striatal regions linked to impulsive behavior in ASPD and suggest that phenotype-based brain markers of ASPD have relevance to understanding brain function. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  4. Genetic studies of two inherited human phenotypes : Hearing loss and monoamine oxidase activity

    OpenAIRE

    Balciuniene, Jorune

    2001-01-01

    This thesis focuses on the identification of genetic factors underlying two inherited human phenotypes: hearing loss and monoamine oxidase activity. Non-syndromic hearing loss segregating in a Swedish family was tested for linkage to 13 previously reported candidate loci for hearing disabilities. Linkage was found to two loci: DFNA12 (llq22-q24) and DFNA2 (lp32). A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the hypothesis of digenic inheri...

  5. Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.

    LENUS (Irish Health Repository)

    Seymour, C B

    2003-11-17

    l-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.

  6. Selective monoamine oxidase B inhibition by an Aphanizomenon flos-aquae extract and by its constitutive active principles phycocyanin and mycosporine-like amino acids.

    Science.gov (United States)

    Scoglio, Stefano; Benedetti, Yanina; Benvenuti, Francesca; Battistelli, Serafina; Canestrari, Franco; Benedetti, Serena

    2014-06-15

    Aphanizomenon flos-aquae (AFA) is a fresh water unicellular blue-green alga that has been traditionally used for over 25 years for its health-enhancing properties. Recent studies have shown the ability of a proprietary AFA extract (Klamin(®)) to improve mood, counteract anxiety, and enhance attention and learning. Aim of this study was to test the monoamine oxidase (MAO) inhibition activity of the same AFA extract and of its constituents phycocyanin (AFA-PC) and mycosporine-like aminoacids (AFA-MAAs). All compounds showed a dose-dependent selective inhibition of MAO-B activity as compared to MAO-A. The IC50 values of the AFA extract (concentration 10 mg/ml), AFA-PC and AFA-MAAs were 6.4 μl/ml, 1.33 μM and 1.98 μM, respectively, evidencing a mixed-type of inhibition for the AFA extract (Ki 0.99 μl/ml), a non-competitive inhibition for AFA-PC (Ki 1.06 μM) and a competitive inhibition for AFA-MAAs (Ki 0.585 μM). These results are important to explain the neuromodulating properties of the AFA extract Klamin(®), which is rich in phenylethylamine, a general neuromodulator, that would nevertheless rapidly destroyed by MAO-B enzymes without the inhibitory activity of the synergic active principles AFA-PC and AFA-MAAs. The present investigation thus proposes the extract as potentially relevant in clinical areas such as mood disorders and neurodegenerative diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    Science.gov (United States)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  8. Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties.

    Science.gov (United States)

    Les, Francisco; Deleruyelle, Simon; Cassagnes, Laure-Estelle; Boutin, Jean A; Balogh, Balázs; Arbones-Mainar, José M; Biron, Simon; Marceau, Picard; Richard, Denis; Nepveu, Françoise; Mauriège, Pascale; Carpéné, Christian

    2016-10-25

    Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when

  9. Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer's disease: a tribute to Moussa Youdim.

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    Weinreb, Orly; Mandel, Silvia; Bar-Am, Orit; Amit, Tamar

    2011-03-01

    It is for these authors a great privilege to dedicate this review article to Moussa Youdim, who is one of the most imperative pharmacologists and pioneer investigators in the search and development of novel therapeutics for neurodegenerative diseases. 40 years ago, Moussa Youdim has started studying brain iron, catecholamine receptor and monoamine oxidase (MAO)-A and -B functions. Although Moussa Youdim succeeded in exploring the novel anti-Parkinsonian, selective MAO-B inhibitor drug, rasagiline (Azilect, Teva Pharmaceutical Co.), he did not stop searching for superior therapeutic approaches for neurodegenerative disorders. To date, Moussa Youdim and his research group are designing and synthesizing pluripotential drug candidates possessing diverse pharmacological properties that can act on multiple targets and pathological features ascribed to Parkinson's disease, Alzheimer's disease (AD) and amyotrophic lateral sclerosis. One such example is the multimodal non-toxic, brain-permeable iron-chelating compound, M30 (5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline), which amalgamates the propargyl moiety of rasagiline with the backbone of the potent iron chelator, VK28. This review discusses the multiple effects of several leading compounds of this series, concerning their neuroprotective/neurorestorative molecular mechanisms in vivo and in vitro, with a special focus on the pathological features ascribed to AD, including antioxidant and iron chelating activities, regulation of amyloid precursor protein and amyloid β peptide expression processing, activation of pro-survival signaling pathways and regulation of cell cycle and neurite outgrowth.

  10. DNA cloning of human liver monoamine oxidase A and B: Molecular basis of differences in enzymatic properties

    Energy Technology Data Exchange (ETDEWEB)

    Back, A.W.J.; Lan, N.C.; Johnson, D.L.; Abell, C.W.; Bembenek, M.E.; Kwan, S.W.; Seeburg, P.H.; Shih, J.C. (Univ. of Heidelberg (West Germany))

    1988-07-01

    The monoamine oxidases play a vital role in the metabolism of biogenic amines in the central nervous system and in peripheral tissues. Using oligonucleotide probes derived from three sequenced peptide fragments, the authors have isolated cDNA clones that encode the A and B forms of monoamine oxidase and have determined the nucleotide sequences of these cDNAs. Comparison of the deduced amino acid sequences shows that the A and B forms have subunit molecular weights of 59,700 and 58,800, respectively, and have 70% sequence identity. Both sequences contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, in which the obligatory cofactor FAD is covalently bound to cysteine. Based on differences in primary amino acid sequences and RNA gel blot analysis of mRNAs, the A and B forms of monoamine oxidase appear to be derived from separate genes.

  11. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins.

    Science.gov (United States)

    Zhang, De Lu; Zhang, Jing; Hu, Chun Xiang; Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding

    2014-12-01

    Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1-24h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3-12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish liver. All alterations were dose- and time-dependent. Overall, the results indicate that aphantoxins/PSPs induce oxidative stress through inhibition of AChE and MAO activities, leading to neurotoxicity in zebrafish liver. The above parameters may be useful as bioindicators for investigating aphantoxins/PSPs and cyanobacterial blooms in nature

  12. Modification of Monoaminergic Activity by MAO Inhibitors Influences Methamphetamine Actions

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2006-01-01

    Full Text Available Methamphetamine (METH abuse is a serious health and social problem worldwide. At present, however, there are no effective medications for the treatment of METH abuse. Of the intracellular METH target proteins, monoamine oxidase (MAO is involved in the regulation of monoaminergic tone in the brain, resulting in the modulation of METHinduced behavioral abnormalities in mammals. The METH-induced expression of increased motor activity, stereotypy, and sensitization is closely associated with monoaminergic transmission in the brain. Modifi cation of MAO activity by MAO inhibitors can influence METH action. Of the MAO inhibitors, the propargylamine derivative clorgyline, an irreversible MAO-A inhibitor, effectively blocks METH-induced hyperlocomotion and behavioral sensitization in rodents. Analysis of the associated monoaminergic activity indicates an involvement of altered striatal serotonergic transmission as well as an increased dopaminergic tone. Some effects of MAO inhibitors on METH action appear to be independent of MAO, suggesting complex mechanisms of action of MAO inhibitors in METH abuse. This review describes current research to find effective treatment for METH abuse, using MAO inhibitors.

  13. Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.

    Science.gov (United States)

    Kupsch, A; Sautter, J; Götz, M E; Breithaupt, W; Schwarz, J; Youdim, M B; Riederer, P; Gerlach, M; Oertel, W H

    2001-01-01

    The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Monoamine-oxidase B (MAO-B) has been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease, since selegiline (L-deprenyl), an irreversible MAO-B inhibitor, prevents MPTP-induced neurotoxicity in numerous species including mice, goldfish and drosophyla. However, one disadvantage of this substance relates to its metabolism to (-)-methamphetamine and (-)-amphetamine. Rasagiline (R-(+)-N-propyl-1-aminoindane) is a novel irrevesible MAO-B-inhibitor, which is not metabolized to metamphetamine and/or amphetamine. The present study compared the effects of high doses of selegiline and rasagiline (10 mg/kg body weight s.c.) on MPTP-induced dopaminergic neurotoxicity in a non-human primate (Callithrix jacchus) model of PD. Groups of four monkeys were assigned to the following six experimental groups: Group I: Saline, Group II: Selegiline/Saline, Group III: Rasagiline/Saline, Group IV: MPTP/Saline, Group V: Rasagiline/MPTP, Group VI: Selegiline/MPTP. Daily treatment with MAO-B-inhibitors (either rasagiline or selegiline, 10 mg/kg body weight s.c.) was initiated four days prior to MPTP-exposure (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 hours for a total of four days) and was continued until the end of the experiment, i.e. 7 days after the cessation of the MPTP-injections, when animals were sacrificed. MPTP-treatment caused distinct behavioural, histological, and biochemical alterations: 1. significant reduction of motor activity assessed by clinical rating and by computerized locomotor activity measurements; 2. substantial loss (approx. 40%) of dopaminergic (tyrosine-hydroxylase-positive) cells in the substantia nigra, pars compacta; and 3. putaminal dopamine depletion of 98% and its metabolites DOPAC (88%) and HVA (96%). Treatment with either rasagiline or selegiline markedly

  14. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-chromen-2-One Core: Structure-Based and Ligand-Based Derived 3-D QSAR Predictive Models.

    Science.gov (United States)

    Mladenovic, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-03-14

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including: (1) definition of optimized and validated structure-based (SB) 3-D QSAR models derived from available co-crystallized inhibitor-MAO B complexes; (2) elaboration of structure-activity relationships (SAR) features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rules assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSARs training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a result of rational SB/LB 3-D QSAR design

  15. Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, De Lu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Hu, Chun Xiang, E-mail: cxhu@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Wang, Gao Hong; Li, Dun Hai; Liu, Yong Ding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

    2014-12-15

    Highlights: • Aphantoxins induced zebrafish hepatic physiological and morphological changes. • AChE and MAO inhibition reflected abnormality of neurotransmitter inactivation. • ROS advance and T-AOC reduction suggested oxidative stress. • ALT, AST, histological and ultrastructural alterations indicated hepatic damage. - Abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1–24 h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3–12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish

  16. ”Ping-pong gaze” secondary to monoamine oxidase inhibitor overdose

    Directory of Open Access Journals (Sweden)

    Amy Attaway

    2016-01-01

    Full Text Available An infrequent manifestation of monoamine oxidase inhibitor (MAOI toxicity is “ping-pong gaze” (PPG. We describe the case of a 26-year-old female who was found unresponsive after taking 40 tablets of phenelzine. On presentation to the hospital, her eyes were moving in characteristic “ping pong” fashion. After 6 hours her gaze terminated. The following day her neurologic exam was benign and she had no long-term sequelae. While the etiology of PPG is unknown, it is most often seen with irreversible structural brain damage. However, a detailed literature review revealed that previous cases of MAOI toxicity where the patient survived have all had complete neurologic recovery.

  17. Resistance of the golden hamster to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity is not only related with low levels of cerebral monoamine oxidase-B.

    Science.gov (United States)

    Rodríguez, Sebastián; Ito, Tsuyoshi; He, Xi Jun; Uchida, Kazuyuki; Nakayama, Hiroyuki

    2013-01-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been proved to be a potent neurotoxin on dopaminergic neurons inducing most of the symptoms and cerebral lesions observed in the idiopathic Parkinson's disease (PD). Although there is a substantial body of theory and researches about the effects of MPTP on susceptible mice and nonhuman primates, there are only few studies in resistant animals, such as golden hamsters (GH). The low levels of cerebral monoamine oxidase-B (MAO-B) enzyme have been proposed as the cause of the GH insensitivity to MPTP. The aim of this study was to elucidate whether MAO-B is the only factor which confer GH resistance to MPTP. Neither loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) nor cell death in the subventricular zone (SVZ) were found in female GH in response to an acute intraperitoneal (ip) MPTP treatment. To prove the role of MAO-B in the MPTP-resistance, female and male GH was intracerebroventricularly (icv) injected with either MPTP or 1-methyl-4-phenylpyridinum (MPP(+)). Neither depletion in the number of dopaminergic neurons, nor astrogliosis, cell death in the SVZ of female and male GH were registered after an icv treatment with MPTP or MPP(+). Furthermore, we demonstrated that MAO-B is located predominantly within the endothelial cells in the blood brain barrier (BBB), but not in the astroglia. The present results raise the possibility that, in GH, other mechanisms, apart from the low levels of regional MAO-B, confer resistance to MPTP and its metabolites.

  18. Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors

    Science.gov (United States)

    Halberstadt, Adam L.; Buell, Mahalah R.; Masten, Virginia L.; Risbrough, Victoria B.; Geyer, Mark A.

    2010-01-01

    RATIONALE The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. OBJECTIVE The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)1A antagonist WAY-100635 (1.0 mg/kg) and the 5-HT2A antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. RESULTS 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAOA inhibitor clorgyline, whereas the selective MAOB inhibitor (−)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. CONCLUSIONS The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by inhibition of MAOA. Further, 5-HT2A receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAOA inhibitors. PMID:18604652

  19. Synthesis, crystal structures, molecular docking, in vitro monoamine oxidase-B inhibitory activity of transition metal complexes with 2-{4-[bis (4-fluorophenyl)methyl]piperazin-1-yl} acetic acid

    Science.gov (United States)

    Yang, Dan-dan; Wang, Riu; Zhu, Jin-long; Cao, Qi-yue; Qin, Jie; Zhu, Hai-liang; Qian, Shao-song

    2017-01-01

    Three novel complexes, [Cu(L)2(H2O)](1), [Zn(L)2(H2O)2]·CH3OH·1.5H2O(2), and [Ni(L)2(H2O)1.8]·CH3OH·1.2H2O (3) (HL = 2-{4-[bis(4-fluorophenyl)methyl]pipera-zin-1-yl} acetic acid), were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential Monoamine oxidase B inhibitory activity. All acquired compounds were tested against rat brain MAO-B in vitro. In accordance with the result of calculation, it showed complex 1 (IC50 = 1.85 ± 0.31 μM) have good inhibitory activity against MAO-B at the same micromolar concentrations with positive control Iproniazid Phosphate (IP, IC50 = 7.59 ± 1.17 μM). These results indicated that complex 1 was a potent MAO-B inhibitor.

  20. Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits.

    Science.gov (United States)

    Soliman, A; Bagby, R M; Wilson, A A; Miler, L; Clark, M; Rusjan, P; Sacher, J; Houle, S; Meyer, J H

    2011-05-01

    Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior. Participants were aged 19-49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R). Prefrontal MAOA binding correlated negatively with angry-hostility (r=-0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions. We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

  1. The role of the monoamine oxidase A gene in moderating the response to adversity and associated antisocial behavior: a review

    Directory of Open Access Journals (Sweden)

    Buades-Rotger M

    2014-07-01

    Full Text Available Macià Buades-Rotger,1,2 David Gallardo-Pujol1,3 1Department of Personality, Faculty of Psychology, University of Barcelona, Barcelona, Spain; 2Department of Neurology, University of Lübeck, Lübeck, Germany; 3Institute for Brain, Cognition and Behavior (IR3C, University of Barcelona, Barcelona, Spain Abstract: Hereditary factors are increasingly attracting the interest of behavioral scientists and practitioners. Our aim in the present article is to introduce some state-of-the-art topics in behavioral genetics, as well as selected findings in the field, in order to illustrate how genetic makeup can modulate the impact of environmental factors. We focus on the most-studied polymorphism to date for antisocial responses to adversity: the monoamine oxidase A gene. Advances, caveats, and promises of current research are reviewed. We also discuss implications for the use of genetic information in applied settings. Keywords: behavioral genetics, antisocial behaviors, monoamine oxidase A

  2. Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status.

    Science.gov (United States)

    Jiang, Xi-Ling; Shen, Hong-Wu; Mager, Donald E; Yu, Ai-Ming

    2013-05-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT or street name "5-MEO") is a newer designer drug belonging to a group of naturally occurring indolealkylamines. Our recent study has demonstrated that coadministration of monoamine oxidase A (MAO-A) inhibitor harmaline (5 mg/kg) increases systemic exposure to 5-MeO-DMT (2 mg/kg) and active metabolite bufotenine. This study is aimed at delineating harmaline and 5-MeO-DMT pharmacokinetic (PK) interactions at multiple dose levels, as well as the impact of CYP2D6 that affects harmaline PK and determines 5-MeO-DMT O-demethylation to produce bufotenine. Our data revealed that inhibition of MAO-A-mediated metabolic elimination by harmaline (2, 5, and 15 mg/kg) led to a sharp increase in systemic and cerebral exposure to 5-MeO-DMT (2 and 10 mg/kg) at all dose combinations. A more pronounced effect on 5-MeO-DMT PK was associated with greater exposure to harmaline in wild-type mice than CYP2D6-humanized (Tg-CYP2D6) mice. Harmaline (5 mg/kg) also increased blood and brain bufotenine concentrations that were generally higher in Tg-CYP2D6 mice. Surprisingly, greater harmaline dose (15 mg/kg) reduced bufotenine levels. The in vivo inhibitory effect of harmaline on CYP2D6-catalyzed bufotenine formation was confirmed by in vitro study using purified CYP2D6. Given these findings, a unified PK model including the inhibition of MAO-A- and CYP2D6-catalyzed 5-MeO-DMT metabolism by harmaline was developed to describe blood harmaline, 5-MeO-DMT, and bufotenine PK profiles in both wild-type and Tg-CYP2D6 mouse models. This PK model may be further employed to predict harmaline and 5-MeO-DMT PK interactions at various doses, define the impact of CYP2D6 status, and drive harmaline-5-MeO-DMT pharmacodynamics.

  3. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids

    Directory of Open Access Journals (Sweden)

    Bautista-Aguilera OM

    2014-10-01

    Full Text Available Oscar M Bautista-Aguilera,1,* Gerard Esteban,2,* Mourad Chioua,1 Katarina Nikolic,3 Danica Agbaba,3 Ignacio Moraleda,4 Isabel Iriepa,4 Elena Soriano,5 Abdelouahid Samadi,1 Mercedes Unzeta,2 José Marco-Contelles1 1Laboratory of Medicinal Chemistry (Institute of General Organic Chemistry [IQOG], National Research Council [CSIC], Madrid, Spain; 2Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Autonomous Barcelona University, Barcelona, Spain; 3Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia; 4Department of Organic Chemistry, Faculty of Pharmacy, University of Alcalá, Ctra Barcelona, Alcalá de Henares, Spain; 5Synthesis, and Structure of Organic Compounds (SEPCO (IQOG, CSIC, Madrid, Spain *These authors have equally contributed to this work Abstract: The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs as multipotent cholinesterase (ChE and monoamine oxidase (MAO inhibitors for the potential treatment of Alzheimer’s disease (AD is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE, and butyrylcholinesterase (BuChE enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (­Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE. Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for h

  4. Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors.

    Science.gov (United States)

    Hammuda, Arwa; Shalaby, Raed; Rovida, Stefano; Edmondson, Dale E; Binda, Claudia; Khalil, Ashraf

    2016-05-23

    A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site.

  5. Monoamine oxidase A genotype is associated with gang membership and weapon use.

    Science.gov (United States)

    Beaver, Kevin M; DeLisi, Matt; Vaughn, Michael G; Barnes, J C

    2010-01-01

    A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene has been found to be associated with a broad range of antisocial phenotypes, including physical violence. At the same time, it is well known that gang members represent some of the most serious violent offenders. Even so, no research has ever examined the association between MAOA and gang membership. The aim of this study is to examine the association between MAOA and gang membership and between MAOA and weapon use. We examined the effects of MAOA by using a molecular genetic association research design. A nonclinical sample was used in this study. Participants were drawn from the National Longitudinal Study of Adolescent Health (1155 females, 1041 males). The outcome measures of this study are gang membership and weapon use. The low MAOA activity alleles conferred an increased risk of joining a gang and using a weapon in a fight for males but not for females. Moreover, among male gang members, those who used weapons in a fight were more likely to have a low MAOA activity allele when compared with male gang members who do not use weapons in a fight. Male carriers of low MAOA activity alleles are at risk for becoming a gang member and, once a gang member, are at risk for using weapons in a fight. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Monoamine oxidase A gene DNA hypomethylation - a risk factor for panic disorder?

    Science.gov (United States)

    Domschke, Katharina; Tidow, Nicola; Kuithan, Henriette; Schwarte, Kathrin; Klauke, Benedikt; Ambrée, Oliver; Reif, Andreas; Schmidt, Hartmut; Arolt, Volker; Kersting, Anette; Zwanzger, Peter; Deckert, Jürgen

    2012-10-01

    The monoamine oxidase A (MAOA) gene has been suggested as a prime candidate in the pathogenesis of panic disorder. In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. Sixty-five patients with panic disorder (44 females, 21 males) and 65 healthy controls were analysed for DNA methylation status at 42 MAOA CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. The occurrence of recent positive and negative life events was ascertained. Male subjects showed no or only very minor methylation with some evidence for relative hypomethylation at one CpG site in intron 1 in patients compared to controls. Female patients exhibited significantly lower methylation than healthy controls at 10 MAOA CpG sites in the promoter as well as in exon/intron 1, with significance surviving correction for multiple testing at four CpG sites (p≤0.001). Furthermore, in female subjects the occurrence of negative life events was associated with relatively decreased methylation, while positive life events were associated with increased methylation. The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.

  7. 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.

  8. Monoamine oxidase A polymorphism moderates stability of attention problems and susceptibility to life stress during adolescence.

    Science.gov (United States)

    Zohsel, K; Bianchi, V; Mascheretti, S; Hohm, E; Schmidt, M H; Esser, G; Brandeis, D; Banaschewski, T; Nobile, M; Laucht, M

    2015-11-01

    Attention problems affect a substantial number of children and adolescents and are predictive of academic underachievement and lower global adaptive functioning. Considerable variability has been observed with regard to the individual development of attention problems over time. In particular, the period of adolescence is characterized by substantial maturation of executive functioning including attentional processing, with the influence of genetic and environmental factors on individual trajectories not yet well understood. In the present investigation, we evaluated whether the monoamine oxidase A functional promoter polymorphism, MAOA-LPR, plays a role in determining continuity of parent-rated attention problems during adolescence. At the same time, a potential effect of severe life events (SLEs) was taken into account. A multi-group path analysis was used in a sample of 234 adolescents (149 males, 85 females) who took part in an epidemiological cohort study at the ages of 11 and 15 years. Attention problems during early adolescence were found to be a strong predictor of attention problems in middle adolescence. However, in carriers of the MAOA-LPR low-activity variant (MAOA-L), stability was found to be significantly higher than in carriers of the high-activity variant (MAOA-H). Additionally, only in MAOA-L carriers did SLEs during adolescence significantly impact on attention problems at the age of 15 years, implying a possible gene × environment interaction. To conclude, we found evidence that attention problems during adolescence in carriers of the MAOA-L allele are particularly stable and malleable to life stressors. The present results underline the usefulness of applying a more dynamic GxE perspective. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

    Science.gov (United States)

    Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

    2014-01-01

    Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

  10. Intoxications with the monoamine oxidase inhibitor tranylcypromine: an analysis of fatal and non-fatal events.

    Science.gov (United States)

    Gahr, Maximilian; Schönfeldt-Lecuona, Carlos; Kölle, Markus A; Freudenmann, Roland W

    2013-11-01

    Tranylcypromine (TCP) is a non-selective and irreversible monoamine oxidase inhibitor and an effective agent in the treatment of major depression. It features a complex pharmacologic profile and overdoses might induce severe intoxications. To identify typical clinical presentations of TCP-intoxications, range of associated TCP-dosages and possible differences between fatal and non-fatal intoxications a systematic review of all previously published cases of TCP-intoxications was conducted. We detected n=20 reports of TCP-intoxications in the literature (fatalities n=10). Mean age was 36.7 years (median 37); the majority of patients were female (60%). Frequent findings in patients with TCP-intoxications were disturbance of consciousness/cognitive dysfunction (90%), cardio-vascular symptoms (55%), hyperthermia (50%), respiratory distress (45%), delirium (45%), muscular rigidity (30%) and renal failure (20%). Suicidal intent was present in n=18 (90%) patients. First clinical symptoms related to TCP-intoxication developed on average in less than 1 day. The average dosage related to TCP-intoxication was 677 mg. The highest survived TCP-dosage was 4000 mg and the lowest fatal dosage was 170 mg. Patients with fatal intoxications were on average older (40.5 vs. 32.8 years) and developed a more rapid onset of symptoms (0.2 vs. 0.8 days). Death occurred after a mean time of 0.6 days; symptom relief in patients with non-fatal intoxications developed on average after 3.2 days. Considering the large dose spectrum between survived and lethal TCP-dosages individual susceptibility factors might play a role regarding the severity of clinical symptoms independently of the ingested dosage.

  11. New 2H-chromene-3-carboxamide derivatives: design, synthesis and use as inhibitors of hMAO.

    Science.gov (United States)

    Pan, Zhi-Xiang; He, Xu; Chen, Yan-Yan; Tang, Wen-Jian; Shi, Jing-Bo; Tang, Yu-Lan; Song, Bao-An; Li, Jun; Liu, Xin-Hua

    2014-06-10

    A series new 2H-chromene-3-carboxamide derivatives 4a-4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC(50 iproniazid) = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi-Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics.

    Science.gov (United States)

    Shen, Hong-Wu; Wu, Chao; Jiang, Xi-Ling; Yu, Ai-Ming

    2010-07-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural psychoactive indolealkylamine drug that has been used for recreational purpose. Our previous study revealed that polymorphic cytochrome P450 2D6 (CYP2D6) catalyzed 5-MeO-DMT O-demethylation to produce active metabolite bufotenine, while 5-MeO-DMT is mainly inactivated through deamination pathway mediated by monoamine oxidase (MAO). This study, therefore, aimed to investigate the impact of CYP2D6 genotype/phenotype status and MAO inhibitor (MAOI) on 5-MeO-DMT metabolism and pharmacokinetics. Enzyme kinetic studies using recombinant CYP2D6 allelic isozymes showed that CYP2D6.2 and CYP2D6.10 exhibited 2.6- and 40-fold lower catalytic efficiency (V(max)/K(m)), respectively, in producing bufotenine from 5-MeO-DMT, compared with wild-type CYP2D6.1. When co-incubated with MAOI pargyline, 5-MeO-DMT O-demethylation in 10 human liver microsomes showed significantly strong correlation with bufuralol 1'-hydroxylase activities (R(2)=0.98; P<0.0001) and CYP2D6 contents (R(2)=0.77; P=0.0007), whereas no appreciable correlations with enzymatic activities of other P450 enzymes. Furthermore, concurrent MAOI harmaline sharply reduced 5-MeO-DMT depletion and increased bufotenine formation in human CYP2D6 extensive metabolizer hepatocytes. In vivo studies in wild-type and CYP2D6-humanized (Tg-CYP2D6) mouse models showed that Tg-CYP2D6 mice receiving the same dose of 5-MeO-DMT (20mg/kg, i.p.) had 60% higher systemic exposure to metabolite bufotenine. In addition, pretreatment of harmaline (5mg/kg, i.p.) led to 3.6- and 4.4-fold higher systemic exposure to 5-MeO-DMT (2mg/kg, i.p.), and 9.9- and 6.1-fold higher systemic exposure to bufotenine in Tg-CYP2D6 and wild-type mice, respectively. These findings indicate that MAOI largely affects 5-MeO-DMT metabolism and pharmacokinetics, as well as bufotenine formation that is mediated by CYP2D6. (c) 2010 Elsevier Inc. All rights reserved.

  13. [Association between the canine monoamine oxidase B (MAOB) gene polymorphisms and behavior of puppies in open-field test].

    Science.gov (United States)

    Li, Xiao-Hui; Xu, Han-Kun; Mao, Da-Gan; Ma, Da-Jun; Chen, Peng; Yang, Li-Guo

    2006-11-01

    Excitability, activity and exploration behavior of puppies in a novel open-field were tested in a total of 204 two-month-old German shepherd dog, labrador retriever or English springer spaniel puppies. The polymorphisms of monoamine oxidase B gene (MAOB) were detected by PCR-RFLP. Statistics analysis indicated that genotype and allele frequencies of the polymorphisms were significantly different among three breeds (P open-field test. The results showed that MAOB gene polymorphisms had a significant effect on walking time, squares crossed, lying time, the times of standing up against walls(P open-field test and TT genotype has favorable effects in these behavior traits.

  14. Allosteric modulation of semicarbazide-sensitive amine oxidase activities in vitro by imidazoline receptor ligands

    OpenAIRE

    2004-01-01

    Evidence indicates that imidazoline I2 binding sites (I2BSs) are present on monoamine oxidase (MAO) and on soluble (plasma) semicarbazide-sensitive amine oxidase enzymes. The binding site on MAO has been described as a modulatory site, although no effects on activity are thought to have been observed as a result of ligands binding to these sites.We examined the effects in vitro of several imidazoline binding site ligands on activities of bovine plasma amine oxidase (BPAO) and porcine kidney d...

  15. [{sup 11}C]S.L.(25.1188), a new radioligand to study the monoamine oxidase type B with PET: preclinical characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Saba, W.; Valette, H.; Peyronneau, M.A.; Bramoulle, Y.; Coulon, C.; Dolle, F.; Bottlaender, M. [Service Hospitalier Frederic Joliot, IIBM/DSV, 91 - Orsay (France); Curet, O.; George, P. [Sanofi-Aventis, 92 - Bagneux (France)

    2008-02-15

    Introduction. - Monoamine oxidase (M.A.O.) is a flavin containing enzyme, that catalyzes the oxidative deamination of various amines and neurotransmitters. Two isoforms exist, M.A.O.-A and M.A.O.-B. Variations in M.A.O. activity may be associated to human disease such as Parkinson and Alzheimer disease. Few radiotracers have been developed for M.A.O. PET studies such as [{sup 11}C]deprenyl, an irreversible M.A.O.-B inhibitor. Recently an oxazolidinone derivative, S.L.- 25.1188 ((S)-5-methoxy-methyl-3-[6-(4,4,4-tri-fluoro butoxy)- benzo[d]isoxazol-3-yl]-oxazolidin-2-one), belonging to a new generation of selective and reversible M.A.O.-B inhibitors was developed and showed in vitro a high selectivity for M.A.O.B. [1]. The aim of this study was to characterize [{sup 11}C]S.L.- 25.1188 as radioligand for in vivo PET examination of M.A.O.-B. Materials and methods. - PET studies of the brain distribution were carried out in male Papio anubis baboons. Selectivity and reversibility of [{sup 11}C]S.L.-25.1188 binding for M.A.O.-B was assessed by pre-treatment or displacement experiments (30 min before and after tracer injection, respectively) using reference ligands for M.A.O.-B (deprenyl: 2 mg/kg i.v. and lazabemide: 0.5 mg/kg i.v.) or by displacement experiments using unlabelled S.L.-25.1188 (1 mg/kg, i.v., 30 min after tracer injection). Distribution volume (D.V.) was calculated using 2-tissue-compartment model. The saturable binding following pre-treatment with deprenyl was considered as the specific binding. Results. - After injection, [1{sup 1C}]S.L.-25.1188 presents a rapid phase of distribution in blood (about 5 min), followed by a elimination with T1/2 of 75 min. The Blood to plasma concentration ratio was constant during the experimentation (0.9 {+-} .04) consistent with a similar kinetic of [{sup 11}C]S.L.- 25.1188 in both blood and plasma. Metabolism analysis showed that [{sup 11}C]S.L.-25.1188 is stable in vivo. In the brain, uptake in different areas was

  16. Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

    Science.gov (United States)

    Zumárraga, Mercedes; Dávila, Ricardo; Basterreche, Nieves; Arrue, Aurora; Goienetxea, Biotza; Zamalloa, María I; Erkoreka, Leire; Bustamante, Sonia; Inchausti, Lucía; González-Torres, Miguel A; Guimón, José

    2010-01-01

    Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

  17. Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid schizophrenia among a Chinese population.

    Science.gov (United States)

    Sun, Yuhui; Zhang, Jiexu; Yuan, Yanbo; Yu, Xin; Shen, Yan; Xu, Qi

    2012-01-01

    Monoamine oxidase A (MAOA) is the enzyme responsible for degradation of several monoamines, such as dopamine and serotonin that are considered as being two of the most important neurotransmitters involved in the pathophysiology of schizophrenia. To study a possible role of the MAOA gene in conferring susceptibility to schizophrenia, the present study genotyped the variable number of tandem repeat (VNTR) polymorphism and 41 SNPs across this gene among 555 unrelated patients with paranoid schizophrenia and 567 unrelated healthy controls. Quantitative real-time PCR analysis was employed to quantify expression of MAOA mRNA in 73 drug-free patients. While none of these genotyped DNA markers showed allelic association with paranoid schizophrenia, haplotypic association was found for the VNTR-rs6323, VNTR-rs1137070, and VNTR-rs6323-rs1137070 haplotypes in female subjects. Nevertheless, no significant change of the expression of MAOA mRNA was detected in either female or male patients with paranoid schizophrenia. Our study suggests that the interaction between genetic variants within the MAOA gene may contribute to an increased risk of paranoid schizophrenia, but the precise mechanism needs further investigation.

  18. Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

    Science.gov (United States)

    Sergutina, A V; Rakhmanova, V I

    2016-06-01

    Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

  19. Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.

    Directory of Open Access Journals (Sweden)

    Ryan R Gordon

    Full Text Available To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA. In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.

  20. Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents

    Science.gov (United States)

    Zhang, Yun; Ming, Qing-sen; Yi, Jin-yao; Wang, Xiang; Chai, Qiao-lian; Yao, Shu-qiao

    2017-01-01

    Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR “SS” genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions. PMID:28203149

  1. Kaempferol as Selective Human MAO-A Inhibitor: Analytical Detection in Calabrian Red Wines, Biological and Molecular Modeling Studies.

    Science.gov (United States)

    Gidaro, Maria Concetta; Astorino, Christian; Petzer, Anél; Carradori, Simone; Alcaro, Francesca; Costa, Giosuè; Artese, Anna; Rafele, Giancarlo; Russo, Francesco M; Petzer, Jacobus P; Alcaro, Stefano

    2016-02-17

    The purpose of this work was to determine the kaempferol content in three red wines of Calabria, a southern Italian region with a great number of certified food products. Considering that wine cultivar, climate, and soil influence the qualitative and quantitative composition in flavonoids of Vitis vinifera L. berries, the three analyzed samples were taken from the 2013 vintage. Moreover, the Gaglioppo samples, with assigned Controlled Origin Denomination (DOC), were also investigated in the production of years 2008, 2010, and 2011. In addition to the analysis of kaempferol, which is present in higher concentration than in other Italian wines, in vitro assays were performed to evaluate, for the first time, the inhibition of the human monoamine oxidases (hMAO-A and hMAO-B). Molecular recognition studies were also carried out to provide insight into the binding mode of kaempferol and selectivity of inhibition of the hMAO-A isoform.

  2. Design, Synthesis and hMAO Inhibitory Screening of Novel 2-Pyrazoline Analogues.

    Science.gov (United States)

    Aksöz, Begüm Evranos; Uçar, Gülberk; Yelekçi, Kemal

    2017-05-03

    A series of 3,5-diaryl-2-pyrazoline derivatives was synthesized via the reaction of various chalcones with hydrazide compounds in ethanol. Structural elucidation of the compounds was performed by IR, 1H NMR, 13C NMR, mass spectral data, and elemental analyses. The new compounds were tested for their human monoamine oxidase (hMAO) inhibitory activities. All compounds were found to be competitive, reversible, and selective inhibitors for hMAO-A. Compounds 5a, 5b, 5f, 5h, 5i and 5l showed higher selectivity towards hMAO than moclobemide, the known selective and competitive hMAO-A inhibitor. Compounds 5c, 5d, 5i and 5l exhibited also higher inhibitory potency towards hMAO-A than moclobemide. The AutoDock 4.2 program was employed to perform automated molecular docking. The calculated results obtained computationally were in good agreement with the experimental values. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. MAO NOW

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    With his legacy in flux, some Chinese people are appropriating the life and words of Chairman Mao to meet the challenges of modern life His face is no longer ubiquitous in China, but it remains by far the most recognizable. The image of the Great Helmsman, Mao Zedong, is the only one on the country's currency. A

  4. Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor

    Science.gov (United States)

    Halberstadt, Adam L.; Nichols, David E.; Geyer, Mark A.

    2012-01-01

    RATIONALE Ayahuasca is a psychoactive tea prepared from a combination of plants that contain a hallucinogenic tryptamine and monoamine oxidase inhibitors (MAOIs). Behavioral Pattern Monitor (BPM) experiments demonstrated that the combination of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and a behaviorally inactive dose of an MAOA inhibitor such as harmaline or clorgyline induces biphasic effects on locomotor activity in rats, initially reducing locomotion and then increasing activity as time progresses. OBJECTIVES The present study investigated whether the biphasic locomotor profile induced by the combination of 5-MeO-DMT and an MAOI is a consequence of a reduction in the rate of 5-MeO-DMT metabolism. This hypothesis was tested using a deuterated derivative of 5-MeO-DMT (α,α,β,β-tetradeutero-5-MeO-DMT) that is resistant to metabolism by MAO. RESULTS Confirming our previous findings, 1.0 mg/kg 5-MeO-DMT (s.c.) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the nonselective MAOI pargyline (10 mg/kg). Administration of 5-MeO-DMT alone, even at doses greater than 1.0 mg/kg, produced only reductions in locomotor activity. Although low doses of α,α,β,β-tetradeutero-5-MeO-DMT (0.3 and 1.0 mg/kg, s.c.) produced only hypoactivity in the BPM, a dose of 3.0 mg/kg induced a biphasic locomotor profile similar to that produced by the combination of 5-MeO-DMT and an MAOI. Receptor binding studies demonstrated that deuterium substitution had little effect on the affinity of 5-MeO-DMT for a wide variety of neurotransmitter binding sites. CONCLUSIONS The finding with α,α,β,β-tetradeutero-5-MeO-DMT indicates that the hyperactivity induced by 5-MeO-DMT after MAO inhibition is a consequence of reduced metabolism of 5-MeO-DMT, leading to prolonged occupation of central serotonin receptors. These results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of

  5. Immunocytochemical localization of monoamine oxidase type B in rat’s peripheral nervous system%单胺氧化酶B在大鼠外周神经系统中的定位

    Institute of Scientific and Technical Information of China (English)

    陈强; 徐洋

    2015-01-01

    Objective To investigate the expression of monoamine oxidase type B (MAOB)in rat’s peripheral nerv-ous system to provide morphologic basis for further study about MAOB and the relationship between axon transporta-tion and nerve impulse transduction.Methods The present study used immunohistochemical method to observe the lo-calization of MAOB in rat’s peripheral nervous system.Results Light microscopy reveals that MAOB immunoreactivi-ty is presented in epithelium above the lamina propria and lamina propria of rat’s tongue.Electron microscopy reveals that MAOB immunoreactivity is found in the myelinated axons and unmyelinated axons.MAOB immunoreactivity is al-so observed in the Schwann cell.In these MAO-B-positive structures,MAOB immunohistochemical reaction products are found on and around the mitochondrial outer membrane.Conclusion The abundeant MAOB in rat’s peripheral nervous system indicates that MAO-B plays a critical role in axon transportation and nerve impulse transduction.%目的:研究单胺氧化酶 B(MAOB)在大鼠外周神经系统中的表达,为进一步研究 MAOB 与外周神经系统中轴突运输和神经传导的关系提供形态学依据。方法采用免疫组织化学的方法,通过光镜和电镜观察 MAOB 在大鼠外周神经系统中的分布。结果光镜下,MAOB 免疫反应阳性细胞分布在舌体的上皮及固有层中。电镜下, MAOB 免疫反应阳性细胞分布在大鼠舌体有髓鞘和无髓鞘轴突中。阳性物质分布于细胞质中,准确来说为线粒体外膜上。结论 MAOB 在大鼠外周神经系统轴突的表达,提示 MAOB 可能与轴突的运输和神经传导有着非常重要的作用。

  6. Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of some 6-nitrobenzothiazole-derived semicarbazones.

    Science.gov (United States)

    Tripathi, Rati K P; Goshain, Omprakash; Ayyannan, Senthil Raja

    2013-03-01

    Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders. A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme. Most of the compounds were found to be potent inhibitors of MAO-B, with IC(50) values in the nanomolar to micromolar range. Molecular docking studies were performed with AutoDock 4.2 to deduce the affinity and binding mode of these inhibitors toward the MAO-B active site. The free energies of binding (ΔG) and inhibition constants (K(i)) of the docked compounds were calculated by the Lamarckian genetic algorithm (LGA) of AutoDock 4.2. Good correlations between the calculated and experimental results were obtained. 1-[(4-Chlorophenyl)(phenyl)methylene]-4-(6-nitrobenzothiazol-2-yl)semicarbazide emerged as the lead MAO-B inhibitor, with top ranking in both the experimental MAO-B assay (IC(50): 0.004±0.001 μM) and in computational docking studies (K(i): 1.08 μM). Binding mode analysis of potent inhibitors suggests that these compounds are well accommodated by the MAO-B active site through stable hydrophobic and hydrogen bonding interactions. Interestingly, the 6-nitrobenzothiazole moiety is stabilized in the substrate cavity with the aryl or diaryl residues extending up into the entrance cavity of the active site. According to our results, docking experiments could be an interesting approach for predicting the activity and binding interactions of this class of semicarbazones against MAO-B. Thus, a binding site model consisting of three essential pharmacophoric features is proposed, and this can be used for the design of future MAO-B inhibitors.

  7. Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by L-tryptophan or 5-methoxy-N,N-dimethyltryptamine in rats treated with a monoamine oxidase inhibitor

    Science.gov (United States)

    Grahame-Smith, D. G.

