Sample records for reda ach franois

  1. Reda Marks : "Moi korol Mindaugas molodoi, silnõi i bez borodõ" / Eteri Kekelidze

    Kekelidze, Eteri, 1944-


    Eesti Kunstiakadeemia nahakunstnikuna lõpetanud leedulanna Reda Marksi maalid kaunistasid Tallinna Matkamaja Leedu kuninga Mindaugase 750-nda kroonimisaastapäeva pidustuste ajal. Autori selgitusi kuningas Mindaugase porteele. Kunstnikust ja tema loomingust

  2. New potential AChE inhibitor candidates.

    de Paula, A A N; Martins, J B L; dos Santos, M L; Nascente, L de C; Romeiro, L A S; Areas, T F M A; Vieira, K S T; Gambôa, N F; Castro, N G; Gargano, R


    We have theoretically studied new potential candidates of acetylcholinesterase (AChE) inhibitors designed from cardanol, a non-isoprenoid phenolic lipid of cashew Anacardium occidentale nut-shell liquid. The electronic structure calculations of fifteen molecule derivatives from cardanol were performed using B3LYP level with 6-31G, 6-31G(d), and 6-311+G(2d,p) basis functions. For this study we used the following groups: methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine, pyrrolidine, and N,N-methylbenzylamine. Among the proposed compounds we identified that the structures with substitution by N,N-dimethycarbamoyl, N,N-dimethylamine, and pyrrolidine groups were better correlated to rivastigmine, and represent possible AChE inhibitors against Alzheimer disease.

  3. Novel AChE inhibitors for sustainable insecticide resistance management.

    Haoues Alout

    Full Text Available Resistance to insecticides has become a critical issue in pest management and it is particularly chronic in the control of human disease vectors. The gravity of this situation is being exacerbated since there has not been a new insecticide class produced for over twenty years. Reasoned strategies have been developed to limit resistance spread but have proven difficult to implement in the field. Here we propose a new conceptual strategy based on inhibitors that preferentially target mosquitoes already resistant to a currently used insecticide. Application of such inhibitors in rotation with the insecticide against which resistance has been selected initially is expected to restore vector control efficacy and reduce the odds of neo-resistance. We validated this strategy by screening for inhibitors of the G119S mutated acetylcholinesterase-1 (AChE1, which mediates insensitivity to the widely used organophosphates (OP and carbamates (CX insecticides. PyrimidineTrione Furan-substituted (PTF compounds came out as best hits, acting biochemically as reversible and competitive inhibitors of mosquito AChE1 and preferentially inhibiting the mutated form, insensitive to OP and CX. PTF application in bioassays preferentially killed OP-resistant Culex pipiens and Anopheles gambiae larvae as a consequence of AChE1 inhibition. Modeling the evolution of frequencies of wild type and OP-insensitive AChE1 alleles in PTF-treated populations using the selectivity parameters estimated from bioassays predicts a rapid rise in the wild type allele frequency. This study identifies the first compound class that preferentially targets OP-resistant mosquitoes, thus restoring OP-susceptibility, which validates a new prospect of sustainable insecticide resistance management.

  4. Preliminary Screening a Potential AChE Inhibitor in Thai Golden Shower (Leguminosae mimosoideae Extracts

    Jakkaphun Nanuam


    Full Text Available Pesticides are used to control pests of agriculture products in many countries including Thailand. Since they can exert harmful effects not only on target pests but also on other useful organisms, alternative agents are investigated. We studied the capacity of the Thai golden shower (Leguminosae mimosoideae extracts (root and pod to inhibit acetyl cholinestarese (AChE in the golden apple snail (Pomacea canaliculata as a pest representative. The results showed that the percentage of AChE inhibition increased with increasing in exposure times. The inhibition expressed the same trend in both male and female apple snails. AChE inhibition was higher in extracts from root than from pod. Chromatography-Mass Spectrometer (GC-MS chromatograms demonstrated anthraquinone, an AChE inhibitor, in extracts of golden shower. Our data indicate that a potential AChE inhibitor tends to accumulate more in the root part than in the pod.