    1971-01-01

    1. The hyperactivity and hyperpyrexia produced by L-tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine. 2. Chlorpromazine did not inhibit the increased rate of synthesis of brain 5-hydroxytryptamine (5-HT) produced by tryptophan loading. 3. Hyperactivity and hyperpyrexia were also produced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p-chlorophenylalanine did not inhibit hyperactivity produced by 5-MeODMT. 4. Chlorpromazine inhibits hyperactivity caused by tryptophan or 5-MeODMT after monoamine oxidase inhibition either by competition with 5-HT or 5-MeODMT, respectively, at receptor sites or by physiological antagonism. PMID:4261561

  8. Effects of hexabromocyclododecane(HBCD) on monoamine neurotransmitters contents and monoamine oxidase activity of developmental rat brain%六溴环十二烷对发育期大鼠脑单胺类神经递质质量比及单胺氧化酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    刘芳; 冀秀玲; 赵文娟; 殷明; 蒋惠男; 张江

    2012-01-01

    通过研究发育期大鼠脑单胺类神经递质质量比及单胺氧化酶活性,探讨环境暴露水平的六溴环十二烷对发育期大鼠的神经毒性作用.选择10 μg/kg、50 μg/kg、100μg/kg、300 μg/kg的剂量对新生3d大鼠进行暴露,饲养42d后断头取脑组织,测定多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)的质量比及单胺氧化酶(MAO)的活性.结果表明,在10 - 100 μg/kg的暴露剂量范围,DA质量比随暴露剂量的升高而下降,NE质量比呈现上升趋势,5- HT质量比则极显著性升高(p <0.01);与此同时,MAO的活性随剂量增加而升高,在100μg/kg剂量出现显著性升高(p<0.05).而300μμg/kg的剂量作为较高暴露水平的参照,只对DA产生显著性影响(p<0.05).DA、5 - HT、NE的质量比及MAO活性的变化可能在大鼠的中枢神经系统的发育障碍中发挥了重要作用,并且环境暴露水平的HBCD对发育期大鼠脑具有低剂量高效应的毒性反应特征.%The paper is aimed to study the hexabromocyclododecane (HBCD) as a kind of brominated flame retardants extensively used in the industrial production. The spectrophotometry and enzyme-linked immunosorbent assay (ELISA) can be used for examining the contents of dopamine(DA), noradrenalin(NE) , 5-hydroxytryptamine(5- HT) and monoamine oxidase (MAO) activity when the sprague-dawley 3-day old rats were exposed to the different dosages (10μg/kg, 50 μg/kg, 100 fig/kg, 300 μg/kg body weight) of HBCD in a period of 42 days. The results of our experiments with the rats show that, compared with the controlled group, DA contents of 10 μg/kg and 300 μg/kg exposures tends to drop significantly(p < 0.05) , in a decreasing rate in a range of 10 - 100 μg/kg exposure doses. However, no significant changes were detected of NE. In addition, an increase trend can be found in the range of 10 μg/kg to 100 μg/kg doses, with the 5 - HT contents of 10 - 100 μg/kg exposures increased sig-nificantly(p < 0

  9. Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

    OpenAIRE

    2016-01-01

    The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H-chromen-2-one skeleton. Co...

  10. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer's disease and elderly controls after oral administration of sembragiline

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, Stefan [Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel (Switzerland); F. Hoffmann-La Roche Ltd, Basel (Switzerland); Forsberg, Anton; Stenkrona, Per; Varrone, Andrea; Fazio, Patrik; Nakao, Ryuji; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm (Sweden); Nave, Stephane; Jamois, Candice; Ricci, Benedicte [Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel (Switzerland); Seneca, Nicholas [AstraZeneca Translational Science Center, Stockholm (Sweden); Comley, Robert A. [AbbVie, North Chicago, IL (United States); Ejduk, Zbigniew [Miedzyleski Specialistic Hospital, Internal Disease and Gastroenterology, Warsaw (Poland); Al-Tawil, Nabil [Karolinska University Hospital, Karolinska Trial Alliance Phase 1 Unit, Stockholm (Sweden); Akenine, Ulrika; Andreasen, Niels [Karolinska University Hospital, Karolinska Institutet Alzheimer Disease Research Centre and Clinical Trial Unit, Geriatric Clinic, Huddinge (Sweden)

    2017-03-15

    In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD. This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [{sup 11}C]-{sub L}-deprenyl-D{sub 2} radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days. At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an E{sub max} of ∝80-90 % across brain regions of interest and in an EC{sub 50} of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD. (orig.)

  11. Association of a Monoamine Oxidase-A Gene Promoter Polymorphism with ADHD and Anxiety in Boys with Autism Spectrum Disorder

    Science.gov (United States)

    Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli; Gadow, Kenneth D.

    2009-01-01

    The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism in the promoter region of the MAO-A gene and severity of ADHD and anxiety in boys with ASD. Parents and teachers completed a DSM-IV-referenced rating scale for 5- to 14-year-old boys with ASD (n = 43). Planned…

  12. Identification of Indole-Based Chalcones: Discovery of a Potent, Selective, and Reversible Class of MAO-B Inhibitors.

    Science.gov (United States)

    Sasidharan, Rani; Manju, Sreedharannair Leelabaiamma; Uçar, Gülberk; Baysal, Ipek; Mathew, Bijo

    2016-08-01

    A series of 11 indole-based chalcones (IC1-11) with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized. All the compounds were tested for their human monoamine oxidase (hMAO)-A and hMAO-B inhibitory potencies. Most of the synthesized candidates proved to be potent and selective inhibitors of MAO-B rather than MAO-A, with a reversible and competitive mode. Among them, compound IC9 was found to be a potent inhibitor of hMAO-B with Ki  = 0.01 ± 0.005 μM and a selectivity index of 120. It was found to be better than the standard drug, selegiline (hMAO-B with Ki  = 0.20 ± 0.020 μM) with a selectivity index of 30.55. PAMPA assays were carried out for all the compounds in order to evaluate the capacity of the compounds to cross the blood-brain barrier. Moreover, the most potent MAO-B inhibitor, IC9, was nontoxic at 5 and 25 μM, with 95.20 and 69.17% viable cells, respectively. The lead compound IC9 has an antioxidant property of 1.18 Trolox equivalents by ABTS assay. Molecular modeling studies were performed against hMAO-B to observe binding site interactions of the lead compound. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Psychobiology of borderline personality traits related to subtypes of eating disorders: a study of platelet MAO activity.

    Science.gov (United States)

    Díaz-Marsá, Marina; Carrasco, Jose L; de Anta, Laura; Molina, Rosa; Sáiz, Jerónimo; Cesar, Jesus; López-Ibor, Juan J

    2011-12-30

    Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating-purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating-purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge-purge patients with comorbid BPD than in binge-purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.

  14. 胆道恶性肿瘤中单胺氧化酶-A对肿瘤相关巨噬细胞抗肿瘤免疫功能的影响%Effect of monoamine oxidase-A on the anti-tumor immunity of tumor-associated macrophages in biliary tract cancers

    Institute of Scientific and Technical Information of China (English)

    赖佳明; 陈健聪; 陈伟; 张朝晖; 黄力; 梁力建

    2015-01-01

    Objective To investigate the effect of monoamine oxidase-A (MAO-A) in biliary tract cancers (BTCs) on the immunity of tumor-associated macrophages.Methods MAO-A expression plasmid and control plasmid were constructed and transiently transfected into BTC cell lines respectively.Macrophages were derived from peripheral blood mononuclear cells donated by healthy volunteers.Macrophages were then cocultured with aforementioned transfected cancer cell lines for 48 h respectively,Western blotting and enzyme linked immunosorbent assay (ELISA) were applied to assess the expression of immune effector proteins and the excretion of cytokines from cocultured macrophages.24 h priming of macrophages with human recombinant interferon-γ (IFN-γ) were performed after their first stage of coculture;then the second stage of coculture with corresponding transfected cancer cell lines for 48 h were followed.Flow cytometry was employed to detect necrosis and apotosis of cancer cells induced by cocultured macrophages.Results The expression of MAO-A was down-regulated in BTC cell lines,which polarized the cocultured macrophages into M2 type tumor-associated macrophages,and promoted their excretion of interleukin (IL)-10 and expression of PD-L1,while suppressed their excretion of tumor necrosis factor-α (TNF-α),IL-1β and IL-12p70 (18.8±2.3 vs.31.7±1.9,75.0±0.4 vs.150.2±17.0 and 49.1 ± 15.2 vs.135.2 ± 1.0,respectively,P < 0.05),as well as the expression of Human leukocyte antigen-DR (HLA-DR).On the contrary,however,macrophages cocultured with MAO-A overexpressing BTC cells exhibited pro-inflammatory phenotype (M1 type) which opposite to above suppressive immunity phenotype (M2 type).After priming of IFN-γ,macrophages cocultured with MAO-A overexpressing BTC cells induced tumor necrosis and apoptosis more effectively than those cocultured with control BTCcells [(84.85±5.66)% vs.(1.56±0.46)% and (76.73 ±6.31)% vs.(1.28±0.57)%,respectively,P < 0.05].Conclusion Down

  15. Association between monoamine oxidase A gene promoter 30 bp repeat polymorphism and tardive dyskinesia in Chinese schizophrenics

    Institute of Scientific and Technical Information of China (English)

    Changhe Fan; Lihua Li; Yan Fu; Hehuang Deng; Xiangjiao Liao; Youcai Zhou

    2006-01-01

    BACKGROUND: The pathophysiology of tardive dyskinesia (TD) is not yet fully understood. With the hypothesis of altered dopaminergic neurotransmission, altered activities of dopamine degrading enzymes such as monoamine oxidase A (MAOA) and their coding genes are supposed to be related to the pathophysiology of TD.OBJECTIVE: To investigate possible association between 30 bp variable number tandem repeat (VNTR) polymorphism in the promoter of MAOA gene and susceptibility, severity of neuroleptic induced TD in Chinese Han people in Guandong Province.DESIGN: Non-randomization-synchronization controlled study. SETTING: Guangdong Mental Health Institute, Guangdong Provincial People's Hospital; Guangzhou Psychiatric Hospital; Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration. PARTICIPANTS: A total of 179 subjects were enrolled in the study. All subjects were sporadic and genetically unrelated Chinese schizophrenic patients who were hospitalizing in Guangzhou Psychiatric Hospital or Affiliated Psychiatric Hospital of Guangzhou Municipal Bureau of Civil Administration during January to April 2005. The diagnosis of schizophrenia was made according to the criteria of Diagnostic and Statistic Manual of Mental Disorder-the third edition-revised (DSM-Ⅲ-R). Among all patients, 88 were diagnosed as with TD and 91 without TD according to the research diagnostic criteria described by Schooler-Kane. Informed consent was obtained from all subjects or their relatives.METHODS: ① TD severity was assessed with the AIMS which was a 5-degree rating scale from 0 to 4 (corresponding to none, minimal, mild, moderate and severe, respectively). The study was approved by the Ethics Committees of the two hospitals and informed consent was obtained from all subjects or their relatives. ② The polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) techniques were used to detect MAOA gene 30 bp VNTR polymorphism in schizophrenic patients

  16. Association study of MAO-A and DRD4 genes in schizophrenic patients with aggressive behavior.

    Science.gov (United States)

    Fresan, Ana; Camarena, Beatriz; Apiquian, Rogelio; Aguilar, Alejandro; Urraca, Nora; Nicolini, Humberto

    2007-01-01

    Genes involved in dopamine neurotransmission are interesting candidates to be analyzed in schizophrenia and aggressive behavior. Therefore, we analyzed the functional polymorphisms of the dopamine receptor D4 (DRD4) and monoamine oxidase A (MAO-A) genes in a sample of 71 schizophrenic patients assessed with the Overt Aggression Scale to measure aggressive behavior. CLUMP analysis of the DRD4 48-bp repeat-exon III polymorphism in schizophrenic patients showed significant differences between the aggressive behavior and the nonaggressive groups (T1 = 18.77, d.f. = 6, p = 0.0046; T3 = 6.54, p = 0.0195). However, analysis of the promoter polymorphism of the MAO-A gene revealed no significant association between aggressive and nonaggressive patients. Finally, analysis of Overt Aggression Scale dimensions exhibited significant differences for the DRD4 and MAO-A genes. Our preliminary findings suggest that the DRD4 and MAO-A genes may be involved in aggressive schizophrenic patients.

  17. MAO A knockout attenuates adrenocortical response to various kinds of stress.

    Science.gov (United States)

    Popova, Nina K; Maslova, Larissa N; Morosova, Ekaterina A; Bulygina, Veta V; Seif, Isabelle

    2006-02-01

    The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg 8 mice on the corticosterone response to restraint, cold, water deprivation-induced, or social acute stress as well as chronic variable stress was studied. It was found that Tg 8 mice with genetic MAO A knockout and wild-type C3H/HeJ (C3H) strain showed similar plasma corticosterone resting level. MAO A knockout mice differed from C3H mice by attenuated response to restraint (60 min), cold (4 degrees C, 60 min), and water deprivation (48 h) as well as to a chronic (15 days) variable stress. No difference between Tg 8 and C3H strains in the response to psychosocial stress (encounters for 30 min of six previously isolated mice) has been found. ACTH administration to dexamethasone-pretreated mice produced a similar corticosterone effect in Tg 8 and C3H mice, indicating that the decreased stress response in MAO A-deficient mice was due rather to the central mechanisms regulating stress-induced ACTH release than to adrenocortical responsiveness to ACTH.

  18. Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson’s Disease with Neuroprotective Potential

    Directory of Open Access Journals (Sweden)

    John P.M. Finberg

    2010-07-01

    Full Text Available Rasagiline (Azilect is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitrogen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the compound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major metabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl. Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but following loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of β-phenylethylamine, which is an excellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine transporter (DAT. Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demonstrated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.

  19. Dietary Phenolic Compounds Interfere with the Fate of Hydrogen Peroxide in Human Adipose Tissue but Do Not Directly Inhibit Primary Amine Oxidase Activity

    Directory of Open Access Journals (Sweden)

    Christian Carpéné

    2016-01-01

    Full Text Available Resveratrol has been reported to inhibit monoamine oxidases (MAO. Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO in peripheral organs, such as semicarbazide-sensitive AO (SSAO, known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [14C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.

  20. Dietary Phenolic Compounds Interfere with the Fate of Hydrogen Peroxide in Human Adipose Tissue but Do Not Directly Inhibit Primary Amine Oxidase Activity.

    Science.gov (United States)

    Carpéné, Christian; Hasnaoui, Mounia; Balogh, Balázs; Matyus, Peter; Fernández-Quintela, Alfredo; Rodríguez, Víctor; Mercader, Josep; Portillo, Maria P

    2016-01-01

    Resveratrol has been reported to inhibit monoamine oxidases (MAO). Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO) in peripheral organs, such as semicarbazide-sensitive AO (SSAO), known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid) behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [(14)C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.

  1. Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion: Role of renal monoamine-oxidase Perfiles de secreción de dopamina renal en la expansión de volumen para regular diuresis y natriuresis: Rol de la monoaminoxidasa renal

    Directory of Open Access Journals (Sweden)

    Verónica de Luca Sarobe

    2010-02-01

    Full Text Available Diuretic and natriuretic effects of renal dopamine (DA are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO and aromatic amino-acid decarboxylase (AADC in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control, IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v. and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.. Results revealed that in C rats U DA V (ng/30 min/100g BWt increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p La dopamina (DA intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO y decarboxilasa de aminoácidos aromáticos (AADC en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control, IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v. y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.. Se observó que en C la U DA V (ng/30min/100gPC aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05, disminuyendo posteriormente. IMAO mostr

  2. Apple fruit copper amine oxidase isoforms: peroxisomal MdAO1 prefers diamines as substrates, whereas extracellular MdAO2 exclusively utilizes monoamines.

    Science.gov (United States)

    Zarei, Adel; Trobacher, Christopher P; Cooke, Alison R; Meyers, Ashley J; Hall, J Christopher; Shelp, Barry J

    2015-01-01

    4-Aminobutyrate (GABA) accumulates in apple fruit during controlled atmosphere storage. A potential source of GABA is the polyamine putrescine, which can be oxidized via copper-containing amine oxidase (CuAO), resulting in the production 4-aminobutanal/Δ(1)-pyrroline, with the consumption of O2 and release of H2O2 and ammonia. Five putative CuAO genes (MdAO genes) were cloned from apple (Malus domestica Borkh. cv. Empire) fruit, and the deduced amino acid sequences found to contain the active sites typically conserved in CuAOs. Genes encoding two of these enzymes, MdAO1 and MdAO2, were highly expressed in apple fruit and selected for further analysis. Amino acid sequence analysis predicted the presence of a C-terminal peroxisomal targeting signal 1 tripeptide in MdAO1 and an N-terminal signal peptide and N-glycosylation site in MdAO2. Transient expression of green fluorescent fusion proteins in Arabidopsis protoplasts or onion epidermal cells revealed a peroxisomal localization for MdAO1 and an extracellular localization for MdAO2. The enzymatic activities of purified recombinant MdAO1 and MdAO2 were measured continuously as H2O2 production using a coupled reaction. MdAO1 did not use monoamines or polyamines and displayed high catalytic efficiency for 1,3-diaminopropane, putrescine and cadaverine, whereas MdAO2 exclusively utilized aliphatic and aromatic monoamines, including 2-phenylethylamine and tyramine. Together, these results indicate that MdAO1 may contribute to GABA production via putrescine oxidation in the peroxisome of apple fruit under controlled atmosphere conditions. MdAO2 seems to be involved in deamination of 2-phenylethylamine, which is a step in the biosynthesis of 2-phenylethanol, a contributor to fruit flavor and flower fragrance.

  3. COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

    Directory of Open Access Journals (Sweden)

    Aline Santos Sampaio

    Full Text Available Obsessive-compulsive disorder (OCD is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT and monoamine oxidase A (MAO-A genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013 in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A in 783 OCD trios (probands and their parents. Four different OCD phenotypes (from narrow to broad OCD definitions and a SNP x SNP epistasis were also analyzed.OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

  4. Antiparkinsonian effects of aqueous methanolic extract of Hyoscyamus niger seeds result from its monoamine oxidase inhibitory and hydroxyl radical scavenging potency.

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    Sengupta, T; Vinayagam, J; Nagashayana, N; Gowda, B; Jaisankar, P; Mohanakumar, K P

    2011-01-01

    Hyoscyamus species is one of the four plants used in Ayurveda for the treatment of Parkinson's disease (PD). Since Hyoscyamus niger was found to contain negligible levels of L-DOPA, we evaluated neuroprotective potential, if any, of characterized petroleum ether and aqueous methanol extracts of its seeds in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice. Air dried authenticated H. niger seeds were sequentially extracted using petroleum ether and aqueous methanol and were characterized employing HPLC-electrochemistry and LCMS. Parkinsonian mice were treated daily twice with the extracts (125-500 mg/kg, p.o.) for two days and motor functions and striatal dopamine levels were assayed. Administration of the aqueous methanol extract (containing 0.03% w/w of L-DOPA), but not petroleum ether extract, significantly attenuated motor disabilities (akinesia, catalepsy and reduced swim score) and striatal dopamine loss in MPTP treated mice. Since the extract caused significant inhibition of monoamine oxidase activity and attenuated 1-methyl-4-phenyl pyridinium (MPP+)-induced hydroxyl radical (·OH) generation in isolated mitochondria, it is possible that the methanolic extract of Hyoscyamus niger seeds protects against parkinsonism in mice by means of its ability to inhibit increased ·OH generated in the mitochondria.

  5. Identification of Single Nucleotide Polymorphism (SNP in Mono Amine Oxidase A (MAO-A Gene as a genetic marker for aggressiveness in sheep

    Directory of Open Access Journals (Sweden)

    Eko Handiwirawan

    2012-12-01

    Full Text Available In the population, there are aggressive sheep in a small number which requires special management those specific animal house and routine management. The purpose of this study was to identify the variation of DNA marker SNP (single nucleotide polymorphism as a genetic marker for the aggressive trait in several of sheep breed. The identification of point mutations in exon 8 of MAO-A gene associated with aggressive behavior in sheep may be further useful to become of DNA markers for the aggressive trait in sheep. Five of sheep breed were used, i.e.: Barbados Black belly Cross sheep (BC, Composite Garut (KG, Local Garut (LG, Composite Sumatra (KS and St. Cross Croix (SC. Duration of ten behavior traits, blood serotonin concentrations and DNA sequence of exon 8 of MAO-A gene from the sheep aggressive and nonaggressive were observed. PROC GLM of SAS Ver. 9.0 program was used to analyze variable behavior and blood serotonin concentrations. DNA polymorphism in exon 8 of MAO-A gene was analyzed using the MEGA software Ver. 4.0. The results show that the percentage of the aggressive rams of each breed was less than 10 percent; except for the KS sheep is higher (23%. Based on the duration of behavior, aggressive sheep group was not significantly different with non aggressive sheep group, except duration of care giving and drinking behavior. It is known that concentration of blood serotonin in aggressive and non aggressive rams was not significantly different. The aggressive trait in sheep has a mechanism or a different cause like that occurs in mice and humans. In this study, aggressive behavior in sheep was not associated with a mutation in exon 8 of MAO-A gene.

  6. Influence of protonation on substrate and inhibitor interactions at the active site of human monoamine oxidase-A.

    Science.gov (United States)

    Zapata-Torres, Gerald; Fierro, Angelica; Miranda-Rojas, Sebastian; Guajardo, Carlos; Saez-Briones, Patricio; Salgado, J Cristian; Celis-Barros, Cristian

    2012-05-25

    Although substrate conversion mediated by human monoaminooxidase (hMAO) has been associated with the deprotonated state of their amine moiety, data regarding the influence of protonation on substrate binding at the active site are scarce. Thus, in order to assess protonation influence, steered molecular dynamics (SMD) runs were carried out. These simulations revealed that the protonated form of the substrate serotonin (5-HT) exhibited stronger interactions at the protein surface compared to the neutral form. The latter displayed stronger interactions in the active site cavity. These observations support the possible role of the deprotonated form in substrate conversion. Multigrid docking studies carried out to rationalize the role of 5-HT protonation in other sites besides the active site indicated two energetically favored docking sites for the protonated form of 5-HT on the enzyme surface. These sites seem to be interconnected with the substrate/inhibitor cavity, as revealed by the tunnels observed by means of CAVER program. pK(a) calculations in the surface loci pointed to Glu³²⁷, Asp³²⁸, His⁴⁸⁸, and Asp¹³² as candidates for a possible in situ deprotonation step. Docking analysis of a group of inhibitors (structurally related to substrates) showed further interactions with the same two docking access sites. Interestingly, the protonated/deprotonated amine moiety of almost all compounds attained different docking poses in the active site, none of them oriented to the flavin moiety, thus producing a more variable and less productive orientations to act as substrates. Our results highlight the role of deprotonation in facilitating substrate conversion and also might reflect the necessity of inhibitor molecules to adopt specific orientations to achieve enzyme inhibition.

  7. Differential expression of serotonin, tryptophan hydroxylase and monoamine oxidase A in the mammary gland of the Myotis velifer bat.

    Directory of Open Access Journals (Sweden)

    Cristián Vela Hinojosa

    Full Text Available The mammary gland has long drawn the attention of the scientific community due to the limited knowledge of some fundamental aspects involved in the control of its function. Myotis velifer, a microchiropteran species, provides an interesting model to study some of the regulatory factors involved in the control of the mammary gland cycle. Having an asynchronous, monoestrous reproductive pattern, female M. velifer bats undergo drastic morphological changes of the breast during the reproductive cycle. Current research on non-chiropteran mammals indicates that serotonin (5-HT plays a major role in the intraluminal volume homeostasis of the mammary gland during lactation; however, an analysis of both the expression and localization of the main components of the serotonergic system in the bat mammary gland is lacking. Thus, the objectives of the present study were: to describe the gross and histological anatomy of the mammary gland of M. velifer to establish the lactation period for this species; to analyze the distribution and expression of the main serotonergic components in the mammary tissues of these bats under the physiological conditions of lactation, involution and the resting phase; and to provide information on the involvement of 5-HT in the regulation of the physiological function of this organ. To assess the expression and localization of serotonergic components, multiple immunofluorescence, Western blot and HPLC methods were used. 5-HT and the enzyme that catalyzes its synthesis (TPH were located in both myoepithelial and luminal epithelial cells, while the enzyme responsible for the catabolism of this neurohormone (MAO A was found in luminal epithelial cells as well as in secreted products. We also found an increased expression of serotonergic components during lactation, indicating that elements of the serotonergic system may play an important role in lactation in this species of bat in a way similar to that of other mammal species.

  8. Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes.

    Science.gov (United States)

    Peng, Zheng-Wu; Xue, Fen; Zhou, Cui-Hong; Zhang, Rui-Guo; Wang, Ying; Liu, Ling; Sang, Han-Fei; Wang, Hua-Ning; Tan, Qing-Rong

    2017-09-25

    Repetitive transcranial magnetic stimulation (rTMS) is a useful monotherapy for depression or adjunctive therapy for resistant depression. However, the anti-depressive effects of different parameters and the underlying mechanisms remain unclear. Here, we aimed to assess the effect of rTMS with different parameters (1/5/10 Hz, 0.84/1.26 T) on the depressive-like behaviors, 5-hydroxytryptamine (5-HT), 5-HIAA (5-hydroxyindoleacetic acid) and DA and NE levels, and monoamine oxidase A (MAO-A) activity in chronic unpredictable stress-treated rats, along with the expression of sirtuin 1 (Sirt1) and MAO-A in the prefrontal cortex (PFC) and cortex-derived astrocytes from new-born rats. Moreover, the depressive-like behaviors were monitored following the transcranial injection of the Sirt1 inhibitor EX527 (1 mM) daily for 1 week. We found that rTMS treatment (5/10 Hz, 0.84/1.26 T) ameliorated depressive-like behaviors, increased 5-HT, DA and NE levels, decreased the 5-HIAA level and Sirt1 and MAO-A expression, and reduced MAO-A activity in the PFC. The depressive-like behaviors were also ameliorated after the transcranial injection of EX527. Importantly, rTMS (5/10 Hz, 0.84/1.26 T) inhibited Sirt1 and MAO-A expressions in astrocytes and Sirt1 knockdown with short hairpin RNA decreased MAO-A expression in astrocytes. These results suggest that the inhibition of Sirt1/MAO-A expression in astrocytes in the PFC may contribute to the different anti-depressive effects of rTMS with different parameters, and may also provide a novel insight into the mechanisms underlying major depressive disorder.

  9. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    Science.gov (United States)

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  10. Down-regulation of MAO-B activity and imidazoline receptors in rat brain following chronic treatment of morphine%吗啡长期给药后大鼠脑内MAO-B活性及咪唑啉受体的下调

    Institute of Scientific and Technical Information of China (English)

    苏瑞斌; 李锦; 李昕; 秦伯益

    2001-01-01

    关键词吗啡;单胺氧化酶;咪唑克生;胍丁胺目的:探讨吗啡长期给药处理后大鼠不同脑区MAO-B活性及咪唑啉受体含量的变化.方法:用[3H]咪唑克生配体结合试验测定咪唑啉受体含量,用高效液相色谱法测定MAO-B活性.结果:咪唑克生和吗啡能剂量依赖性地抑制大鼠脑匀浆MAO-B活性.咪唑啉受体的内源性配体胍丁胺既不影响MAO-B活性,也不影响咪唑克生及吗啡对MAO-B活性的抑制作用.吗啡连续给药16 d后大鼠大脑、海马、丘脑、纹状体及小脑内MAO-B活性均显著下调(P<0.01).纳洛酮及咪唑克生单次给药对吗啡依赖大鼠上述脑区MAO-B活性均没有进一步影响;胍丁胺伴随吗啡给药后能显著抑制吗啡降低MAO-B活性的作用.吗啡连续给药后大鼠皮层和小脑咪唑啉受体数量减少而亲和力上调(P<0.05或P<0.01).结论:MAO-B活性与吗啡依赖大鼠发生戒断综合征相关,但与胍丁胺对吗啡镇痛作用的影响无关;胍丁胺对吗啡药理作用的影响与其激活咪唑啉受体有关.%AIM: To study the regulation of monoamine oxidase-B (MAO-B) activity and imidazoline receptors (I-R) dur ing long term treatment of morphine. METHODS: MAO-B activity was detected by high performance liquid chromatography; I-R was detected by [3H] idazoxan binding test. RESULTS: Idazoxan and morphine in hibited whole brain homogenate MAO-B activity in a dose-dependent manner, while agmatine, an endogenous imidazoline ligand, didn't affect the activity of MAO-B, and it had no effect on the inhibition of MAO-B activity by idazoxan or morphine. MAO-B activity of rats de creased markedly in all five brain regions detected (cere bral cortex, hippocampus, thalamus, cerebellum, and striatum) after chronic administration of morphine for 16 d ( P < 0.01). Acute challenge with naloxone or ida zoxan didn't influence MAO-B activity in morphine chronically treated rats. Although agmatine

  11. G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Jianjun; Luo, Jiansong; Aryal, Dipendra K; Wetsel, William C; Nass, Richard; Benovic, Jeffrey L

    2017-04-07

    G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive grk-2 or by the selective expression of grk-2 in hermaphrodite-specific neurons. The addition of 5-HT or inhibition of 5-HT metabolism also rescued the egg laying defect. Furthermore, we demonstrate that AMX-2 is the primary monoamine oxidase that metabolizes 5-HT in C. elegans, and we also found that grk-2 loss-of-function strains have abnormally high levels of AMX-2 compared with wild-type nematodes. Interestingly, GRK-2 was also found to interact with and promote the phosphorylation of AMX-2. Additional studies reveal that 5-HIAA functions to inhibit egg laying in a manner dependent on the 5-HT receptor SER-1 and the G protein GOA-1. These results demonstrate that GRK-2 modulates 5-HT metabolism by regulating AMX-2 function and that 5-HIAA may function in the SER-1 signaling pathway. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Association between monoamine oxidase B A644G polymorphism and Parkinson's disease risk: a meta-analysis in the Chinese population.

    Science.gov (United States)

    Liu, J J; Wang, W; Meng, M; Liang, C S; Zhang, J W

    2016-07-14

    Although various individual studies have evaluated the correlation between monoamine oxidase B (MAOB), polymorphism, and Parkinson's disease (PD), the results remain inconclusive. Therefore, we performed a meta-analysis in the Chinese population to provide comprehensive data on the association between the MAOB polymorphism and PD. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of these associations. Eight studies documenting a total of 1385 cases of PD and 1426 controls were included in this meta-analysis. Overall, no significant association was found between the MAOB A644G polymorphism and PD risk in the Chinese population. However, in subgroup analyses, where results were stratified by geographical areas and source of controls, increased risk for PD in Northern China was observed (allele A vs G: OR = 1.33, 95%CI = 1.11-1.58; AA vs GG: OR = 1.46, 95%CI = 1.09-1.97; AA + AG vs GG: OR = 1.42, 95%CI = 1.06-1.90). Similarly, population-based studies also showed significant association between the MAOB A644G polymorphism and PD risk among different populations (allele A vs G: OR = 1.29, 95%CI = 1.11-1.51; AA vs GG: OR = 1.41, 95%CI = 1.09-1.82; AA + AG vs GG: OR = 1.34, 95%CI = 1.04- 1.71). In conclusion, this meta-analysis provided evidence that the MAOB A644G polymorphism may contribute to PD development in Northern China. Further studies conducted in other ethnic groups are required for definite conclusions.

  13. The effects of child maltreatment on early signs of antisocial behavior: genetic moderation by tryptophan hydroxylase, serotonin transporter, and monoamine oxidase A genes.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A; Thibodeau, Eric L

    2012-08-01

    Gene-environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes were examined: tryptophan hydroxylase 1 (TPH1), serotonin transporter linked polymorphic region (5-HTTLPR), and monoamine oxidase A (MAOA) upstream variable number tandem repeat. In addition to child maltreatment status, we considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer, and adult counselor reports. In a series of analyses of covariance, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all report forms. Genetic effects operated primarily in the context of gene-environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5-HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer reports of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. The TPH1 and 5-HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult reports of antisocial behavior; again, the genetic effects were strongest for children who were abused. In addition, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult reports of antisocial behavior. The findings elucidate how genetic

  14. The effects of 5-HT uptake- and MAO-inhibitors on L-5-HTP-induced excitation in rats.

    Science.gov (United States)

    Ortmann, R; Waldmeier, P C; Radeke, E; Felner, A; Delini-Stula, A

    1980-03-01

    The behavioural syndrome caused by L-5-HTP in rats was used for the study of effects of selective 5-HT uptake inhibitors and inhibitors of MAO on central 5-HT receptors. A good correlation was found between the relative potencies of drugs in inhibiting the 5-HT uptake in the rat brain and in intensifying L-5-HTP-induced behavioural stimulation. The potentiation of the L-5-HTP syndrome by the MAO inhibitors correlated with the inhibition of the A- but not of the B-form of the brain monoamine oxidase. In rats treated with the maximally inhibiting dose of a 5-HT uptake inhibitor, MAO inhibitors were still able to increase the intensity of the L-5-HTP syndrome, while the combination of maximal doses of two 5-HT uptake inhibitors did not produce a more intense syndrome than that produced by one 5-HT uptake inhibitor alone. The L-5-HTP-induced behavioural syndrome in rats seems to afford an experimental model allowing the quantification and characterization of the interaction of drugs with serotonin metabolism in the brain.

  15. Radiosynthesis and in vivo evaluation of [{sup 11}C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A

    Energy Technology Data Exchange (ETDEWEB)

    De Bruyne, Sylvie [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium); La Regina, Giuseppe [Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universita di Roma, I-00185 Rome (Italy); Staelens, Steven [IBITECH-Medisip, Ghent University-IBBT, 9000 Ghent (Belgium); Wyffels, Leonie [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium); Deleye, Steven [IBITECH-Medisip, Ghent University-IBBT, 9000 Ghent (Belgium); Silvestri, Romano [Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universita di Roma, I-00185 Rome (Italy); De Vos, Filip [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium)], E-mail: filipx.devos@ugent.be

    2010-05-15

    Introduction: Since MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [{sup 11}C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties. Methods: The radiolabelling of [{sup 11}C]-RS 2315 and [{sup 11}C]-RS 2360 was accomplished by alkylation of their amide precursors with [{sup 11}C]CH{sub 3}I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [{sup 11}C]-RS 2360. Results: Both tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [{sup 11}C]-RS 2360 was more stable than [{sup 11}C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [{sup 11}C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [{sup 11}C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points. Conclusions: [{sup 11}C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [{sup 11}C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.

  16. Antidepressant treatment with MAO-inhibitors during general and regional anesthesia: a review and case report of spinal anesthesia for lower extremity surgery without discontinuation of tranylcypromine.

    Science.gov (United States)

    Krings-Ernst, Ilana; Ulrich, Sven; Adli, Mazda

    2013-10-01

    Monoamine oxidase-(MAO)-inhibitors are a treatment of last resort in treatment resistant depression, which is regarded as a condition of increased psychiatric risk. General and regional anesthesia for elective surgery during use of long-term MAO-inhibitors remains a matter of debate because of an increased risk of drug interactions and decreased sympathetic stability. A series of case reports and new comparative studies reveal the safety of anesthesia/analgesia in non-cardiac surgery without discontinuation of the MAO-inhibitor if best effort is made for maintenance of sympathetic homeostasis and if known drug interactions are avoided. Very few reports with severe adverse incidents have been noted. Severe cardiovascular morbidity, a contraindication of MAO-inhibitors, probably contributed to peri- and postoperative complications. According to new studies, the risk of pharmacokinetic drug interactions is lower for tranylcypromine than for phenelzine. In the present case, a 66-year-old psychiatric patient on permanent treatment with 20 mg/day tranylcypromine was admitted for forefoot surgery. Anesthetic premedication consisted of 7.5 mg oral midazolam. Intravenous midazolam (0.5 mg) was dispensed for intraoperative sedation. After local anesthesia of the puncture site with 30 mg isobar prilocaine, spinal anesthesia was achieved by a single shot of 13.5 mg hyperbar bupivacaine (0.5%) intrathecally. Postoperative regional and general analgesia were accomplished by a peripheral nerve block with 50 mg isobar bupivacaine as well as oral etoricoxib and oxycodone. No peri- or postoperative complications were encountered. It is concluded that general or regional anesthesia for noncardiac surgery without discontinuation of MAO-inhibitor treatment may be a safe intervention after careful evaluation of an individual's perioperative and psychiatric risk. The increased psychiatric risk in patients treated with MAO-inhibitors outweighs the increased, however manageable

  17. Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Joubert, Jacques; Foka, Germaine B; Repsold, Benjamin P; Oliver, Douglas W; Kapp, Erika; Malan, Sarel F

    2017-01-05

    A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC50: 0.5-73 nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC50 = 0.96 μM, hMAO-A IC50 = 2.13 μM, hMAO-B IC50 = 0.0021 μM). Within the N-benzylpiperidine (16-19) and p-bromo-N-benzylpiperizine (21-24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC50 = 9.10 μM and 5.90 μM, respectively), and relatively potent and selective hMAO-B inhibition (IC50 = 0.30 μM, SI = >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds.

  18. Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.

    Science.gov (United States)

    Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

    2016-06-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907. Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

    Science.gov (United States)

    Chandrasekhar, Y; Ramya, E M; Navya, K; Phani Kumar, G; Anilakumar, K R

    2017-02-01

    Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder.

  20. Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products.

    Science.gov (United States)

    Ghislieri, Diego; Green, Anthony P; Pontini, Marta; Willies, Simon C; Rowles, Ian; Frank, Annika; Grogan, Gideon; Turner, Nicholas J

    2013-07-24

    The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine.

  1. The c.1460C>T Polymorphism of MAO-A Is Associated with the Risk of Depression in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    R. Słopień

    2012-01-01

    Full Text Available Objective. The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. Methods. We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17β-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A, 1B (HTR1B, and 2C (HTR2C; tryptophan hydroxylase 1 (TPH1 and 2 (TPH2, and monoamine oxidase A (MAO-A were evaluated using polymerase chain reaction-restriction. Results. We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070 appeared with a significantly higher frequency in depressed female patients than in the control group (P=0.011 and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P=0.0198. Patients with the 1460TT genotype had a significantly higher 17β-estradiol concentration than patients with the 1460CT genotype (P=0.0065 and 1460CC genotype (P=0.0018. Conclusions. We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A.

  2. Syntheses of 8-(phenoxymethyl)caffeine analogues and their evaluation as inhibitors of monoamine oxidase and as antagonists of the adenosine A2A receptor / Rozanne Harmse.

    OpenAIRE

    Harmse, Rozanne

    2013-01-01

    Background and rationale: Parkinson’s disease (PD) is a progressive, degenerative disorder of the central nervous system and is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The loss of functional dopamine in the striatum is thought to be responsible for the typical symptoms of PD. Cardinal features of PD include bradykinesia, muscular rigidity, resting tremor and impairment of postural balance. This study focuses on the inhibition of monoamine oxida...

  3. Recension: Mao - The Unknown Story

    DEFF Research Database (Denmark)

    Clausen, Søren

    2005-01-01

    Anmeldelse - kritisk! - til Sveriges førende Kinatidsskrift af Jung Chang & Jon Halliday's sensationelle "Mao - the Unknown Story".......Anmeldelse - kritisk! - til Sveriges førende Kinatidsskrift af Jung Chang & Jon Halliday's sensationelle "Mao - the Unknown Story"....

  4. Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

    Science.gov (United States)

    Sofic, E; Salkovic-Petrisic, M; Tahirovic, I; Sapcanin, A; Mandel, S; Youdim, M; Riederer, P

    2015-04-01

    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.

  5. Monoamine Oxidase A (MAOA) and Catechol-O-Methyltransferase (COMT) Gene Polymorphisms Interact with Maternal Parenting in Association with Adolescent Reactive Aggression but not Proactive Aggression: Evidence of Differential Susceptibility.

    Science.gov (United States)

    Zhang, Wenxin; Cao, Cong; Wang, Meiping; Ji, Linqin; Cao, Yanmiao

    2016-04-01

    To date, whether and how gene-environment (G × E) interactions operate differently across distinct subtypes of aggression remains untested. More recently, in contrast with the diathesis-stress hypothesis, an alternative hypothesis of differential susceptibility proposes that individuals could be differentially susceptible to environments depending on their genotypes in a "for better and for worse" manner. The current study examined interactions between monoamine oxidase A (MAOA) T941G and catechol-O-methyltransferase (COMT) Val158Met polymorphisms with maternal parenting on two types of aggression: reactive and proactive. Moreover, whether these potential G × E interactions would be consistent with the diathesis-stress versus the differential susceptibility hypothesis was tested. Within the sample of 1399 Chinese Han adolescents (47.2 % girls, M age = 12.32 years, SD = 0.50), MAOA and COMT genes both interacted with positive parenting in their associations with reactive but not proactive aggression. Adolescents with T alleles/TT homozygotes of MAOA gene or Met alleles of COMT gene exhibited more reactive aggression when exposed to low positive parenting, but less reactive aggression when exposed to high positive parenting. These findings provide the first evidence for distinct G × E interaction effects on reactive versus proactive aggression and lend further support for the differential susceptibility hypothesis.

  6. Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

    Directory of Open Access Journals (Sweden)

    Petrak Jiri

    2011-11-01

    Full Text Available Abstract Background Chronic hemodynamic overloading leads to heart failure (HF due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF and sham-operated rats harvested at the advanced, decompensated stage of HF. Methods We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. Results In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. Conclusions The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.

  7. Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

    Directory of Open Access Journals (Sweden)

    Leonardo Pisani

    2016-03-01

    Full Text Available The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD, shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE-monoamine oxidase B (MAO-B inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 µM and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM. Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone. In a Madin-Darby canine kidney (MDCKII-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp substrate, showing an efflux ratio = 0.96, close to that of diazepam.

  8. Searching for Multi-Targeting Neurotherapeutics against Alzheimer's: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif.

    Science.gov (United States)

    Pisani, Leonardo; Farina, Roberta; Soto-Otero, Ramon; Denora, Nunzio; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio; Mendez-Alvarez, Estefania; Altomare, Cosimo Damiano; Catto, Marco; Carotti, Angelo

    2016-03-17

    The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer's disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 µM) and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM) under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone). In a Madin-Darby canine kidney (MDCK)II-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp) substrate, showing an efflux ratio = 0.96, close to that of diazepam.

  9. Mao to Now.

    Science.gov (United States)

    Gillespie, Ros; Collins, Colin

    After the death of Chairman Mao in 1976, the educational and economic policies of the People's Republic of China changed dramatically. From 1966 to 1976, the central concern of the Cultural Revolution was the distribution of wealth and power. The primary educational goal of this period was to transform the attitudes and thinking of the Chinese…

  10. Long-term exposure to xenoestrogens alters some brain monoamines and both serum thyroid hormones and cortisol levels in adult male rats

    Directory of Open Access Journals (Sweden)

    Nashwa M. Saied

    2014-10-01

    Full Text Available The present study was designed to examine the effect of long-term treatment with the phytoestrogen soy isoflavone [(SIF; 43 mg/kg body weight/day] and/or the plastics component bisphenol-A [(BPA; 3 mg/kg body weight/day] on some monoamines in the forebrain and both serum thyroid hormones and cortisol levels of adult rats. Significant increases in serotonin (5-HT and norepinephrine (NE level, and significant decreases in 5-hydroxyindoleacetic acid (5-HIAA level and 5-HIAA/5-HT ratio, were observed after treatment with SIF or BPA. Level of dopamine (DA was increased in SIF-treated group and decreased in BPA-treated group. Activity of monoamine oxidase (MAO was decreased in all treated groups. The level of serum thyroid hormones (fT3 and fT4 was increased after treatment with SIF and decreased after exposure to BPA, while cortisol level was increased in all treated groups. It may be concluded that long-term exposure to SIF or BPA disrupts monoamine levels in the forebrain of adult rats through alteration in the metabolic pathways of amines and disorders of thyroid hormones and cortisol levels.

  11. Patient compliance with MAO inhibitor therapy.

    Science.gov (United States)

    Walker, J I; Davidson, J; Zung, W W

    1984-07-01

    Exaggerated fears of monoamine oxidase inhibitors (MAOIs) and of their interactions with foods often restrict their use. A review of the literature reveals seven food items most likely to produce a hypertensive crisis in combination with MAOI administration: aged cheeses, smoked or pickled fish, beef or chicken liver, dry fermented sausage, pods of broad beans, brewer's yeast products, and certain alcoholic beverages. Improved understanding of the dietary restrictions, benefits, and mechanism of action of the MAOIs can enhance cooperation with the prescribed treatment program.

  12. ADP competes with FAD binding in putrescine oxidase.

    Science.gov (United States)

    van Hellemond, Erik W; Mazon, Hortense; Heck, Albert J; van den Heuvel, Robert H H; Heuts, Dominic P H M; Janssen, Dick B; Fraaije, Marco W

    2008-10-17

    Putrescine oxidase from Rhodococcus erythropolis NCIMB 11540 (PuO(Rh)) is a soluble homodimeric flavoprotein of 100 kDa, which catalyzes the oxidative deamination of putrescine and some other aliphatic amines. The initial characterization of PuO(Rh) uncovered an intriguing feature: the enzyme appeared to contain only one noncovalently bound FAD cofactor per dimer. Here we show that this low FAD/protein ratio is the result of tight binding of ADP, thereby competing with FAD binding. MS analysis revealed that the enzyme is isolated as a mixture of dimers containing two molecules of FAD, two molecules ADP, or one FAD and one ADP molecule. In addition, based on a structural model of PuO(Rh) that was built using the crystal structure of human monoamine oxidase B (MAO-B), we constructed an active mutant enzyme, PuO(Rh) A394C, that contains covalently bound FAD. These findings show that the covalent FAD-protein linkage can be formed autocatalytically and hint to a new-found rationale for covalent flavinylation: covalent flavinylation may have evolved to prevent binding of ADP or related cellular compounds, which would prohibit formation of flavinylated and functional enzyme.

  13. Effect of Monoamine Oxidase Inhibitor on the Differentiation of Malignant Glioma Cell%单胺氧化酶抑制剂诱导胶质瘤细胞的体外分化

    Institute of Scientific and Technical Information of China (English)

    邵根宝; 薄丹丹; 韩晓娟; 贺清华; 张严; 桑建荣

    2012-01-01

    To investigate the effect of monoamine oxidase inhibitor tranylcypromine (TCP) on the differentiation of human U251 glioma cells, we treated U251 cells with TCP and/or 100 nmol/L histone deacetylase inhibitor trychos-tatin A (TSA). The differentiation of U251 cells was observed with inverted microscopy. The cell proliferation and cell cycle distribution were determined by MTT assay and flow cytometry. respectively. Apoptosis was observed by Hoechst 33258 staining. The levels of differentiation-related genes were assessed by real-time PCR and Western blotting. TCP-induced differentiation was characterized by typical morphological changes, inhibition of cellular proliferation, accumulation of cells in the Gl phase of the cell cycle, decreased expression of the pluripotency transcription factors Oct4 and Sox2, and increased expression of glial fibrillary acid protein (GFAP). The combination of TCP and TSA treatment also triggered an over-expression of GFAP. These findings suggest that TCP may induce differentiation of U251 glioma cells, and the differentiation process may be promoted by histone deacetylase inhibitor TSA,%为研究单胺氧化酶抑制剂(TCP)对体外培养的入脑胶质瘤U251细胞的诱导分化作用,以不同浓度TCP单独或与100 nmol/L组蛋白去乙酰化酶抑制剂(TSA)联合处理U251细胞,采用倒置显微镜观察细胞形态学变化;噻唑蓝( MTT)比色法检测细胞增殖变化;流式细胞仪检测细胞周期变化;Hoechst 33258染色显示细胞凋亡;Real-time PCR和Western印迹法检测分化相关基因mRNA和蛋白表达水平的改变.结果表明:TCP可诱导细胞突起增多且变细长,抑制细胞增殖,阻滞细胞周期于G1期,抑制全能性转录因子Oct4和Sox2的表达,上调分化标志基因胶质纤维酸性蛋白(GFAP)的表达,TCP联合TSA也诱导了GFAP的高表达.这些结果提示:TCP可诱导胶质瘤U251细胞分化,TSA对TCP诱导细胞分化有协同作用.

  14. 漆黄素联合胡椒碱的抗抑郁作用及其机制研究%Antidepressant like effect of acute administration with fisetin combined with piperine and its monoamine mechanism

    Institute of Scientific and Technical Information of China (English)

    王钱东; 吴淑娟; 朱国文; 潘建春

    2014-01-01

    目的:探讨低剂量漆黄素(Fisetin)联合阈下剂量胡椒碱的抗抑郁作用是否涉及单胺机制。方法采用行为绝望抑郁模型,即小鼠强迫游泳实验和悬尾实验,观察低剂量漆黄素与阈下剂量胡椒碱急性给药对小鼠绝望模型不动时间的影响,同时观察两药联用对小鼠自主活动的影响。高效液相-电化学检测脑区中单胺递质的含量,荧光分光光度法检测单胺氧化酶(MAO)活性。结果漆黄素(1.25 mg/kg,2.5 mg/kg,5 mg/kg, ig)与阈下剂量胡椒碱2.5 mg/kg·ip联合应用能显著减少小鼠强迫游泳和悬尾实验中的不动时间,且实验剂量范围内药物不影响小鼠的自主活动。低剂量漆黄素与阈下剂量胡椒碱合用能升高海马、皮层和杏仁核中的单胺递质水平同时降低脑内的MAO活性,并且具有统计学意义。结论低剂量漆黄素与阈下剂量胡椒碱联合用药能改善抑郁症样行为,该机制可能是通过抑制单胺氧化酶的活性,从而增加相关的神经递质。%Objective To explore the antidepressant effects of low dose fisetin combined with piperine and its possible mechanism. Methods The tail suspension test and the forced swimming test were used to explore the antidepressant ef-fects of low dose fisetin combined with piperine. In addition, the locomotor activity test was used to exclude the false positive effect in behavioral despair tests. High performance liquid chromatography (HPLC) was used to determine the expression of monoamine. The monoamine oxidase activity in the mouse brain was also determined by fluorospec-trophotometry. Results The results showed that fisetin (1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, ig) combined with piperine (2.5 mg/kg, ip) significantly reduced the duration of immobility in both tail suspension and forced swimming tests. The effective doses did not alter locomotor activity. Moreover, neurochemical assays showed that its produced an increase in monoamine levels in the

  15. Kinetic mechanism of putrescine oxidase from Rhodococcus erythropolis

    NARCIS (Netherlands)

    Kopacz, Malgorzata; Heuts, Dominic P. H. M.; Fraaije, Marco W.

    2014-01-01

    Putrescine oxidase from Rhodococcus erythropolis (PuO) is a flavin-containing amine oxidase from the monoamine oxidase family that performs oxidative deamination of aliphatic diamines. In this study we report pre-steady-state kinetic analyses of the enzyme with the use of single-and double-mixing st

  16. Kinetic mechanism of putrescine oxidase from Rhodococcus erythropolis

    NARCIS (Netherlands)

    Kopacz, Malgorzata; Heuts, Dominic P. H. M.; Fraaije, Marco W.

    2014-01-01

    Putrescine oxidase from Rhodococcus erythropolis (PuO) is a flavin-containing amine oxidase from the monoamine oxidase family that performs oxidative deamination of aliphatic diamines. In this study we report pre-steady-state kinetic analyses of the enzyme with the use of single-and double-mixing

  17. Understanding MAOS through computational chemistry.

    Science.gov (United States)

    Prieto, P; de la Hoz, A; Díaz-Ortiz, A; Rodríguez, A M

    2017-01-23

    The importance of microwave irradiation in organic synthesis today is unquestionable, but in many cases the nature of these improvements remains unknown. Exploiting the benefits that microwave irradiation has in chemistry is still hindered by a lack of understanding of the physical principles of the interaction of microwave irradiation with the components of a reaction. Moreover, dielectric properties vary with temperature and along the reaction coordinate and this makes the situation more complex. Experimental determinations employed to date in Microwave-Assisted Organic Chemistry (MAOS) are characterized by the importance of thermal heating. In this way the separation of thermal heating from any other effect of electromagnetic radiation is completely impossible. This review provides an overview of the use of Computational Chemistry in MAOS to provide a theoretical understanding of the factors that can be used to explain the improvements in MAOS and how computational calculations can be used as a predictive tool.

  18. Selective inhibition of MAO-A activity results in an antidepressant-like action of 2-benzoyl 4-iodoselenophene in mice.

    Science.gov (United States)

    Velasquez, Daniela; Quines, Caroline; Pistóia, Renan; Zeni, Gilson; Nogueira, Cristina W

    2017-03-01

    Depression is a leading cause of disability worldwide. For this reason, the aim of this study was to investigate the possible antidepressant-like activity of 2-benzoyl-4-iodoselenophene (C17H11IOSe), a selenophene compound, in two well-consolidated behavioral assays for screening antidepressant activity (forced swimming test and tail suspension test) in mice. In order to investigate the mechanism of action of C17H11IOSe, it was investigated the activities of cerebral enzymes: monoamine oxidase MAO A and B and Na(+), K(+) ATPase, and if an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA) (100mg/kg) blocks the antidepressant-like effect of C17H11IOSe. Swiss mice received (C17H11IOSe) (5-50mg/kg) or canola oil by the intragastric (i.g.) route before behavioral tests. The results showed that C17H11IOSe at dose range of 5-50mg/kg decreased immobility time in the tail suspension test. In the forced swimming test, C17H11IOSe reduced the immobility time at the doses of 10 and 50mg/kg. C17H11IOSe differently affected the cerebral cortical Na(+), K(+) ATPase; the effects on this enzyme were dependent of the dose tested. At a dose of 10mg/kg, the compound increased Na(+), K(+) ATPase activity, while the activity was inhibited at a dose of 50mg/kg. pCPA blocked the antidepressant-like action of C17H11IOSe in mice. Therefore, C17H11IOSe (5-50mg/kg) selectively inhibited MAO-A activity in cerebral cortices of mice. The modulation of serotonergic system contributed to the antidepressant-like action of C17H11IOSe in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Pathological changes in platelet histamine oxidases in atopic eczema

    Directory of Open Access Journals (Sweden)

    Reinhold Kiehl

    1993-01-01

    Full Text Available Increased plasma histamine levels were associated with significantly lowered diamine and type B monoamine oxidase activities in platelet-rich plasma of atopic eczema (AE patients. The diamine oxidase has almost normal cofactor levels (pyridoxal phosphate and Cu2+ but the cofactor levels for type B monoamine oxidase (flavin adenine dinucleotide and Fe2+ are lowered. The biogenic amines putrescine, cadaverine, spermidine, spermine, tyramine and serotonin in the sera, as well as dopamine and epinephrine in EDTA-plasma were found to be normal. It is unlikely, therefore, that these amines are responsible for the decreased activities of monoamine and diamine oxidase in these patients. The most likely causative factors for the inhibition of the diamine oxidase are nicotine, alcohol, food additives and other environmental chemicals, or perhaps a genetic defect of the diamine oxidase.

  20. The MAO A genotype does not modulate resting brain metabolism in adults

    Science.gov (United States)

    Alia-Klein, Nelly; Kriplani, Aarti; Pradhan, Kith; Ma, Jim Yeming; Logan, Jean; Williams, Benjamin; Craig, Ian W.; Telang, Frank; Tomasi, Dardo; Goldstein, Rita Z.; Wang, Gene-Jack; Volkow, Nora D.; Fowler, Joanna S.

    2008-01-01

    Variation in the monoamine-oxidase-A gene has been associated with volumetric changes in corticolimbic regions with differences in their response to relevant emotional tasks. Here we show no changes in baseline regional brain metabolism as a function of genotype indicating that, unchallenged, corticolimbic activity is not modulated by the MAOA genotype. PMID:18706791

  1. Aspects of Northern Mao Phonology

    Directory of Open Access Journals (Sweden)

    Michael Ahland

    2009-01-01

    Full Text Available In general terms, the phonology of Omotic languages has received little attention. This paper presents core phonological properties of on Omotic language, Norther Mao. The discussion includes inventories of contrastive consonants, contrastive vowels, an examination of the vowel space, contrastive vowel length, vowel harmony in roots, syllable patterns, sibilant harmony, and an inventory of surface tonal melodies in nouns and verbs in citation form.

  2. Multiple amine oxidases in cucumber seedlings.

    Science.gov (United States)

    Percival, F W; Purves, W K

    1974-10-01

    Cell-free extracts of cucumber (Cucumis sativus L. cv. National Pickling) seedlings were found to have amine oxidase activity when assayed with tryptamine as a substrate. Studies of the effect of lowered pH on the extract indicated that this activity was heterogeneous, and three amine oxidases could be separated by ion exchange chromatography. The partially purified enzymes were tested for their activities with several substrates and for their sensitivities to various amine oxidase inhibitors. One of the enzymes may be a monoamine oxidase, although it is inhibited by some diamine oxidase inhibitors. The other two enzymes have properties more characteristic of the diamine oxidases. The possible relationship of the amine oxidases to indoleacetic acid biosynthesis in cucumber seedlings is discussed.

  3. Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.

    Science.gov (United States)

    Lyytinen, J; Kaakkola, S; Ahtila, S; Tuomainen, P; Teräväinen, H

    1997-07-01

    The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, repeated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest that entacapone can be safely administered together

  4. Anti-inflammatory and protective effects of MT-031, a novel multitarget MAO-A and AChE/BuChE inhibitor in scopolamine mouse model and inflammatory cells.

    Science.gov (United States)

    Liu, Wei; Rabinovich, Alon; Nash, Yuval; Frenkel, Dan; Wang, Yuqiang; Youdim, Moussa B H; Weinreb, Orly

    2017-02-01

    Previous study demonstrated that the novel multitarget compound, MT-031 preserved in one molecule entity the beneficial properties of its parent drugs, rasagiline and rivastigmine, and exerted high dual potencies of monoamine oxidase-A (MAO-A) and cholinesterase (ChE) inhibition in acute-treated mice and neuroprotective effects against H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. The present study aimed to further investigate the anti-inflammatory and protective effects of MT-031 in scopolamine mouse model and inflammatory cell cultures. Our findings demonstrated that once daily chronic administration of MT-031 (5-10 mg/kg) to mice antagonized scopolamine-induced memory and cognitive impairments, displayed brain selective MAO-A and AChE/BuChE inhibition, increased the levels of striatal dopamine (DA), serotonin (5-HT) and norepinephrine and prevented the metabolism of DA and 5-HT. In addition, MT-031 upregulated mRNA expression levels of Bcl-2, the neurotrophic factors, (e.g., brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF)), the antioxidant enzyme catalase and the anti-inflammatory cytokine, neurotrophic tyrosine kinase receptor (Ntrk), and down-regulated the mRNA expression levels of the pro-inflammatory interleukin (IL)-6 in scopolamine-induced mice. In accordance, MT-031 was shown to reduce reactive oxygen species accumulation, increase the levels of anti-inflammatory cytokines, IL-10 and decrease the levels of the pro-inflammatory cytokines, IL-1β, IL-6, IL-17 and interferon-gamma (IFN-γ) in activated mouse splenocytes and microglial cells. Taken together, these pharmacological properties of MT-031 can be of clinical importance for developing this novel multitarget compound as a novel drug candidate for the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Research on Mao Zedong and Culture

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    IN the past 10 years many mon-ographs and papers on researchinto the thought of Mao Ze-dong have appeared,but few ofthem have concentrated on the topicof culture.It seems to me that sincethe research is into Mao Zedong’sthought.it should take the conceptof culture given by Mao Zedong inhis writings as the standard.Maowrites,″Any given culture(as anideological form)is a reflection ofthe politics and economics of a giv-en society.″

  6. Study on the Correlation between Single Nucleotide Polymorphism of Monoamine Oxidase A Gene and Anger Regulation%单胺氧化酶A基因单核苷酸多态性与愤怒调节的关系研究

    Institute of Scientific and Technical Information of China (English)

    闫秀娟; 詹向红; 侯俊林; 刘永; 王淑玲; 李伟; 闫国立; 王友杰; 杨丽萍

    2012-01-01

    目的 研究单胺氧化酶A( monoamine oxidase A,MAOA)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与怒的调节关系.方法 以某学院健康大学生为研究对象,根据状态-特质愤怒表达量表2(State-Trait Anger Expression Inventory-Ⅱ,STAXI-2)特质怒得分筛选受试者,其中高特质怒者225名,低特质怒者221名,经采血后,采用酚-氯仿法提取DNA,聚合酶链反应-连接酶检测反应(PCR-LDR)法对MAOA基因上的4个tag SNP位点(rs5906957、rs2235186、rs1181275和rs5905613)进行基因分型,对高、低特质怒不同性别组MAOA基因4个tag SNP位点不同基因型受试者怒的表达量表得分和怒的控制量表得分进行统计分析.结果 低特质怒女性MAOA基因rs2235186位点不同基因型组控制发怒得分比较,差异有统计学意义(P =0.037),其余3个tag SNP位点的不同基因型受试者在怒的表达及控制得分上比较,差异均无统计学意义(P>0.05).结论 MAOA基因tag SNP rs2235186多态性与我国健康大学生低特质怒女性的控制发怒特质有关.%Objective To study the correlation between single nucleotide polymorphism (SNP) of monoamine oxidase A gene (MAOA) and anger regulation. Methods Enrolled were healthy students from some college , including 225 of the high trait anger and 221 of the low trait anger. Subjects were recruited referring to the State-Trait Anger Expression Inventory 2 (STAXI-2) and their blood sampled. The DNA was extracted using phenol-chloroform method, 4 tag SNPs of MAOA (rs5906957, rs2235186, rs1181275, and rs5905613) were genotyped by PCR-based ligase detection reaction (PCR-LDR). The scores for trait anger expression inventory and the scores for trait anger expression control at the 4 tag SNPs of MAOA in the different sexes groups of the high and the low trait anger were statistical analyzed. Results There was statistical difference in anger control score of locus rs2235186 of MAOA gene group (P=0.037). There was no

  7. Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

    Science.gov (United States)

    Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

    2016-08-04

    Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning.

  8. SINTESIS DE DERIVADOS DE FENILALQUILAMINAS CON POSIBLE ACTIVIDAD INHIBITORIA FRENTE A MAO A Y MAO B.

    OpenAIRE

    OSORIO OLIVARES, MAURICIO ENRIQUE

    2004-01-01

    La flavoenzima monoaminooxidasa es la encargada de la desaminación oxidativa de monoaminas endogenas y exogenas. Existen dos ¡soformas de esta enzima la MAO A y la MAO B, las que se diferencian tanto en la selectividad como en la afinidad frente a sus sub 98p.

  9. In Memory of Professors Chen Yaozhen (Eugene Chan) and Mao Wenshu (Winifred Mao)

    Institute of Scientific and Technical Information of China (English)

    Lezheng Wu

    2002-01-01

    @@ It has been 16 and 14 years respectively since Professor Chen Yaozhen (Eugene Chan) and Pro-fessor Mao Wenshu (Winifred Mao) passed away. We recollect the great and extraordinary lives ofthese two seniors, their outstanding achievements and contributions as well as the unforgettable andvaluable academic heritages left by them to the ophthalmology in China.

  10. Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology

    Directory of Open Access Journals (Sweden)

    John Paul Maurice Finberg

    2016-10-01

    Full Text Available Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines (cheese effect. A number of reversible MAO-A inhibitors which are devoid of cheese effect have been described in the literature, but only one, moclobemide, is currently in clinical use. The irreversible inhibitors of MAO-B, selegiline and rasagiline, are used clinically in treatment of Parkinson’s disease, and a recently introduced reversible MAO-B inhibitor, safinamide, has also been found efficacious. Modification of the pharmacokinetic characteristics of selegiline by transdermal administration has led to the development of a new drug form for treatment of depression. The clinical potential of MAO inhibitors together with detailed knowledge of the enzyme’s binding site structure should lead to future developments with these drugs.

  11. Speech after Mao: Literature and Belonging

    Science.gov (United States)

    Hsieh, Victoria Linda

    2012-01-01

    This dissertation aims to understand the apparent failure of speech in post-Mao literature to fulfill its conventional functions of representation and communication. In order to understand this pattern, I begin by looking back on the utility of speech for nation-building in modern China. In addition to literary analysis of key authors and works,…

  12. Speech after Mao: Literature and Belonging

    Science.gov (United States)

    Hsieh, Victoria Linda

    2012-01-01

    This dissertation aims to understand the apparent failure of speech in post-Mao literature to fulfill its conventional functions of representation and communication. In order to understand this pattern, I begin by looking back on the utility of speech for nation-building in modern China. In addition to literary analysis of key authors and works,…

  13. Coumarin versus Chromone Monoamine Oxidase B Inhibitors: Quo Vadis?

    Science.gov (United States)

    Fonseca, André; Reis, Joana; Silva, Tiago; Matos, Maria João; Bagetta, Donatella; Ortuso, Francesco; Alcaro, Stefano; Uriarte, Eugenio; Borges, Fernanda

    2017-08-24

    Because of the lack of significant disease-modifying drugs for neurodegenerative disorders, a pressing need for new chemical entities endowed with IMAO-B still exists. Within this framework, and for the first time, a study was performed to compare coumarin- and chomone-3-phenylcarboxamide scaffolds. Compounds 10a and 10b were the most potent, selective, and reversible noncompetitive IMAO-B. The benzopyrone sp(2) oxygen atom was found to be position independent and a productive contributor for the ligand-enzyme complex stability.

  14. Substantial protection against MPTP-associated Parkinson's neurotoxicity in vitro and in vivo by anti-cancer agent SU4312 via activation of MEF2D and inhibition of MAO-B.

    Science.gov (United States)

    Guo, Baojian; Hu, Shengquan; Zheng, Chengyou; Wang, Hongyu; Luo, Fangcheng; Li, Haitao; Cui, Wei; Yang, Xifei; Cui, Guozhen; Mak, Shinghung; Choi, Tony Chung-Lit; Ma, Edmond Dik-Lung; Wang, Yuqiang; Lee, Simon Ming Yuen; Zhang, Zaijun; Han, Yifan

    2017-08-12

    We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312. Additionally, Western blotting analysis revealed that SU4312 potentiated pro-survival PI3-K/Akt pathway to down-regulate MEF2D inhibitor glycogen synthase kinase-3beta (GSK3β). Furthermore, using the in vivo PD model of C57BL/6 mice insulted with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we found that intragastrical administration of SU4312 (0.2 and 1 mg/kg) greatly ameliorated Parkinsonian motor defects, and restored protein levels of MEF2D, phosphorylated-Ser473-Akt and phosphorylated-Ser9-GSK3β. Meanwhile, SU4312 effectively reversed the decrease in protein expression of tyrosine hydroxylase in substantia nigra pars compacta dopaminergic neurons, inhibited oxidative stress, maintained mitochondrial biogenesis and partially prevented the depletion of dopamine and its metabolites. Very encouragingly, SU4312 was able to selectively inhibit monoamine oxidase-B (MAO-B) activity both in vitro and in vivo, with an IC50 value of 0.2 μM. These findings suggest that SU4312 provides therapeutic benefits in cellular and animal models of PD, possibly through multiple mechanisms including enhancement of MEF2D

  15. 抑郁症单胺氧化酶A基因活性对表情识别脑功能的影响%Influence of monoamine oxidase A gene and brain function in the dynamic facial expression recognition in depressed patients

    Institute of Scientific and Technical Information of China (English)

    唐勇; 张婧; 姚志剑; 刘海燕; 卢青

    2011-01-01

    目的 应用影像基因组学的原理,探讨单胺氧化酶A基因串联重复序列多态性(MAOA-uVNTR)对抑郁症患者及健康对照不同面部表情识别过程中脑功能的影响.方法 28例抑郁症患者及33例性别比例、年限、受教育年限匹配的健康对照,应用聚合酶链式反应(PCR)技术扩增目的 基因,将61名受试者进行基因型分组,并利用1.5T功能核磁共振成像系统检测每个受试在识别喜悦、悲伤、及中性面部表情视频时的脑激活反应.结果 识别悲伤面部表情时,高活性基因型健康组较低活性基因型健康组左楔叶、左额下回、右额中回、左顶下小叶脑区激活显著增强(P<0.005,K≥10).识别喜悦面部表情时,高活性基因型患者组较低活性基因型患者组左右壳核、左中央后回,右颞上回、右丘脑、左梭状回脑区激活降低(P<0.005,K≥10).结论 高活性基因型与健康人群负性情绪识别的优先激活趋势及抑郁症患者正性情绪的抑制状态均存在关联性,该基因型可能是健康者罹患抑郁症的危险因素之一,同时部分导致该类患者情绪症状较为显著.%Objective To explore the impact of the variable number of tandem repeats of monoamine oxidase A gene (MAOA-uVNTR) on the intensity of brain activation during the recognition of facial expression in patients with depression and healthy controls.Methods 28 cases of depression,as well as 33 healthy controls who were matched in gender, age and years of education were divided into different genotypes with the methods of polymerase chain reaction (PCR) amplification and 1.5% agarose gel electrophoresis separation.61 cases were scanned to compare the intensity of brain activation in the recognition of happy, sad and neutral facial expression.Results In healthy controls,cases with high-activity genotype showed increased activation in left cuneus,left inferior frontal gyrus, right medial frontal gyrus and left inferior

  16. 单胺氧化酶A基因多态性与儿童期虐待对青少年攻击行为的影响%Association of monoamine oxidase A variable number of tandem repeats and child abuse with aggressive behavior among Chinese adolescents

    Institute of Scientific and Technical Information of China (English)

    张芸; 明庆森; 朱熊兆; 蚁金瑶; 姚树桥

    2014-01-01

    目的 探讨单胺氧化酶A串联重复序列(monoamine oxidase A variable number of tandem repeats)基因多态性及儿童期虐待对中国青少年攻击行为影响.方法 采用整群随机抽样法抽取某中学637名年龄13~18岁汉族青少年样本(男388名,女249名),采用儿童创伤经历问卷评定儿童期虐待,采用儿童行为量表评定攻击行为,并从研究对象外周静脉血提取DNA进行MAOA-VNTR基因分型,采用直线回归方法检验儿童期虐待和MAOA-VNTR基因多态性各自对攻击行为的主效应及两者间的交互作用.结果 共有513名(男367名,女146名)进入研究,男性攻击行为平均得分(10.13±6.67)分,女性攻击行为平均得分(9.18 ±6.36)分,不同性别间攻击行为差异无统计学意义(P=0.08).367名男性青少年被试中,MAOA低、高活性组分别为58.3%与41.7%,且不同组间攻击行为得分差异无统计学意义(P=0.93).回归模型显示MAOA基因型对男性青少年攻击行为无预测作用,儿童期虐待经历对攻击行为有显著预测作用(P<0.01),且MAOA基因型与不同类型童年虐待对攻击行为存在显著交互作用(MAOA×虐待总分:P <0.01;MAOA×躯体虐待:P=0.02;MAOA×情感虐待:P <0.01;MAOA×性虐待:P =0.04),MAOA低活性男性在经历儿童期躯体虐待和情感虐待后更易出现攻击倾向;146名女性青少年被试中,MAOA低活性、高活性及杂合子组分别占39.4%、22.5%和38.1%,MAOA不同基因型之间攻击行为得分差异无统计学意义(P=0.69).回归模型显示MAOA基因型对女性青少年攻击行为无预测作用,但儿童期虐待经历对其有显著预测作用(P<0.01),且MAOA与性虐待及MAOA与情感虐待对攻击行为分别存在交互作用(P值分别为0.03和0.04),MAOA低活性女性在受到儿童期性虐待/情感虐待后更易出现攻击倾向.结论 我国13 ~18岁青少年攻击行为受到儿童期虐待经历与MAOA-VNTR基因-环境间交互作用的

  17. 快眼动睡眠剥夺对抑郁模型大鼠不同脑区色氨酸羟化酶和单胺氧化酶A的影响%Effects of REM sleep deprivation on behavioral depression and brain tryptophan hydroxylase and monoamine oxidase in rats treated with chronic stresses

    Institute of Scientific and Technical Information of China (English)

    金叶华; 李丽所

    2008-01-01

    目的:探讨睡眠剥夺对抑郁模型大鼠不同脑区色氨酸羟化酶(TPH)和单胺氧化酶A(MAO-A)的影响.方法:对抑郁模型大鼠进行睡眠剥夺,应用旷场实验观察大鼠实验前后自主行为的变化,用紫外分光光度计和免疫印迹技术检测大鼠大脑中脑、海马、下丘脑和前额叶四个部位的MAO-A的活性和11PH.结果:抑郁模型大鼠经过睡眠剥夺后自主行为显著增加,睡眠剥夺后大鼠海马、中脑、下丘脑和额叶的TPH显著升高,大鼠海马MAO-A活性显著增加.结论:睡眠剥夺对抑郁模型大鼠的抑郁样行为有改善作用,可能与色氨酸羟化酶和单胺氧化酶A有关.

  18. RED CAPITALIST A life changed by a chat with Mao

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Tang Ruiren, 76, a peasant-turned-restaurateur, has led a charmed life. The founder of Mao Jia Restaurant Development Corp., with 145 franchise restaurants in 20 provinces, she heads an empire that employs 20,000 people and last year paid more than 60 million yuan in taxes. What's so special about her restaurants? Mao Zedong's favorite dishes.

  19. The post-Mao gazes: Chinese backpackers in Macau

    NARCIS (Netherlands)

    Ong, C.E.; Cros, du H.

    2012-01-01

    This paper offers insights into backpacker tourism from the People’s Republic of China. Chinese backpackers are a distinctively post-Mao reform generation growing up at a time when China shifts from Mao Zedong’s socialist policies to Deng Xiaoping’s policy explorations with capitalism. Through dista

  20. The post-Mao gazes: Chinese backpackers in Macau

    NARCIS (Netherlands)

    Ong, C.E.; Cros, du H.

    2012-01-01

    This paper offers insights into backpacker tourism from the People’s Republic of China. Chinese backpackers are a distinctively post-Mao reform generation growing up at a time when China shifts from Mao Zedong’s socialist policies to Deng Xiaoping’s policy explorations with capitalism. Through dista

  1. Chairman Mao, The Chinese Revolution, and the Banality of Evil

    DEFF Research Database (Denmark)

    Clausen, Søren

    2006-01-01

    This article surveys the new biographies on Mao Zedong that have come out in the last few years and discusses the trends of the research.......This article surveys the new biographies on Mao Zedong that have come out in the last few years and discusses the trends of the research....

  2. The moderating effect of monoamine oxidase A gene polymorphism in relationship between childhood abuse of male adolescents and externalizing behaviors%单胺氧化酶A基因多态性对男性青少年儿童期虐待与外化性行为关系的调节效应

    Institute of Scientific and Technical Information of China (English)

    明庆森; 姚树桥; 张芸; 陈海燕

    2012-01-01

    Objective To explore the relationship between male adolescents' childhood abuse and externalizing behaviors,and the moderating effect of monoamine oxidase A (MAOA) gene promoter region variable number tandem repeat (VNTR) polymorphism.Methods Through random cluster sampling,352 Han male middle school students from Changsha were tested by Achenbach child behavior checklist-youth self reports (CBCL-YSR)and childhood trauma questionnaire-28 item short form (CTQ-SF),their MAOA genotypes were also identified.A hierarchical multiple regression analysis was used to test the moderating effect.Results ( 1 ) Compared participates with high activity MAOA gene and that with low activity MAOA gene,there were no significant differences on age ( ( 15.82 ± 1.52) vs ( 15.94 ± 1.62 ) ),externalizing behaviors ( ( 15.13 ± 10.14 ) vs ( 14.33 ± 9.70 ) ),total abuse ( (52.59 ± 10.46) vs (51.39 ± 7.56 ) ),emotional abuse( ( 7.63 ± 3.31 ) vs ( 7.11 ± 2.68 ) ),physical abuse ( ( 6.40 ± 2.82) vs (6.12 ± 2.05 ) ),sexual abuse ( ( 6.42 ± 3.24 ) vs ( 5.94 ± 1.72 ) ),emotional neglect ((13.44±5.12) vs (13.16 ±4.83) ),physical neglect( (10.27 ±2.64) vs (10.44±2.53))(t=-1.789~0.678,P > 0.05 ).(2)Except emotional neglect and physical neglect,emotional abuse,physical abuse and sexual abuse could predict externalizing behaviors( Sβ =0.141 ~0.347,P < 0.01 ).(3) MAOA gene was not directly related to externalizing behaviors( Sβ =- 0.023,P > 0.05 ).There was a significant interaction between MAOA gene and emotional abuse( Sβ =-0.148,P < 0.01 ).The interaction between MAOA gene and physical abuse or sexual abuse showed no statistical significance( Sβ =- 0.067,- 0.005,P > 0.05 ).Conclusion MAOA gene polymorphism can moderate the relationship between male adolescents'childhood emotional abuse and externalizing behaviors.%目的 探讨男性青少年的儿童期虐待与外化性行为的关系以及单胺氧化酶A (MAOA)基因启动子区域可变重复序列(VNTR)多态

  3. Drug: D03731 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Antidepressant [MAO inhibitor], Antiparkinsonian [in combination with levodopa/carbidopa] [DS:H00057] Same a..., CYP3A4 [HSA:1576] map07027 Antidepressants map07057 Antiparkinsonian agents map07216 Catecholamine transfe...Oxidase Inhibitors Selegiline D03731 Selegiline (USAN/INN) Antiparkinson Agents Monoamine Oxidase B (MAO-B)

  4. Efectos del clodimeformo sobre el desarrollo de los sistemas de neurotransmisores monoaminérgicos en el sistema nervioso central de rata

    OpenAIRE

    García Sánchez, José Manuel

    2015-01-01

    Se ha descrito para algunos compuestos formamidínicos la inducción de alteraciones permanentes sobre el desarrollo del sistema nervioso central tales como perturbaciones permanentes sobre los sistemas de neurotransmisores monoaminérgicos, para los cuales se ha sugerido como posible mecanismo la inhibición de la monoamino oxidasa (MAO), no pudiéndose descartar otros mecanismos como la disrrupcion endocrina de hormonas sexuales las cuales controlan la expresión de las enzimas que catalizan la s...

  5. [Monoamines stimulations in experimental carcinogenesis].

    Science.gov (United States)

    Popov, I; Spuzić, I; Rakić, Lj

    1994-01-01

    Facts about the role of CNS monoamines in cancerogenesis have been accumulated for many years. The aim of the present study was to investigate the effect of interaction of psychoactive drug (Piracetam) and other treatments on survival time of tumour-bearing rats. 138 Wistar rats were used in the experiment. The animals were injected 1% 3--Methilcholantren suspension in 10% Tylose, s.c. under the dorsal skin of the neck in a dose of 3 mg/animal. Within 4-9 months after a single injection, the rats developed tumours at the site of injection. The surgical removal was performed when tumours reached the size of 1-3 cm. After surgical extirpation of tumours different groups of animals were treated by cyclophosphamide (s.c. one-time dose of 50 mg/kg for female and 100 mg/kg for male) or by psychoactive drug (Piracetam) administrated by GE tube 5 time/week, 100 mg/kg. Autopsy and histological examinations were carried out in all animals. Survival time (> 120 days) was the greatest in group B (Piracetam, after surgical removal of tumours) 81.2%, and group C (Cyclophosphamid, after surgical removal of tumours) 68.8% and in group A (only surgical removal of tumours) 50%. In group B the incidence of metastases was the smallest (87.1% of animals were without metastases), compared with group C (45.4% of animals were without metastases) and group A (27.3% of animals were without metastases). The diference is statistically significant. The mechanism of antineoplastic effect of Piracetam consisted of the interaction of influences both on metabolism of the Central nervous system and the tumour. Probably, it is the neurotransmitter modulation that had its effect on carcinogenesis not only by regulation/disregulation of brain homeostasis, but also via direct effect on intracellular processes during cell development and differentation.

  6. Monoamine theories of depression: historical impact on biomedical research.

    Science.gov (United States)

    Mulinari, Shai

    2012-01-01

    Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.

  7. Monoamine transporters: Insights from molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Julie eGrouleff

    2015-10-01

    Full Text Available The human monoamine transporters facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia and Parkinson’s disease. Inhibition of the monoamine transporters is thus an important strategy for treatment of such diseases. The monoamine transporters are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the monoamine transporters, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors.

  8. [Uphold and develop Mao Zedong's thoughts on population].

    Science.gov (United States)

    Wang, J

    1984-03-29

    Mao Zedong's thoughts on population were based upon the positions, viewpoints, methods, and basic theory of Marxism, with some adjustments made according to China's practical situation. The population theory of Marxism was developed and used with creative elements. Mao Zedong's thoughts on population can be summarized in three points: (1) An understanding of China's backwar economy and culture and their relationship to overpopulation. There is an urgent need to solve the population problem. (2) An understanding of the close relationship between material production and the reproduction of human beings themselves. A balance between the two should be achieved. (3) Family planning should be practiced so that population growth may be put under control. Under the leadership of Deng Xiaoping, the Party's Central Committee has reconfirmed and developed Mao Zedong's population thoughts in various important official documents and writings. In such new writings, special emphasis is placed on the fact that with limited arable land, China has to plan its population growth and that family planning should be made part of the national policy. With ideological education serving as a foundation, special administrative actions and economic measures should be taken to motivate and transform the general public. Mao Zedong's thoughts on population and related new developments represent the crystallization of the Party's collective wisdom.

  9. Rhetoric, Literacy, and Social Change in Post-Mao China

    Science.gov (United States)

    Wexler, Steven

    2009-01-01

    State, citizen, and corporate readings of a multifarious "Chineseness" fundamentally shape the space where East and West clash in post-Mao China. This dialectic represents a citizen's working-through a crisis of agency and a nation's negotiation of its role within a global economy. Given that China's subaltern literacies operate within…

  10. Role of amine oxidase expression to maintain putrescine homeostasis in Rhodococcus opacus.

    Science.gov (United States)

    Foster, Alexander; Barnes, Nicole; Speight, Robert; Morris, Peter C; Keane, Mark A

    2013-04-10

    While applications of amine oxidases are increasing, few have been characterised and our understanding of their biological role and strategies for bacteria exploitation are limited. By altering the nitrogen source (NH4Cl, putrescine and cadaverine (diamines) and butylamine (monoamine)) and concentration, we have identified a constitutive flavin dependent oxidase (EC 1.4.3.10) within Rhodococcus opacus. The activity of this oxidase can be increased by over two orders of magnitude in the presence of aliphatic diamines. In addition, the expression of a copper dependent diamine oxidase (EC 1.4.3.22) was observed at diamine concentrations>1mM or when cells were grown with butylamine, which acts to inhibit the flavin oxidase. A Michaelis-Menten kinetic treatment of the flavin oxidase delivered a Michaelis constant (KM)=190μM and maximum rate (kcat)=21.8s(-1) for the oxidative deamination of putrescine with a lower KM (=60μM) and comparable kcat (=18.2s(-1)) for the copper oxidase. MALDI-TOF and genomic analyses have indicated a metabolic clustering of functionally related genes. From a consideration of amine oxidase specificity and sequence homology, we propose a putrescine degradation pathway within Rhodococcus that utilises oxidases in tandem with subsequent dehydrogenase and transaminase enzymes. The implications of PUT homeostasis through the action of the two oxidases are discussed with respect to stressors, evolution and application in microbe-assisted phytoremediation or bio-augmentation.