  5. AChE and the amyloid precursor protein (APP) - Cross-talk in Alzheimer's disease.

    Nalivaeva, Natalia N; Turner, Anthony J


    The amyloid precursor protein (APP) and acetylcholinesterase (AChE) are multi-faceted proteins with a wide range of vital functions, both crucially linked with the pathogenesis of Alzheimer's disease (AD). APP is the precursor of the Aβ peptide, the pathological agent in AD, while AChE is linked to its pathogenesis either by increasing cholinergic deficit or exacerbating Aβ fibril formation and toxicity. As such, both proteins are the main targets in AD therapeutics with AChE inhibitors being currently the only clinically available AD drugs. In our studies we have demonstrated an important inter-relation in functioning of these proteins. Both can be released from the cell membrane and we have shown that AChE shedding involves a metalloproteinase-mediated mechanism which, like the α-secretase dependent cleavage of APP, is stimulated by cholinergic agonists. Overexpression of the neuronal specific isoform APP695 in neuronal cells substantially decreased levels of the AChE mRNA, protein and catalytic activity accompanied by a similar decrease in mRNA levels of the AChE membrane anchor, PRiMA (proline rich membrane anchor). We further established that this regulation does not involve APP processing and its intracellular domain (AICD) but requires the E1 region of APP, specifically its copper-binding domain. On the contrary, siRNA knock-down of APP in cholinergic SN56 cells resulted in a significant upregulation of AChE mRNA levels. Hence APP may influence AChE physiology while released AChE may regulate amyloidogenesis through multiple mechanisms suggesting novel therapeutic targets.

  6. Metamorfoses do contrato representativo: jornalismo, democracia e os manuais da redação da Folha de S.Paulo

    Afonso de Albuquerque


    Full Text Available Resumo O texto analisa as três primeiras edições do Manual da Redação editado pelo jornal Folha de S.Paulo: 1984, 1987 e 1992. Mais do que fundamental na estruturação do novo jornalismo brasileiro pós-ditadura, as edições constituem um manifesto no qual o jornal reivindica ocupar um papel de destaque na nova democracia em formação. A análise se prende, em especial, ao modo como os manuais buscam legitimar esse papel baseado em um tipo particular de contrato representativo; um vínculo comercial, antes que eleitoral. Palavras-chave: Jornalismo; democracia; contrato representativo; Manual da Redação da Folha de S.Paulo. Resumen El texto se propone analizar las tres primeras ediciones del Manual da Redação editado por el diario Folha de S.Paulo: 1984, 1987 y 1992. Además de desempeñar un papel fundamental en la estructuración del nuevo periodismo brasileño posterior a la dictadura, las ediciones constituyen un manifiesto en el cual el diario pretende desempeñar un papel destacado en la nueva democracia que estaba en formación. El objetivo de este análisis es determinar la manera en que los manuales buscan legitimar ese papel basado en un tipo especial de contrato representativo en el cual el vinculo comercial es más importante que el vinculo electoral. Palabras-clave: Periodismo; democracia; contrato representativo; Manual da Redação del diario Folha de S.Paulo. Abstract The main purpose of this paper is to analyze the first three editions of the Writing Manuals (Manual da Redação – 1984, 1987 and 1992, edited by th daily newspaper Folha de S.Paulo. These manuals were fundamental for the structuring of the new Brazilian journalism during the post-dictatorship period. Furthermore, they are a manifest where the newspaper claims for an important place in the new Brazilian democracy in formation. The aim of this analysis is to ascertain how these manuals try to legitimate this position. They have a sort of special

  7. A first principles investigation of aging processes in soman conjugated AChE.

    Chandar, Nellore Bhanu; Ganguly, Bishwajit


    We have examined the aging process of soman inhibited AChE using Density functional theory (DFT) calculations. The catalytic serine of AChE can be phosphonylated by the nerve agent soman, and subsequently can undergo an aging process. The consequences of irreversible inhibition of AChE due to the aging process is fatal for mammals. The DFT calculations shed light on some intricate features of aging process of soman inhibited AChE, which has been pondering in the literature. The DFT calculations (M05-2X/6-31G(∗) level of theory) performed with the model systems revealed that the dealkylation of pinacolyl group and the methyl migration takes place simultaneously. The role of pre-protonation and electrostatic stabilization by histidine (His440(+)) in catalyzing the aging process of soman inhibited AChE is energetically comparable. The aging process catalyzed by the histidine (His440(+)) residue reduces the free energy of activation by ∼14.0kcal/mol, which is in good agreement with the reported experimental results. Further, the calculated results reveal that tryptophan residue (Trp84) of the catalytic anionic subsite (CAS) assists the rearrangement reaction in the rearrangement process via cation-π interactions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Preventing Tech Aches: Using Smart Phones Wisely

    ... Media Guidelines Copyright Permissions Preventing Tech Aches: Using Smart Phones Wisely BETHESDA, MD (Dec. 26, 2013) — If you received a new smart phone or tablet this holiday season, chances are you’ ...

  9. Nanoparticles Ease Aching Joints in Mice

    ... page: Nanoparticles Ease Aching Joints in Mice Treatment might one ... News) -- New research in mice suggests that tiny nanoparticles might one day be a better way to ...

  10. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease.

    Tommonaro, Giuseppina; García-Font, Nuria; Vitale, Rosa Maria; Pejin, Boris; Iodice, Carmine; Cañadas, Sixta; Marco-Contelles, José; Oset-Gasque, María Jesús


    Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 ± 0.24 μM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of

  11. Design, synthesis, and AChE inhibitory activity of new benzothiazole-piperazines.

    Demir Özkay, Ümide; Can, Özgür Devrim; Sağlık, Begüm Nurpelin; Acar Çevik, Ulviye; Levent, Serkan; Özkay, Yusuf; Ilgın, Sinem; Atlı, Özlem


    In the current study, 14 new benzothiazole-piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7-20) were confirmed using IR, (1)H NMR, (13)C NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C., from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate-enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds.

  12. Centrally acting oximes in reactivation of tabun-phosphoramidated AChE.

    Kovarik, Zrinka; Maček, Nikolina; Sit, Rakesh K; Radić, Zoran; Fokin, Valery V; Barry Sharpless, K; Taylor, Palmer


    Organophosphates (OP) inhibit acetylcholinesterase (AChE, EC, both in peripheral tissues and central nervous system (CNS), causing adverse and sometimes fatal effects due to the accumulation of neurotransmitter acetylcholine (ACh). The currently used therapy, focusing on the reactivation of inhibited AChE, is limited to peripheral tissues because commonly used quaternary pyridinium oxime reactivators do not cross the blood brain barrier (BBB) at therapeutically relevant levels. A directed library of thirty uncharged oximes that contain tertiary amine or imidazole protonable functional groups that should cross the BBB as unionized species was tested as tabun-hAChE conjugate reactivators along with three reference oximes: DAM (diacetylmonoxime), MINA (monoisonitrosoacetone), and 2-PAM. The oxime RS150D [N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide] was highlighted as the most promising reactivator of the tabun-hAChE conjugate. We also observed that oximes RS194B [N-(2-(azepan-1-yl)ethyl)-2-(hydroxyimino)acetamide] and RS41A [2-(hydroxyimino)-N-(2-(pyrrolidin-1-yl)ethyl)acetamide], which emerged as lead uncharged reactivators of phosphylated hAChE with other OPs (sarin, cyclosarin and VX), exhibited only moderate reactivation potency for tabun inhibited hAChE. This implies that geometry of oxime access to the phosphorus atom conjugated to the active serine is an important criterion for efficient reactivation, along with the chemical nature of the conjugated moiety: phosphorate, phosphonate, or phosphoramidate. Moreover, modification of the active center through mutagenesis enhances the rates of reactivation. The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide derivative (RS194B) than with 2PAM.