  11. Alkylamino derivatives of 4-aminomethylpyridine as inhibitors of copper-containing amine oxidases.

    Science.gov (United States)

    Bertini, Vincenzo; Buffoni, Franca; Ignesti, Giovanni; Picci, Nevio; Trombino, Sonia; Iemma, Francesca; Alfei, Silvana; Pocci, Marco; Lucchesini, Francesco; De Munno, Angela

    2005-02-10

    The first substratelike, reversible inhibitors of different copper amine oxidases (CAOs) with IC50 (M) as low as 2.0 x 10(-8) corresponding to derivatives of 4-aminomethylpyridine with alkoxy (1a-d), alkylthio (2a,b), and alkylamino (3a-e, 4a-j) groups in the positions 3 and 5 have been prepared and studied. The inhibitors 1a-d are active on benzylamine oxidase and semicarbazide-sensitive amine oxidase and are very selective with respect to diamine oxidase, lysyl oxidase, and monoamine oxidases. The inhibitors 2a,b are selective for benzylamine oxidase whereas 2a is also a new type of good substrate of diamine oxidase. The inhibitors 3a-e and 4a-j are substratelike, reversible, nonselective inhibitors of various CAOs including pea seedling amine oxidase and Hansenula polymorpha amine oxidase, whose enzymatic sites are known from X-ray structure determinations. The inhibitors 3b,c and 4b,c are excellent substratelike tools for studies correlating CAOs that afford crystals suitable for X-ray structure determinations with CAOs from mammals.

  12. Exercise Benefits Brain Function: The Monoamine Connection

    OpenAIRE

    Tzu-Wei Lin; Yu-Min Kuo

    2013-01-01

    The beneficial effects of exercise on brain function have been demonstrated in animal models and in a growing number of clinical studies on humans. There are multiple mechanisms that account for the brain-enhancing effects of exercise, including neuroinflammation, vascularization, antioxidation, energy adaptation, and regulations on neurotrophic factors and neurotransmitters. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) are the three major monoamine neurotransmitters that are known...

  13. The Storage Stability of Anthocyanins in Mao (Antidesma thwaitesianum Müll. Arg. Juice and Concentrate

    Directory of Open Access Journals (Sweden)

    Prommakool Arunya

    2016-01-01

    Full Text Available Mao or Makmao (Antidesma thwaitesianum Müll. Arg. is a wild plant found in the northeast of Thailand. Mao is one of fruits which are source of anthocyanins. Mao fruits are used for juice and concentrate which are consumed for healthy drinks. Determination of the kinetic parameters is essential to predict the quality changes and stability of anthocyanins in Mao juice and concentrate that occur during storage. The purpose of this research was to study the degradation of anthocyanins in Mao juice and concentrate during storage at 5, 30 and 37°C for 15 days. The storage stability of Mao anthocyanins was studied in 15°Brix juice and 45°Brix concentrate. The degradation kinetic (k, half-life (t1/2, activation energy (Ea and Q10 values for Mao anthocyanins degradation were determined. The results indicated that analysis of kinetic data for the degradation of anthocyanins followed a first-order reaction. An increase storage temperature from 5 to 30 and 37°C increased k value of anthocyanins in Mao juice and concentrate. Increasing storage temperature decreased t1/2 value of anthocyanins in both concentrations. At 5, 30 and 37°C, the t1/2 of anthocyanins decreased from 35 to 13 and 5 days for Mao juice and 32 to 25 and 21 days for Mao concentrate. The Ea value of the anthocyanins degradation in Mao juice and concentrate were 38.03 and 8.42 kJ/mol, respectively. Q10 values of both Mao juice and concentrate at 30-37°C were higher than those were storaged at 5-30°C. Thus higher stability of anthocyanins was achieved by using concentration and storage at lower temperature.

  14. The MAO NASU Plate Archive Database. Current Status and Perspectives

    Science.gov (United States)

    Pakuliak, L. K.; Sergeeva, T. P.

    2006-04-01

    The preliminary online version of the database of the MAO NASU plate archive is constructed on the basis of the relational database management system MySQL and permits an easy supplement of database with new collections of astronegatives, provides a high flexibility in constructing SQL-queries for data search optimization, PHP Basic Authorization protected access to administrative interface and wide range of search parameters. The current status of the database will be reported and the brief description of the search engine and means of the database integrity support will be given. Methods and means of the data verification and tasks for the further development will be discussed.

  15. MAO-A inhibition profiles of some benzophenone glucosides from Gentiana verna subsp. pontica

    DEFF Research Database (Denmark)

    Kaya, Duygu; Jäger, Anna; Yalçin, Funda N;

    2014-01-01

    Gentiana verna L. subsp. pontica (Soltok.) Hayek, G. pyrenaica L., and G. verna L. subsp. balcanica Pritchard from Turkey were tested for their MAO-A inhibitory effects. A photometric peroxidase linked MAO-A bioassay performed on the H20 extracts prepared from the methanolic extracts of the title...

  16. MAO-A inhibition profiles of some benzophenone glucosides from Gentiana verna subsp. pontica

    DEFF Research Database (Denmark)

    Kaya, Duygu; Jäger, Anna; Yalçin, Funda N

    2014-01-01

    Gentiana verna L. subsp. pontica (Soltok.) Hayek, G. pyrenaica L., and G. verna L. subsp. balcanica Pritchard from Turkey were tested for their MAO-A inhibitory effects. A photometric peroxidase linked MAO-A bioassay performed on the H20 extracts prepared from the methanolic extracts of the title...

  17. Preparation and corrosion resistance of MAO/Ni-P composite coat on Mg alloy

    Science.gov (United States)

    Fan, Xizhi; Wang, Ying; Zou, Binglin; Gu, Lijian; Huang, Wenzhi; Cao, Xueqiang

    2013-07-01

    Microarc oxidation (MAO) coat was designed as an intermediate layer for the electroless plated Ni-P top coat, providing inert surface and necessary hardness for Mg alloy substrate. The composite coat was successfully prepared to improve the corrosion resistance of Mg alloy. The preparation and the characterization of the composite coat were investigated. The results show that the pre-treatment of MAO before electroless plating plays an important role in the deposition of compact composite coat. The activation (by HF solution) makes the MAO coat dense with uniform cracks which supply excellent bonding interface for Ni-P coat. Compared with monolithic MAO or Ni-P coat, the composite coat has excellent corrosion resistance and stable bonding interface. There is main pit corrosion at substrate after the corrosive medium penetrating through the whole coat. With the inert MAO interlayer, the electrochemical corrosion between the Ni-P and substrate is effectively inhibited.

  18. [Concentration of monoamines and activity of several enzymes in the arcuate nucleus of the hypothalamus in young and aging rats during the estrous cycle].

    Science.gov (United States)

    Grantyn', V A

    1976-07-01

    The arcuate nucleus (AN) and the median eminence (ME) of the hypothalamus were investigated in young and ageing female rats. During the estral cycle (EC) the monoamine (MA) content, the monoaminoxidase (MAO), NADP and NAD-diaphorase activities were determined in the AN, and the MA content and the activity of alkaline phosphatase (AP) -- in the ME. In young rats in the proestrus-estrus there was an increase in the activity of the NADP and NAD-diaphorase and of the MA content, but a decrease of the MAO activity. This indicated an intensified function of the nucleus at these stages of the EC. Accumulation of the MA in the ME was noted in the diestrus, while in the proestrus their concentration sharply fell; on the other hand, the activity of the AP was considerably increased. In the ageing rats the dynamics of the indices under study during the EC were largely unchanged. However, the functional activity of the AN proved to increase, and in the ME and elevation of the MA concentration and disturbance of its release from the nerve terminals was seen.

  19. LSP/MAO composite bio-coating on AZ80 magnesium alloy for biomedical application.

    Science.gov (United States)

    Xiong, Ying; Hu, Qiang; Song, Renguo; Hu, Xiaxia

    2017-06-01

    A composite bio-coating was fabricated on AZ80 magnesium (Mg) alloy by using micro-arc oxidation (MAO) under the pretreatment of laser shock peening (LSP) in order to improve the bio-corrosion resistance and the mechanical integrity. LSP treatment could induce grain refinement and compressive residual stress field on the surface of material. MAO bio-coating was grown in alkaline electrolyte with hydroxyapatite (HA, Ca10(PO4)6(OH)2) to improve the biological properties of the material. The microstructure, element and phase composition for untreated based material (BM) and treated samples (LSP layer, MAO bio-coating and LSP/MAO composite bio-coating) were investigated by transmission electron microscopy (TEM), scanning electron microscope (SEM), energy dispersion spectroscopy (EDS) and X-ray diffraction (XRD). Electrochemical tests and slow strain rate tensile (SSRT) tests were used to evaluate the corrosion resistance and the stress corrosion susceptibility in simulated body fluid (SBF). The results indicated that LSP/MAO composite bio-coating can not only improve the corrosion resistance of Mg alloy substrate evidently but also increase the mechanical properties in SBF compared to LSP layer and MAO bio-coating. Mg alloy treated by LSP/MAO composite technique should be better suited as biodegradable orthopedic implants. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Age and Heat Stress Related Changes in Monoamine Contents and Cholinesterase Activity in Some Central Nervous System Regions of Albino Rat Newborns

    Directory of Open Access Journals (Sweden)

    M. Bahgat

    2007-01-01

    Full Text Available The normal monoamine [norepinephrine (NE, epinephrine (E, dopamine (DA and serotonin (5-HT] contents and cholinestrase (chE activity were significantly and gradually increased with age progress between postnatal days 7 and 21 in cerebrum, cerebellum, medulla oblongata and spinal cord of rat newborns. The daily exposure of the newborns to 401C for 2 h induced deteriorated effects and the withdrawal period of 7 days failed to return these altered variables to normal levels. On the other hand, the high temperature exerted its most potent decreased effect on monoamine contents at 21 days old. This decrease may be attributed to the elevated activity of monoamine oxidase and/or the decreased activity of the key enzymes responsible for monoamine synthesis. The chE activity exhibited different effects in the tested CNS regions as a result of high temperature exposure; the enzyme activity was decreased markedly at days 7, 14 and 21 in cerebellum and medulla oblongata and lowered only at days 7 and 14 in cerebrum and at day 14 in spinal cord. The subsequent withdrawal for 7 days beyond day 21 produced marked weakening of effect of high temperature exposure on monoamine contents in all examined CNS regions except NE and 5-HT contents in cerebellum and DA level in medulla oblongata. In spite of this attenuation, the values recorded in the withdrawal group were still significantly lower than the normal levels. On the other hand, the chE activity became more deleteriously affected at day 28 in the treated CNS regions except in the medulla oblongata where it was profoundly ameliorated after the withdrawal period.

  1. Discovery of Monoamine Oxidase A Inhibitors Derived from in silico Docking

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Geunhyeong; Sung, Suhyun; Lee, Younggiu; Kim, Bonggyu; Yoon, Junwie; Lee, Hyeok; Ahn, Joonghoon; Lim, Yoongho [Konkuk Univ., Seoul (Korea, Republic of); Ji, Sangyun [Rural Development Administration, Suwon (Korea, Republic of); Koh, Dongsoo [Dongduk Women' s Univ., Seoul (Korea, Republic of)

    2012-11-15

    MAOA inhibitors (MAOAIs) have been used as antidepressants for over forty years. Iproniazid was introduced in 1957, but it was withdrawn because of hepatotoxicity. Tranylcypromine was developed in the mid-1960s, withdrawn from the market because of problems related to hypertension, then reintroduced for limited usage. Many MAOAIs have been developed and used for treating atypical depression after the failure of other classes of antidepressant drugs such as selective serotonin reuptake inhibitors and tricyclic antidepressants. While iproniazid and tranylcypromine were nonselective MAOAIs, a selective MAOAI, clorgyline, was introduced in the latter half of the 1960s. Recently, more selective and safe MAOAIs, namely moclobemide, toloxatone, and tetrindol, were launched. However, their side effects and activities need further improvement. Therefore, we have made efforts to discover new MAOAIs. In conclusion, even though the number of compounds tested here is not enough for evaluation, the current result demonstrates that phenylpyrazole moiety is not necessary for showing good inhibitory effects. Because benzoflavanones have not previously been reported to act on MAOA as inhibitors, and the inhibitory effect of one of benzo-flavones, 3-(4-methoxyphenyl)-2,3-dihydro-1H-benzo[ f ] chromen-1-one used in this study is comparable to that of clorgyline which is known as MAOA inhibitor,31 our findings are meaningful.

  2. Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer

    Science.gov (United States)

    2013-10-01

    Target for Progression and Metastasis of Prostate Cancer PRINCIPAL INVESTIGATOR: Jean C. Shih, Ph.D. CONTRATING ORGANIZATION...aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services

  3. Linezolid, a novel oxazolidinone antibiotic: assessment of monoamine oxidase inhibition using pressor response to oral tyramine.

    Science.gov (United States)

    Antal, E J; Hendershot, P E; Batts, D H; Sheu, W P; Hopkins, N K; Donaldson, K M

    2001-05-01

    The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the pressor response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the pressor effect. Subjects received linezolid (625 mg bid orally), moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a >30 mmHg increase in systolic blood pressure (SBP) (PD>30), a positive pressor response was defined as a PD>30 index (pretreatment/treatment ratio of PD>30) of > or = 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively. Responses returned to baseline within 2 days of drug discontinuation. The ratio of mean greatest SBP and heart rate at the time of greatest SBP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine-containing foods are not warranted when taking linezolid.

  4. Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer

    Science.gov (United States)

    2015-12-01

    217–31. [PubMed: 22034868] 8. Gao X, Cui Y, Levenson RM, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol...16285907] 11. Wu X, Liu H, Liu J, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots...containing the reaction products was extracted, and radioactivity was determined by liquid scintillation spectroscopy. Microarray data sets. Two PCa

  5. Kinetic mechanism of putrescine oxidase from Rhodococcus erythropolis.

    Science.gov (United States)

    Kopacz, Malgorzata M; Heuts, Dominic P H M; Fraaije, Marco W

    2014-10-01

    Putrescine oxidase from Rhodococcus erythropolis (PuO) is a flavin-containing amine oxidase from the monoamine oxidase family that performs oxidative deamination of aliphatic diamines. In this study we report pre-steady-state kinetic analyses of the enzyme with the use of single- and double-mixing stopped-flow spectroscopy and putrescine as a substrate. During the fast and irreversible reductive half-reaction no radical intermediates were observed, suggesting a direct hydride transfer from the substrate to the FAD. The rate constant of flavin reoxidation depends on the ligand binding; when the imine product was bound to the enzyme the rate constant was higher than with free enzyme species. Similar results were obtained with product-mimicking ligands and this indicates that a ternary complex is formed during catalysis. The obtained kinetic data were used together with steady-state rate equations derived for ping-pong, ordered sequential and bifurcated mechanisms to explore which mechanism is operative. The integrated analysis revealed that PuO employs a bifurcated mechanism due to comparable rate constants of product release from the reduced enzyme and reoxidation of the reduced enzyme-product complex.

  6. MAO-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull

    DEFF Research Database (Denmark)

    Saaby, Lasse; Rasmussen, Hasse Bonde; Jäger, Anna Katharina

    2009-01-01

    and water. The three fractions were tested in a photometric peroxidase linked MAO-A bioassay. The ethyl acetate phase showed the highest MAO-A inhibitory activity. Quercetin was isolated by VLC through bioassay-guided fractionation and purified by re-crystallisation. The structure was elucidated by LC......-MS and (1)H NMR. RESULTS: The IC(50)-value for MAO-A inhibition by quercetin was 18+/-0.2muM in an assay where the IC(50)-value for MAO-A inhibition by clorgylin was 0.2+/-0.02muM. CONCLUSION: The content of quercetin in Calluna vulgaris might explain the reported nerve calming effect of the plant....

  7. Monoamine transporters: insights from molecular dynamics simulations

    Science.gov (United States)

    Grouleff, Julie; Ladefoged, Lucy Kate; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The human monoamine transporters (MATs) facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson’s disease. Inhibition of the MATs is thus an important strategy for treatment of such diseases. The MATs are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS) family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the MATs, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors. PMID:26528185

  8. Old Book, New Lessons: Mao, Osama, and the Global Qutbist Insurgency

    Science.gov (United States)

    2008-03-01

    ideology of some modem insurgents creates a different dynamic.,,87 Ian Beckett Old Book, New Lessons - 20 observed of the Iraqi insurgencies...Studies Institute, 2004), 1. 5 Muckian, "Structural Vulnerabilities", 1. 6 Mao Tse-tung,. Mao Tse-tung on Guerrilla Warfare. Translated by Samuel B...2001), 34. 87 Kilcullen, Counterinsurgency Redux, 5. 88 Ian F. W. Beckett . Insurgency In Iraq: An Historical Perspective. (Carlisle: Strategic Studies

  9. Isolated sulfite oxidase deficiency.

    Science.gov (United States)

    Relinque, B; Bardallo, L; Granero, M; Jiménez, P J; Luna, S

    2015-03-10

    Sulfite oxidase deficiency is an uncommon metabolic disease. Only few cases of its isolated form have been reported in the literature. We report a case of severe neonatal onset. A newborn baby of 41 weeks gestational age, weighted at birth of 3240 grams and had an Apgar score of 6-10-10. Fifty-three hours after being born, the baby started with seizures that were refractory to antiepileptic treatment. Brain function was monitored using a-EEG. Laboratory and imaging tests were performed. All of them were consistent with sulfite oxidase deficiency. The diagnosis was confirmed by genetic testing. We highlight the importance of this disease as part of the differential diagnosis of seizures during the neonatal period, as well as the importance of the therapeutic support based on dietary restrictions. It's also remarkable the possibility of prenatal diagnosis by quantifying enzyme activity and it's also possible carrying out DNA mutational analysis.

  10. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available BACKGROUND: Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. CONCLUSIONS/SIGNIFICANCE: The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  11. A Genetic Basis for Motivated Exercise.

    Science.gov (United States)

    Good, Deborah J; Li, Mengjiao; Deater-Deckard, Kirby

    2015-10-01

    Prior research has demonstrated a genetic basis for motivated exercise, with evidence of a role for nescient helix-loop-helix-2 (NHLH2/Nhlh2). Nhlh2 transcriptionally regulates the monoamine oxidase A (MAO-A) gene. This article examines the evidence for the hypothesis that polymorphisms in NHLH2 or MAO-A contribute to differences in the human motivation for exercise and physical activity. The genetic pathways that link exercise and motivation are discussed.

  12. The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue.

    Science.gov (United States)

    Marusich, Julie A; Antonazzo, Kateland R; Blough, Bruce E; Brandt, Simon D; Kavanagh, Pierce V; Partilla, John S; Baumann, Michael H

    2016-02-01

    In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users.

  13. The Effectiveness of Mao’s Influence Operations at the Beginning of the Chinese Civil War

    Science.gov (United States)

    2014-05-22

    planned operations to convey selected information and indicators to audiences to influence their emotions , motives, objective reasoning, and ultimately...defeat at the hands of the Nationalist Army. Defeated and without support, Mao sought refuge in the mountainous hinterlands of southern and western

  14. Ideology Manipulation Reflected in the Translation of Selected Works of Mao Zedong

    Institute of Scientific and Technical Information of China (English)

    张艳丽; 谢建平

    2009-01-01

    This paper tries to discuss Lefevere's manipulation theory how to manipulate the translation of Selected Works of Mao Zedong (hereafter shortened by Selected Works) through the translation strategy. In the analysis of the translation of Selected Works, the author concludes that the translation of Selected Works is the result of the manipulation of the social-political ideology.

  15. Gandhi and Mao on manual labour in the school: A retrospective analysis

    Science.gov (United States)

    Zachariah, Mathew; Hoffman, Arlene

    1985-12-01

    Mahatma Gandhi's views on relating the world of formal education to the world of work were developed first in his experimental `Tolstoy Farm' in South Africa. On his return to India, Gandhi insisted that a required manual labour component in the curriculum would help regenerate India's village economy, develop in India's children a deeper understanding of India's cultural roots, motivate children to relate `book learning' to life in society, and destroy invidious caste distinctions. The major proposals and suggestions in Gandhi's writing will be discussed in the context of his hopes for using schooling as an agent of progress in India. Mao Ze-Dong's views, on the other hand, were developed in the context of his Yenan experience in the 1930s, i.e. the decision to consolidate a power base in the interior of China before waging a class war against the landlords and capitalists of China. Mao's views were also, to some extent, rooted in the Chinese reality of stagnant, poverty-stricken rural areas. But, Mao's writings indicate that Marxist hopes to relate theory and practice (as understood in dialectical materialism) and to ensure that everyone participated in mental as well as manual labour in a socialist society had led him to formulate his proposals. Both Gandhi's and Mao's views and proposals have been more or less abandoned in India and China respectively. The similar and dissimilar reasons which led to such a fate are examined in this retrospective analysis.

  16. Post-Mao Chinese Literary Women's Rhetoric Revisited: A Case for an "Enlightened" Feminist Rhetorical Theory

    Science.gov (United States)

    Wu, Hui

    2010-01-01

    Identifying the specific complexities and historical context of post-Mao Chinese literary women's rhetoric, along with ways they have been misread, the author argues in general that Western feminist critics need to be cautious about applying their concepts to non-Western women's literature. (Contains 7 notes.)

  17. Specific responses of monoamine neurotransmitters to various acute stressors

    Institute of Scientific and Technical Information of China (English)

    Rongrong He; Guanyu Lin; Yifang Li; Keiich Abe; Xinsheng Yao; Hiroshi Kurihara

    2011-01-01

    This study determined the composition of histamine, serotonin and dopamine using high performance liquid chromatography and electrochemical detection, and compared the changes in monoamine levels in plasma, the cortex and midbrain of mice exposed to acute stressors, such as blood-drawing stimulation or restraint. Results demonstrated that plasma histamine levels were markedly increased when mice were exposed to blood-drawing stimulation and restraint stress. However, serotonin levels decreased in plasma of mice treated with restraint stress, and dopamine levels in plasma had no significant response to the two acute stressors. The three monoamines (histamine, serotonin and dopamine) increased at different degrees in restraint mice, but not in brain regions of blood-drawing stressed mice. Results indicated that histaminergic, serotonergic or dopaminergic systems have their own specific response to different acute stressors.

  18. Designing Modulators of Monoamine Transporters using Virtual Screening Techniques

    Directory of Open Access Journals (Sweden)

    Ole Valente Mortensen

    2015-09-01

    Full Text Available The plasma-membrane monoamine transporters (MATs, including the serotonin (SERT, norepinephrine (NET and dopamine (DAT transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homologue of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and noncompetitive inhibitors have been determined. In addition, several structures of the drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques.

  19. Designing modulators of monoamine transporters using virtual screening techniques

    Science.gov (United States)

    Mortensen, Ole V.; Kortagere, Sandhya

    2015-01-01

    The plasma-membrane monoamine transporters (MATs), including the serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homolog of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and non-competitive inhibitors have been determined. In addition, several structures of the Drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques. PMID:26483692

  20. Food-derived serotonergic modulators: effects on mood and cognition

    NARCIS (Netherlands)

    Hulsken, S.; Martin, A.; Mohajeri, M.H.; Homberg, J.R.

    2013-01-01

    The most frequently described drugs in the treatment of mood disorders are selective serotonin reuptake and monoamine oxidase (MAO) inhibitors, enhancing serotonin levels in the brain. However, side-effects have been reported for these drugs. Because serotonin levels in the brain are dependent on

  1. Drug: D02560 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02560 Drug Brofaromine (INN); Consonar (TN) C14H16BrNO2 309.0364 310.1863 D02560.g... [BR:br08310] Enzymes Oxidoreductases monoamine oxidase A (MAO-A) [HSA:4128] [KO:K00274] Brofaromine D02560 Brofaro

  2. Drug: D01888 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01888 Drug Safrazine hydrochloride (JAN) C11H16N2O2. HCl 244.0979 244.7179 D01888.gif Antidepressant withdr...awal drug monoamine oxidase (MAO) inhibitor [HSA:4128 4129] [KO:K00274] hsa00260(41

  3. Drug: D08349 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08349 Drug Phenelzine (BAN) C8H12N2 136.1 136.1943 D08349.gif Antidepressant, MAO-... metabolism - cytochrome P450 hsa04726(4128+4129) Serotonergic synapse hsa04728(4128+4129) Dopaminergic synapse map07027 Antidepress...drug classification [BR:br08302] Antidepressants Monoamine Oxidase Inhibitors Phe

  4. Food-derived serotonergic modulators: effects on mood and cognition

    NARCIS (Netherlands)

    Hulsken, S.; Martin, A.; Mohajeri, M.H.; Homberg, J.R.

    2013-01-01

    The most frequently described drugs in the treatment of mood disorders are selective serotonin reuptake and monoamine oxidase (MAO) inhibitors, enhancing serotonin levels in the brain. However, side-effects have been reported for these drugs. Because serotonin levels in the brain are dependent on th

  5. Lysyl oxidase in colorectal cancer.

    Science.gov (United States)

    Cox, Thomas R; Erler, Janine T

    2013-11-15

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent advancements in the field of colorectal cancer.

  6. Neuronal monoamine reuptake inhibitors enhance in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

    OpenAIRE

    Coutaux, A F; Mooney, J. J.; Wirth, D. F.

    1994-01-01

    Chloroquine resistance in Plasmodium falciparum was reversed in vitro by the neuronal monoamine reuptake inhibitors and antidepressants desipramine, sertraline, fluoxetine, and norfluoxetine but not by carbamazepine, an antiseizure and mood-stabilizing tricyclic drug resembling desipramine which only weakly inhibits neuronal monoamine reuptake. These findings have important clinical implications for drug combination therapy.

  7. A study on photocatalytic activity of micro-arc oxidation TiO{sub 2} films and Ag{sup +}/MAO-TiO{sub 2} composite films

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, N. [School of Materials Science and Engineering, Changzhou University, Changzhou 213164 (China); Jiangsu Key Laboratory of Materials Surface Science and Technology, Changzhou University, Changzhou 213164 (China); Jiangsu Collaborative Innovation Center of Photovolatic Science and Engineering, Changzhou University, Changzhou 213164, Jiangsu (China); Song, R.G., E-mail: songrg@hotmail.com [School of Materials Science and Engineering, Changzhou University, Changzhou 213164 (China); Jiangsu Key Laboratory of Materials Surface Science and Technology, Changzhou University, Changzhou 213164 (China); Jiangsu Collaborative Innovation Center of Photovolatic Science and Engineering, Changzhou University, Changzhou 213164, Jiangsu (China); Xiang, B.; Li, H.; Wang, Z.X.; Wang, C. [School of Materials Science and Engineering, Changzhou University, Changzhou 213164 (China); Jiangsu Key Laboratory of Materials Surface Science and Technology, Changzhou University, Changzhou 213164 (China); Jiangsu Collaborative Innovation Center of Photovolatic Science and Engineering, Changzhou University, Changzhou 213164, Jiangsu (China)

    2015-08-30

    Highlights: • The optimum voltage and concentration of micro-arc oxidation (MAO) for photocatalytic activity have been studied. • The most superior treatment time and concentration for Ag{sup +} impregnation have been discussed under the optimum MAO condition above. • Mechanism of influence on impregnation time for Ag+MAO-TiO{sub 2} composite films have been well investigated. • MAO-TiO{sub 2} films and Ag+MAO-TiO{sub 2} composite films were compared each other on photocatalytic efficiency. - Abstract: First, micro-arc oxidation (MAO) TiO{sub 2} films have been prepared on pure titanium in a phosphate-based electrolyte, and then the Ag{sup +}/MAO-TiO{sub 2} composite films have been fabricated by Ag{sup +} impregnation in this paper. The microstructure and composition of MAO-TiO{sub 2} films and Ag{sup +}/MAO-TiO{sub 2} composite films have been studied by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS). The photocatalytic activity of both films was evaluated by photocatalytic decolorization of methylene blue (MB) in aqueous solution as a model pollutant under sunlight irradiation simulation with homemade ultraviolet–visible spectroscopy (UV–vis). The results showed that the photocatalytic activity of MAO-TiO{sub 2} films increased with increasing the applied voltage and concentration in a certain scope. The morphology of Ag{sup +}/MAO-TiO{sub 2} composite films were of significantly difference and superior photocatalytic activity compared to the MAO-TiO{sub 2} film. Also, Ag{sup +} impregnation was able to enhance the photocatalytic efficiency of MAO-TiO{sub 2} film.

  8. The kulaks assertion of Mao between the final form of the socialist transformation of agriculture

    Institute of Scientific and Technical Information of China (English)

    陈君锋

    2013-01-01

    In the transition period, Mao's attitudes to the kulak and kulak economy turned a few degrees. This article at-tempts to elaborate on the whole process of saving the rich peasant economy economically, and remaining neutral kulak politically at the formation beginning of the People's Republic, moreover,this article also analyses its causes, in order to understand the initial conditions of the attitude to the kulak policy conversion.

  9. PCT MAO’s Enhanced Performance by Specially Designed Sealers for Superior Service & Environments

    Science.gov (United States)

    2014-11-01

    Micro-arc oxidation (lower energy) • Organo-ceramic sealing • Organic Sealing in Vacuum • Aluminized Steel 2 The PCT Layer Dense Oxide...Functional Layer Intermediate Bonding Layer Substrate 3 PCT Aluminized Steel For MAO Aluminized Steel Facts • Aluminized steel became commercially...reflectivity and corrosion protection. • Traditional Aluminized Steel (ASTM-A463) is hot-dip coated on both sides with an aluminum/silicon alloy coating

  10. Computação biologicamente inspirada aplicada ao estudo da interação da monoamina oxidase e inibidores

    OpenAIRE

    Moraes, Fernanda Pretto

    2011-01-01

    A Doença de Parkinson (DP) é uma doença neurológica intrigante que afeta a população em geral, atacando principalmente nos países em desenvolvimento. Com isso, criase a necessidade da descoberta de agentes terapêuticos para o tratamento da DP. A monoamina oxidase (MAO) é uma enzima de grande importância na neuroquímica, pois catalisa a desaminação oxidativa de aminas biogênicas, como monoaminas neurotransmissoras e neuromoduladoras, assim como monoaminas bioativas exógenas. Com base na especi...

  11. Rasagiline induced hypersexuality in Parkinson's disease.

    Science.gov (United States)

    Reyes, Dennys; Kurako, Kateryna; Galvez-Jimenez, Nestor

    2014-03-01

    Impulse control disorders (ICD) are increasingly recognized in patients with Parkinson's disease (PD), particularly when treated with commonly used dopamine agonists such as pramipexole and ropinirole. Less evident is the possible association between monoamine oxidase inhibitors type B (MAO-B) and the development of ICD. Rasagiline is a second generation MAO-B I inducing moderate symptomatic and possibly disease modifying benefits with apparently good tolerability and safety profile in PD patients. Rasagiline is effective and well tolerated in PD as a monotherapy or in combination with levodopa. Here, we report a patient with PD who developed ICD when treated de novo with MAO-B inhibitors.

  12. Tetrahydropapaveroline in Parkinson's disease and alcoholism: a look back in honor of Merton Sandler.

    Science.gov (United States)

    Collins, Michael A

    2004-01-01

    Although Dr. Merton Sandler's extensive and vigorous research program over the years has been concerned mainly with classical biogenic amines, monoamine oxidase (MAO), and MAO inhibitors, he and his group contributed a significant early Parkinson's disease-related study of a non-classical or "aberrant" biogenic amine. The formation and production of this amine, the dopamine-derived mammalian alkaloid, tetrahydropapaveroline (THP), is in fact dependent on MAO activity. As reviewed here, that study provided the groundwork for and indeed stimulated many later investigations of mammalian alkaloids in numerous laboratories around the world.

  13. Quantum chemical analysis of potential anti-Parkinson agents

    Indian Academy of Sciences (India)

    Nima Razzaghi-Asl; Sara Shahabipour; Ahmad Ebadi; Azam Bagheri

    2015-07-01

    Monoamine oxidases (MAOs) are amine oxidoreductase falvoenzymes that belong to the integral proteins of the outer mitochondrial membrane. MAO exists in two distinct isoforms; MAO-A and MAO-B. Inhibition of MAO-A and MAO-B is important for developing antidepressant and antiparkinson agents, respectively. In the light of the above explanations, detailed structure binding relationship studies on the intermolecular binding components of MAO-B complexes may unravel the way toward developing novel anti-Parkinson agents. In the present contribution, intermolecular binding pattern for a series of experimentally validated 3-arylcoumarin MAO-B inhibitors (1–9) have been elucidated via molecular docking and density functional theory (DFT) calculations. Intermolecular binding energy components could not be analyzed by docking and due to this limitation, quantum mechanical (QM) calculations including functional B3LYP in association with split valence basis set (Def2-SVP) were applied to estimate the ligand-residue binding energies in the MAO-B active site. Moreover; results were interpreted in terms of calculated polarization effects that were induced by individual amino acids of the MAO-B active site. The results of the present study provide an approach to pharmacophore-based modification within the 3-arylcoumarin scaffold for potent MAO-B inhibitors.

  14. Lysyl oxidase in colorectal cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine T

    2013-01-01

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... advancements in the field of colorectal cancer....

  15. Inhibition of in vivo histamine metabolism in rats by foodborne and pharmacologic inhibitors of diamine oxidase, histamine N-methyltransferase, and monoamine oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Hui, J.Y.; Taylor, S.L.

    1985-11-01

    When (/sup 14/C)histamine was administered orally to rats, an average of 80% of the administered radioactivity was recovered in the urine at the end of 24 hr. About 10% of the total dose was excreted via the feces. Analysis of 4-hr urine samples found imidazoleacetic acid to be the predominant metabolite (60.6%), with N tau-methylimidazoleacetic acid (8.6%), N tau-methylhistamine (7.3%), and N-acetylhistamine (4.5%) to be the minor metabolites. Histamine metabolism was inhibited by simultaneous oral administration of aminoguanidine, isoniazid, quinacrine, cadaverine, putrescine, tyramine, and beta-phenylethylamine. The administration of inhibitors resulted in an increased amount of unmetabolized histamine and a decreased amount of metabolites reaching the urine. Pharmacologic inhibitors were found to be more potent and have a longer duration of action than foodborne ones. The inhibitors could potentiate food poisoning caused by histamine by inhibiting its metabolism.

  16. Expression of alternative oxidase in tomato

    Energy Technology Data Exchange (ETDEWEB)

    Kakefuda, M.; McIntosh, L. (Michigan State Univ., East Lansing (USA))

    1990-05-01

    Tomato fruit ripening is characterized by an increase in ethylene biosynthesis, a burst in respiration (i.e. the climacteric), fruit softening and pigmentation. As whole tomatoes ripened from mature green to red, there was an increase in the alternative oxidase capacity. Aging pink tomato slices for 24 and 48 hrs also showed an increase of alternative oxidase and cytochrome oxidase capacities. Monoclonal antibodies prepared to the Sauromatum guttatum alternative oxidase were used to follow the appearance of alternative oxidase in tomato fruits. There is a corresponding increase in a 36kDa protein with an increase in alternative oxidase capacity. Effects of ethylene and norbornadiene on alternative oxidase capacity were also studied. We are using an alternative oxidase cDNA clone from potato to study the expression of mRNA in ripening and wounded tomatoes to determine if the gene is transcriptionally regulated.

  17. The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition.

    Science.gov (United States)

    Wang, J

    2016-11-01

    Plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter that transports a variety of biogenic amines and xenobiotic cations. Highly expressed in the brain, PMAT represents a major uptake2 transporter for monoamine neurotransmitters. At the blood-cerebrospinal fluid (CSF) barrier, PMAT is the principal organic cation transporter for removing neurotoxins and drugs from the CSF. Here I summarize our latest understanding of PMAT and its roles in monoamine uptake and xenobiotic disposition. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  18. 浅析毛泽东的政治建设思想%MAO zedong's political construction thought

    Institute of Scientific and Technical Information of China (English)

    曹宇明

    2011-01-01

    毛泽东作为我国一代伟人,为后人留下了丰厚的精神遗产和巨大的物质遗产。精神遗产主要是指毛泽东的人格魅力和毛泽东思想。毛泽东的政治建设思想对于我们今天的改革开放仍然具有重要的指导意义。%MAO zedong as our country generation great men, left for later generations rich spiritual heritage and huge material heritage. Spiritual heritage is mainly refers to MAO zedong personality charm and MAO zedong thought. MAO zedong thought including content is very wide, MAO's revolutionary ideals, army-building thought, military thought strategy, tactics, united front thought, economic development theory, the conceptions, national policy, foreign policy, and so on. The report of MAO zedong's legacy will briefly introduced and commented, this paper mainly from his personality charm and political construction to make a comment.

  19. Flavoprotein oxidases : classification and applications

    NARCIS (Netherlands)

    Dijkman, Willem P.; de Gonzalo, Gonzalo; Mattevi, Andrea; Fraaije, Marco W.

    2013-01-01

    This review provides an overview of oxidases that utilise a flavin cofactor for catalysis. This class of oxidative flavoenzymes has shown to harbour a large number of biotechnologically interesting enzymes. Applications range from their use as biocatalysts for the synthesis of pharmaceutical compoun

  20. Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

    Science.gov (United States)

    Sitte, Harald H; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

  1. Amphetamines, new psychoactive drugs and the monoamine transporter cycle

    Science.gov (United States)

    Sitte, Harald H.; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects. PMID:25542076

  2. Don DeLillo: Mao II / Underworld / Falling Man. Ed. Stacey Olster.

    Directory of Open Access Journals (Sweden)

    Angeliki Tseti

    2011-10-01

    Full Text Available The latest volume of the Continuum Studies in Contemporary North American Fiction is dedicated to three of the most influential recent novels written by Don DeLillo: Mao II, Underworld and Falling Man. These novels are set in pivotal moments of recent history, the end of the Cold War, the millennium and 9/11 and, so, offer fertile ground for the investigation of themes, such as terrorism, consumerism and globalism, that are dominant in the author’s entire oeuvre; what is more, the contributio...

  3. A lost chance? Birth control policies in the Mao's China (1949-1976

    Directory of Open Access Journals (Sweden)

    Daniel Gomá

    2010-12-01

    Full Text Available This article analyzes the birth control policies in China during the Maoist era (1949- 1976. Considering Chinese and foreign sources, it is explained how the different campaigns of family planning took place and how these campaigns were subjected positively and negatively to the policies of the supreme leader Mao Zedong. Although only the last one had a real impact on the fight against overpopulation, all campaigns helped to promote the necessity of confronting this phenomenon. More importantly, they laid the foundations of the birth control policies that currently take place in China.

  4. Influencing factors of surface roughness of MAO ceramic coating on AZ91D

    Institute of Scientific and Technical Information of China (English)

    DI Shi-chun; PAN Ming-qiang; CHI Guan-xin

    2006-01-01

    To investigate the treating parameters' influence on the surface roughness of the MAO ceramic coating on AZ91D, experiments were implemented in the alkaline electrolyte by using a pulse power source with positive and negative pulse, and the surface roughness was measured and analyzed by using a Times roughness-meter and an optical microscope. The machining parameters' influencing rule on the coating surface roughness was investigated. The result indicates that the influence of all parameters is interactive, while the positive voltage and the electrolyte concentration, or increasing the frequency and the positive and negative voltage ratio are appropriate, the coating surface roughness will be improved.

  5. Chromate reduction by rabbit liver aldehyde oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Banks, R.B.; Cooke, R.T. Jr.

    1986-05-29

    Chromate was reduced during the oxidation of 1-methylnicotinamide chlorine by partially purified rabbit liver aldehyde oxidase. In addition to l-methylnicotinamide, several other electron donor substrates for aldehyde oxidase were able to support the enzymatic chromate reduction. The reduction required the presence of both enzyme and the electron donor substrate. The rate of the chromate reduction was retarded by inhibitors or aldehyde oxidase but was not affected by substrates or inhibitors of xanthine oxidase. These results are consistent with the involvement of aldehyde oxidase in the reduction of chromate by rabbit liver cytosolic enzyme preparations.

  6. Phenolics and Ascorbic Acid Related to Antioxidant Activity of MaoFruit Juice and Their Thermal Stability Study (Review Article

    Directory of Open Access Journals (Sweden)

    Thitiya Sripakdee

    2017-02-01

    Full Text Available Antioxidantand/or anti-aging activities are always linedwith people’s minds as major potential benefits concerning human health in the recent commercial features for an economicworld of foodstuffs and medical uses. Total phenolics includingflavonoids and anthocyanins,and ascorbic acid in the Mao juices areclosely related to their antioxidant activity.Numerous research approaches on these functional foods, in particular the colored fruits and vegetableshave been investigated. Method validation and determination ofthe potential compounds have been increasingly developedwith highly sensitive and selective procedures and applications including thermal stability of the Mao juice.Their antioxidant activities obtained from different assays related to the contents of both phenolics and ascorbic acid in the anthocyanins-richMao juicesin Thailand are reported and discussed.

  7. Historia del maoísmo en América Latina: entre la lucha armada y servir al pueblo

    OpenAIRE

    Miguel Ángel Urrego

    2017-01-01

    El artículo propone elaborar una síntesis de la historia del maoísmo en América Latina. Para el logro de este objetivo, estudiamos las particularidades políticas del maoísmo, el impacto de la Guerra Fría, el cisma del comunismo internacional y el tipo de relaciones que se establecieron entre China y América Latina. Así mismo, se consideran los caminos seguidos para la constitución de las organizaciones, la hegemonía de la versión extremo izquierdista del maoísmo en la década de los ochenta y ...