  13. Altered GPI modification of insect AChE improves tolerance to organophosphate insecticides.

    Kakani, Evdoxia G; Bon, Suzanne; Massoulié, Jean; Mathiopoulos, Kostas D


    The olive fruit fly Bactrocera oleae is the most destructive and intractable pest of olives. The management of B. oleae has been based on the use of organophosphate (OP) insecticides, a practice that induced resistance. OP-resistance in the olive fly was previously shown to be associated with two mutations in the acetylcholinesterase (AChE) enzyme that, apparently, hinder the entrance of the OP into the active site. The search for additional mutations in the ace gene that encodes AChE revealed a short deletion of three glutamines (Δ3Q) from a stretch of five glutamines, in the C-terminal peptide that is normally cleaved and substituted by a GPI anchor. We verified that AChEs from B. oleae and other Dipterans are actually GPI-anchored, although this is not predicted by the "big-PI" algorithm. The Δ3Q mutation shortens the unusually long hydrophilic spacer that follows the predicted GPI attachment site and may thus improve the efficiency of GPI anchor addition. We expressed the wild type B. oleae AChE, the natural mutant Δ3Q and a constructed mutant lacking all 5 consecutive glutamines (Δ5Q) in COS cells and compared their kinetic properties. All constructs presented identical K(m) and k(cat) values, in agreement with the fact that the mutations did not affect the catalytic domain of the enzyme. In contrast, the mutants produced higher AChE activity, suggesting that a higher proportion of the precursor protein becomes GPI-anchored. An increase in the number of GPI-anchored molecules in the synaptic cleft may reduce the sensitivity to insecticides.

  14. A selective molecularly imprinted polymer for immobilization of acetylcholinesterase (AChE): an active enzyme targeted and efficient method.

    Demirci, Gökhan; Doğaç, Yasemin İspirli; Teke, Mustafa


    In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme-specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25-65 °C), optimum pH (3-10), thermal stability (4-70 °C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE.

  15. Jornalismo em segunda tela. Webjornal produzido com dispositivos móveis em redação virtual

    Zanei Ramos Barcellos


    Full Text Available Este artigo inicialmente aborda o uso de dispositivos móveis pessoais, portáteis, interativos e multimídias nas várias etapas da produção, distribuição e consumo de produtos e conteúdos jornalísticos. Discute a possibilidade de o trabalho jornalístico ser feito totalmente no ciberespaço de forma remota. Também propõe o uso dos termos “redação virtual” e “jornalismo em segunda tela” amparado pela narrativa transmidiática. Num segundo momento, o trabalho relata a experiência de produção, formatação e distribuição de conteúdos jornalísticos multimídia em segunda tela, usando dispositivos móveis e em redação virtual. O objetivo é produzir matérias direcionada a mídias que sejam mais adequadas à cada notícia, tendo um telejornal de grande audiência como primeira tela. A transmissão paralela ao Jornal Nacional, da Rede Globo de Televisão, levantou antecipadamente suas pautas e produziu matérias sobre os mesmos temas, mas com foco local. Esse jornal, o #Tela2, foi produzido por alunos do curso de Jornalismo da Pontifícia Universidade Católica do Paraná (PUCPR. O artigo expõe também o processo de criação e de planejamento, e detalha todas as etapas da produção realizada pelos alunos, acompanhadas de avaliações críticas. As turmas mesclaram-se e dividiram-se em equipes para desempenhar diferentes tarefas: conselho editorial, rádio-escuta, redes sociais, reportagem de televisão, reportagem de rádio, reportagem de jornal (texto e foto, reportagem com texto coletivo em tempo real. Também foram designadas equipes para a realização de três entradas ao vivo: câmera fixa para televisão, matéria de televisão ao vivo (câmara viva e entrevista de rádio. Os resultados apontam que a experimentação foi satisfatória ao demonstrar ser possível realizar jornalismo integralmente em redações virtuais, usando apenas dispositivos móveis comuns na atualidade em todas as etapas do fazer jornal

  16. Acetylcholinesterase (AChE inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    Shin-Ichi Yokota


    Full Text Available Although fasting induces hepatic triglyceride (TG accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1 and liver-fatty acid binding-protein (L-FABP. Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

  17. Formação profissional em rede: MOOC de redação oficial em LibreOfficeWriter

    Liliane Silveira Bonorino


    Full Text Available Este estudo objetiva inovar na oferta de formação mediada pelas Tecnologias Educacionais em Rede (TER através de um MOOC (Massive Open Online Courses - Cursos On-line Abertos e Massivos, pela plataforma Moodle (Modular Object Oriented Dynamic Learning Enviroment. Esta pesquisa foi implementada em duas fases: 1 módulo-piloto, a fim de verificar se a organização didático-metodológica estava bem encaminhada; e 2 MOOC, para promover a formação profissional e o aprimoramento de conhecimentos acerca da redação oficial em LibreOfffice Writer. Após a análise dos dados coletados no MOOC, constatou-se que houve processo de ensino-aprendizagem mediado pelas Tecnologias Educacionais em Rede (TER, dado que promoveu a formação profissional dos envolvidos.

  18. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Francisco Javier Carvajal


    Full Text Available Acetylcholinesterase (AChE; EC plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN5706 for 10 weeks increases brain AChE activity in seven month-old double transgenic mice (APPswe - PS1 and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE-Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.

  19. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Carvajal, Francisco J.; Inestrosa, Nibaldo C.


    Acetylcholinesterase (AChE; EC plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β (Aβ) peptide accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN 5706 for 10 weeks increases brain AChE activity in 7-month-old double transgenic mice (APPSWE–PS1) and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE–Aβ interaction and this effect might be of therapeutic interest in the treatment of AD. PMID:21949501

  20. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer


    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  1. Generation of Recombinant Human AChE OP-Scavengers with Extended Circulatory Longevity


    positions of analogous residues in TcAChE according to the recommended nomenclature (Massoulie et al., 1992) 99 contributing to the inherent...1997). A single amino acid substitution Gly117His confers phosphotriesterase (organophosphorus acid anhydride hydrolase) activity on human...Silman, I. and Taylor, P. (1992) Recommendations for nomenclature in cholinesterases, in Multidisciplinary Approaches to Cholinesterase Functions

  2. Neurophysiological predictors of long term response to AChE inhibitors in AD patients.

    Di Lazzaro, V; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Ghirlanda, S; Ranieri, F; Gainotti, G; Tonali, P


    In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI. We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of approximately 50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors.

  3. Novel bis-(-)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property.

    Zheng, Wei; Li, Juan; Qiu, Zhuibai; Xia, Zheng; Li, Wei; Yu, Lining; Chen, Hailin; Chen, Jianxing; Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao; Xie, Qiong; Chen, Hongzhuan


    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(-)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC(50) values of 9.63μM (for ZLA) and 8.64μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC(50) values of 49.1μM (for ZLA) and 55.3μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD.

  4. In vitro inhibitory profile of NDGA against AChE and its in silico structural modifications based on ADME profile.

    Remya, Chandran; Dileep, Kalarickal Vijayan; Tintu, Ignatius; Variyar, Elessery Jayadevi; Sadasivan, Chittalakkottu


    Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer's disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC(50) of NDGA on AChE was 46.2 μM. However, NDGA showed very poor central nervous system (CNS) activity and blood-brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD.

  5. Residues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs

    Bo Lin


    Full Text Available Nicotinic acetylcholine receptors (nAChRs are targets for developing new drugs to treat severe pain, nicotine addiction, Alzheimer disease, epilepsy, etc. α-Conotoxins are biologically and chemically diverse. With 12–19 residues and two disulfides, they can be specifically selected for different nAChRs. Acetylcholine-binding proteins from Aplysia californica (Ac-AChBP are homologous to the ligand-binding domains of nAChRs and pharmacologically similar. X-ray structures of the α-conotoxin in complex with Ac-AChBP in addition to computer modeling have helped to determine the binding site of the important residues of α-conotoxin and its affinity for nAChR subtypes. Here, we present the various α-conotoxin residues that are selective for Ac-AChBP or nAChRs by comparing the structures of α-conotoxins in complex with Ac-AChBP and by modeling α-conotoxins in complex with nAChRs. The knowledge of these binding sites will assist in the discovery and design of more potent and selective α-conotoxins as drug leads.


    Ze-wenLiu; Zhao-junHan; Ling-chunZhang


    Methamidophos resistance of brown planthopper (Nilaparvata lugens Stal, BPH) was selected in laboratory. After successive selection for 9 generations, the selection was ceased by rearing BPH without contact with any insecticide for 9 generations. In the full course, the successive changes of esterase activity, MFO activity, GSTs activity and AChE insensitivity were analyzed. The results showed that the change of esterase activity was high correlated with that of methamidophos in the full course, which indicated that esterase played very important role both in the resistance development and in the resistance decline. However, the change of AChE insensitivity only significantly correlated with that of resistance in the development stage, and the change of MFO activity or GSTs activity only significantly correlated with that of the resistance in the decline stage, which indicated the changes of AChE insensitivity, MFO activity or GSTs activity only played some roles in different stages of the resistance change.