  8. Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Zhu Shijie

    2010-01-01

    Full Text Available Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18, while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1 from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW and organ weights including heart (HW, lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4% was significantly improved compared with group A, B or D (0% of each, P < 0.05. HW and HW/BW ratio in group C was significantly (P < 0.05 lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

  9. The Chinese Character of Mao Zedong's "Theory of Practice"%毛泽东"实践论"的中国性格

    Institute of Scientific and Technical Information of China (English)

    李维武

    2007-01-01

    @@ "On Practice" is the most important philosophical work Mao Zedong wrote in the 1930s and the core text of his philosophical thought. The related work "On Contradictions" is a further expansion of "On Practice" methodologically. Mao Zedong' s philosophical thinking unfolded with "On Practice" as a marker and its core may be called the "theory of practice."

  10. Mao Zedong and the Populace Education%毛泽东与平民教育

    Institute of Scientific and Technical Information of China (English)

    王征国

    2017-01-01

    Mao Zedong not only engaged himself early into the populace education,but also paid much attention to the equality and popularization of populace education,the female's rights to be educated,the elimination of illiteracy,the diversity of education forms and other issues.He also set forth some principles of populace education,such as combination of education with labor,all-around development of morality,intelligence and physique,combination of intellectuals with the masses,and so forth.Mao Zedong's explorative practices and insights are valuable treasure in the education theory and the education development history of the CPC.%毛泽东不仅较早投身于平民教育,而且重视平民教育的公平与普及、妇女受教育的权利、扫除文盲、办学形式的多样性等问题,他还提出教育与劳动相结合、德智体全面发展、知识分子与工农相结合等平民教育的原则.毛泽东这些具有开拓性意义的实践和真知灼见,是中国共产党教育理论和教育发展史的宝贵财富.

  11. Wettability and corrosion of alumina embedded nanocomposite MAO coating on nanocrystalline AZ31B magnesium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Gheytani, M.; Aliofkhazraei, M., E-mail: maliofkh@gmail.com; Bagheri, H.R.; Masiha, H.R.; Rouhaghdam, A. Sabour

    2015-11-15

    In this paper, micro- and nanocrystalline AZ31B magnesium alloy were coated by micro-arc oxidation method. In order to fabricate nanocrystalline surface layer, surface mechanical attrition treatment was performed and nano-grains with average size of 5–10 nm were formed on the surface of the samples. Coating process was carried out at different conditions including two coating times and two types of electrolyte. Alumina nanoparticles were utilized as suspension in electrolyte to form nanocomposite coatings by micro-arc oxidation method. Potentiodynamic polarization, percentage of porosity, and wettability tests were performed to study various characteristics of the coated samples. The results of scanning electron microscope imply that samples coated in silicate-based electrolyte involve much lower surface porosity (∼25%). Besides, the results of wettability test indicated that the maximum surface tension with deionized water is for nanocrystalline sample. In this regard, the sample coated in silicate-based suspension was 4 times more hydrophilic than the microcrystalline sample. - Highlights: • MAO in phosphate electrolyte needs higher energy as compared to silicate electrolyte. • Less porosity and finer grain size on free surface of the silicate-based coatings. • Observed porosity from top surface of coating shows the effect of the final MAO sparks. • SMAT affects surface roughness and accelerates growth kinetics.

  12. In Vitro and in Vivo Neuroprotective Effects of Walnut (Juglandis Semen in Models of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jin Gyu Choi

    2016-01-01

    Full Text Available Monoamine oxidase (MAO catalyzes the oxidative deamination of monoamines including dopamine (DA. MAO expression is elevated in Parkinson’s disease (PD. An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B participates in the generation of reactive oxygen species (ROS, such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP+- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP+ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.

  13. Lysyl oxidase in cancer research.

    Science.gov (United States)

    Perryman, Lara; Erler, Janine T

    2014-01-01

    Metastasis is the main reason for cancer-associated deaths and therapies are desperately needed to target the progression of cancer. Lysyl oxidase (LOX) plays a pivotal role in cancer progression, including metastasis, and is therefore is an attractive therapeutic target. In this review we will breakdown the process of cancer progression and the various roles that LOX plays has in the advancement of cancer. We will highlight why LOX is an exciting therapeutic target for the future.

  14. On Mao Zedong in His Late Years and Mao Zedong Thought-Inspirations from Reading A Chronicle of Mao Zedong’s Life (1949- 1976)%晚年毛泽东与毛泽东思想--读《毛泽东年谱(1949-1976)》的启示

    Institute of Scientific and Technical Information of China (English)

    雷云

    2015-01-01

    The issue concerning the relationship between Mao and Mao Zedong Thought,in essence,lies in how Mao himself approached and applied Mao Zedong Thought in practice,and how he integrated his own theory with practice. This article explores how Mao in his late years demonstrated himself on this issue. The abundant o-riginal and objective information from the book,A Chronicle of Mao Zedong’s Life (1949-1976),shows that Mao in his late years,could define and treat Mao Zedong Thought realistically and enriched it with a lot of good ideas, but breached from the Thought on some major issues. Judgment on this subject should be based on the historical resolutions made on the Sixth Plenary Session of the 11th CPC Central Committee,and we should keep an objec-tive,comprehensive,fair attitude,avoid subjectivity and partiality,neither demonizing him with total negation,nor deifying him with absolute acceptance.%毛泽东与毛泽东思想的关系问题,说到底是毛泽东在自己的实践中如何对待和运用毛泽东思想的问题,是理论与实践如何在毛泽东身上实现统一的问题。本文要探讨的是晚年毛泽东在这个问题上呈现的状况。从《毛泽东年谱(1949-1976)》提供的大量第一手客观材料看,晚年毛泽东基本上能实事求是界定和对待毛泽东思想,以许多好见解丰富了毛泽东思想,但在一些重大问题上自己违反了毛泽东思想。我们对这个问题的评述,要以十一届六中全会历史决议为根本立论依据,既不能全盘否定把他妖魔化,也不能全盘肯定把他神明化,坚持客观、全面、公正,防止主观性和片面性。

  15. The effect of high-intensity pulsed ion beam on surface structures of MAO film on magnesium alloy AZ31

    Energy Technology Data Exchange (ETDEWEB)

    Han, X.G.; Zhu, F. [Transportation Equipments and Ocean Engineering College, Dalian Maritime University, Dalian 116026 (China); Zhu, X.P.; Lei, M.K. [Surface Engineering Laboratory, School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China); Xu, J.J., E-mail: jjxu@dlmu.edu.cn [Transportation Equipments and Ocean Engineering College, Dalian Maritime University, Dalian 116026 (China)

    2013-07-15

    Micro-arc oxidation (MAO) films on AZ31 magnesium alloy were modified by high-intensity pulsed ion beam (HIPIB) irradiation with ion energy of 300 keV at 200 A/cm{sup 2} with up to 10 shots. Scanning electron microscopy, X-ray diffractometry and micro-hardness testers were used to characterize the surface properties of the irradiated MAO films. The thickness of remelted layer increased and then decreased, and the maximal value of 10 μm was obtained at 200 A/cm{sup 2} with 5 shots. The phase structure of the ablated surface still consisted of Mg{sub 2}SiO{sub 4} and MgO, which are the same as that of the original ones. Surface roughness of the ablated surface increased and then decreased with the increase of shot number. The surface roughness for the original MAO film is about 2.10 μm, it decreased to 1.18 μm with 1 shot irradiation and then increased to 4.13 μm with irradiation shots up to 10. Correspondingly, the surface energy of the ablated surface augmented, resulting in the tedious decrease of static contact angle from 145.9° for original film to 49.7° for the film with 10 shots. The ablation modification enhanced the continuity and compaction of the MAO films on AZ31 magnesium alloy.

  16. A Student-Centered First-Semester Introductory Organic Laboratory Curriculum Facilitated by Microwave-Assisted Synthesis (MAOS)

    Science.gov (United States)

    Russell, Cianán B.; Mason, Jeremy D.; Bean, Theodore G.; Murphree, S. Shaun

    2014-01-01

    An instructional laboratory curriculum for a first-semester introductory organic chemistry course has been developed using microwave-assisted organic synthesis (MAOS). Taking advantage of short reaction times, materials were developed to facilitate collaborative experimental design, analysis, and debriefing of results during the normal laboratory…

  17. Mao and Gandhi: Alternative Paths to National Independence and Social Change. A Unit of Study for Grades 9-12.

    Science.gov (United States)

    Johnson, Donald James; Johnson, Jean Elliott

    This unit of study focuses on the historic period from 1920 to 1966 when China's Mao Zedong and India's Mohandas Gandhi constructed and applied their social and moral visions to their respective nationalist movements. These leaders developed contrasting methods to achieve social change and to establish the goals set for achieving the ideal…

  18. Mysterious MAO : Towards a better structural understanding of Methylalumoxane and the development of well-defined Alumoxanes

    NARCIS (Netherlands)

    Zijlstra, Harmen Sijde

    2016-01-01

    Since its discovery in the early eighties, methylalumoxane (MAO) has grown from an academic serendipity to an industrial commodity. Today it is produced on a large scale and widely used as a cocatalyst for various olefin oligomerization and polymerization processes. Despite years of investigation, n

  19. A Student-Centered First-Semester Introductory Organic Laboratory Curriculum Facilitated by Microwave-Assisted Synthesis (MAOS)

    Science.gov (United States)

    Russell, Cianán B.; Mason, Jeremy D.; Bean, Theodore G.; Murphree, S. Shaun

    2014-01-01

    An instructional laboratory curriculum for a first-semester introductory organic chemistry course has been developed using microwave-assisted organic synthesis (MAOS). Taking advantage of short reaction times, materials were developed to facilitate collaborative experimental design, analysis, and debriefing of results during the normal laboratory…

  20. Riding over Socialism and Global Capitalism: Changing Education Governance and Social Policy Paradigms in Post-Mao China

    Science.gov (United States)

    Mok, Ka Ho

    2005-01-01

    In coping with the challenges of globalization, various reform measures, in the field of social policy, have been initiated in post-Mao China. Strategies such as privatization, marketization, commodification and societalization have been adopted to redefine the relationship between the state, the market and other non-state sectors involved in…

  1. Influence of electrolyte temperature on properties and infrared emissivity of MAO ceramic coating on 6061 aluminum alloy

    Science.gov (United States)

    Al Bosta, Mohannad M. S.; Ma, Kung-Jeng

    2014-11-01

    6061 aluminum alloy was treated by MAO at various temperatures of the alkali silicate electrolyte using pulsed bipolar current mode for ten minutes. The surface microstructures and properties were studied using SEM, EDX, and XRD. The infrared emissivities of the MAO ceramic coatings were measured at the 70 °C using FTIR spectrometer. The electrolyte temperature strongly affected all the surface properties. The MAO alumina ceramics prepared in cold electrolytes have volcano-like and accumulated particles microstructures, while those prepared in hot electrolytes were: rougher, thinner and contained grainy spherical hollow bulgy microstructures with more pore density and more sillimanite and cristobalite phases which enhanced the IR emissivity. Also, the increment of sillimanite and cristobalite phases moved the apparent peaks toward longer wavelengths, and broadened the opaque region of the IR spectra. As a result, the increment of electrolyte temperature from 12.3 °C to 90.5 °C increased the average of LWIR emissivity from 80.4% to 94.4%, respectively, for the MAO ceramic coatings.

  2. The effects of two chronic intermittent stressors on brain monoamines.

    Science.gov (United States)

    Campmany, L; Pol, O; Armario, A

    1996-03-01

    The effects of chronic exposure (27 days) to two different stressors on brain monoaminergic activity was studied in adult male rats. The stressors used were restraint in tubes (RES) and immobilization in wooden boards (IMO). Both chronically stressed and stress naive (control) rats were subjected to 0, 15, and 60 min of the same stressor to which they were chronically exposed. Previous chronic exposure to either RES or IMO significantly reduced ACTH response to the same stressor. Monoaminergic response to these stressors was studied by measuring the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3-methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. The regions studied were: pons plus medulla, midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic exposure to the stressors induced only few changes in the resting levels of the monoamines and their metabolites. In addition, monoaminergic response to the same stressor to which they were chronically exposed was always similar in control and chronically stressed rats. These data indicate that brain NA and 5-HT metabolism is less sensitive than ACTH to the process of habituation to a repeated stressor, at least in the gross areas of the brain analyzed in the present study.

  3. The terminal oxidases of Paracoccus denitrificans

    OpenAIRE

    de Gier, Jan-Willem L.; Lübben, Mathias; Reijnders, Willem N.M.; Tipker, Corinne A.; Slotboom, Dirk-Jan; Van Spanning, Rob J. M.; Stouthamer, Adriaan H.; van der Oost, John

    1994-01-01

    Three distinct types of terminal oxidases participate in the aerobic respiratory pathways of Paracoccus denitrificans. Two alternative genes encoding subunit I of the aa3-type cytochrome c oxidase have been isolated before, namely ctaDI and ctaDII. Each of these genes can be expressed separately to complement a double mutant (ΔctaDI, ΔctaDII), indicating that they are isoforms of subunit I of the aa3-type oxidase. The genomic locus of a quinol oxidase has been isolated: cyoABC. This protohaem...

  4. NEW MATERIALS BY POLYMERIZATION OF OLEFINS AND STYRENE BY METALLOCENE/MAO CATALYSTS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Metallocenes and other transition metal compounds comprise a newgeneration of single site catalysts for the production of precisely designed polyolefins and engineering plastics. The discovery of metallocene methylalumoxane (MAO) catalysts has opened a frontier in the area of polymer synthesis and processing. A great number of symmetric and chiral zirconocenes have been synthesized to give isotactic,syndiotactic,isoblock,or stereoblock polymers with increased impact strength and toughness,better melt characteristics or elasticity,and improved clarity in films. Cycloolefin copolymers (COC) and syndiotactic polystyrene can be produced by metallocene catalysts. These are new types of polymers with special properties and a high potential as engineering plastics. Norbornene-ethene copolymers are most interesting for technical uses because of the easily available monomers. Due to different incorporation values of the cyclic olefin in the copolymer,the glass transition temperature can vary over a wide range and reaches 180 ℃.

  5. Fabrication of ceramic layer on an Al-Si alloy by MAO process

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The MAO (Micro-Arc Oxidation) process is applied to a eutectic Al-Si alloy (Al-12.0%Si-l.0%Cu-0.9%Mg(mass fraction)). The oxide ceramic layer was fabricated with about 220 μm thickness and 3000 Hv micro-hardness. ByXRD (X-ray diffractometry) and DSC (differential scanning calorimetry) analyses, the oxide layer consists of amorphousAl2O3, which is distinct from the results reported by the other researchers. The SEM photographs of such layer show that thelayer is fixed tightly on the substrate alloy. So this alloy can be used in the high temperature and friction environment after itis treated with such process.

  6. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    Science.gov (United States)

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same

  7. Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

    Directory of Open Access Journals (Sweden)

    Kevin D Lominac

    2014-05-01

    Full Text Available Methamphetamine (MA is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5-10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC and prefrontal cortex (PFC is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6 mice revealed short- (1 day, as well as longer-term (21 days, changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high versus low MA drinking (respectively, MAHDR vs. MALDR mice, provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction.

  8. Mitochondrial cytochrome c oxidase deficiency.

    Science.gov (United States)

    Rak, Malgorzata; Bénit, Paule; Chrétien, Dominique; Bouchereau, Juliette; Schiff, Manuel; El-Khoury, Riyad; Tzagoloff, Alexander; Rustin, Pierre

    2016-03-01

    As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.

  9. Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

    Science.gov (United States)

    Abhilash, M; Alex, Manju; Mathews, Varghese V; Nair, R Harikumaran

    2014-05-28

    Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

  10. Brain monoamine metabolism is altered in rats following spontaneous, long-distance running.

    Science.gov (United States)

    Elam, M; Svensson, T H; Thorén, P

    1987-06-01

    Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise.

  11. A kinome wide screen identifies novel kinases involved in regulation of monoamine transporter function

    DEFF Research Database (Denmark)

    Vuorenpää, Anne Elina; Ammendrup-Johnsen, Ina; Jorgensen, Trine N.

    2016-01-01

    cells (CAD) and rat chromocytoma (PC12) cells. Whereas SIK3 likely transcriptionally regulated expression of the three transfected transporters, depletion of PKA C-α was shown to decrease SERT function. Depletion of PrKX caused decreased surface expression and function of DAT without changing protein...... levels, suggesting that PrKX stabilizes the transporter at the cell surface. Summarized, our data provide novel insight into kinome regulation of the monoamine transporters and identifies PrKX as a yet unappreciated possible regulator of monoamine transporter function....... in regulation of monoamine transporter function and surface expression. A primary screen in HEK 293 cells stably expressing DAT or SERT with siRNAs against 573 human kinases revealed 93 kinases putatively regulating transporter function. All 93 hits, which also included kinases previously implicated...

  12. Oxidase-based biocatalytic processes

    DEFF Research Database (Denmark)

    Ramesh, Hemalata; Woodley, John; Krühne, Ulrich

    the reaction species (substrate and product volatility for example) and the process (such as oxygen supply, ability to control pH) and are classified as reaction-related and process-related constraintsrespectively. Although the development of biocatalyst and process engineering tools offers a number...... ofsolutions to overcome the limitations, it is often complicated to identify the key limitation of the system that prevents economic scale-up. Hence, development of a systematic method for identifying the limitations during early-stage development of a biocatalytic process and potentially the order in which...... theyneed to be tackled would offer a valuable tool for process development.Biocatalytic oxidationsare potentially of great value because of theselective chemistry that they offer,resulting in higher yieldscompared to thoseachievable through chemical catalysis. Oxidases areparticularly...

  13. Cucumber Seedling Indoleacetaldehyde Oxidase 1

    Science.gov (United States)

    Bower, Peter J.; Brown, Hugh M.; Purves, William K.

    1978-01-01

    Extracts of light-grown Cucumis sativus L. seedlings catalyzed the oxidation of indole-3-acetaldehyde to indole-3-acetic acid. No added cofactors were required. Inhibitor studies indicated that the enzyme is a metalloflavoprotein. While indole-3-aldehyde, benzaldehyde, and phenylacetaldehyde partially inhibited the oxidation of indole-3-acetaldehyde, suggesting that they may serve as alternative substrates, it is proposed that indoleacetaldehyde is the major substrate in vivo. 2,4-Dichlorophenoxyacetic acid strongly inhibited the indoleacetaldehyde oxidase activity, and it is proposed that this enzyme may be subject in vivo to feedback inhibition by indole-3-acetic acid. The enzyme was activated by brief heating or by treatment with mercaptoethanol. PMID:16660220

  14. Evaluation of magnesium ions release, biocorrosion, and hemocompatibility of MAO/PLLA-modified magnesium alloy WE42.

    Science.gov (United States)

    Lu, Ping; Cao, Lu; Liu, Yin; Xu, Xinhua; Wu, Xiangfeng

    2011-01-01

    Magnesium alloys may potentially be applied as biodegradable metallic materials in cardiovascular stent. However, the high corrosion rate hinders its clinical application. In this study, a new approach was adopted to control the corrosion rate by fabricating a biocompatible micro-arc oxidation/poly-L-lactic acid (MAO/PLLA) composite coating on the magnesium alloy WE42 substrate and the biocompatibility of the modified samples was investigated. The scanning electronic microscope (SEM) images were used to demonstrate the morphology of the samples before and after being submerged in hanks solution for 4 weeks. The degradation was evaluated through the magnesium ions release rate and electrochemical impedance spectroscopy (EIS) test. The biocompatibility of the samples was demonstrated by coagulation time and hemolysis behavior. The result shows that the poly-L-lactic acid (PLLA) effectively improved the corrosion resistance by sealing the microcracks and microholes on the surface of the MAO coating. The modified samples had good compatibility.

  15. Phenolics and Ascorbic Acid Related to Antioxidant Activity of MaoFruit Juice and Their Thermal Stability Study (Review Article)

    OpenAIRE

    Thitiya Sripakdee; Ratana Mahachai; Saksit Chanthai

    2017-01-01

    Antioxidantand/or anti-aging activities are always linedwith people’s minds as major potential benefits concerning human health in the recent commercial features for an economicworld of foodstuffs and medical uses. Total phenolics includingflavonoids and anthocyanins,and ascorbic acid in the Mao juices areclosely related to their antioxidant activity.Numerous research approaches on these functional foods, in particular the colored fruits and vegetableshave been investigated. Method validation...

  16. Evaluation of the Relationship between 5-HTT and MAO Gene Polymorphisms, Mood and Level of Anxiety among Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Elżbieta Grochans

    2014-12-01

    Full Text Available Objective: The aim of this study was to analyze how mood and anxiety level are related to the functional genetic polymorphism in the promoter region of SLC6A4 (5-HTTLPR and the 30-bp VNTR polymorphism in the MAO A promoter region. Methods: The study involved 272 postmenopausal women from Poland. The authors employed the State-Trait Anxiety Inventory for measuring levels of anxiety, the Mood Adjective Check List for measuring mood, and genetic tests. Results: Analysis did not show any statistically significant differences in the mean levels of anxiety, and mood disorders in women in relation to genotypes of the 5-HTTLPR (SLC6A4 polymorphism and the 30-bp VNTR polymorphism in the MAO A promoter region. However, these problems were more severe among women with s/s genotype. In the case of MAO A gene polymorphism, the level of anxiety was higher in women with a 4/4 genotype. Conclusions: The study did not prove the possibility of the identification of homogeneous groups of women with an elevated risk of developing anxiety and mood disorders during the post-menopausal period. Nevertheless, it showed that respondents with s/s genotype of the 44-bp polymorphism in the 5-HTT (SLC6A4 promoter region had the highest average anxiety levels both as a state and as a trait. Furthermore, the analysis of the 30-bp VNTR polymorphism in the MAO A promoter region demonstrated slight differences in anxiety levels between the women, indicating that those with a 4/4 genotype had higher severity of anxiety symptoms.

  17. Evaluation of the Relationship between 5-HTT and MAO Gene Polymorphisms, Mood and Level of Anxiety among Postmenopausal Women

    Science.gov (United States)

    Grochans, Elżbieta; Jurczak, Anna; Szkup, Małgorzata; Samochowiec, Agnieszka; Włoszczak-Szubzda, Anna; Karakiewicz, Beata; Grzywacz, Anna; Brodowska, Agnieszka; Samochowiec, Jerzy

    2014-01-01

    Objective: The aim of this study was to analyze how mood and anxiety level are related to the functional genetic polymorphism in the promoter region of SLC6A4 (5-HTTLPR) and the 30-bp VNTR polymorphism in the MAO A promoter region. Methods: The study involved 272 postmenopausal women from Poland. The authors employed the State-Trait Anxiety Inventory for measuring levels of anxiety, the Mood Adjective Check List for measuring mood, and genetic tests. Results: Analysis did not show any statistically significant differences in the mean levels of anxiety, and mood disorders in women in relation to genotypes of the 5-HTTLPR (SLC6A4) polymorphism and the 30-bp VNTR polymorphism in the MAO A promoter region. However, these problems were more severe among women with s/s genotype. In the case of MAO A gene polymorphism, the level of anxiety was higher in women with a 4/4 genotype. Conclusions: The study did not prove the possibility of the identification of homogeneous groups of women with an elevated risk of developing anxiety and mood disorders during the post-menopausal period. Nevertheless, it showed that respondents with s/s genotype of the 44-bp polymorphism in the 5-HTT (SLC6A4) promoter region had the highest average anxiety levels both as a state and as a trait. Furthermore, the analysis of the 30-bp VNTR polymorphism in the MAO A promoter region demonstrated slight differences in anxiety levels between the women, indicating that those with a 4/4 genotype had higher severity of anxiety symptoms. PMID:25547397

  18. Mao Zedong as the Last Confucian Ruler? The Moral-Didactic Aspect of “Confucian” Art

    Directory of Open Access Journals (Sweden)

    Nataša Vampelj Suhadolnik

    2016-05-01

    Full Text Available The present article deals with the moral-didactic aspect of “Confucian” art, as seen primarily in the form of narrative illustration. In order to legitimize their authority, many rulers used visual media to promote or affirm Confucian social and political values, and thereby presented themselves as ideal Confucian rulers. The article analyses the use of narrative illustration by two exemplary historical figures – the first emperor of the Tang dynasty, Taizong (589–649 and the founder of the Southern Song dynasty, Gaozong (1107–1187 – in order to define the concept of the “Confucian ideal ruler”. Based on this concept, the article then analyses the pictorial propaganda of the great Chinese communist leader, Mao Zedong (1893–1976. Mao also used didactic illustrations, in the form of propaganda posters, to disseminate communist ideology. He implicitly followed the model of the “Confucian ruler”, even if the figure was couched in the symbols of a 20th-century ideology. The article concludes by arguing that Mao Zedong can thus be considered the last “Confucian ideal ruler”.

  19. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines.

    Science.gov (United States)

    Michel, Haidy E; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

    2013-06-07

    Liquorice extract was reported to have nootropic and/or antiamnestic effects. Prepulse inhibition (PPI) of startle response is a multimodal, cross-species phenomenon used as a measure of sensorimotor gating. Previous studies indicated that liquorice/its constituents augmented mouse brain monoamine levels. Increased brain monoamines' transmission was suggested to underlie PPI disruption. However, the effect of antiamnestic dose(s) of the extract on PPI has not been investigated despite the coexistence of impaired memory and PPI deficit in some neurological disorders. The effect of administration of the antiamnestic dose of the extract (150 mg/kg for 7 days) was tested on PPI of acoustic startle response in mice. It resulted in PPI disruption and therefore its effect on monoamines' levels was investigated in a number of mouse brain areas involved in PPI response mediation. Results demonstrated that the extract antiamnestic dose augmented cortical, hippocampal and striatal monoamine levels. It was therefore concluded that liquorice extract (150 mg/kg)-induced PPI deficit was mediated through augmenting monoaminergic transmission in the cortex, hippocampus and striatum. These findings can be further investigated in experimental models for autism, psychosis and Huntington's disease to decide the safety of using liquorice extract in ameliorating memory disturbance in disorders manifesting PPI deficit.

  20. Effects of rhynchophylline on monoamine transmitters of striatum and hippocampus in cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    LUYuan-Fu; XIEXiao-Long; WUQin; WENGuo-Rong; YANGSu-Fen; SHIJing-Shan

    2004-01-01

    AIM To investigate the effects of rhynchophylline ( Rhy on monoamine transmitters and its metabolites in striatum and hippocampus of cerebral ischemic rats. METItODS The cerebral ischemic injury of rat was induced by middle cerebral artery occlusion (MCAO). The extracellular fluid of striatum and hippocampus in cerebral ischemic rats was collected by using

  1. Double-staining techniques allows electrophysiological identification of monoamine-containing neurons.

    Science.gov (United States)

    Audesirk, T E; Audesirk, G J

    1985-08-01

    Electrophysiological recording provides important evidence for positive identification of many neurons in gastropods. We describe a technique which combines intracellular recording and injection of a persistent, non-fluorescent dye (Fast Green) with subsequent histofluorescence treatment using a modification of the wholemount glyoxylic acid procedure developed by Barber (1983) to establish the presence or absence of monoamine transmitters in positively identified single gastropod neurons.

  2. Landslide Hazard Zonation Along NH-39 From Kangpokpi To Mao, Manipur, India

    Directory of Open Access Journals (Sweden)

    TH. DEVALA DEVI

    2011-06-01

    Full Text Available Due to the prevailing high rainfall and complex nature of terrain, hilly areas of Manipur are vulnerable to instability and mass wasting which have been aggravated by rapid pace of anthropogenic activities and high seismicity. To categorize the land surface into areas and arrange them according to degree of actual or potential hazard from landslide or other mass movements on slopes, an effort is made to prepare landslide hazard zonation map along NH-39 from Kangpokpi to Mao, covering an area of 650km2. Based on the hazardousness to landslide the study area has been divided into four different zones. The major part of the study area about 380km2 (58% falls under the category of high risk zone, followed by moderate risk zone covering an area of 152km2, low risk zone (115 km2, and very high hazard zone (3 km2. Such zonation maps are useful for identifying and delineating unstable hazard prone areas so that suitable mitigative measures can be adopted to minimize the hazards. It also helps planners to choose the favorable sites for developmental schemes like road and building constructions.

  3. Polyethylene/Clay Nanocomposites Produced by In Situ Polymerization with Zirconocene/MAO Catalyst

    Directory of Open Access Journals (Sweden)

    Pimpatima Panupakorn

    2013-01-01

    Full Text Available Two commercial nanoclays were used here as catalytic fillers for production of polyethylene (PE and linear low-density polyethylene (LLDPE nanocomposites via in situ polymerization with zirconocene/MAO catalyst. It was found that both types of nanoclays designated as clay A and clay B can improve thermal stability to the host polymers as observed from a thermal gravimetric analysis (TGA. The distribution of the clays inside the polymer matrices appeared good due to the in situ polymerization system into which the clays were introduced during the polymer forming reaction. Upon investigating the clays by X-ray diffractometer (XRD and Fourier transform infrared spectroscopy (FTIR, it was observed that the crucial differences between the two clays are the crystallite sizes (A < B and the amounts of amine group (A < B. The higher amount of amine group in clay B was supposed to be a major reason for the lower catalytic activity of the polymerization systems compared to clay A resulting from its deactivating effect on zirconocene catalyst. However, for both clays, increasing their contents in the polymerization systems reduced the catalytic activity due to the higher steric hindrance occurring.

  4. Influence of phytic acid concentration on coating properties obtained by MAO treatment on magnesium alloys

    Science.gov (United States)

    Zhang, R. F.; Zhang, S. F.; Duo, S. W.

    2009-06-01

    Anodic coatings were prepared by microarc oxidation (MAO) on AZ91HP in a base solution of 10 g/L NaOH with and without the addition of 0-12 g/L phytic acid (C 6H 18O 24P 6). The influences of C 6H 18O 24P 6 and its concentration on the conductivity and breakdown voltage were studied. The morphologies and compositions of anodic coatings were determined by environmental scanning electron microscope (ESEM) and energy dispersive X-ray spectroscopy (EDX). Potentiodynamic polarization test was performed in 3.5 wt.% NaCl solution to evaluate the corrosion resistance of anodic coatings. The results showed that with the increase of C 6H 18O 24P 6 concentration, the solution conductivity decreased while the values of breakdown voltage increased. EDX analysis showed that the coatings formed in solutions with C 6H 18O 24P 6 addition contained Mg, Al, O, C, P and a trance of Na. The addition of C 6H 18O 24P 6 into the base solution was helpful in coating formation and the coatings formed in the solution containing 8 g/L C 6H 18O 24P 6 exhibited the best pore uniformity and corrosion resistance.

  5. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

    OpenAIRE

    Valle, Marta; Ana Elda, Maqueda; Rabella, Mireia; Rodríguez Pujadas, Aina; Antonijoan Arbós, Rosa Maria; Romero Lafuente, Sergio; Alonso López, Joan Francesc; Mañanas Villanueva, Miguel Ángel; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

    2016-01-01

    Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus ß-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimental...

  6. Drug: D00785 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 223.7417 D00785.gif Antidyskinetic; Antiparkinsonian [in combination with levodopa/carbidopa] [DS:H00057] T...YP2D6 [HSA:1565], CYP3A4 [HSA:1576] map07027 Antidepressants map07057 Antiparkinsonian agents map07216 Catec...us system and sensory organs 11 Agents affecting central nervous system 116 Antiparkinson...elegiline hydrochloride (JAN/USP) Antiparkinson Agents Monoamine Oxidase B (MAO-B) Inhibitors Selegiline D00

  7. Drug: D10191 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10191 Drug Safinamide mesylate (USAN) C17H19FN2O2. CH4SO3 398.1312 398.449 D10191....[BR:br08310] Enzymes Oxidoreductases monoamine oxidase B (MAO-B) [HSA:4129] [KO:K00274] Safi...namide D10191 Safinamide mesylate (USAN) CAS: 202825-46-5 PubChem: 135626909 LigandBox: D10191 AT

  8. Maternal factors and monoamine changes in stress-resilient and susceptible mice: cross-fostering effects.

    Science.gov (United States)

    Prakash, Priya; Merali, Zul; Kolajova, Miroslava; Tannenbaum, Beth M; Anisman, Hymie

    2006-09-21

    Genetic factors influence stressor-provoked monoamine changes associated with anxiety and depression, but such effects might be moderated by early life experiences. To assess the contribution of maternal influences in determining adult brain monoamine responses to a stressor, strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) were assessed as a function of whether they were raising their biological offspring or those of the other strain. As adults, offspring were assessed with respect to stressor-provoked plasma corticosterone elevations and monoamine variations within discrete stressor-sensitive brain regions. BALB/cByJ mice demonstrated poorer maternal behaviors than C57BL/6ByJ dams, irrespective of the pups being raised. In response to a noise stressor, BALB/cByJ mice exhibited higher plasma corticosterone levels and elevated monoamine turnover in several limbic and hypothalamic sites. The stressor-provoked corticosterone increase in BALB/cByJ mice was diminished among males (but not females) raised by a C57BL/6ByJ dam. Moreover, increased prefrontal cortical dopamine utilization was attenuated among BALB/cByJ mice raised by a C57BL/6ByJ dam. These effects were asymmetrical as a C57BL/6ByJ mice raised by a BALB/cByJ dam did not exhibit increased stressor reactivity. It appears that stressors influence multiple neurochemical systems that have been implicated in anxiety and affective disorders. Although monoamine variations were largely determined by genetic factors, maternal influences contributed to stressor-elicited neurochemical changes in some regions, particularly dopamine activation within the prefrontal cortex.

  9. Insulin modulates cocaine-sensitive monoamine transporter function and impulsive behavior.

    Science.gov (United States)

    Schoffelmeer, Anton N M; Drukarch, Benjamin; De Vries, Taco J; Hogenboom, François; Schetters, Dustin; Pattij, Tommy

    2011-01-26

    Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [(3)H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [(3)H]norepinephrine in nucleus accumbens slices, but not on that of [(3)H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocaine-sensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

  10. Vanillyl-alcohol oxidase, a tasteful biocatalyst

    NARCIS (Netherlands)

    Heuvel, Robert H.H. van den; Fraaije, Marco W.; Mattevi, Andrea; Laane, Colja; Berkel, Willem J.H. van

    2001-01-01

    The covalent flavoenzyme vanillyl-alcohol oxidase (VAO) is a versatile biocatalyst. It converts a wide range of phenolic compounds by catalysing oxidation, deamination, demethylation, dehydrogenation and hydroxylation reactions. The production of natural vanillin, 4-hydroxybenzaldehyde, coniferyl al

  11. Galactose oxidase nanoaggregates: Preparation and characterization

    OpenAIRE

    Mamta Sharma; Minakshi Sharma

    2016-01-01

    Galctose oxidase nanoaggregates have been prepared by chemical desolvation method involving the crosslinkng agent glutaraldehyde. These enzyme nanoagregates have been characterized by transmission electron microscopy(TEM), UV visible spectroscopy, Fourier transform infrared spectroscopy (FTIR). TEM reveals the globular spherical nanostructured form upto the range of 20nm. UV visible spectroscopy of galactose oxidase nanoaggregates shows maximum absorption peak at 237nm. FTIR spectra obtaine...

  12. Drug: D02562 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ate (USAN) USP drug classification [BR:br08302] Antiparkinson Agents Monoamine Ox...D02562 Drug Rasagiline mesylate (USAN); Azilect (TN) C12H13N. CH4SO3 267.0929 267.344 D02562.gif Antiparkins... cytochrome P450 hsa04726(4129) Serotonergic synapse hsa04728(4129) Dopaminergic synapse map07027 Antidepressants map07057 Antiparkin...sonian agents map07216 Catecholamine transferase inhibit...onian [DS:H00057] ATC code: N04BD02 monoamine oxidase B (MAO-B) inhibitor [HSA:4129

  13. Influence of phytic acid concentration on coating properties obtained by MAO treatment on magnesium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R.F., E-mail: rfzhang-10@163.com [Jiangxi Key Laboratory of Surface Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China) and School of Material Science and Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); Zhang, S.F.; Duo, S.W. [Jiangxi Key Laboratory of Surface Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China); School of Material Science and Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013 (China)

    2009-06-30

    Anodic coatings were prepared by microarc oxidation (MAO) on AZ91HP in a base solution of 10 g/L NaOH with and without the addition of 0-12 g/L phytic acid (C{sub 6}H{sub 18}O{sub 24}P{sub 6}). The influences of C{sub 6}H{sub 18}O{sub 24}P{sub 6} and its concentration on the conductivity and breakdown voltage were studied. The morphologies and compositions of anodic coatings were determined by environmental scanning electron microscope (ESEM) and energy dispersive X-ray spectroscopy (EDX). Potentiodynamic polarization test was performed in 3.5 wt.% NaCl solution to evaluate the corrosion resistance of anodic coatings. The results showed that with the increase of C{sub 6}H{sub 18}O{sub 24}P{sub 6} concentration, the solution conductivity decreased while the values of breakdown voltage increased. EDX analysis showed that the coatings formed in solutions with C{sub 6}H{sub 18}O{sub 24}P{sub 6} addition contained Mg, Al, O, C, P and a trance of Na. The addition of C{sub 6}H{sub 18}O{sub 24}P{sub 6} into the base solution was helpful in coating formation and the coatings formed in the solution containing 8 g/L C{sub 6}H{sub 18}O{sub 24}P{sub 6} exhibited the best pore uniformity and corrosion resistance.

  14. A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

    Directory of Open Access Journals (Sweden)

    Rafael Romero-Calderón

    2008-11-01

    Full Text Available Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

  15. New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates

    Science.gov (United States)

    Li, Guangyue; Yao, Peiyuan; Cong, Peiqian; Ren, Jie; Wang, Lei; Feng, Jinhui; Lau, Peter C. K.; Wu, Qiaqing; Zhu, Dunming

    2016-05-01

    To further expand the substrate range of the cyclohexylamine oxidase (CHAO) from Brevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8 is an irreversible inhibitor of monoamine oxidase and (S)-13 is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of 8 and 13 were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8 and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines.

  16. Antidepressant Drugs Transactivate TrkB Neurotrophin Receptors in the Adult Rodent Brain Independently of BDNF and Monoamine Transporter Blockade

    OpenAIRE

    Tomi Rantamäki; Liisa Vesa; Hanna Antila; Antonio Di Lieto; Päivi Tammela; Angelika Schmitt; Klaus-Peter Lesch; Maribel Rios; Eero Castrén

    2011-01-01

    BACKGROUND: Antidepressant drugs (ADs) have been shown to activate BDNF (brain-derived neurotrophic factor) receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their ne...

  17. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

    OpenAIRE

    Erickson, J.D.; Schafer, M K; Bonner, T I; Eiden, L. E.; Weihe, E.

    1996-01-01

    A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpr...

  18. On the Relationship between Traditional Culture and MAO Zedong's Philosophy%试论传统文化与毛泽东哲学思想的关系

    Institute of Scientific and Technical Information of China (English)

    曾婷

    2015-01-01

    中国传统文化是毛泽东哲学思想形成的重要理论来源,原因是:从毛泽东本人的读书经历来看,毛泽东一生读得最多的是中国传统文化书籍并深受其影响;毛泽东对中国传统文化有正确的批判继承的态度、毛泽东哲学思想中蕴含着"实事求是""一分为二""知行合一""民本主义"等古代哲学的观点.%Chinese traditional culture is an important theoretical source of the philosophy of MAO Zedong. The reason is that from the point of view of Mao's own reading experience. MAO Zedong read the most books on Chinese traditional culture, and impacted much. MAO Zedong on Chinese traditional culture have correct criticism following the bearing attitude;the philosophy of MAO Zedong thought contains a view of ancient philosophy of "seeking truth from facts","one divides into two","the unity of knowledge and action"and"humanism".

  19. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    Science.gov (United States)

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

  20. Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.

    Science.gov (United States)

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-06-17

    Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland.

  1. Changes in free amino acid and monoamine concentrations in the chick brain associated with feeding behavior.

    Science.gov (United States)

    Tran, Phuong V; Chowdhury, Vishwajit S; Nagasawa, Mao; Furuse, Mitsuhiro

    2015-01-01

    Domesticated chicks are precocial and therefore have relatively well-developed feeding behavior. The role of hypothalamic neuropeptides in food-intake regulation in chicks has been reported for decades. However, we hypothesized that nutrients and their metabolites in the brain may be involved in food intake in chicks because these animals exhibit a very frequent feeding pattern. Therefore, the purpose of this study was to examine the feeding behavior of chicks as well as the associated changes in free amino acid and monoamine concentrations in the chick brain. The feeding behavior of chicks was recorded continuously for 6 h. The next day, brain and blood samples were collected when the chicks either attempted to have food (hungry group) or turned food down (satiated group), in order to analyze the concentrations of the free amino acids and monoamines. We confirmed that the feeding behavior of neonatal chicks was characterized by short resting periods between very brief times spent on food intake. Several free amino acids in the mesencephalon were significantly lower in the satiated group than in the hungry group, while l-histidine and l-glutamine were significantly higher. Notably, there was no change in the free amino acid concentrations in other brain regions or plasma. As for monoamines, serotonin and norepinephrine were significantly lower in the mesencephalon of the hungry group compared with the satiated group, but 5 hydroxyindolacetic acid (5-HIAA) was higher. In addition, serotonin and norepinephrine levels were significantly higher in the brain stem of the hungry chicks compared with the satiated group, but levels of 5-HIAA and homovanillic acid were lower. Levels of both dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid, were significantly higher in the diencephalon and telencephalon of the chicks in the hungry group. In conclusion, the changes in the free amino acids and monoamines in the brain may have some role in the feeding behavior of

  2. Altered monoamine and acylcarnitine metabolites in HIV-positive and HIV-negative subjects with depression

    Science.gov (United States)

    Cassol, Edana; Misra, Vikas; Morgello, Susan; Kirk, Gregory D.; Mehta, Shruti H.; Gabuzda, Dana

    2015-01-01

    Background Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood. Methods The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across three independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R. Results Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of IFN responses, suggesting inter-relationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection. Conclusions Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for

  3. Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters.