  7. Modified Rapid AChE Method (MRAM) for Hirschsprung Disease Diagnosis: A Journey from Meier-Ruge Until Now.

    Naguib, Mina M; Robinson, Haynes; Shoffeitt, Carla; Howe, Helena; Metry, Diana; Shehata, Bahig M


    Hirschsprung disease (HSCR) can be diagnosed using a variety of histological and immunohistochemical methods and stains. Because of the nature of the condition and the need for a rapid diagnostic confirmation, those methods with high accuracy and fast turnaround times are preferred. The authors of this paper have used rapid acetylcholinesterase (AChE) immunohistochemistry in conjunction with standard H&E in order to optimize diagnostic accuracy, and present a modified rapid AChE method (MRAM) that has been successfully utilized for over 20 years. The authors also present a list of over 30 different methods and stains that have been proposed for Hirschsprung disease diagnosis.

  8. [Achetylcholinesterase (AChE) inhibition and serum lipokines in Alzheimer's disease: friend or foe?].

    Kovacs, Janos; Pakaski, Magdolna; Juhasz, Anna; Feher, Agnes; Drotos, Gergely; Fazekas, Csilla Orsike; Horvath, Tamas Laszlo; Janka, Zoltan; Kalman, Janos


    Throughout the natural progression of Alzheimer's disease (AD), the body mass index (BMI) decreases. This is believed to be brought on by the disturbance in the central lipid metabolism, but the exact mechanism is yet unknown. Adipokines (adiponectin, leptin), hormones produced by the adipose tissue, change glucose and lipid metabolism, and have an anorectic effect through increasing energy consumption in the hypothalamus. The goal of our study was to examine donepezil - an acetylcholinesterase inhibitor (AChEI) currently used in AD therapy -, and to what degree it influences the serum adipokine levels and metabolic parameters of AD patients. During the self-evaluation of 26 clinically diagnosed mild to moderate AD patients, therapy with 10 mg/day donepezil was started according to current protocols. We measured serum adiponectin, leptin, LDL, HDL, trigliceride levels, and BMI and ApoE polymorphism at the beginning of our study, and at 3 and 6-months intervals respectively. All data were analyzed with SPSS 17. In comparison with pre-donepezil therapy values, at the third month interval serum adiponectin levels showed an increasing and leptin levels a decreasing tendency. At the six month interval, adiponectin levels significantly increased (p=0.007), leptin levels decreased (p=0.013), BMI (p=0.001) and abdominal circumference (p=0.017) was significantly lower at 6 months as compared to control values. We did not observe any changes in the lipid profile, and ApoE4 allele carrying showed no association with the parameters. To our knowledge, we are the first to publish that AChEI therapy with donepezil alters lipokine levels, which positively influences the currently known pathomechanism and numerous risk factors of AD. The AChEI treatment-induced weight loss should be considered in the long-term therapy of AD patients.

  9. Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study.

    Khan, Md Abdul Shafeeuulla; Ganguly, Bishwajit


    Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

  10. Integrative Characterization of Toxic Response of Zebra Fish (Danio rerio) to Deltamethrin Based on AChE Activity and Behavior Strength.

    Ren, Qing; Zhang, Tingting; Li, Shangge; Ren, Zongming; Yang, Meiyi; Pan, Hongwei; Xu, Shiguo; Qi, Li; Chon, Tae-Soo


    In order to characterize the toxic response of zebra fish (Danio rerio) to Deltamethrin (DM), behavior strength (BS) and muscle AChE activity of zebra fish were investigated. The results showed that the average values of both BS and AChE activity showed a similarly decreased tendency as DM concentration increased, which confirmed the dose-effect relationship, and high and low levels of AChE and BS partly matched low and high levels of exposure concentrations in self-organizing map. These indicated that AChE and BS had slight different aspects of toxicity although overall trend was similar. Behavior activity suggested a possibility of reviving circadian rhythm in test organisms after exposure to the chemical in lower concentration (0.1 TU). This type of rhythm disappeared in higher concentrations (1.0 TU and 2.0 TU). Time series trend analysis of BS and AChE showed an evident time delayed effect of AChE, and a 2 h AChE inhibition delay with higher correlation coefficients (r) in different treatments was observed. It was confirmed that muscle AChE inhibition of zebra fish is a factor for swimming behavior change, though there was a 2 h delay, and other factors should be investigated to illustrate the detailed behavior response mechanism.