    Science.gov (United States)

    Petersen, Mikkel Due; Boye, Søren Valdgård; Nielsen, Erik Holm; Willumsen, Jeanette; Sinning, Steffen; Wiborg, Ove; Bols, Mikael

    2007-06-15

    A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with Ki values ranging from 0.1 to 1000 microM.

  4. 论毛泽东整风思想的发展历程%The Analysis on the Development Process of Mao Zedong Consolidating and Rectification Party Thought

    Institute of Scientific and Technical Information of China (English)

    谈家水

    2012-01-01

    毛泽东整风思想是毛泽东建党思想的重要组成部分。结合中国共产党成长的历史,文章将毛泽东整风思想的发展历程大体划分为萌芽、初步形成、成熟、发展和曲折五个阶段,并分别进行了详细阐述。%Mao Zedong consolidating and rectification party thought is the important component of Mao Ze- dong party - building thought. Based on the history of the Chinese communist party growth. This article roughly divided the development process of Mao Zedong consolidating and rectification party thought into five stages which are germination, preliminary formation, development , Mature and twists, and explants the five stages in details.

  5. A proteomics study reveals a predominant change in MaoB expression in platelets of healthy volunteers after high protein meat diet

    DEFF Research Database (Denmark)

    Zellner, Maria; Babeluk, Rita; Jakobsen, Lene Holm

    2011-01-01

    and the shortened reaction time (cognitive function) which is in accordance with reports that dementia patients show increased MaoB activity. Plasma vitamin B(12) concentration was increased by the HP diet and correlates inversely with platelet MaoB expression (r = -0.35; P ... showed improved cognitive function and counteract well-known dementia biomarkers such as platelet MaoB and components of the methylation cycle such as vitamin B(12) and homocysteine....... for neurons. The study individuals were assigned to either a UP diet (15% energy) or a HP diet (30% energy) for 3 weeks with controlled intake of food and beverages. Blood samples were taken along with measurements of cognitive functions at the beginning and at the end of the intervention period. Among 908...

  6. Monoamine fluctuations during the reproductive cycle of the Pacific lion's paw scallop Nodipecten subnodosus.

    Science.gov (United States)

    López-Sánchez, J Armando; Maeda-Martínez, Alfonso N; Croll, Roger P; Acosta-Salmón, Héctor

    2009-11-01

    The Pacific lion's paw scallop Nodipecten subnodosus has been one of the most important commercial species of mollusc in the Baja California peninsula in Mexico since 1990. This species is a functional hermaphrodite with tropical and sub-tropical distributions and experiences wide annual temperature oscillations influencing its physiological functions. We determined norepinephrine (NE), dopamine (DA), and serotonin (5-HT) concentrations in different organs (female and male gonads, digestive gland, adductor muscle, gill, mantle, and foot) of N. subnodosus, at 6 reproductive stages (resting, initial, maturing, mature, partially spent and fully spent). Monoamine concentrations were determined by HPLC fitted with an electrochemical detector. Results indicated that monoamine concentrations increased during maturing stage, peaked at mature stage and declined after spawning. NE concentrations were higher than the rest of monoamines followed by DA, and 5-HT. NE was present in all organs at all reproductive stages. DA concentrations were higher in the gill and digestive gland during all stages. 5-HT was only detectable in the male gonadic portion at all stages except at spent stage. NE was the most abundant neurotransmitter found in the female gonad of N. subnodosus, while 5-HT was the most abundant neurotransmitter found in the male gonad. Furthermore, these two neurotransmitters accumulated in the respective gonad tissues during the initial reproductive stages I to IV and then declined after spawning (stages V and VI). This suggests that this species utilized different neurotransmitters specific for each gender and that this utilization was related to the reproductive cycle.

  7. Altered serous levels of monoamine neurotransmitter metabolites in patiens with refractory and non-refractory depression

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Yanxia Zhang; Jianxia Yang; Min Hu; Yueqi Zhang; Xia Liang

    2012-01-01

    The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression (TRD) and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

  8. multicopper oxidases important for human iron metabolism

    Directory of Open Access Journals (Sweden)

    Diana Wierzbicka

    2014-01-01

    Full Text Available Multi-copper oxidases are a group of proteins which demonstrate enzymatic activity and are capable of oxidizing their substrates with the concomitant reduction of dioxygen to two water molecules. For some multi-copper oxidases there has been demonstrated ferroxidase activity which is related to their specific structure characterized by the presence of copper centres and iron-binding sites. Three multi-copper oxidases have been included in this group: ceruloplasmin, hephaestin and zyklopen. Multi copper oxidases which are expressed in different tissues are capable of oxidizing a wide spectrum of substrates. Multi-copper oxidases are capable of oxidizing a wide spectrum of substrates. Ceruloplasmin exhibits antioxidant activity as well as being involved in many other biological processes. The observations of phenotypic effects of absence or low expression of multi-copper ferroxidase-coding genes suggest that the main role of these proteins is taking part in iron metabolism. The main role of ceruloplasmin in iron turnover is oxidizing Fe2+ into Fe3+, a process which is essential for iron binding to transferrin (the main iron-transporting protein, as well as to ferritin (the main iron-storage protein. The function of hephaestin as ferroxidase is essential for iron binding to apotransferrin in the lamina propria of the intestinal mucosa, a process that is important for further transport of iron to the liver by the portal vein. Available data indicate that zyklopen is responsible for the placental iron transport. The presence of three multi-copper oxidases with ferroxidase activity emphasizes the significance of oxidation for iron metabolism. The distribution of multi-copper ferroxidases in many tissues ensures the proper iron turnover in the body as well as preventing toxic effects related to the presence of Fe2+ ions. These ions contribute to generation of free radicals, including the highly reactive hydroxyl radical, through the Fenton and Haber

  9. Ability of Kocuria varians LTH 1540 To Degrade Putrescine: Identification and Characterization of a Novel Amine Oxidase.

    Science.gov (United States)

    Callejón, Sara; Sendra, Ramón; Ferrer, Sergi; Pardo, Isabel

    2015-04-29

    This work describes the identification and characterization of an amine oxidase from Kocuria varians LTH 1540 (syn. Micrococcus varians) primarily acting on putrescine. Data from MALDI-TOF MS/MS and the identification of Δ(1)-pyrroline as degradation product from putrescine indicate that the enzyme is a flavin-dependent putrescine oxidase (PuO). Properties of partially purified enzyme have been determined. The enzyme oxidizes diamines, putrescine and cadaverine, and, to a lesser extent, polyamines, such as spermidine, but not monoamines. The kinetic constants (Km and Vmax) for the two major substrates were 94 ± 10 μM and 2.3 ± 0.1 μmol/min·mg for putrescine and 75 ± 5 μM and 0.15 ± 0.02 μmol/min·mg for cadaverine. Optimal temperature and pH were 45 °C and 8.5, respectively. Enzyme was stable until 50 °C. K. varians PuO is sensitive to human flavin-dependent amine oxidase inhibitors and carboxyl-modifying compounds. The new enzyme has been isolated from a bacterial starter used in the manufacture of fermented meat. One of the problems of fermented foods or beverages is the presence of toxic biogenic amines produced by bacteria. The importance of this works lies in the description of a new enzyme able to degrade two of the most abundant biogenic amines (putrescine and cadaverine), the use of which could be envisaged to diminish biogenic amines content in foods in the future.

  10. VINYL POLYMERIZATION OF NORBORNENE CATALYZED BY[2-(2-BENZIMIDAZOLYL)-6-((1-ARYLIMINOETHYL)PYRIDYL)]NICKEL CHLORIDE/MAO SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Qi-song Shi; Wei-wei Zuo

    2008-01-01

    The catalytic system of[2-(2-benzimidazolyl)-6-((1-arylirninoethyl)pyridyl)]nickel chloride/MAO (methylalu-minoxane)was found to be good active for vinyl polymerization of norbornene and provided polymers with relative narrow molecular distributions.Various reaction parameters,such as the ratios of nickel precursor to MAO or monomer norbornene,and the nature of the ligands in complexes were carefully investigated to realize their effects on the catalytic activities,polymer molecular weight and molecular weight distributions.

  11. BANGUNAN TINGGI MULTI FUNGSI SEBAGAI SINTESIS ARSITEKTUR DAN STRUKTUR Studi Analisis Jin Mao Tower Grand Hyatt Shanghai

    Directory of Open Access Journals (Sweden)

    Jimmy Priatman

    2005-01-01

    Full Text Available More than two decades, after the emerging of post- modern architecture, the split between construction technology and cultural expression in architecture appeared to become wider and wider. With the exception of a few "high-tech" buildings, the unity of art and applied science (technology in design seems facing challenges. It is interesting to see how fast and unexpectedly the situation has changed. Many factors and people played a role in this reversal, many new buildings demonstrate that utilitarian artifacts do not have to be oppressive to creativity but can evoke new innovation. One of the most significant contributors was JIN MAO TOWER at Shanghai, China. The paper analyses this building as a genuine synthesis of rational intelligence with art poetry that is still possible. Abstract in Bahasa Indonesia : Lebih dari dua dekade setelah timbulnya arsitektur pasca modern, pemisahan antara tekknologi konstruksi dan ekspresi kultural dalam arsitektur menjadi semakin lebar. Dengan perkecualian beberapa gedung "high-tech", kesatuan antara seni dan teknologi dalam tahap desain terlihat menghadapi tantangan tantangan. Tetapi menarik untuk diamati bahwa situasi telah berubah. Banyak faktor dan tokoh tokoh arsitek memegang peranan penting dalam perubahan ini, banyak bangunan bangunan baru mendemontrasikan bahwa artefak fungsionil tidak bearti menindas kreativitas namun dapat membangkitkan inovasi baru. Salah satu kontributor yang sangat penting adalah JIN MAO TOWER di Shanghai-China. Makalah ini membahas bangunan tersebut sebagai sintesis orijinal yang masih memungkinkan antara kecerdasan rasional dengan puisi seni arsitektur. Kata kunci: Sintesis.

  12. 21 CFR 866.2420 - Oxidase screening test for gonorrhea.

    Science.gov (United States)

    2010-04-01

    ... Section 866.2420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2420 Oxidase... ingredient that will react with cytochrome oxidase. When cytochrome oxidase is present, the swab turns a dark...

  13. Bilirubin Oxidase Activity of Bacillus subtilis CotA

    OpenAIRE

    Sakasegawa, S; Ishikawa, H.; Imamura, S.; Sakuraba, H.; Goda, S.; Ohshima, T.

    2006-01-01

    The spore coat protein CotA from Bacillus subtilis was previously identified as a laccase. We have now found that CotA also shows strong bilirubin oxidase activity and markedly higher affinity for bilirubin than conventional bilirubin oxidase. This is the first characterization of bilirubin oxidase activity in a bacterial protein.

  14. THERMOSTABILITY OF RESPIRATORY TERMINAL OXIDASES IN THE LIPID ENVIRONMENT

    NARCIS (Netherlands)

    Elferink, Marieke G.L.; Bosmal, Tjibbe; Lolkema, Juke S.; Gleiszner, Michael; Driessen, Arnold J.M.; Konings, Wil N.

    1995-01-01

    The effect of the lipid environment on the thermostability of three respiratory terminal oxidases was determined. Cytochrome-e oxidase from beef heart and Bacillus stearothermophilus were used as representative proteins from mesophilic and thermophilic origin, respectively. Quinol oxidase from the a

  15. Occurrence and Biocatalytic Potential of Carbohydrate Oxidases.

    NARCIS (Netherlands)

    Hellemond, van E.W.; Leferink, N.G.H.; Heuts, D.P.H.M.; Fraaije, M.W.; Berkel, van W.J.H.

    2006-01-01

    Carbohydrate oxidases are found in all kingdoms of life but are mostly found in fungi. Their natural role is not always clear. Usage of molecular oxygen as electron acceptor is not a logical choice when the enzyme is part of a catabolic pathway. This chapter provides an overview of the occurrence

  16. A colorimetric assay for cytokinin oxidase.

    Science.gov (United States)

    Libreros-Minotta, C A; Tipton, P A

    1995-11-01

    A simple and rapid colorimetric assay for cytokinin oxidase is described. The assay is based on the formation of a Schiff base between the enzymatic reaction product 3-methyl-2-butenal and p-aminophenol. The assay is effective in the submicromolar concentration range and can be used in crude plant extracts as well as in more highly purified preparations.

  17. Spectrophotometric Assay of Immobilized Glucose Oxidase

    Directory of Open Access Journals (Sweden)

    Nojan Noorbehesht

    2016-06-01

    Full Text Available Enzyme results in change the substrate of product. Each enzyme may act on specific substrates, resulting in product or different products. The enzyme glucose oxidase (GOX is a bio catalyst. It accelerates the process of transforming glucose into hydrogen peroxide (H2O2 . These enzymes are used in the chemical industry, food industry, cosmetics and kits for diagnosis of glucose. There are many researches about immobilizations of Glucose Oxide to increase specifications such as repeated use, recovery, stability, shelf life and other features In this work, glucose oxidase enzyme using covalent bonding is placed on the carrier of carbon nanotubes. In this study, multi-walled carbon nanotubes have been used as adsorbents. Also, carbon nanotubes have been functionalized by sulfuric acid and nitric acid with a high concentration. Glucose oxidase is a biological biocatalyst enzyme. It accelerates changing glucose to H2O2. This enzyme is used in the chemical industry, food industry, cosmetics and glucose diagnostic kits. For example, as a result of ongoing research working focuses on the development of glucose biosensors, GOX in practice as standard enzyme has been revealed for immobilization of oxidative enzyme.GOX correct fixation on the MWNTs carrier is a way to reuse enzyme and miniature of biosensor devices and structures. In this study, a spectrophotometer was used to determine the absorbance of the enzyme glucose oxidase (GOX to review its activities after stabilizing the carbon nanotubes.

  18. Lysyl oxidase mediates hypoxic control of metastasis

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Giaccia, Amato J

    2006-01-01

    Hypoxic cancer cells pose a great challenge to the oncologist because they are especially aggressive, metastatic, and resistant to therapy. Recently, we showed that elevation of the extracellular matrix protein lysyl oxidase (LOX) correlates with metastatic disease and is essential for hypoxia...

  19. Structure-function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family.

    Science.gov (United States)

    Yin, DeLu Tyler; Urresti, Saioa; Lafond, Mickael; Johnston, Esther M; Derikvand, Fatemeh; Ciano, Luisa; Berrin, Jean-Guy; Henrissat, Bernard; Walton, Paul H; Davies, Gideon J; Brumer, Harry

    2015-12-18

    Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6-oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure-function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-à-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications.

  20. CHARACTERIZATIONS OF DLC/MAO COMPOSITE COATINGS ON AZ80 MAGNESIUM ALLOY%镁基表面微弧氧化/类金刚石膜的性能表征

    Institute of Scientific and Technical Information of China (English)

    杨巍; 汪爱英; 柯培玲; 蒋百灵

    2011-01-01

    利用MgO多孔膜结构取代传统制备DLC膜所需的金属过渡层(如Ti),采用离子束复合磁控溅射技术制备出了DLC/MAO/AZ80膜基系统,并通过与MAO/AZ80,DLC/Ti/MAO/AZ80及DLC/Ti/AZ80对比,系统研究了此类膜基系统的表面微观形貌、租糙度、纳米压痕行为、摩擦学特性及电化学性能.结果表明:MgO多孔膜表面沉积DLC膜使其粗糙度减小,硬度增加,而弹性模量与MgO多孔膜相差较小;借助表层微孔特征及DLC膜的润滑特性,使得DLC/MAO/AZ80膜基系统的平均摩擦系数、磨痕宽度与传统的DLC/Ti/AZ80膜基系统相当,并进一步制备出了具有最小平均摩擦系数和磨痕宽度的DLC /Ti/MAO/AZ80膜基系统;由于MgO多孔膜结构的极化阻力使得MAO/AZ80,DLC/MAO/AZ80和DLC/Ti/MAO/AZ80膜基系统的耐蚀性均明显优于DLC/Ti/AZ80.%Diamond-like carbon (DLC) coating has been widely used to modify the surface mechanical and tribological properties of materials. In most cases, a metallic buffer (e.g., Ti) is used as an interlayer between DLC coating and the substrate to improve the adhesion. In this work, the DLC coating was deposited on the AZ80 Mg alloy substrate using ion beam deposition technique. Specially, a pretreatment of microarc oxidation (MAO) was applied to the Mg alloy substrates to form the DLC/MAO composite coating instead of the metallic interlayer process. As a comparation, the DLC/Ti/MAO and DLC/Ti composite coatings were also deposited on the substrates. The surface morphology and roughness, mechanical, tribological and corrosion properties of the as-deposited coatings were studied. The results indicated that the DLC/MAO composite coating could significantly improved the hardness and wear resistance of the Mg alloy substrates compared with the MAO monolayer. Although the surface roughness of the DLC/MAO coating showed an increase due to the micropores of the MAO coating surface, the friction coefficient and the wear tracks exhibited a

  1. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats.

    Science.gov (United States)

    Xue, Rui; He, Xin-Hua; Yuan, Li; Chen, Hong-Xia; Zhang, Li-Ming; Yong, Zheng; Yu, Gang; Fan, Shi-Yong; Li, Yun-Feng; Zhong, Bo-Hua; Zhang, You-Zhi

    2016-01-01

    Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS) model. Results in pharmacological models indicated that acute administration of 071031B at 5-20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo.

  2. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats

    Directory of Open Access Journals (Sweden)

    Rui Xue

    2016-01-01

    Full Text Available Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS model. Results in pharmacological models indicated that acute administration of 071031B at 5–20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo.

  3. Status and Advances of Researches on GA 20-oxidases

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Chen Xiaoyang; Li Hui; Guo Hai

    2003-01-01

    GA 20-oxidase, the most important limiting enzyme, can catalyze a series of oxidization of GA biosynthesis pathwayfrom GA12 to GA9 and from GA53 to GA20 in the higher plants. This paper reviews the studies on the characters of GA 20-oxidase,the gene and the protein of GA 20-oxidase and the regulation of GA 20-oxidase gene expression in recent years. At the same time,the prospects for the gene transformation of GA 20-oxidase in agriculture, forestry and horticulture are also discussed.

  4. Speech at the Meeting Commemorating the 50th Anniversary of Chairman MAO Ze-dong's Important Instruction on Western Medicine Doctors Learning Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhu

    2009-01-01

    @@ Respected leaders, distinguished guests, venerable seniors and comrades, Today, the Meeting Commemorating the 50th Anniversary of Chairman MAO Ze-dong's Important Instructions on Western Medicine Doctors Learning Traditional Chinese Medicine was inaugurated by the Chinese Association of Integrative Medicine, and it is also an important occasion to review the past and look forward to the future.

  5. Metallocene-catalyzed ethylene−α-olefin isomeric copolymerization: A perspective from hydrodynamic boundary layer mass transfer and design of MAO anion

    KAUST Repository

    Adamu, Sagir

    2015-11-28

    This study reports a novel conceptual framework that can be easily experimented to evaluate the effects of hydrodynamic boundary layer mass transfer, methylaluminoxane (MAO) anion design, and comonomer steric hindrance on metallocene-catalyzed ethylene polymerization. This approach was illustrated by conducting homo- and isomeric copolymerization of ethylene with 1-hexene and 4-methyl-1-pentene in the presence of bis(n-butylcyclopentadienyl) zirconium dichloride (nBuCp)2ZrCl2, using (i) MAO anion 1 (unsupported [MAOCl2]−) and pseudo-homogeneous reference polymerization, and (ii) MAO anion 2 (supported Si−O−[MAOCl2]−) and in-situ heterogeneous polymerization. The measured polymer morphology, catalyst productivity, molecular weight distribution, and inter-chain composition distribution were related to the locus of polymerization, comonomer effect, in-situ chain transfer process, and micromixing effect, respectively. The peak melting and crystallization temperatures and %crystallinity were mathematically correlated to the parameters of microstructural composition distributions, melt fractionation temperatures, and average lamellar thickness. These relations showed to be insightful. The comonomer-induced enchainment defects and the eventual partial disruption of the crystal lattice were successfully modeled using Flory and Gibbs–Thompson equations. The present methodology can also be applied to study ethylene−α-olefin copolymerization, performed using MAO-activated non-metallocene precatalysts.

  6. [Comrade Mao Ze-dong's contribution to Marxist theory on population--in commemoration of the 60th anniversary of the birth of the Chinese Communist Party].

    Science.gov (United States)

    Wen, T Z

    1981-07-01

    Is it good or bad to have a large population in China? Comrade Mao Ze-dong said "it is good and it is also bad." Our population is an asset, and we should use this asset and wisdom in our nation's "Four Modernizations" program. On the other hand we should control the population growth and reduce the resulting burden. Marxism recognizes 2 types of production, material production and human production. Both are interrelated, mutually dependent, and beneficial. Comrade Mao criticized concepts and practices that disregard the interrelationship of these 2 types of production. According to Comrade Mao both types of production should be included in the national economic plan, and the proportions of material production and human production should be the basic proportions of our socialistic economic development. Comrade Mao mentioned that population growth should be planned to fit and benefit social development. He suggested establishment of a series of family planning offices or committees to study and implement the family planning program, to develop a longterm plan, to consider the people's wishes in family planning, to meet the people's requirements and desires, to educate people about family planning, and to recommend government funds for the program.

  7. The ligand redox behavior and role in 1,2-bis[(2,6-diisopropylphenyl)imino]-acenaphthene nickel-TMA(MAO) systems for ethylene polymerization.

    Science.gov (United States)

    Gao, Wei; Xin, Lan; Hao, Zhiqiang; Li, Guodong; Su, Ji-Hu; Zhou, Lijing; Mu, Ying

    2015-04-25

    The BIAN ligands in Brookhart catalysts were proved to be redox-active during the catalyst activation with alkylaluminum or MAO, and the neutral catalytically active species with a radical anionic BIAN rather than the cationic ones with a neutral BIAN ligand were confirmed to be formed in the catalytic system.

  8. EFFECT OF CROSSLINKING ON MITOCHONDRIAL CYTOCHROME c OXIDASE

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, Maurice; Packer, Lester

    1979-12-01

    Purified and reconstituted cytochrome {und c} oxidase and mitochondria were crosslinked with biimidates in the presence and absence of cytochrome {und c}. These experiments indicate that oxidase subunit interactions are required for activity and that cytochrome {und c} mobility may be required for electron transport activity. Biimidate treatment of purified and reconstituted oxidase crosslinks all of the oxidase protomers except subunit I when {ge} 20% of the free amines are modified and inhibits steady state oxidase activity. Transient kinetics of ferrocytochrome {und c} oxidation and ferricytochrome {und a} reduction indicates inhibition of electron transfer from heme {und a} to heme {und a}{sub 3}. Crosslinking oxidase molecules to form large aggregates displaying rotational correlation times {ge} 1 ms does not affect oxidase activity. Crosslinking of mitochondria covalently binds the bc{sub 1} and {und aa}{sub 3} complexes to cytochrome {und c}, and inhibits steady-state oxidase activity considerably more than in the case of the purified oxidase. Addition of cytochrome {und c} to the purified oxidase or to {und c}-depleted mitoplasts increases inhibition slightly. Cytochrome {und c} oligomers act as competitive inhibitors of native {und c}, however, crosslinking of cytochrome {und c} to {und c}-depleted mitoplasts or purified oxidase (with dimethyl suberimidate or hetrobifunctional crosslinking reagents) results in a catalytically inactive complex.

  9. The MAO-A inhibitor clorgyline reduces ethanol-induced locomotion and its volitional intake in mice.

    Science.gov (United States)

    Ledesma, Juan Carlos; Escrig, Miguel Angel; Pastor, Raúl; Aragon, Carlos M G

    2014-01-01

    Hydrogen peroxide is the co-substrate used by the enzyme catalase to form Compound I (the catalase-H2O2 system), which is the major pathway for the conversion of ethanol (EtOH) into acetaldehyde in the brain. This acetaldehyde has been involved in many of the effects of EtOH. Previous research demonstrated that treatments that change the levels of cerebral H2O2 available to catalase modulate the locomotor-stimulating effects of EtOH and its volitional intake in rodents. However, the source of H2O2 which is used by catalase to form Compound I and mediates the psychoactive actions of EtOH is unknown. One cause of the generation of H2O2 in the brain comes from the deamination of biogenic amines by the activity of MAO-A. Here we explore the consequences of the administration of the MAO-A inhibitor clorgyline on EtOH-induced locomotion and voluntary EtOH drinking. For the locomotor activity tests, we injected Swiss (RjOrl) mice intraperitoneally (IP) with clorgyline (0-10mg/kg) and later (0.5-8h) with EtOH (0-3.75 g/kg; IP). Following these treatments, mice were placed in locomotor activity chambers to measure their locomotion. For the drinking experiments, mice of the C57BL/6J strain were injected IP with clorgyline prior to offering them an EtOH (20%) solution following a drinking-in-the-dark procedure. Additional experiments were performed to assess the selectivity of this compound in altering EtOH-stimulated locomotion and EtOH intake. Moreover, we indirectly tested the ability of clorgyline to reduce brain H2O2 levels. We showed that this treatment selectively reduced EtOH-induced locomotion and its self-administration. Moreover, this compound decreased central H2O2 levels available to catalase. We suggest that H2O2 derived from the deamination of biogenic amines by the activity of MAO-A could determine the formation of brain EtOH-derived acetaldehyde. This centrally-formed acetaldehyde within the neurons of the aminergic system could play a role in the

  10. A role for NADPH oxidase in antigen presentation

    Directory of Open Access Journals (Sweden)

    Gail J Gardiner

    2013-09-01

    Full Text Available The nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.-. This radical is an important precursor of hydrogen peroxide (H2O2 and other reactive oxygen species (ROS needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD, a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC crosspresentation by major histocompatibility complex class I molecules (MHC-I through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules (MHC-II.

  11. 毛泽东社会正义思想研究综述%Summary of Mao Zedong Thought on social justice

    Institute of Scientific and Technical Information of China (English)

    张颖

    2016-01-01

    Mao Zedong was not only a great Marxist in China,but also an influential statesman,thinker and strategist significant on modern Chinese history. As the main founder of the Communist Party of China,People’s Liberation Ar-my and the People’s Republic of China,Mao Zedong Thought and his whole life has a profound impact on China and the Chinese people. In today’s appeal for social justice background,both at the macro political,economic and cultur-al fields throughout the community,or in people’s ethical orientation,values,everyday practices,even in the field of people’s thinking,are still profoundly remaining Mao Zedong,Mao Zedong Thought and the imprint of that era. Mao Zedong’s ideology of social justice,in essence,mainly for the fairness and justice,democracy and freedom unique understanding of Mao Zedong Thought of social justice is an important part of his ideological system,and is an im-portant theoretical basis of socialist modernization. This paper focuses on the political justice,economic justice,cul-tural and other aspects to carry out justice. Social Ethics Mao Zedong in his life to the pursuit of fairness and jus-tice,democracy and freedom in the process of formation for the construction of our modern social justice in order to provide valuable experience and lessons.%分析指出,毛泽东的社会公正思想,实质上主要表现为对公平正义、民主与自由等的独到理解,毛泽东社会正义思想是毛泽东思想体系的重要组成部分,也是社会主义现代化建设的重要理论依据。本文围绕着政治公正、经济公正、文化公正等方面开展,认为毛泽东在其一生追求公平正义、民主与自由的过程中形成的社会伦理思想,为我们现代社会公正秩序的建设提供了宝贵的经验和教训。

  12. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille

    2016-01-01

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical d...... and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry....

  13. Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters.

    Science.gov (United States)

    Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S; Partilla, John S; Seddik, Amir; Zhang, Yuan-Wei; Cao, Jianjing; Holy, Marion; Steinkellner, Thomas; Rudnick, Gary; Baumann, Michael H; Ecker, Gerhard F; Newman, Amy Hauck; Sitte, Harald H

    2016-01-01

    Determining the structural elements that define substrates and inhibitors at the monoamine transporters is critical to elucidating the mechanisms underlying these disparate functions. In this study, we addressed this question directly by generating a series of N-substituted 3,4-methylenedioxyamphetamine analogs that differ only in the number of methyl substituents on the terminal amine group. Starting with 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA) and 3,4-methylenedioxy-N,N,N-trimethylamphetamine (MDTMA) were prepared. We evaluated the functional activities of the compounds at all three monoamine transporters in native brain tissue and cells expressing the transporters. In addition, we used ligand docking to generate models of the respective protein-ligand complexes, which allowed us to relate the experimental findings to available structural information. Our results suggest that the 3,4-methylenedioxyamphetamine analogs bind at the monoamine transporter orthosteric binding site by adopting one of two mutually exclusive binding modes. 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy-N-methylamphetamine adopt a high-affinity binding mode consistent with a transportable substrate, whereas MDDMA and MDTMA adopt a low-affinity binding mode consistent with an inhibitor, in which the ligand orientation is inverted. Importantly, MDDMA can alternate between both binding modes, whereas MDTMA exclusively binds to the low-affinity mode. Our experimental results are consistent with the idea that the initial orientation of bound ligands is critical for subsequent interactions that lead to transporter conformational changes and substrate translocation.

  14. Liquid chromatography-electrochemical detection for studying the effects of tetrahydrobiopterin on monoamine neurotransmitters in rat striatum

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Wen; ZHU; Wei; XU; Haihong; WAN; Fangli; GU; Jing; HA

    2005-01-01

    Tetrahydrobiopterin (BH4) is an essential co-factor in the biosynthesis of monoamine neurotransmitters.A nano-Pt/Pd modified electrode as the electrochemical detector (ED) for high-performance liquid chromatography (HPLC) coupled with microdialysis sampling, is used to explore the effect of administration of BH4 on the monoamine neurotransmitters in the rat striatum.The researches demonstrate that the contents of dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) increase significantly with the administration of BH4.The pharmaceutical kinetics is carried out to research into the time course of BH4 effect on the concentration of monoamine neurotransmitters in rat striatum, which provides reliable data for pathology and pharmacology research on neuroscience.

  15. The molecular mechanism for overcoming the rate-limiting step in monoamine neurotransmitter transport

    DEFF Research Database (Denmark)

    Sinning, Steffen; Said, Saida; Malinauskaite, Lina

    structures of the bacterial homolog, LeuT, captured in a new conformation without substrate or sodium bound shows a dramatic rotation of an absolutely conserved leucine into the substrate site. Molecular dynamics simulations combined with functional studies on SERT support that this leucine must act...... membrane. The rate-limiting step in monoamine reuptake is the return of the empty transporter from an inward-facing to an outward-facing conformation without neurotransmitter and sodium bound. The molecular mechanism underlying this important conformational transition has not been described. Crystal...

  16. Monoamines and sexual function in rats bred for increased catatonic reactivity.

    Science.gov (United States)

    Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

    2009-07-01

    Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

  17. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas

    OpenAIRE

    Saisho, Yoshifumi; Harris, Paul E.; Butler, Alexandra E.; Galasso, Ryan; GURLO, TATYANA; Rizza, Robert A.; Butler, Peter C.

    2008-01-01

    Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for ins...

  18. 茅盾的功利性选择%Mao Dun's Choice in a Utilitarian Way

    Institute of Scientific and Technical Information of China (English)

    郑志慧

    2011-01-01

    Mao Dun's life is great,who is famous as a revolutionist and a man of letters.He made a significant contribution.All these are closely related with his choice in a utilitarian way.This text will explore them.%茅盾的一生是伟大的,主要表现在他作为革命家和文学家对国家和人民做出的贡献上。而这样的贡献的取得与茅盾的功利性选择是密切相关的。本文将从功利性选择方面对茅盾进行分析。

  19. El maoísmo en las iniciativas político-editoriales del grupo pasadopresentista (1963-1976)

    OpenAIRE

    Celentano, Adrián

    2014-01-01

    Hacia comienzos de la década del sesenta, la ruptura entre el Partido Comunista de la Unión Soviética (PCUS) y el de China instalaba un nuevo escenario en el comunismo internacional. Los grupos argentinos que emprendían la renovación del pensamiento teórico y político comunista no podían dejar de pronunciarse ante ese nuevo escenario. Es así que el maoísmo formó parte, junto a la experiencia cubana, al debate teórico de los comunistas italianos y a los movimientos de liberación nacional de...

  20. Influence of Organoboron Compounds on Ethylene Polymerization Using Cp2ZrCl2/MAO as Catalyst System

    Directory of Open Access Journals (Sweden)

    Luis Alexandro Valencia López

    2014-01-01

    Full Text Available Organoboron compounds of nonionic and ionic nature, tris(pentafluorophenylborane, and N,N-dimethylanilinium tetra(pentafluorophenylborate were evaluated to act in conjunction with MAO as activators on ethylene polymerization by using the catalyst Cp2ZrCl2. A decrease on the catalytic activity was observed in both cases in relation with a reference polyethylene which was synthesized in absence of any organoboron compound. An increase on the crystallinity degree and molecular weight, as well as an improvement in thermal and dynamic-mechanical properties, was observed in polyethylenes synthetized in presence of tris(pentafluorophenylborane. A low density polyethylene with improved thermal stability was obtained when N,N-dimethylanilinium tetra(pentafluorophenylborate was employed as activator.

  1. Dressing the Older Woman in Post-Mao China: Perspectives from Official Feminist Mass Media and Ordinary Chinese Women

    Directory of Open Access Journals (Sweden)

    Jeanne L. Shea

    2014-12-01

    Full Text Available This article examines Chinese discourses on dressing the aging female body as a window into the tensions involved in the historical transformation of habitus in early post-Mao China.  Drawing on Chinese media articles and ethnographic interviews conducted with Chinese women in their 40s-60s, the analysis compares depictions of new official ideals for older women’s dress that appeared in Chinese government-sponsored feminist media with ordinary older Chinese women’s personal sensibilities about dress.  Assessing the applicability of dominant western feminist theories of gender, dress, and age, this article provides a historicized culture-specific application of practice theory, examining older women’s struggles with competing moral logics associated with past and present, and with official media versus personal experience.  Overall, it documents experiences of ambivalence and compromise accompanying lifecycle adjustment in embodiment in the context of rapid social change.

  2. El maoísmo en las iniciativas político-editoriales del grupo pasadopresentista (1963-1976)

    OpenAIRE

    Celentano, Adrián

    2014-01-01

    Hacia comienzos de la década del sesenta, la ruptura entre el Partido Comunista de la Unión Soviética (PCUS) y el de China instalaba un nuevo escenario en el comunismo internacional. Los grupos argentinos que emprendían la renovación del pensamiento teórico y político comunista no podían dejar de pronunciarse ante ese nuevo escenario. Es así que el maoísmo formó parte, junto a la experiencia cubana, al debate teórico de los comunistas italianos y a los movimientos de liberación nacional de...

  3. The First Results of the Photometric Observation of Selected Asteroids on KT-50 Telescope of Mobitel Complex of RI MAO

    Directory of Open Access Journals (Sweden)

    Pomazan, A.V.

    2017-01-01

    Full Text Available The first results of the photometric observations of asteroids performed on the telescope KT-50 of Mobitel complex (SRI MAO during 2016 are presented in the paper. Asteroids were selected based on the infrared survey NEOWISE, moving objects catalog SDSS MOC-3 and MPC database. Selected asteroids have a relatively high albedo (pV>0.2 and are located in the Outer Main Belt (semi-major axis a>0.28a.u.. The observations were made using filter close to the Rc standard band of Cousins system. Standard deviations of the instrumental differential magnitude measurements were in the range of 0.01m-0.03m for a 10m-15.5m reference stars. The light curve based on the results of the differential aperture photometry was obtained from long series of observations of the asteroid (2144 Marietta.

  4. The effect of cultivation media and washing whole-cell biocatalysts on monoamine oxidase catalyzed oxidative desymmetrization of 3-azabicyclo[3,3,0]octane

    DEFF Research Database (Denmark)

    Ramesh, Hemalata; Zajkoska, Petra; Rebros, Martin

    2016-01-01

    It is well known that washing whole-cells containing enzyme activities after fermentation, but prior to biocatalysis can improve their activity in the subsequent reaction. In this paper, we quantify the impact of both the fermentation media and cell washing on the performance of whole-cell....... Unlike cells grown in LB medium, washing of the cells was essential for cells grown on TB medium. With TB media, washing the cells improved the final conversion by approximately a factor of two. Additionally, over 50-fold improvement was achieved in initial activity. A potential reason...... for this improvement in activity was identified to be the increase in transfer of substrates across the cell membrane as a result of cell washing. (C) 2015 Elsevier Inc. All rights reserved....

  5. Gene Expression of Serotonin and Dopamine Receptors and Monoamine Oxidase-A in the Brain of Dominant and Subordinate Pubertal Pigs Fed a ß-Adrenoreceptor Agonist

    Science.gov (United States)

    Aggression is a major source of social stress and injuries, negatively affecting the health and well-being of those involved in the fight. The serotonergic and dopaminergic systems are widely implicated in aggression regulation in several animal species, but information on molecular mechanisms media...

  6. [Life-threatening serotonin syndrome following a single dose of a serotonin reuptake inhibitor during maintenance therapy with a monoamine oxidase inhibitor

    NARCIS (Netherlands)

    Zonneveld, A.M.; Hagenaars, M.; Voermans, N.C.; Gelissen, H.P.; Claassen, J.A.H.R.

    2006-01-01

    A 72-year-old man presented to the emergency clinic with motor restlessness and diminished consciousness 24 hours after he had mistakenly been given venlafaxine. He was referred from the psychiatric clinic where he was treated with tranylcypromine. Shortly after arrival, a severe serotonin syndrome

  7. Similarity in temperament between mother and offspring rhesus monkeys: sex differences and the role of monoamine oxidase-a and serotonin transporter promoter polymorphism genotypes.

    Science.gov (United States)

    Sullivan, Erin C; Mendoza, Sally P; Capitanio, John P

    2011-09-01

    Temperament is usually considered biologically based and largely inherited, however, the environment can shape the development of temperament. Allelic variation may confer differential sensitivity to early environment resulting in variations in temperament. Here we explore the relationship between measures of temperament in mothers and their first-born offspring and the role of genetic sensitivity in establishing the strength of these associations. Temperament ratings were conducted on 3- to 4-month-old rhesus monkeys after a 25-hr biobehavioral assessment. Factor analysis revealed a four-factor structure of temperament. Females assessed as infants have reproduced and their offspring have also been evaluated through the standardized testing paradigm. Canonical correlation analysis revealed statistically significant associations between factor scores of mothers and sons, but not mothers and daughters. Further, offspring possessing the high activity, "low risk," alleles of the rhMAOA-LPR or rh5-HTTLPR showed statistically significant canonical correlations, whereas those possessing other alleles did not, suggesting differential genetic sensitivity to the normative early experience of maternal temperament.

  8. Xanthine oxidase biosensor for monitoring meat spoilage

    Science.gov (United States)

    Vanegas, D. C.; Gomes, C.; McLamore, E. S.

    2014-05-01

    In this study, we have designed an electrochemical biosensor for real-time detection of specific biomarkers of bacterial metabolism related to meat spoilage (hypoxanthine and xanthine). The selective biosensor was developed by assembling a `sandwich' of nanomaterials and enzymes on a platinum-iridium electrode (1.6 mm tip diameter). The materials deposited on the sensor tip include amorphous platinum nanoclusters (i.e. Pt black), reduced graphene oxide, nanoceria, and xanthine oxidase. Xanthine oxidase was encapsulated in laponite hydrogel and used for the biorecognition of hypoxanthine and xanthine (two molecules involved in the rotting of meat by spoilage microorganisms). The developed biosensor demonstrated good electrochemical performance toward xanthine with sensitivity of 2.14 +/- 1.48 μA/mM, response time of 5.2 +/- 1.5 sec, lower detection limit of 150 +/- 39 nM, and retained at least 88% of its activity after 7 days of continuous use.

  9. Plasma diamine oxidase activity in asthmatic children

    Directory of Open Access Journals (Sweden)

    Kyoichiro Toyoshima

    1996-01-01

    Full Text Available Histamine plays an important role in the development of asthmatic symptoms. Diamine oxidase (DAO histaminase, which inactivates histamine, is located in the intestine and kidney and is released into plasma. Plasma DAO activity in asthmatic children was measured by a recently developed high performance liquid chromatographic method using histamine as the DAO substrate. Diamine oxidase activity was higher in severely asthmatic children than in those with mild asthma. A time course study during the acute exacerbation phase revealed that DAO activity rose during acute asthmatic attacks and then decreased gradually over several days. Although the mechanisms of plasma DAO activity increase during acute asthmatic attacks could not be explained, data showed that plasma DAO activity is an important index of histamine metabolism in asthmatics and may relate to some mechanisms of acute exacerbation of airway inflammation. Consequently, fluctuations in plasma DAO can be used as one of various indices of instability in management of asthma.

  10. Characterization of polyphenol oxidase from plants

    Institute of Scientific and Technical Information of China (English)

    LEI Dongfeng; FENG Yi; JIANG Dazong

    2004-01-01

    Polyphenol oxidase (PPO) which can mediate browning reaction is a bifunctional copper-containing enzyme encoded by plant nucleolus gene. It usually leads to excessive browning reaction which reduces the coercial profits of fruits and vegetables. In this paper, PPO genes and enzymes in plants are characterized systematically, and the latest progress is reviewed. Some clonings of PPOs genes are reported; the specific temporal and spatial expression pattern of PPOs genes is described; the model of the structure of the precursor form of catechol oxidase is introduced; the possible functions of PPOs in defending against pathogen, wounding, surrounding stress and other inducing factors are demonstrated; the induction and activation of latent PPOs in some plants is elucidated; the scheme of browning inhibition by L-cysteine is clarified; the mechanism of suicide inhibition of latent PPO and kinetic synergism are established. Furthermore, the area for future study is also discussed.

  11. An analysis on flavonoids contents in Mao Luang fruits of fifteen cultivars (Antidesma bunius), grown in northeast Thailand.

    Science.gov (United States)

    Butkhup, L; Samappito, S

    2008-04-01

    This investigation was carried out at the Department of Biotechnology, Faculty of Technology, Mahasarakham University, Mahasarakham Province, Northeast Thailand. The study aimed to analyze flavonoids contents in ripe fruits of fifteen Mao Luang cultivars (Antidesma bunius) harvested from dipterocarp forest of the mountainous areas of Phupan Valley, Sakon Nakhon Province, Northeast Thailand. The experiment was laid in a Completely Randomised Design (CRD) with five replications. The fifteen cultivars were used as treatments. An amount of 2 kg of ripe fruits of each cultivar was collected and extracted for juice solutions. The analysis was carried out with the use of RP-HPLC laboratory system. The results showed that fruits of the fifteen Mao Luang cultivars contained three different kinds of flavonoids, i.e., catechin, procyanidin B1 and procyanidin B2. These three chemical compounds were the major flavonoids in all analyzed fruit samples of the fifteen cultivars. The highest amount of procyanidin B1 was found with Lompat followed by Maeloogdog with values of 4122.75 and 3993.88 mg 100 g(-1) of fresh weight, respectively and the highest amount of procyanidin B2 was found with Sangkrow 2 followed by Fapratan with values of 5,006.39 and 3,689.42 mg 100 g(-1) of fresh weight, respectively. Catechin contents in fruits of the fifteen cultivars varied from 73.39 to 316.22 mg 100 g(-1) of fresh weight for Sangkrow 5 and Fapratan, respectively where Fapratan was the highest among the fifteen cultivars followed by Sangkrow 2 with values of 316.22 and 175.40 mg 100 g(-1) of fresh weight, respectively. In terms of grand total amounts of flavonoids, Sangkrow 2 was the best followed by Fapratan, Sangkrow 1 and Maeloogdog, whilst the rest were of secondary importance.

  12. 茅元仪与《孙子兵法》%Mao Yuanyi and The Art of War

    Institute of Scientific and Technical Information of China (English)

    赵娜

    2011-01-01

    The famous works in ancient Chinese military science called Wu Bei Zhi ,which written by Mao Yuanyi,was called "Military Encyclopedia in China ". One part of the annotations, called Bing Jue Ping, tidied nine books intensively,including The Art of War. Mao highly praised Sun Tzu ,said "Sun Tzu including all the things before it, and after this, all works can't leave Sun Tzu". He synthesize eleven scholars' views on Sun Tzu in his book, meanwhile expressed his political idea.%茅元仪所作《武备志》,为中国古代著名兵学著作,被称为“军事学的百科全书”。其中《兵诀评》部分,集中整理、注释了包括《孙子兵法》在内的九部兵学典籍。茅元仪高度评价《孙子兵法》,称“前孙子者,孙子不遗;后孙子者,不能遗孙子”,并综合宋本《十一家注孙子》,重新对《孙子兵法》加以注解,其中不乏精辟见解。同时借军事言政治,表达了其报效朝廷的政治理想。

  13. Effects of Condensed Tannins in Mao ( Muell. Arg. Seed Meal on Rumen Fermentation Characteristics and Nitrogen Utilization in Goats

    Directory of Open Access Journals (Sweden)

    P. Gunun

    2016-08-01

    Full Text Available Mao seed is a by-product of the wine and juice industry, which could be used in animal nutrition. The current study was designed to determine the effect of supplementation of mao (Antidesma thwaitesianum Muell. Arg. seed meal (MOSM containing condensed tannins (CT on rumen fermentation, nitrogen (N utilization and microbial protein synthesis in goats. Four crossbred (Thai Native×Anglo Nubian goats with initial body weight (BW 20±2 kg were randomly assigned to a 4×4 Latin square design. The four dietary treatments were MOSM supplementation at 0%, 0.8%, 1.6%, and 2.4% of total dry matter (DM intake, respectively. During the experimental periods, all goats were fed a diet containing roughage to concentrate ratio of 60:40 at 3.0% BW/d and pangola grass hay was used as a roughage source. Results showed that supplementation with MOSM did not affect feed intake, nutrient intakes and apparent nutrient digestibility (p>0.05. In addition, ruminal pH and ammonia nitrogen (NH3-N were not influenced by MOSM supplementation, whilst blood urea nitrogen was decreased quadraticly (p0.05. There were linear decreases in urinary N (p0.05. From the current study, it can be concluded that supplementation of MOSM at 1.6% to 2.4% of total DM intake can be used to modify ruminal fermentation, especially propionate and N utilization in goats, without affecting the nutrient digestibility, microbial populations and microbial protein synthesis.

  14. Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    John M Tauber

    Full Text Available Fragile X Syndrome (FXS is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS.

  15. Clorgyline effect on pineal melatonin biosynthesis in adrenalectomized rats pretreated with 6-hydroxydopamine.

    Science.gov (United States)

    Reuss, S; Requintina, P J; Riemann, R; Oxenkrug, G F

    1994-01-01

    The response to administration of the specific monoamine oxidase A (MAO-A) blocker clorgyline was investigated in adult male Sprague-Dawley rats which were adrenalectomized four days prior to treatment or were additionally sympathectomized as newborns by injection of 6-hydroxydopamine. In both groups, the contents of pineal indoles melatonin and N-acetylserotonin were augmented, and the contents of 5-hydroxyindoleacetic acid and 5-hydroxyindoletryptophol decreased 90 min following clorgyline injections when compared to rats receiving saline. The observed responses were less pronounced in rats both adrenalectomized and sympathectomized. The results are in line with the hypothesis that preservation from oxidation of both MAO-A substrates, noradrenaline and serotonin, upon clorgyline administration contributes to the observed increase in melatonin biosynthesis thought to be associated with the anti-depressant effects of MAO inhibition.

  16. Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy.

    Science.gov (United States)

    Larson, Kelly J; Wittwer, Erica D; Nicholson, Wayne T; Weingarten, Toby N; Price, Daniel L; Sprung, Juraj

    2015-05-01

    Serotonin released in the nerve synapses is cleared through reuptake into presynaptic neurons and metabolism with monoamine oxidase (MAO). Therapy with selective serotonin reuptake inhibitors (SSRIs) or MAO inhibitors increases serotonin concentration in the synaptic cleft and may result in serotonin syndrome (SS). Our patient undergoing sentinel lymph node biopsy was on fluoxetine (SSRI) and intraoperatively developed SS after receiving fentanyl (200 μg) and methylene blue (MAO inhibitor), 7 mg subcutaneously into the scalp. Initial presentation was several episodes of generalized muscle activity, which was later diagnosed as lower extremity myoclonus consistent with SS. Upon awakening, the patient showed no evidence of encephalopathy, and the clonus was less intense. The patient was discharge home the next day. Our case suggests the possibility that even a small dose of methylene blue, when administered simultaneously with other serotoninergic medications, may be associated with serotonin toxicity.

  17. Drug design, synthesis, in vitro and in silico evaluation of selective monoaminoxidase B inhibitors based on 3-acetyl-2-dichlorophenyl-5-aryl-2,3-dihydro-1,3,4-oxadiazole chemical scaffold.

    Science.gov (United States)

    Distinto, Simona; Meleddu, Rita; Yanez, Matilde; Cirilli, Roberto; Bianco, Giulia; Sanna, Maria Luisa; Arridu, Antonella; Cossu, Pietro; Cottiglia, Filippo; Faggi, Cristina; Ortuso, Francesco; Alcaro, Stefano; Maccioni, Elias

    2016-01-27

    With the aim to identify new, potent and selective monoamine oxidase B (MAO-B) inhibitors, molecular interaction field analysis has been applied to a MAO-B complex with 3-acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazole chemical structure, known as a privileged scaffold for this target. Several compounds displayed potent in vitro activity, exhibiting IC50 values in the medium to low nanomolar range. The enantiomers of most promising derivatives were separated by enantioselective HPLC and in vitro evaluated. Experimental results, according to theoretical drug design, clearly indicated a key role of the ligand stereochemistry in the target recognition/inhibition. In particular the (R)- enantiomers showed the best activity with respect to the (S)- stereoisomer. Finally, docking experiments coupled to molecular dynamics (MD) simulations, were applied for understanding the putative MAO -B binding modes of the new compounds providing detailed information for further structural optimization.

  18. Long-lasting effects of feline amygdala kindling on monoamines, seizures and sleep.

    Science.gov (United States)

    Shouse, M N; Staba, R J; Saquib, S F; Farber, P R

    2001-02-16

    This report describes the relationship between monoamines, sleep and seizures before and 1-month after amygdala kindling in young cats (kindling (n=2); 5-min recording epochs were temporally adjusted to correspond to dialysate samples and differentiated according to dominant sleep or waking state (lasting > or =80% of 5-min epoch) and degree of spontaneous seizure activity (number and duration of focal versus generalized spikes and spike trains and behavioral seizure correlates). Post-kindling records in each cat were divided into two groups (n=1 record each) based on higher or lower spontaneous EEG and behavioral seizure activity and compared to pre-kindling records. We found: (1) before and after kindling, NE and 5-HT but not DA concentrations were significantly lower in sleep than waking at both sites; (2) after kindling, each cat showed cyclic patterns, as follows: (a) higher NE, 5-HT and DA concentrations accompanied increased seizure activity with delayed sleep onset latency and increased sleep fragmentation (reduced sleep state percentages, number of epochs and/or epoch duration) in one recording versus (b) lower monoaminergic concentrations accompanied reduced seizure activity, rapid sleep onset and reduced sleep disruption in the other recording. The alternating, post-kindling pattern suggested "rebound" effects which could explain some controversies in the literature about chronic effects of kindling on monoamines and sleep-waking state patterns.

  19. Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression—An Animal Model Study

    Directory of Open Access Journals (Sweden)

    O. Malkesman

    2009-01-01

    Full Text Available Basal levels of monoamines and DHEA in four main limbic brain regions were measured in prepubertal Wistar Kyoto (WKY rats (a putative animal model of childhood depression. Basal levels of “Brain-Derived Neurotrophic Factor (BDNF” were also determined in two regions in the hippocampus, compared with Wistar strain controls. In the second phase, we examined the responsiveness of prepubertal WKY rats to different types of chronic antidepressant treatments: Fluoxetine, Desipramine, and dehydroepiandrosterone sulfate (DHEAS. WKY prepubertal rats exhibited different monoamine levels in the limbic system, reduced DHEA levels in the VTA and lower levels of BDNF in the hippocampus CA3 region compared to controls. In prepubertal WKY rats, only treatment with DHEAS produced a statistically significant decrease in immobility, compared to saline-administered controls in the forced swim test. Wistar controls were not affected by any antidepressant. The results imply that DHEA(S and BDNF may be involved in the pathophysiology and pharmacotherapy of childhood depression.

  20. Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis

    Science.gov (United States)

    Shaw, J.C.; Korzan, W.J.; Carpenter, R.E.; Kuris, A.M.; Lafferty, K.D.; Summers, C.H.; Overli, O.

    2009-01-01

    California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators. ?? 2008 The Royal Society.

  1. Effect of ultrasonic cold forging technology as the pretreatment on the corrosion resistance of MAO Ca/P coating on AZ31B Mg alloy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lingling, E-mail: daisy_chenlingling@163.com [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China); College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Gu, Yanhong, E-mail: gu_yanhong@163.com [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China); Liu, Lu, E-mail: liulu@bipt.edu.cn [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China); Liu, Shujing, E-mail: liushujing@bipt.edu.cn [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China); Hou, Binbin, E-mail: sohu19880815@126.com [School of Engineering and Technology, China University of Geosciences, Beijing 100083 (China); Liu, Qi, E-mail: 13521196884@sina.cn [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China); Ding, Haiyang, E-mail: dinghaiyang@bipt.edu.cn [College of Mechanical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617 (China)

    2015-06-25

    Highlights: • Ultrasonic cold forging technology was used as the pretreatment for MAO coating. • Nano layer with the grain size of 30–80 nm was formed on the UCFT treated surface. • Calcium phosphate contained coating was obtained by MAO process. • The remained nano layer underlying MAO coating could impact the corrosion resistance greatly. - Abstract: A calcium phosphate contained (Ca/P) coating was obtained on AZ31B Mg alloy by micro-arc oxidation (MAO) process under the pretreatment of ultrasonic cold forging technology (UCFT). The surface nanograins were introduced after UCFT pretreatment on AZ31B Mg alloy. Optical microscope (OM) was employed to observe the microstructures of the untreated and UCFT treated samples. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were employed to observe the microstructures of nanograins and the surface roughness of the UCFT treated Mg alloys. The grain size of the UCFT treated Mg alloy is 48.67 nm and the surface roughness is 17.03 nm. The microstructures and the phase compositions of MAO samples were observed and analyzed by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. The XRD results show that the coating include Ca/P phase, including hydroxyapatite (Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}), HA), tertiary calcium phosphate (Ca{sub 3}(PO{sub 4}){sub 2}, TCP) and calcium phosphate dehydrate (CaHPO{sub 4}⋅2H{sub 2}O, DCPD). The hardness of the samples was measured by the micro-hardness tester under the loads of 10 g, 25 g and 50 g. 3D topographies of hardness indenter were characterized by 3D profiler. The immersion tests and potentiodynamic polarization tests were used to evaluate the weight loss rate and corrosion current density in simulated body fluid (SBF). The results show that the corrosion resistance of Ca/P MAO coating on Mg alloy was improved greatly by the pretreatment of UCFT.

  2. The nature of CuA in cytochrome c oxidase

    OpenAIRE

    Stevens, Tom H.; Martin, Craig T.; Wang, Hsin; Brudvig, Gary W.; Scholes, Charles P.; Chan, Sunney I.

    1982-01-01

    The isolation and purification of yeast cytochrome c oxidase is described. Characterization of the purified protein indicates that it is spectroscopically identical with cytochrome c oxidase isolated from beef heart. Preparations of isotopically substituted yeast cytochrome c oxidase are obtained incorporating [1,3-15N2]histidine or [beta,beta- 2H2]cysteine. Electron paramagnetic resonance and electron nuclear double resonance spectra of the isotopically substituted proteins identify unambigu...

  3. Regional brain monoamine concentrations and their alterations in bovine hypomagnesaemic tetany experimentally induced by a magnesium-deficient diet.

    Science.gov (United States)

    McCoy, M A; Young, P B; Hudson, A J; Davison, G; Kennedy, D G

    2000-12-01

    Monoamines are important brain neurotransmitters. An investigation was carried out to determine if hypomagnesaemic tetany was associated with alterations in regional brain monoamine concentrations in bovines. The results, established in cows with normal magnesium status, demonstrated that regional differences existed in the distribution and concentration of brain monoamines in the adult bovine, which were similar to those in other species. In magnesium-deficient cows, severe hypomagnesaemia and lowered cerebrospinal fluid (CSF) magnesium concentrations were associated with significant alterations in monoamine concentrations in some brain regions. Alterations in 3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) concentrations in the corpus striatum, and dopamine (DA) in the cerebral cortex and cerebellum were recorded. These regions play an important role in both voluntary and involuntary motor function, and therefore these alterations may play a role in the aetiology of hypomagnesaemic tetany. However, there was no significant change in DA concentrations in the corpus striatum (the main dopaminergic region in the brain) associated with hypomagnesaemia. In addition, a significantly lower norepinephrine (NE) concentration in the corpus striatum of hypomagnesaemic animals was also recorded. Norephinephrine is generally excitatory and therefore lowered NE concentrations would be expected to result in depression rather than stimulation of motor function. Copyright 2000 Harcourt Publishers Ltd.

  4. Effects of lamotrigine on PCP-evoked elevations in monoamine levels in the medial prefrontal cortex of freely moving rats.

    Science.gov (United States)

    Quarta, Davide; Large, Charles H

    2011-12-01

    Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on basal levels of the monoamines, but significantly reduced PCP-evoked overflow of dopamine and serotonin; PCP-evoked overflow of noradrenaline was also reduced by lamotrigine, but not to a significant degree. In contrast, PCP-induced hyperactivity was unaffected by lamotrigine. It is concluded that lamotrigine can modify PCP-evoked monoamine overflow in the cortex, consistent with an ability to prevent the psychotomimetic effects of NMDA receptor antagonists in rodents and humans. The dissociation between monoamine overflow and locomotor activity suggests the involvement of different brain circuits; relevance to the treatment of schizophrenia is also discussed.

  5. Monoamine content during the reproductive cycle of Perna perna depends on site of origin on the Atlantic Coast of Morocco.

    Science.gov (United States)

    Klouche, Mounia S; De Deurwaerdère, Philippe; Dellu-Hagedorn, Françoise; Lakhdar-Ghazal, Nouria; Benomar, Soumaya

    2015-09-09

    Bivalve molluscs such as Perna perna display temporal cycles of reproduction that result from the complex interplay between endogenous and exogenous signals. The monoamines serotonin, dopamine and noradrenaline represent possible endocrine and neuronal links between these signals allowing the molluscs to modulate reproductive functions in conjunction with environmental constraints. Here, we report a disruption of the reproductive cycle of mussels collected from two of three sites along the Moroccan atlantic coast soiled by industrial or domestic waste. Using high pressure liquid chromatography, we show that the temporal pattern of monoamine content in the gonads, pedal and cerebroid ganglia varied throughout the reproductive cycle (resting, developing, maturing, egg-laying) of mussels from the unpolluted site. Marked modification of monoamine tissue content was found between sites, notably in noradrenaline content of the gonads. Discriminant statistics revealed a specific impact of mussel location on the temporal variations of noradrenaline and serotonin levels in gonads and cerebroid ganglia. Correlation analyses showed profound and temporal changes in the monoamine content between organs and ganglia, at the two sites where the reproduction was disrupted. We suggest that environmental constraints lead to profound changes of monoaminergic systems, which thereby compromises the entry of mussels into their reproductive cycle.

  6. 铝合金表面纳米化--微弧氧化复合涂层摩擦行为%Tribological behavior of SNC-MAO composite coatings formed on the surface of aluminum alloys

    Institute of Scientific and Technical Information of China (English)

    文磊; 王亚明; 金莹

    2015-01-01

    通过表面机械研磨处理在LY12CZ铝合金表面制备表面纳米化( SNC)过渡层,再采用微弧氧化( MAO)技术对纳米晶过渡层进行微结构重构,设计制备出纳米化-微弧氧化( SNC-MAO)复合涂层,并对比研究了铝合金表面微弧氧化涂层及纳米化-微弧氧化复合涂层的摩擦学行为。与微弧氧化涂层相比,纳米化-微弧氧化复合涂层因硬度较高而具有较好的耐磨性。微弧氧化涂层及纳米化-微弧氧化复合涂层与GCr15钢球对磨时具有相同的磨损机理,为对磨钢球向涂层的材料转移和氧化磨损。%A duplex process was designed to modify the surface of LY12CZ aluminum alloy by using surface mechanical attrition treatment ( SMAT) prior to microarc oxidation ( MAO) . A surface nanocrystalline ( SNC) layer was formed on the alloy surface by SMAT, a ceramic outer layer grew on the SNC layer by MAO, and finally an SNC-MAO composite coating was fabricated. The tribo-logical behaviors of the MAO coating and SNC-MAO composite coating were comparatively evaluated. Experimental results showed that the SNC-MAO composite coating had a better wear resistance than the MAO coating in the same test condition due to a higher hardness of the ceramic coating. The wear mechanism of the MAO coating and SNC-MAO composite coating involved materials transfer from the steel ball to the coating and oxidation wear.

  7. NADPH oxidase: an enzyme for multicellularity?

    Science.gov (United States)

    Lalucque, Hervé; Silar, Philippe

    2003-01-01

    Multicellularity has evolved several times during the evolution of eukaryotes. One evolutionary pressure that permits multicellularity relates to the division of work, where one group of cells functions as nutrient providers and the other in specialized roles such as defence or reproduction. This requires signalling systems to ensure harmonious development of multicellular structures. Here, we show that NADPH oxidases are specifically present in organisms that differentiate multicellular structures during their life cycle and are absent from unicellular life forms. The biochemical properties of these enzymes make them ideal candidates for a role in intercellular signalling.

  8. NADH/NADPH Oxidase and Vascular Function.

    Science.gov (United States)

    Griendling, K K; Ushio-Fukai, M

    1997-11-01

    The vascular NADH/NADPH oxidase has been shown to be the major source of superoxide in the vessel wall. Recent work has provided insight into its structure and activity in vascular cells. This enzyme is involved in both vascular smooth muscle hypertrophy and in some forms of impaired endothelium-dependent relaxation. Because oxidative stress in general participates in the pathogenesis of hypertension and atherosclerosis, the enzymes that produce reactive oxygen species may be important determinants of the course of vascular disease. (Trends Cardiovasc Med 1997;7:301-307). © 1997, Elsevier Science Inc.

  9. OXIDASE REACTION OF VARIOUS GROUPS OF BACTERIA.

    Science.gov (United States)

    Felton, L D

    1923-08-31

    1. A simple technique is described for studying the oxidase action of bacteria by means of the oxidation of p-aminoleucomalachite green. 2. It is shown that pneumococci under aerobic conditions produced an oxidase when grown on suitable medium. The sera of any of seven different animal species constitute such a medium, the degree of oxidation by the pneumococcus depending upon the animal from which the serum was taken-rat, guinea pig, rabbit, horse, man, cat, and chicken in order of diminishing suitability. 3. Conditions favoring the oxidation of p-aminoleucomalachite green by a single strain of pneumococci are: the presence of a slight amount of hemoglobin, dextrose, H ion concentration on the add side, and heating of fresh serum for 30 minutes at 56 degrees C. Conditions preventing the oxidation are: sterilized meat infusion, 1 per cent peptone, plain broth, a high concentration of hemoglobin, and absence of oxygen. In a quantitative fashion, meat infusion, 1 per cent peptone, and plain broth interfere with the suitability of serum as a substratum of oxidase production by the pneumococcus. 4. Twenty-three microbic species were studied with reference to oxidative power. They were grown upon 10 per cent horse serum, with and without dextrose, upon 10 per cent guinea pig serum, and upon plain broth. Only three of the twenty-three gave evidence of oxidative power as tested by p-aminoleucomalachite green; namely, the pneumococcus, Streptococcus viridans, and Streptococcus haemolyticus. Among the strains, of these three pneumococci gave the most intense reaction, after which Streptococcus viridans and Streptococcus haemolyticus follow in the order named, but with a noticeable variation among the different strains of Streptococcus haemolyticus. 5. Hemolytic streptococci of human and bovine origin were studied. The only variation in the type of reaction was manifested by the streptococci of milk and cheese origin. Strains from these sources showed definitely the least

  10. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    Science.gov (United States)

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  11. Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice.

    Science.gov (United States)

    Abdel-Salam, Omar M E; Salem, Neveen A; Hussein, Jihan Seid

    2012-04-01

    This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 μg/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-α by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

  12. The main contents of Mao Ze-dong Thought of family education%毛泽东家庭教育思想的主要内容

    Institute of Scientific and Technical Information of China (English)

    许冰

    2013-01-01

    当今社会,高度重视家庭教育,而毛泽东家庭教育思想在理论上形成了具有中国特色的家庭教育思想。毛泽东家庭教育思想的主要内容由世界观,人生观,价值观教育;思想品德教育;文化知识教育三部分构成。%In today's society, attaches great importance to family education, family education of Mao Ze-dong Thought forms family education thought with Chinese characteristics in theory. The main contents of family education of Mao Ze-dong Thought is composed by the world outlook, outlook on life, values education;moral education;cultural education.

  13. Multicopper oxidase-1 orthologs from diverse insect species have ascorbate oxidase activity.

    Science.gov (United States)

    Peng, Zeyu; Dittmer, Neal T; Lang, Minglin; Brummett, Lisa M; Braun, Caroline L; Davis, Lawrence C; Kanost, Michael R; Gorman, Maureen J

    2015-04-01

    Members of the multicopper oxidase (MCO) family of enzymes can be classified by their substrate specificity; for example, ferroxidases oxidize ferrous iron, ascorbate oxidases oxidize ascorbate, and laccases oxidize aromatic substrates such as diphenols. Our previous work on an insect multicopper oxidase, MCO1, suggested that it may function as a ferroxidase. This hypothesis was based on three lines of evidence: RNAi-mediated knock down of Drosophila melanogaster MCO1 (DmMCO1) affects iron homeostasis, DmMCO1 has ferroxidase activity, and DmMCO1 has predicted iron binding residues. In our current study, we expanded our focus to include MCO1 from Anopheles gambiae, Tribolium castaneum, and Manduca sexta. We verified that MCO1 orthologs have similar expression profiles, and that the MCO1 protein is located on the basal surface of cells where it is positioned to oxidize substrates in the hemolymph. In addition, we determined that RNAi-mediated knock down of MCO1 in A. gambiae affects iron homeostasis. To further characterize the enzymatic activity of MCO1 orthologs, we purified recombinant MCO1 from all four insect species and performed kinetic analyses using ferrous iron, ascorbate and two diphenols as substrates. We found that all of the MCO1 orthologs are much better at oxidizing ascorbate than they are at oxidizing ferrous iron or diphenols. This result is surprising because ascorbate oxidases are thought to be specific to plants and fungi. An analysis of three predicted iron binding residues in DmMCO1 revealed that they are not required for ferroxidase or laccase activity, but two of the residues (His374 and Asp380) influence oxidation of ascorbate. These two residues are conserved in MCO1 orthologs from insects and crustaceans; therefore, they are likely to be important for MCO1 function. The results of this study suggest that MCO1 orthologs function as ascorbate oxidases and influence iron homeostasis through an unknown mechanism.

  14. On Mao Zedong’s Counter - Encirclement Thought%论毛泽东反“围剿”思想

    Institute of Scientific and Technical Information of China (English)

    王新生

    2014-01-01

    1930年秋至1931年9月,在毛泽东与朱德的指挥下,红一方面军连续取得了中央苏区三次反“围剿”战争的胜利。在三次反“围剿”战争中,毛泽东正确判断形势和敌我态势,确立了诱敌深入的战略方针;主张认真做好反“围剿”的政治动员等准备工作;积极在运动中寻找战机,化劣势为优势;抓住反“围剿”胜利后的机遇,巩固和发展苏区。毛泽东反“围剿”思想是马克思主义军事思想与中国红军的革命战争实践相结合的产物,为毛泽东军事思想的形成奠定了坚实基础,在毛泽东思想形成过程中起着重要作用。%In the autumn of 1930 to September 1931,the First Red Army,under the command of Mao Zedong and Zhu De,continuously won the three counter - encirclement wars in the Central Soviet Area. In these three wars,Mao Zedong made correct judgment of the situation and the strengths and weaknesses of the Red Army and the enemies,and established the strategic guideline of luring the enemy in deep;asserted that political mobiliza-tion and other preparatory work should be carefully done for the counter - encirclement wars;actively sought for opportunities in moving,and transformed disadvantages into advantages;and grasped the opportunities of the vic-tories to consolidate and develop the soviet area. His thought on counter - encirclement is the product of combi-ning Marxist military thought with the practice of Chinese revolutionary struggle,laying a solid foundation for the forming of Mao’s military thought and playing an important role in the forming of Maoism.

  15. 毛奇龄《诗经》辨伪述略%On MAO Ji-ling's Distinguishment of the "Book of Songs"

    Institute of Scientific and Technical Information of China (English)

    周怀文; 经莉莉

    2012-01-01

    辨伪是毛奇龄《诗经》研究中较有特色和成就、价值较高的部分,考辩作品多,涉及内容广,论据丰富,论证深入,且少有其他作品中习见的粗疏、谩骂风气,并形成了独特的辨伪范式,具有鲜明的体式特点,在明清之际的《诗经》学史上具有一定成就与影响。%The research to the "book of songs" is an important part of the study of MaoJiLing, BianWei is the study with more value and characteristics for the researchers have long been ignored by important aspect. In fact, MaoShi the "book of songs" BianWei, take an examination of argument works, covered a wide, argument is rich, deep argument, and few other works of the find, abuse deficient atmosphere, and it is the study of the "book of songs" higher value and important part of the influence. "The poem by righteousness said the" five volume is MaoShi the "book oi" songs" BianWei representative works, "the poem by the said righteousness", "MAO poetry writing officer to record" four voiumes, "the bird to the name volume" three volumes, the poetry Zagreb "two volumes, the province guofeng article" a roll of, the white continent subject-object said poem "a roll of handed down, also the varying degree involves the book.

  16. Mao Zedong's Awareness of Suffering in Time of Sufficiency and the Great Leap Forward%毛泽东的忧患意识和大跃进

    Institute of Scientific and Technical Information of China (English)

    王青山

    2004-01-01

    The contradiction between the psychological needs and the desires to meet those needs is the cause of the awareness of sufferings in time of sufficiency. After the founding of New China, Mao Zedong was psychologically pressed by the objective environment and greatly depressed. His obligation, his sense of historical mission and his awareness of concerns based on the distance between reality, and desires are closely linked to his waging the campaign of the Great Leap Forward.

  17. 茅盾文学批评的基本特征%The Basic Characteristics of the Literary Critic—Mao Dun

    Institute of Scientific and Technical Information of China (English)

    董蕾

    2012-01-01

    Mao Dun as a modern literary history play a decisive role of critics,the literary criticism in the internal and external factors formed under the combined effect of the unique personality and style.Taken developmental psychology,social psychology,personality psychology,inner thought,theory and practice as the starting point,overviewed the history of Mao Dun's literary criticism study,and revealed its basic characteristics,so as to further promote the work in the field of literary criticism of Mao Dun.%茅盾作为现代文学史上举足轻重的批评家,其文学批评在内外因的综合作用下形成了独特的个性和风采。通过梳理茅盾文学批评研究的历程,以发展心理、社会心理、个性心理、内在思维、理论实践五个方面为切入点,对茅盾文学批评的基本特征进行了阐释,以期进一步推动茅盾文学批评研究工作的开展。

  18. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  19. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  20. A Study on Antitoxic Role of Vesicular Monoamine Transporter 2 in Transgenic Chinese Hamster Overy Cells

    Institute of Scientific and Technical Information of China (English)

    叶民; 丁新生; 董海蓉; 仇镇宁; 管晓虹

    2003-01-01

    Objective:To study the antitoxic role of vesicular monoamine transporter 2 (VMAT2) in transpgenic Chinese Hamster ovary(CHO) cell.Methods:With the technology of transgene from PC12 to CHO,MTT reduction assay was used to detect MPP+ toxic effect on wild type CHO(wtCHO) and transgenic CHO.Meanwhile,the role of reserpine was also observed in MPP+ toxic effects.Results:The sensitivity of transgenic CHO to MPP+ was much less than that of wtCHO with 0.5 mmol/L MPP+.Transgenic CHO had the same sensitivity as wtCHO if rotenone was given.WtCHO,by given reserpine alone,didn''''''''t change its sensitivity to MPP+.Conclusions:VMAT2 has protective effect on transgenic CHO by transporting MPP+ to vesicles.

  1. Enzymatic Characterization and In Vivo Function of Five Terminal Oxidases in Pseudomonas aeruginosa

    OpenAIRE

    Arai, Hiroyuki; Kawakami, Takuro; Osamura, Tatsuya; Hirai, Takehiro; Sakai, Yoshiaki; Ishii, Masaharu

    2014-01-01

    The ubiquitous opportunistic pathogen Pseudomonas aeruginosa has five aerobic terminal oxidases: bo3-type quinol oxidase (Cyo), cyanide-insensitive oxidase (CIO), aa3-type cytochrome c oxidase (aa3), and two cbb3-type cytochrome c oxidases (cbb3-1 and cbb3-2). These terminal oxidases are differentially regulated under various growth conditions and are thought to contribute to the survival of this microorganism in a wide variety of environmental niches. Here, we constructed multiple mutant str...

  2. Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal monoamine transporters.

    Science.gov (United States)

    Wenge, Birger; Bönisch, Heinz

    2009-12-01

    The haloalkylamine DSP4 (N[-2-chloroethyl]-N-ethyl-2-bromobenzylamine) is a noradrenergic neurotoxin, which is used for the chemical denervation of noradrenergic neurons, and it has been proposed to be a selective substrate for the neuronal, Na(+)- and Cl(-)-dependent noradrenaline transporter (NAT). In the present study, we investigated whether DSP4 not only interacts with the human NAT (hNAT) but also with other neuronal monoamine transporters such as the transporters for dopamine (hDAT) and serotonin (hSERT) or with nonneuronal (Na(+)-independent) monoamine transporters also known as organic cation transporters (OCTs), such as hOCT(1), hOCT(2), and hOCT(3). Using human embryonic kidney HEK293 cells heterologously expressing the corresponding transporter, we show that DSP4 irreversibly inhibits the hNAT, hDAT, hSERT, and hOCT(3). However, this inhibition includes a reversible component at the hDAT, hSERT, and hOCT(3) but not at the hNAT. The inhibitory potency of DSP4 at the neuronal transporters was highest at the hNAT (IC(50) about 5 microM), and it was about five and 40 times lower at the hSERT and hDAT, respectively. DSP4 inhibited all three hOCTs with high potency (IC(50) about 1 microM) but in a completely reversible manner at hOCT(1) and hOCT(2). Cytotoxicity by 24-h exposure of hNAT- or hOCT-expressing cells to low DSP4 concentrations (DSP4's high-affinity uptake through the NAT together with its completely irreversible mode of interaction with the NAT may contribute to its selectivity as noradrenergic neurotoxin.

  3. DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.D.; Dean, M.; Goldman, D. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-06-19

    The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson`s disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. 52 refs., 3 figs., 1 tab.

  4. Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

    Science.gov (United States)

    Rasheed, Naila; Tyagi, Ethika; Ahmad, Ausaf; Siripurapu, Kiran Babu; Lahiri, Shawon; Shukla, Rakesh; Palit, Gautam

    2008-05-08

    Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

  5. Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus.

    Science.gov (United States)

    Cavalheiro, E A; Fernandes, M J; Turski, L; Naffah-Mazzacoratti, M G

    1994-01-01

    Rats subjected to structural brain damage induced by sustained convulsions triggered by systemic administration of pilocarpine (PILO) are a useful model for investigation of the mechanisms essential for seizure generation and spread in rodents. After PILO administration, three distinct phases are observed: (a) an acute period of 1-2 days' duration corresponding to a pattern of repetitive limbic seizures and status epilepticus; (b) a seizure-free (silent) period characterized by a progressive return to normal EEG and behavior of 4-44 days' duration; and (c) a period of spontaneous recurrent seizures (SRS) starting 5-45 days after PILO administration and lasting throughout the animal's life. PILO (320-350 mg/kg intraperitoneally, i.p.) was administered to rats, and the content of hippocampal monoamines and amino acids was measured in the acute, silent, and SRS periods by liquid chromatography. Norepinephrine (NE) level was decreased during all periods whereas dopamine (DA) content was increased. Serotonin (5-hydroxytryptamine, 5-HT) was increased only in the acute period. Utilization rate measurement of monoamines showed increased NE consumption and decreased DA consumption during all phases. 5-HT utilization rate was increased only in the acute period. Amino acid content showed a decrease in aspartate (ASP) and glutamate (GLU) concentrations associated with increased gamma-aminobutyric acid (GABA) level during the acute period. The silent phase was characterized by a decrease in glycine (GLY) and GABA levels and an increase in GLU concentration. The SRS period showed an increase in all amino acid concentrations. These findings show important neurochemical changes in the course of establishment of an epileptic focus after brain damage induced by status epilepticus triggered by pilocarpine.

  6. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue.

    Science.gov (United States)

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-04-01

    The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.

  7. The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue

    Science.gov (United States)

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-01-01

    The nonmedical use of ‘designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. PMID:22169943

  8. Laboratory-evolved vanillyl-alcohol oxidase produces natural vanillin

    NARCIS (Netherlands)

    Heuvel, van den R.H.H.; Berg, van den W.A.M.; Rovida, S.; Berkel, van W.J.H.

    2004-01-01

    The flavoenzyme vanillyl-alcohol oxidase was subjected to random mutagenesis to generate mutants with enhanced reactivity to creosol (2-methoxy-4-methylphenol). The vanillyl-alcohol oxidase-mediated conversion of creosol proceeds via a two-step process in which the initially formed vanillyl alcohol

  9. Endothelins and NADPH oxidases in the cardiovascular system.

    Science.gov (United States)

    Dammanahalli, Karigowda J; Sun, Zhongjie

    2008-01-01

    1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardiovascular dysfunction. Thus, NADPH oxidases may mediate the role of endothelins in some cardiovascular diseases. However, the role of reactive oxygen species (ROS) in mediating ET-induced vasoconstriction and cardiovascular disease remains under debate, as evidenced by conflicting reports from different research teams. Conversely, activation of NADPH oxidase can stimulate ET secretion via ROS generation, which further enhances the cardiovascular effects of NADPH oxidase. However, little is known about how ROS activate the endothelin system. It seems that the relationship between ET-1 and ROS may vary with cardiovascular disorders. 3. Endothelins activate NADPH oxidase via the ET receptor-proline-rich tyrosine kinase-2 (Pyk2)-Rac1 pathway. Rac1 is an important regulator of NADPH oxidase. There is ample evidence supporting direct stimulation by Rac1 of NADPH oxidase activity. In addition, Rac1-induced cardiomyocyte hypertrophy is mediated by the generation of ROS.

  10. Priming and activation of NADPH oxidases in plants and animals.

    Science.gov (United States)

    Canton, Johnathan; Grinstein, Sergio

    2014-09-01

    In mammals, engagement of Toll-like receptors by microbe-associated molecular patterns enhances the responsiveness of NADPH oxidases. Two recent papers report a similar 'priming' mechanism for the plant oxidase RbohD. Despite lacking structural homology, the functional parallels between plants and animals reveal that a common regulatory logic arose by convergent evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. MAO-synthesized Al 2O 3-supported V 2O 5 nano-porous catalysts: Growth, characterization, and photoactivity

    Science.gov (United States)

    Bayati, M. R.; Zargar, H. R.; Molaei, R.; Golestani-Fard, F.; Zanganeh, N.; Kajbafvala, A.

    2010-04-01

    V 2O 5-loaded Al 2O 3 layers were successfully grown via micro-arc oxidation (MAO) process for the first time. Surface morphology and topography of the layers were investigated by scanning electron microscope (SEM) and atomic force microscope (AFM). It was found that the composite layers had a porous structure with a rough surface which is suitable for catalytic applications. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray spectroscopy (EDS) techniques were also employed to study phase structure and chemical composition of the composite layers. The layers consisted of γ-alumina, α-alumina, and vanadium pentoxide phases in which their relative contents varied with the applied voltage. Meanwhile, optical properties of the composite layers were investigated using UV-vis spectrophotometry technique, and the band gap energy was calculated as 3.15 eV. Furthermore, photocatalytic performance of the synthesized composite layers was determined by measuring the decomposition rate of methylene blue solution, as a model compound, on the surface of the layers under ultra violet photo-irradiation. It was found that more than 91% of the methylene blue was degraded after 120 min with a rate constant of k = 0.0192 min -1.

  12. The Study of Translator's Roles——Taking two English Versions of Mao Zedong Poems and Ci as Examples

    Institute of Scientific and Technical Information of China (English)

    雷春晓

    2015-01-01

    Translation process concerns five factors: the author, the source text, the source-text readers, the translator, the target text and the target-text readers. The translator lies in central position which has a affiliation with the author, the source text, the source-text readers, the target text and the target-text readers. This paper applies the translation of Mao Zedong Poems and Ci as the corpus to analyze the translator's roles as a writer and a cultural mediator in Gu's and Zhao's version. As a reader, two translators are both Chinese and have some alike understanding of certain words in the comprehending and analysis process. In regard to the translator's acting as a writer, the paper analyzes the distinctions of two versions from three aspects: their different translations in terms of the sound, form and meaning. In regard to the translator acting as a cultural mediator, the translators mediates the cultural factors on the cultural imagery, allusion and the tune.

  13. Modulation of NADPH oxidase activity by known uraemic retention solutes

    DEFF Research Database (Denmark)

    Schulz, Anna Marta; Terne, Cindy; Jankowski, Vera

    2014-01-01

    as the strongest inhibitor of NADPH oxidase (90% of DPI inhibition). Surprisingly, none of the uraemic retention solutes we investigated was found to increase NADPH oxidase activity. Furthermore, plasma from patients with CKD-5D before dialysis caused significantly higher inhibitory effect on NADPH oxidase...... inhibitory effect on NADPH oxidase activity in the presence of plasma from patients with CKD-5D after dialysis compared with before dialysis, we investigated the effect of 48 known and commercially available uraemic retention solutes on the enzymatic activity of NADPH oxidase. METHODS: Mononuclear leucocytes...... isolated from buffy coats of healthy volunteers were isolated, lysed and incubated with NADH in the presence of plasma from healthy controls and patients with CKD-5D. Furthermore, the leucocytes were lysed and incubated in the presence of uraemic retention solute of interest and diphenyleneiodonium...