  11. Integrative Characterization of Toxic Response of Zebra Fish (Danio rerio to Deltamethrin Based on AChE Activity and Behavior Strength

    Qing Ren


    Full Text Available In order to characterize the toxic response of zebra fish (Danio rerio to Deltamethrin (DM, behavior strength (BS and muscle AChE activity of zebra fish were investigated. The results showed that the average values of both BS and AChE activity showed a similarly decreased tendency as DM concentration increased, which confirmed the dose-effect relationship, and high and low levels of AChE and BS partly matched low and high levels of exposure concentrations in self-organizing map. These indicated that AChE and BS had slight different aspects of toxicity although overall trend was similar. Behavior activity suggested a possibility of reviving circadian rhythm in test organisms after exposure to the chemical in lower concentration (0.1 TU. This type of rhythm disappeared in higher concentrations (1.0 TU and 2.0 TU. Time series trend analysis of BS and AChE showed an evident time delayed effect of AChE, and a 2 h AChE inhibition delay with higher correlation coefficients (r in different treatments was observed. It was confirmed that muscle AChE inhibition of zebra fish is a factor for swimming behavior change, though there was a 2 h delay, and other factors should be investigated to illustrate the detailed behavior response mechanism.

  12. Study on the Highly Sensitive AChE Electrode Based on Multiwalled Carbon Nanotubes

    Shuping Zhang


    Full Text Available Using chitosan (CS as carrier, the method named layer-by-layer (LBL self-assembly modification to modify the glassy carbon electrode (GCE with multiwalled carbon nanotubes (MWNTs and acetylcholine esterase (AChE was proposed to prepare the acetylcholine esterase electrode with high sensitivity and stability. The modified electrode was used to detect pesticide of aldicarb, and the enzyme inhibition rate of the electrode showed good linearity with pesticide concentrations in the range of 10−10 g·L−1 to 10−3 g·L−1. The detection limit was 10−11 g·L−1. The modified electrode was also used to detect the actual sample, and the recovery rate range was from 97.72% to 107.15%, which could meet the rapid testing need of the aldicarb residue. After being stored in the phosphate buffer solution (PBS in 4°C for 30 days, the modified electrode showed good stability with the response current that was 80% of the original current.

  13. Influência da redação da prescrição médica na administração de medicamentos em horários diferentes do prescrito

    GIMENES, Fernanda Raphael Escobar; Teixeira,Thalyta Cardoso Alux; Silva,Ana Elisa Bauer de Camargo; Optiz,Simone Perfuro; Mota,Maria Ludermiller Sabóia; CASSIANI, Silvia Helena De Bertoli


    OBJETIVO: Analisar a influência da redação da prescrição médica na administração de medicamentos em horários diferentes do prescrito ocorridas em unidades de clínica médica de cinco hospitais brasileiros. MÉTODOS: Trata-se de estudo descritivo que utilizou dados secundários obtidos de uma pesquisa multicêntrica realizada em 2005. A amostra foi composta por 1084 doses de medicamentos administradas em horários diferentes do prescrito. RESULTADOS: Do total analisado, 96,2% apresentavam siglas e/...

  14. Análise de uma redação nota mil do ENEM 2012: o modo de organização do discurso argumentativo e o emprego dos articuladores textuais

    Oliveira, Maria Isabel Soares; Universidade Cruzeiro do Sul; Cabral, Ana Lúcia Tinoco; Universidade Cruzeiro do Sul


    O artigo aborda a produção textual argumentativa, entendendo que ela retrata uma organização planejada conforme as intenções de dizer do produtor na defesa de um ponto de vista. Tendo como base teórica a Linguística Textual de abordagem sócio-interacional cognitiva, o trabalho analisa uma redação nota mil (1000) resultante da proposta do ENEM 2012, focalizando o modo de organização argumentativo (CHARAUDEAU, 2008) e os articuladores textuais empregados, enquanto estratégias que marcam a direç...