  14. The NADH oxidase-Prx system in Amphibacillus xylanus.

    Science.gov (United States)

    Niimura, Youichi

    2007-01-01

    Amphibacillus NADH oxidase belongs to a growing new family of peroxiredoxin-linked oxidoreductases including alkyl hydroperoxide reductase F (AhpF). Like AhpF it displays extremely high hydroperoxide reductase activity in the presence of a Prx, thus making up the NADH oxidase-Prx system. The NADH oxidase primarily catalyzes the reduction of oxygen by NADH to form H2O2, while the Prx immediately reduces H2O2 (or ROOH) to water (or ROH). Consequently, the NADH oxidase-Prx system catalyzes the reduction of both oxygen and hydrogen peroxide to water with NADH as the preferred electron donor. The NADH oxidase-Prx system is widely distributed in aerobically growing bacteria lacking a respiratory chain and catalase, and plays an important role not only in scavenging hydroperoxides but also in regenerating NAD in these bacteria.

  15. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Directory of Open Access Journals (Sweden)

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  16. Molecular biology of amitraz resistance in cattle ticks of the genus Rhipicephalus.

    Science.gov (United States)

    Jonsson, Nicholas N; Klafke, Guilherme; Corley, Sean W; Tidwell, Jason; Berry, Christina M; Koh-Tan, Hh Caline

    2018-01-01

    Amitraz is an important product for the control of cattle ticks around the world. In comparison with other products for the control of ticks, it is quite affordable and it has a rapid knock-down effect. It binds with and activates adrenergic neuro-receptors of animals and it inhibits the action of monoamine oxidases (MAO). Resistance to amitraz has been documented in Rhipicephalus microplus, R. decoloratus and R. appendiculatus. Four mechanisms of resistance have been proposed, each of which is supported by evidence but none of which has been definitively confirmed as the cause of resistance in the field. The proposed mechanisms include genetic target site insensitivity in two G protein-coupled receptors, the beta-adrenergic octopamine receptor (BAOR) and the octopamine/tyramine receptor (OCT/Tyr), increased expression or activity of monoamine oxidases and increased expression or activity of the ATP binding cassette transporter.

  17. Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices

    OpenAIRE

    John, Carrie E.; Jones, Sara R

    2007-01-01

    Fast scan cyclic voltammetry is an electrochemical technique used to measure dynamics of transporter-mediated monoamine uptake in real time and provides a tool to evaluate the detailed effects of monoamine uptake inhibitors and releasers on dopamine and serotonin transporter function. We measured the effects of cocaine, methylphenidate, 2β-propanoyl–3β-(4tolyl) tropane (PTT), fluoxetine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), phentermine and fenfluramine on do...

  18. Piperidine-Based Nocaine/Modafinil Hybrid Ligands as Highly Potent Monoamine Transporter Inhibitors: Efficient Drug Discovery by Rational Lead Hybridization

    Science.gov (United States)

    Zhou, Jia; He, Rong; Johnson, Kenneth M.; Ye, Yanping; Kozikowski, Alan P.

    2005-01-01

    Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea. PMID:15537337

  19. NADPH Oxidases in Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Joy X. Jiang

    2014-01-01

    Full Text Available Oxidative stress is a common feature observed in a wide spectrum of chronic liver diseases including viral hepatitis, alcoholic, and nonalcoholic steatohepatitis. The nicotinamide adenine dinucleotide phosphate (NADPH oxidases (NOXs are emerging as major sources of reactive oxygen species (ROS. Several major isoforms are expressed in the liver, including NOX1, NOX2, and NOX4. While the phagocytic NOX2 has been known to play an important role in Kupffer cell and neutrophil phagocytic activity and inflammation, the nonphagocytic NOX homologues are increasingly recognized as key enzymes in oxidative injury and wound healing. In this review, we will summarize the current advances in knowledge on the regulatory pathways of NOX activation, their cellular distribution, and their role in the modulation of redox signaling in liver diseases.

  20. Glucose oxidase immobilization onto carbon nanotube networking

    CERN Document Server

    Karachevtsev, V A; Zarudnev, E S; Karachevtsev, M V; Leontiev, V S; Linnik, A S; Lytvyn, O S; Plokhotnichenko, A M; Stepanian, S G

    2012-01-01

    When elaborating the biosensor based on single-walled carbon nanotubes (SWNTs), it is necessary to solve such an important problem as the immobilization of a target biomolecule on the nanotube surface. In this work, the enzyme (glucose oxidase (GOX)) was immobilized on the surface of a nanotube network, which was created by the deposition of nanotubes from their solution in 1,2-dichlorobenzene by the spray method. 1-Pyrenebutanoic acid succinimide ester (PSE) was used to form the molecular interface, the bifunctional molecule of which provides the covalent binding with the enzyme shell, and its other part (pyrene) is adsorbed onto the nanotube surface. First, the usage of such a molecular interface leaves out the direct adsorption of the enzyme (in this case, its activity decreases) onto the nanotube surface, and, second, it ensures the enzyme localization near the nanotube. The comparison of the resonance Raman (RR) spectrum of pristine nanotubes with their spectrum in the PSE environment evidences the creat...

  1. Characterization of Glucose Oxidase from Penicillium notatum

    Directory of Open Access Journals (Sweden)

    Nabeela Saleem

    2009-01-01

    Full Text Available In the present study glucose oxidase (GOD has been isolated from a culture filtrate of Penicillium notatum. The enzyme was purified by ammonium sulphate precipitation, diethylaminoethyl (DEAE cellulose ion-exchange chromatography and Sephadex gel filtration. This protocol gave 16.47-fold purification and 25 % recovery of the enzyme. The optimum pH and temperature for the activity were 5.4 and 45 °C, respectively. The Km and vmax values for the enzyme were 10.5 mM and 456 U/mg, respectively. A detailed kinetic study of thermal inactivation was carried out. Both enthalpy of activation (ΔH* and entropy of activation (ΔS* decreased at higher temperatures. Moreover, free energy of denaturation (ΔG* increased at higher temperature, making the enzyme thermally stable. A possible explanation for the thermal inactivation of GOD at higher temperatures is also discussed.

  2. Portability of oxidase domains in nonribosomal peptide synthetase modules.

    Science.gov (United States)

    Schneider, Tanya L; Walsh, Christopher T

    2004-12-21

    Oxazole and thiazole rings are present in numerous nonribosomal peptide natural products. Oxidase domains are responsible for catalyzing the oxidation of thiazolines and oxazolines to yield fully aromatic heterocycles. Unlike most domains, the placement of oxidase domains within assembly line modules varies. Noting this tolerance, we investigated the portability of an oxidase domain to a heterologous assembly line. The epimerase domain of PchE, involved in pyochelin biosynthesis, was replaced with the oxidase domain from MtaD, involved in myxothiazol biosynthesis. The chimeric module was expressed in soluble form as a flavin mononucleotide-containing flavoprotein. The functionality of the inserted oxidase domain was assayed within PchE and in transfer of the growing siderophore acyl chain from PchE to the next downstream module. While pyochelin-like product release was not observed downstream, the robust activity of the transplanted oxidase domain and the ability of the chimeric module to produce an advanced intermediate bound to the synthetase underscore the possibility of future engineering within nonribosomal peptide synthetase pathways using oxidase domains.

  3. [Changes in the monoamine content in different parts of hypothalamus depending on the stages of the estrous cycle].

    Science.gov (United States)

    Babichev, V N; Adamskaia, E I

    1976-01-01

    Fluorimetric determination of monoamines in various regions of the hypothalamus and at different stages of the estral cycle in rats showed that the serotonin, noradrenaline, and particularly dophamine content changed both in the course of the cycle and at different time (10, 15 and 18 hours) of the same stage of the cycle. Dophamine concentration in the arcuate area--the centre of the tonic activity--reached its maximum at 18 hours of the diestrus-2 (D2) and fell to the minimum at 10 hours of the proestrus (P). Noradrenaline level in the preoptic area increased at 18 hours of the D2 and fell at 10 hours of the P. It is supposed that in the hypothalamic regulation of the estral cycle at least two monoamines (dopamine and noradrenaline) took part; the trigger role belongs to noradrenaline of the preoptic area (the cyclic centre).

  4. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

    -dependent relaxation and endothelial NO synthase (eNOS) were increased in arteries from anhedonic rats. Inhibition of cyclooxygenase (COX) activity revealed increased COX-2-dependent relaxation in anhedonic group. In contrast, eNOS- and COXindependent relaxation to acetylcholine (EDH-like response) was significantly...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  5. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian;

    Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  6. Direct regulation of cytochrome c oxidase by calcium ions.

    Directory of Open Access Journals (Sweden)

    Tatiana Vygodina

    Full Text Available Cytochrome c oxidase from bovine heart binds Ca(2+ reversibly at a specific Cation Binding Site located near the outer face of the mitochondrial membrane. Ca(2+ shifts the absorption spectrum of heme a, which allowed previously to determine the kinetics and equilibrium characteristics of the binding. However, no effect of Ca(2+ on the functional characteristics of cytochrome oxidase was revealed earlier. Here we report that Ca(2+ inhibits cytochrome oxidase activity of isolated bovine heart enzyme by 50-60% with Ki of ∼1 µM, close to Kd of calcium binding with the oxidase determined spectrophotometrically. The inhibition is observed only at low, but physiologically relevant, turnover rates of the enzyme (∼10 s(-1 or less. No inhibitory effect of Ca(2+ is observed under conventional conditions of cytochrome c oxidase activity assays (turnover number >100 s(-1 at pH 8, which may explain why the effect was not noticed earlier. The inhibition is specific for Ca(2+ and is reversed by EGTA. Na(+ ions that compete with Ca(2+ for binding with the Cation Binding Site, do not affect significantly activity of the enzyme but counteract the inhibitory effect of Ca(2+. The Ca(2+-induced inhibition of cytochrome c oxidase is observed also with the uncoupled mitochondria from several rat tissues. At the same time, calcium ions do not inhibit activity of the homologous bacterial cytochrome oxidases. Possible mechanisms of the inhibition are discussed as well as potential physiological role of Ca(2+ binding with cytochrome oxidase. Ca(2+- binding at the Cation Binding Site is proposed to inhibit proton-transfer through the exit part of the proton conducting pathway H in the mammalian oxidases.

  7. CotA, a multicopper oxidase from Bacillus pumilus WH4, exhibits manganese-oxidase activity.

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    Jianmei Su

    Full Text Available Multicopper oxidases (MCOs are a family of enzymes that use copper ions as cofactors to oxidize various substrates. Previous research has demonstrated that several MCOs such as MnxG, MofA and MoxA can act as putative Mn(II oxidases. Meanwhile, the endospore coat protein CotA from Bacillus species has been confirmed as a typical MCO. To study the relationship between CotA and the Mn(II oxidation, the cotA gene from a highly active Mn(II-oxidizing strain Bacillus pumilus WH4 was cloned and overexpressed in Escherichia coli strain M15. The purified CotA contained approximately four copper atoms per molecule and showed spectroscopic properties typical of blue copper oxidases. Importantly, apart from the laccase activities, the CotA also displayed substantial Mn(II-oxidase activities both in liquid culture system and native polyacrylamide gel electrophoresis. The optimum Mn(II oxidase activity was obtained at 53°C in HEPES buffer (pH 8.0 supplemented with 0.8 mM CuCl2. Besides, the addition of o-phenanthroline and EDTA both led to a complete suppression of Mn(II-oxidizing activity. The specific activity of purified CotA towards Mn(II was 0.27 U/mg. The Km, Vmax and kcat values towards Mn(II were 14.85±1.17 mM, 3.01×10(-6±0.21 M·min(-1 and 0.32±0.02 s(-1, respectively. Moreover, the Mn(II-oxidizing activity of the recombinant E. coli strain M15-pQE-cotA was significantly increased when cultured both in Mn-containing K liquid medium and on agar plates. After 7-day liquid cultivation, M15-pQE-cotA resulted in 18.2% removal of Mn(II from the medium. Furthermore, the biogenic Mn oxides were clearly observed on the cell surfaces of M15-pQE-cotA by scanning electron microscopy. To our knowledge, this is the first report that provides the direct observation of Mn(II oxidation with the heterologously expressed protein CotA, Therefore, this novel finding not only establishes the foundation for in-depth study of Mn(II oxidation mechanisms, but also offers

  8. Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine.

    Science.gov (United States)

    Lizarraga, Lucina E; Cholanians, Aram B; Phan, Andy V; Herndon, Joseph M; Lau, Serrine S; Monks, Terrence J

    2015-01-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long-term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in 5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA-induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which increases cytosolic 5-HT concentrations available for release via a carrier-mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is a molecular target for a number of psychostimulant drugs, including methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented the thermogenic effects of MDMA, instead causing a transient decrease in body temperature. MDMA-treated rats exhibited marked increases in horizontal velocity and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA.

  9. Comparison of time-dependent effects of (+-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats

    Directory of Open Access Journals (Sweden)

    Gudelsky Gary A

    2008-05-01

    Full Text Available Abstract Background Methamphetamine (MA use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+-MA (4 doses at 2 h intervals on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session 4 times at 2 h intervals]. Results MA increased corticosterone from 1–72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Conclusion Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone.

  10. Concentration-dependent effects of cocaine on monoamine-induced constriction of cannulated, pressurized cerebral arteries from fetal sheep.

    Science.gov (United States)

    Schreiber, M D; Madden, J A; Covert, R F; Hershenson, M B; Torgerson, L J

    1995-01-01

    Drugs, such as cocaine, which may alter monoamine neurotransmitter responsiveness, could adversely affect the regulation of cerebral vasculature. Cocaine exhibits at least two mechanisms that may alter vascular responsiveness: synaptic uptake inhibition, which may augment response to stimulation, and Na+ channel inhibition, which may attenuate response. To help elicit the concentration-dependent effects of cocaine, the effects of cocaine on monoamine neurotransmitter responsiveness were studied in vitro on fetal sheep cerebral arteries (120 days gestation). The changes in diameter of segments of cannulated, pressurized fetal sheep cerebral artery were measured with a videomicroscaler system. Cumulative concentration-response curves (10(-10) to 10(-4)M) were generated for two monoamines, norepinephrine and serotonin, alone and in the presence of cocaine (10(-5) or 10(-4)M). Cocaine caused concentration-dependent alteration of response. At 10(-4)M, cocaine attenuated mean maximal norepinephrine-induced vasoconstriction 46.2% (P < 0.05). At 10(-5)M, cocaine increased sensitivity to norepinephrine (log EC50 decreased -6.63 +/- 0.09 to -7.11 +/- 0.03) and to serotonin (log EC50 decreased -7.24 +/- 0.04 to -7.81 +/- 0.09) (P < 0.05). The higher concentration of cocaine (10(-4)M) did not significantly decrease log EC50 norepinephrine. Cocaine (10(-4)M) also attenuated the response to single doses of norepinephrine (10(-6)M) and serotonin (10(-6)M) by 26.5% and 40.0%, respectively (P < or = 0.05). It is concluded that cocaine has concentration-dependent effects on vasoconstriction of the fetal sheep cerebral artery in vitro. This cocaine-induced alteration of cerebral vascular responsiveness to monoamines may be important in the regulation of fetal cerebral blood flow.

  11. Multilayered polyelectrolyte microcapsules: interaction with the enzyme cytochrome C oxidase.

    Science.gov (United States)

    Pastorino, Laura; Dellacasa, Elena; Noor, Mohamed R; Soulimane, Tewfik; Bianchini, Paolo; D'Autilia, Francesca; Antipov, Alexei; Diaspro, Alberto; Tofail, Syed A M; Ruggiero, Carmelina

    2014-01-01

    Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components. This work provides a significant input towards the fabrication of an integrated device made of biological components and based on specific biomolecular functions and properties.

  12. Multilayered polyelectrolyte microcapsules: interaction with the enzyme cytochrome C oxidase.

    Directory of Open Access Journals (Sweden)

    Laura Pastorino

    Full Text Available Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components. This work provides a significant input towards the fabrication of an integrated device made of biological components and based on specific biomolecular functions and properties.

  13. 毛泽东执政伦理思想研究%Research on Ruling Ethic Thoughts of Mao Zedong

    Institute of Scientific and Technical Information of China (English)

    赖海燕

    2014-01-01

    In the leading process of Chinese revolution and construction, Mao Zedong formed ruling ethic thoughts with rich con-notation, such as the core ruling value idea with “serving the people heart and soul”, democratic centralism, people’ s national congress system, multi-party cooperation system, the main ruling morality such as taking morality and professional competence as the total requirement for ruling benchmark, and the ruling ethic construction with concrete path such as rectifying the working style of the Party members, setting up advanced moral models, consolidating the moral self-cultivation of the Party members and so on, as a result, these excellent thoughts can inevitably trigger various beneficial thinking at new era.%毛泽东在领导中国革命和建设的过程中,形成了内涵丰富的执政伦理思想。以“全心全意为人民服务”为核心的执政价值理念,以民主集中制、人民代表大会制以及多党合作制为主要内容的执政制度伦理,以才德兼备为总要求的执政主体德性,以整顿党的作风建设、树立先进道德典型、加强党员道德修养等为具体途径的执政伦理建设。这些精辟的思想在新时期无疑可以引发许多有益的思考。

  14. Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.

    Science.gov (United States)

    Nakamura, Tomoka; Honda, Motoko; Kimura, Satoko; Tanabe, Mitsuo; Oda, Sen-ichi; Ono, Hideki

    2005-12-01

    To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant. The DA and 5-HT contents in each tissue did not differ from those of the control, but the concentrations of monoamines, except for DA, were elevated in the brain stem and spinal cord in RMN. In particular, the concentrations of NA, DA and 5-HT in the cerebellum were significantly increased in RMN. Repeated administration of tartilerin hydrate, an analog of thyrotropin-releasing hormone, improved the ataxia of RMN, and elicited no obvious changes in either monoamine content or concentration of cerebellum, brain stem and spinal cord. These results indicate that the concentration of DA, as well as NA and 5-HT, increased in the RMN cerebellum, and that tartilerin improves the motor function of these mice via mechanisms other than changes in the levels of NA, DA and 5-HT in the central nervous system.

  15. Analysis of microdialysate monoamines, including noradrenaline, dopamine and serotonin, using capillary ultra-high performance liquid chromatography and electrochemical detection.

    Science.gov (United States)

    Ferry, Barbara; Gifu, Elena-Patricia; Sandu, Ioana; Denoroy, Luc; Parrot, Sandrine

    2014-03-01

    Electrochemical methods are very often used to detect catecholamine and indolamine neurotransmitters separated by conventional reverse-phase high performance liquid chromatography (HPLC). The present paper presents the development of a chromatographic method to detect monoamines present in low-volume brain dialysis samples using a capillary column filled with sub-2μm particles. Several parameters (repeatability, linearity, accuracy, limit of detection) for this new ultrahigh performance liquid chromatography (UHPLC) method with electrochemical detection were examined after optimization of the analytical conditions. Noradrenaline, adrenaline, serotonin, dopamine and its metabolite 3-methoxytyramine were separated in 1μL of injected sample volume; they were detected above concentrations of 0.5-1nmol/L, with 2.1-9.5% accuracy and intra-assay repeatability equal to or less than 6%. The final method was applied to very low volume dialysates from rat brain containing monoamine traces. The study demonstrates that capillary UHPLC with electrochemical detection is suitable for monitoring dialysate monoamines collected at high sampling rate.

  16. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

    Science.gov (United States)

    Malm, J; Kristensen, B; Ekstedt, J; Adolfsson, R; Wester, P

    1991-03-01

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  17. Changes in Brain Monoamines Underlie Behavioural Disruptions after Zebrafish Diet Exposure to Polycyclic Aromatic Hydrocarbons Environmental Mixtures

    Science.gov (United States)

    Vignet, Caroline; Trenkel, Verena M.; Vouillarmet, Annick; Bricca, Giampiero; Bégout, Marie-Laure; Cousin, Xavier

    2017-01-01

    Zebrafish were exposed through diet to two environmentally relevant polycyclic aromatic hydrocarbons (PAHs) mixtures of contrasted compositions, one of pyrolytic (PY) origin and one from light crude oil (LO). Monoamine concentrations were quantified in the brains of the fish after six month of exposure. A significant decrease in noradrenaline (NA) was observed in fish exposed to both mixtures, while a decrease in serotonin (5HT) and dopamine (DA) was observed only in LO-exposed fish. A decrease in metabolites of 5HT and DA was observed in fish exposed to both mixtures. Several behavioural disruptions were observed that depended on mixtures, and parallels were made with changes in monoamine concentrations. Indeed, we observed an increase in anxiety in fish exposed to both mixtures, which could be related to the decrease in 5HT and/or NA, while disruptions of daily activity rhythms were observed in LO fish, which could be related to the decrease in DA. Taken together, these results showed that (i) chronic exposures to PAHs mixtures disrupted brain monoamine contents, which could underlie behavioural disruptions, and that (ii) the biological responses depended on mixture compositions. PMID:28273853

  18. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

    Directory of Open Access Journals (Sweden)

    Daniel eDavies

    2016-04-01

    Full Text Available Mild traumatic brain injury (mTBI produces symptoms similar to those typifying posttraumatic stress disorder (PTSD in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM, or for contextual fear conditioning and extinction. Brains were collected 24 hr after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

  19. Prion-derived copper-binding peptide fragments catalyze the generation of superoxide anion in the presence of aromatic monoamines

    Directory of Open Access Journals (Sweden)

    Tomonori Kawano

    2007-01-01

    Full Text Available Objectives: Studies have proposed two opposing roles for copper-bound forms of prion protein (PrP as an anti-oxidant supporting the neuronal functions and as a pro-oxidant leading to neurodegenerative process involving the generation of reactive oxygen species. The aim of this study is to test the hypothesis in which putative copper-binding peptides derived from PrP function as possible catalysts for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro. Materials and methods: Four peptides corresponding to the copper (II-binding motifs in PrP were synthesized and used for analysis of peptide-catalyzed generation of superoxide in the presence of Cu (II and other factors naturally present in the neuronal tissues. Results: Among the Cu-binding peptides tested, the amino acid sequence corresponding to the Cu-binding site in the helical region was shown to be the most active for superoxide generation in the presence of Cu(II, hydrogen peroxide and aromatic monoamines, known precursors or intermediates of neurotransmitters. Among monoamines tested, three compounds namely phenylethylamine, tyramine and benzylamine were shown to be good substrates for superoxide-generating reactions by the Cu-bound helical peptide. Conclusions: Possible roles for these reactions in development of prion disease were suggested.

  20. Monoamine transporter availability in Parkinson's disease patients with or without depression

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Meyer, Philipp M.; Barthel, Henryk; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Strecker, Karl; Wegner, Florian; Isaias, Ioannis Ugo; Schwarz, Johannes [University of Leipzig, Department of Neurology, Leipzig (Germany); Oehlwein, Christian [Specialized Parkinson' s Disease Outpatient Centre, Gera (Germany)

    2009-03-15

    Depression is a common symptom in patients suffering from Parkinson's disease (PD) and markedly reduces their quality of life. As post-mortem studies have shown, its presence may reflect extensive cell loss in the midbrain and brainstem with imbalances in monoaminergic neurotransmitters. However, in vivo evidence of specific monoaminergic deficits in depressed PD patients is still sparse. Therefore, we studied PD patients with depression (PD+D) and without depression (PD-D) using high-resolution single-photon emission computed tomography (SPECT) and the monoamine transporter marker [{sup 123}I]FP-CIT. A magnetic resonance imaging-based region-of-interest analysis was applied to quantify the specific-to-nondisplaceable [{sup 123}I]FP-CIT binding coefficient V{sub 3}'' in the striatum, thalamus and midbrain/brainstem regions. PD+D patients had significantly lower V{sub 3}'' compared with PD-D patients in the striatum (p<0.001), thalamus (p=0.002), and midbrain/brainstem (p=0.025). Only PD+D patients without selective serotonin reuptake inhibitor (SSRI) treatment showed lower thalamic and midbrain V{sub 3}'' than controls (p<0.001, p=0.029). In a small sub-group of SSRI-treated PD+D patients neither thalamic V{sub 3}'' nor midbrain/brainstem V{sub 3}'' differed from those in PD-D patients (p=0.168, p=0.201) or controls (p=0.384, p=0.318). Our data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients. These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor

  1. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels.

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    Kate Lykke Lambertsen

    Full Text Available BACKGROUND: The calmodulin/calcium-activated K(+ channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice. METHODOLOGY/PRINCIPAL FINDINGS: In the open field test, KCa3.1-deficiency increased horizontal activity, as KCa3.1(-/- mice travelled longer distances (≈145% of KCa3.1(+/+ and at higher speed (≈1.5-fold of KCa3.1(+/+. Working memory in the Y-maze was reduced by KCa3.1-deficiency. Motor coordination on the rotarod and neuromuscular functions were unchanged. In KCa3.1(-/- mice, HPLC analysis revealed that turn-over rates of serotonin were reduced in frontal cortex, striatum and brain stem, while noradrenalin turn-over rates were increased in the frontal cortex. Dopamine turn-over rates were unaltered. Plasma catecholamine and corticosterone levels were unaltered. Intraperitoneal injections of 10 mg/kg of the KCa3.1/KCa2-activator SKA-31 reduced rearing and turning behavior in KCa3.1(+/+ but not in KCa3.1(-/- mice, while 30 mg/kg SKA-31 caused strong sedation in 50% of the animals of either genotypes. KCa3.1(-/- mice were hyperactive (≈+60% in their home cage and SKA-31-administration reduced nocturnal physical activity in KCa3.1(+/+ but not in KCa3.1(-/- mice. CONCLUSIONS/SIGNIFICANCE: KCa3.1-deficiency causes locomotor hyperactivity and altered monoamine levels in selected brain regions, suggesting a so far unknown functional link of KCa3.1 channels to behavior and monoaminergic neurotransmission in mice. The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders.

  2. Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia

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    Ashwin Jacob Mathai

    2016-08-01

    Full Text Available Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1 type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH dysfunction and tryptophan breakdown to kynurenine via indoleamine 2,3-dioxygenase (IDO. Nicotine also induces tyrosine hydroxylase gene (TH expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine, tyrosine, tryptophan and kynurenine levels using high-performance liquid chromatography (HPLC and calculated phenylalanine: tyrosine (Phe: Tyr and kynurenine: tryptophan (Kyn: Trp ratios in 920 patients with schizophrenia. Analysis of variance (ANOVA and linear regression analyses were used to compare these endpoints between 3 groups of patients with schizophrenia; 1 current smokers, 2 past smokers and 3 non-smokers. There were significant differences among the three groups with regards to tyrosine levels [F(2,789=3.77, p=0.02], with current smokers having lower tyrosine levels when compared to non-smokers (p=0.02. Kynurenine levels and Kyn :Trp ratio were different among the 3 groups [F (2,738=3.17, p=0.04, F(2,738=3.61, p=0.03] with current smokers having lower kynurenine levels (p=0.04 and higher Kyn: Trp ratio (p=0.02 when compared to past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered tyrosine and kynurenine levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking

  3. Xanthine oxidase in human skeletal muscle following eccentric exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik; Orthenblad, N.

    1997-01-01

    1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised and the ......1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised...... the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase...

  4. Aldehyde-induced xanthine oxidase activity in raw milk.

    Science.gov (United States)

    Steffensen, Charlotte L; Andersen, Henrik J; Nielsen, Jacob H

    2002-12-04

    In the present study, the aldehyde-induced pro-oxidative activity of xanthine oxidase was followed in an accelerated raw milk system using spin-trap electron spin resonance (ESR) spectroscopy. The aldehydes acetaldehyde, propanal, hexanal, trans-2-hexenal, trans-2-heptenal, trans-2-nonenal, and 3-methyl-2-butenal were all found to initiate radical reactions when added to milk. Formation of superoxide through aldehyde-induced xanthine oxidase activity is suggested as the initial reaction, as all tested aldehydes were shown to trigger superoxide formation in an ultrahigh temperature (UHT) milk model system with added xanthine oxidase. It was found that addition of aldehydes to milk initially increased the ascorbyl radical concentration with a subsequent decay due to ascorbate depletion, which renders the formation of superoxide in milk with added aldehyde. The present study shows for the first time potential acceleration of oxidative events in milk through aldehyde-induced xanthine oxidase activity.

  5. Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus.

    Science.gov (United States)

    Boyle, Keith B; Stephens, Len R; Hawkins, Phillip T

    2012-12-01

    Upon infection of the respiratory system with the fungus Aspergillus fumigatus various leukoctytes, in particular neutrophils, are recruited to the lung to mount an immune response. Neutrophils respond by both phagocytosing conidia and mediating extracellular killing of germinated, invasive hyphae. Of paramount importance to an appropriate immune response is the neutrophil NADPH oxidase enzyme, which mediates the production of various reactive oxygen species (ROS). This is evidenced by the acute sensitivity of both oxidase-deficient humans and mice to invasive aspergillosis. Herein we briefly review the mechanisms and functions of oxidase activation and discuss our recent work identifying at least some of the important players in hyphal-induced oxidase activation and neutrophil function. Among these we define the phosphoinositide 3-kinase enzyme and the regulatory protein Vav to be of critical importance and allude to a kinase-independent role for Syk.

  6. 毛泽东畜牧业思想述论%Discussing the Thoughts of Mao Zedongˊs Animal Husbandry

    Institute of Scientific and Technical Information of China (English)

    周有健

    2015-01-01

    Upbringing in peasantˊs family,learning from marxist theory of animal husbandry and concerning on the peopleˊs livelihood decided Mao Zedongˊs animal husbandry. The main content Mao Zedongˊs thought of animal hus-bandry included the union of farming,forestry,animal husbandry,peopleˊs meat,foreign exchange-earning,pigs as a center and comprehensive development of animal husbandry. In the practice of building the characteristics of Chi-na socialist,reflecting the animal husbandry thoughts of Mao Zedong requires us to treat complex and center theory carefully,the integrated and coordinated efforts of all works.%出生农家成长经历、自觉地汲取马克思主义畜牧业理论和对民生的关注凝铸成毛泽东在革命战争年代和社会主义革命、建设时期一贯重视畜牧业的情结。强调农、林、牧相结合以及基于养猪对积肥、百姓肉食、出口创汇等作用的思考提出的以养猪为中心,全面发展畜牧业的主张是毛泽东畜牧业思想的具体外显。在建设中国特色社会主义新时期,反思毛泽东畜牧业思想要求谨慎对待情结和中心论,统筹协调抓好各项工作。

  7. On Mao Zedong's Anti-corruption Thoughts and its Practical Significance%试论毛泽东反腐败思想及其现实意义

    Institute of Scientific and Technical Information of China (English)

    赵建宾

    2012-01-01

    毛泽东反腐败思想是毛泽东思想的重要组成部分。毛泽东同志的反腐败思想内容十分丰富,主要有:反腐败关系党和国家兴亡的战略思想;惩治腐败,从严治党的思想;发扬民主,加强人民群众监督的思想;反腐败教育的思想;以身作则,正人先正己等反腐败思想。在新时期,结合改革开放和现代化建设的现实情况,学习和研究毛泽东的反腐败思想,对于正在进行的党风廉政建设和深入开展反腐败斗争,具有十分重要的现实意义。%Mao Zedongls anti-corruption is an important part of the Mao Zedong Thoughts. The contents are very rich, mainly as follows: the strategic thoughts of anti-corruption related to the prosperity and decline of the party and the nation, the thoughts of punishing corruption and governing the party strictly, the thoughts of promoting democracy and strengthening the peoplels supervision, the thoughts of anti-corruption education; the set-an-example and sweep-before-your-own-door thoughts. In the new period of reform, opening-up and modernization construction, combining with the reality, it is of great practical significance to study Mao Zedong's anti-corruption thoughts for the ongoing construction of a clean and honest government and indepth development of anti-corruption struggle.

  8. Mao Zedong' s Brief Comments on the Evaluation of Deng Xiaoping%略论毛泽东对邓小平的评价

    Institute of Scientific and Technical Information of China (English)

    戴平安; 熊明

    2012-01-01

    Mao Zedong and Deng Xiaoping, the two great leaders and long-time colleagues, had carried on a long-term exploration of Sinicization of Marxism. They had cooperated well for a long time while there have been discrepancy between them for a period of time. Mao Zedong spoke highly and correctly of Deng Xiaoping on Deng Xiaoping' s leadership, the political moral character and many other aspects. He gave Deng Xiaoping proper affirmation and high evaluation, and raised Deng Xiaoping as the successor several times. However, when Mao Zedong made significant mistakes in both theory and practice for his personal reasons, he made negative evaluation on Deng Xiaoping and abolished Deng Xiaoping' s positions in and out of the Party twice.%毛泽东和邓小平作为长期共事的伟人,为马克思主义中国化进行了长期的探索,二人既有亲密无间也有严重分歧。毛泽东对邓小平的领导才能、政治品格等方面多次充分的肯定,给予高度的评价,数次作为接班人来培养;但当他自己在理论和实践上都出现重大失误的时候,又对邓小平做出否定性评价,两次撤销其党内外一切职务。

  9. Communication Memoir between Hu Yaobang and Mao Zedong%胡耀邦与毛泽东交往实录(下)

    Institute of Scientific and Technical Information of China (English)

    李佑新; 吴璇

    2016-01-01

    胡耀邦是久经考验的忠诚的共产主义战士,伟大的无产阶级革命家、政治家,我军杰出的政治工作者,长期担任党的重要领导职务的卓越领导人。从20世纪30年代在陕北初识毛泽东,历经难忘的抗大时光和革命岁月,到新中国成立后主政川北、投身青年团工作、整顿中国科学院,胡耀邦得到了毛泽东的关怀、教育和培养,并始终追随毛泽东的事业。%Hu Yaobang was a long-tested loyal communist fighter,a great proletarian revolutionist,a statesman and an outstanding political worker of the people’s army,a brilliant leader who held the important post of the Party for a long time.From the 1930’s in the Northern Shaanxi he met Mao Zedong,and passed an unforgettable time in the Anti-Japanese military and political college and revolution years,to head the admin-istration in the Northern Sichuan Province,devote himself to the Communist Youth League and rectify the Chi-nese Academy of Sciences after the founding of new China,Hu Yaobang had been taken care of,educated and cultivated by Mao Zedong.He followed Mao Zedong’s career all his time.

  10. 毛奇龄批本《西厢记》新探%A New Study on Romance of West Chamber Commented by Mao Qiling

    Institute of Scientific and Technical Information of China (English)

    李克

    2014-01-01

    Mao Qiling was a outstanding Confucian scholar in the early Qing dynasty .The Romance of West Chamber commented by Mao Qiling is a comprehensive version of the drama with explanation and proof after Wang Jide and Ling Mengchu .Mao Qiling ’ s commentary is as rigorous as archaeological studies of Confucian classics ,while showing an addiction to the song style and rhyme of drama .Meanwhile , with some understanding in the ex-planation and proof , his commentary shows a litter feature of appreciation , which deepening the commentary on the Romance of West Chamber.%明末清初是中国古典戏曲评点的鼎盛期,涌现了一批戏曲评点大师,如王骥德、凌濛初、孟称舜、金圣叹、毛纶、毛奇龄,等等。毛奇龄以清初大儒的身份批点《西厢记》,使毛批本《西厢记》成为继王骥德、凌濛初以来《西厢记》“解证式评点”的集大成者,他的批点既有经学考古式的严谨,又展示了偏嗜曲体曲韵之学的风格特色。而毛奇龄在解证中时有会意,又赋予毛批本《西厢记》“鉴赏型”评点的些许特色,进一步推动了《西厢记》评点批评走向深入。

  11. Inventory control: cytochrome c oxidase assembly regulates mitochondrial translation.

    Science.gov (United States)

    Mick, David U; Fox, Thomas D; Rehling, Peter

    2011-01-01

    Mitochondria maintain genome and translation machinery to synthesize a small subset of subunits of the oxidative phosphorylation system. To build up functional enzymes, these organellar gene products must assemble with imported subunits that are encoded in the nucleus. New findings on the early steps of cytochrome c oxidase assembly reveal how the mitochondrial translation of its core component, cytochrome c oxidase subunit 1 (Cox1), is directly coupled to the assembly of this respiratory complex.

  12. Regulation of the NADPH Oxidase RBOHD During Plant Immunity

    OpenAIRE

    2015-01-01

    Pathogen recognition induces the production of reactive oxygen species (ROS) by NADPH oxidases in both plants and animals. ROS have direct antimicrobial properties, but also serve as signaling molecules to activate further immune outputs. However, ROS production has to be tightly controlled to avoid detrimental effects on host cells, but yet must be produced in the right amount, at the right place and at the right time upon pathogen perception. Plant NADPH oxidases belong to the respiratory b...

  13. Mao Zedong ’ s Anti-Corruption Thought and Its Contemporary Value%毛泽东反腐倡廉思想及其当代价值

    Institute of Scientific and Technical Information of China (English)

    张桥

    2014-01-01

    Mao Zedong has attached great importance to anti-corruption work in various periods of revolu-tion and construction .He put forward a series of concepts and measures of anti-corruption , tested them contin-uously through practice , and ultimately formed Mao Zedong ’ s Anti-corruption Thought which guided the party and state to carry out anti-corruption work .Mao Zedong ’ s Anti-corruption Thought is the origin and foundation of the anti-corruption ideas of socialism with Chinese characteristics , and it is a powerful ideological weapon guiding anti-corruption work carried out under the new situation .The paper proposes a series of considerations about further development and refinement of Mao Zedong ’ s Anti-corruption Thought by combining the current new situation of corruption and new anti-corruption practice at home and abroad so as to be of some help to the anti-corruption work of our country .%毛泽东在革命和建设的各个时期都十分重视反腐倡廉工作,提出了一系列反腐倡廉的理念和措施,并通过实践不断检验,最终形成了指导党和国家开展反腐倡廉工作的毛泽东反腐倡廉思想。毛泽东反腐倡廉思想是中国特色社会主义反腐倡廉思想的起源和基础,是指导新形势下开展反腐倡廉工作的强大思想武器。文章结合当前形势和国内外反腐倡廉的新实践,提出了一系列进一步发展和完善毛泽东反腐倡廉思想的思考,以期对我国反腐倡廉事业有所助益。

  14. Effects of K. Lysolecithin on Blood Levels of Monoamines in Mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this research, Lysolecithin - a substance made with 100% natural ingredients - was given to ICR mice as medication to measure its periodic effect on the noradrenalin (NA), dopamine (DA), and serotonin (5-HT) levels of the brain. Both ICR and SAM mice were separated into two groups - control group and Lysolecithin (K. Lysolecithin: hydrolytic lysolecithin) medicated group, and given 1-week preparation period. The K. Lysolecithin group was given 500mg/kg of K. Lysolecithin at 0.2mL per dosage for 4 weeks, and the control group was given the same amount of dosage of water during the same period. NA, DA and 5-HT concentrations were measured from the blood before medication and 8 weeks / 12 weeks / 16 weeks after the first medication. For the SAM mice, 8 weeks after they were medicated with K .Lysolecithin, Morris Water Maze Test was conducted for 7 consecutive days and then the concentrations were measured by drawing blood from the heart. The K. Lysolecithin medicated group showed a tendency to have a statistically significant higher concentrations of 5-HT and NA in the blood. Also, periodic examination showed that the monoamine levels were highest in the 12th week and declined thereafter.

  15. Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.

    Science.gov (United States)

    Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2010-12-01

    Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes.

  16. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity.

    Science.gov (United States)

    Williard, Robin L; Middaugh, Lawrence D; Zhu, Hao-Jie B; Patrick, Kennerly S

    2007-02-01

    Ethylphenidate is formed by metabolic transesterification of methylphenidate and ethanol. Study objectives were to (a) establish that ethylphenidate is formed in C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate plasma and brain distribution and (d) establish in-vitro effects of methylphenidate and ethylphenidate on monoamine transporter systems. Experimental results were that: (a) coadministration of ethanol with the separate methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases in motor activity with stimulation being less for ethylphenidate; (c) plasma and whole-brain concentrations were greater for ethylphenidate than methylphenidate and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor. These experiments establish the feasibility of the B6 mouse model for examining the interactive effects of ethanol and methylphenidate. As reported for humans, concurrent exposure of B6 mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d-ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were biologically inactive. The observed reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate appears not to be the result of brain dispositional factors, but rather may be related to its reduced inhibition of the norepinephrine transporter, perhaps altering the interaction of dopaminergic and noradrenergic neural systems.

  17. CT scanning of the brain and lumbar CSF monoamine metabolites in spinocerebellar degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hidenao; Kanazawa, Ichiro; Nakanishi, Takao; Kuramoto, Kenmei (Tsukuba Univ., Sakura, Ibaraki (Japan))

    1984-08-01

    Eight patients with parenchymatous cerebellar degeneration (PCD) group (3 with late cortical cerebellar atrophy and 5 with Holmes' hereditary ataxia), 14 with olivo-ponto-cerebellar atrophy (OPCA) group (4 with Shy-Drager syndrome, 6 with OPCA without family history and 4 with Menzel type SCS), 15 with Parkinson's disease and 44 control with other neurological diseases were studied. In all the spinocerebellar degenerative disorders (SCD) cases, CVI values corresponding to the cerebellar atrophy were definitely reduced. On the other hand, PVI values corresponding to the pontine atrophy were only significantly decreased in OPCA group. However, since there were several cases showing only questionable pontine atrophy, it seems difficult to clearly differentiate individual OPCA cases from other SCD cases on CT films alone. Concerning monoamine metabolites in CSF, it was noted that a significant reduction of HVA and total MHPG was found in the OPCA group. Among them, the patients with overt autonomic failure showed the lowest HVA level and the cases of Menzel type of SCD showed a slight reduction of HVA but an unexpected elevation of free MHPG values. The cases of Parkinson's disease showed a definite reduction of HVA. On the other hand, the cases of PCD group showed no significant difference against controls. 5-HIAA levels were not significantly different among the SCD subgroups.

  18. Effects of Moxa Smoke on Monoamine Neurotransmitters in SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Huanfang Xu</