  15. A concepção argumentativa de linguagem no ensino de redação de textos dissertativo-argumentativos.

    Telisa Furlanetto Graeff


    Full Text Available A crescente demanda no uso de redações de textos dissertativo-argumentativos como instrumento de seleção em concursos para ingresso no ensino superior ou em recrutamento de pessoal para o mercado de trabalho exerce uma pressão, ainda maior, sobre a escola no sentido de didatizar esse gênero textual/discursivo. O presente trabalho propõe uma aplicação da semântica argumentativa, criada em 1983 por Oswald Ducrot e Jean-Claude Anscombre, denominada Argumentation dans la langue (ADL, ao desenvolvimento da competência argumentativa e retórica, especificamente materializada na forma de textos dissertativo-argumentativos escritos. Mais especificamente serão utilizados princípios e conceitos da Teoria dos Blocos Semânticos, versão técnica mais recente da ADL, introduzida pelos estudos de Marion Carel (1992 e desenvolvida juntamente com Ducrot. Palavras-chave: Argumentação linguística. Argumentação retórica. Ensino de dissertação. Abstract The growing demand for the use of writing expository argumentative texts as selection tools on admittance examinations to higher education institutions or when selecting personnel for the working market has put even greater pressure upon schools so as to make such textual/discursive genre didactic. This work proposes a semantic argumentative application, created in 1983 by Oswald Ducrot and Jean-Claude Anscombre, called Argumentation dans la langue (ADL, to the development of argumentative and rhetorical competence, specifically materialised as written expository argumentative texts. More specifically, principles and concepts from the Theory of Semantic Blocks, a newer technical version of LDA, introduced by Marion Carel (1992 and developed with Ducrot, shall be used. Keywords: Linguistic argumentation. Rhetorical argumentation. Teaching dissertation.

  16. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

    Cristiano Chiapinotto Spiazzi


    Full Text Available Alzheimer’s disease (AD is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL or distilled water was administered via intracerebroventricular (i.c.v. injection. Selenofuranoside (5 mg/kg or vehicle (canola oil was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM and step-down passive-avoidance (SDPA tests. Antioxidant defenses along with reactive species (RS were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

  17. An acetylcholinesterase (AChE) biosensor with enhanced solvent resistance based on chitosan for the detection of pesticides.

    Warner, John; Andreescu, Silvana


    Solvent tolerance of immobilized enzymes is important for many biosensing and biotechnological applications. In this paper we report an acetylcholinesterase (AChE) biosensor based on chitosan that exhibits high solvent resistance and enables sensitive detection of pesticides in presence of a high content of organic solvents. The solvent effect was established comparatively for the enzyme immobilized in chitosan and covalently cross-linked with glutaraldehyde. The activity of the immobilized AChE was dependent on the immobilization method and solvent type. The enzyme entrapped in chitosan fully conserved its activity in up to 25% methanol, 15% acetonitrile and 100% cyclohexane while the enzyme cross-linked with glutaraldehyde gradually lost its activity starting at 5% acetonitrile and methanol, and showed variable levels in cyclohexane. The detection limits of the biosensor for paraoxon were: 7.5 nM in 25% methanol, 100 nM in 15% acetonitrile and 2.5 μM in 100% cyclohexane. This study demonstrates that chitosan provides an excellent immobilization environment for AChE biosensors designed to operate in environments containing high amounts of organic solvents. It also highlights the effect of the immobilization material and solvent type on enzyme stability. These findings can enable future selection of the immobilization matrix and solvent type for the development of organic phase enzyme based systems.

  18. Toxicological and biochemical characterizations of AChE in phosalone-susceptible and resistant populations of the common pistachio psyllid, Agonoscena pistaciae.

    Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad


    The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity (K(M)) and hydrolyzing efficiency (Vmax) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively

  19. Does time difference of the acetylcholinesterase (AChE) inhibition in different tissues exist? A case study of zebra fish (Danio rerio) exposed to cadmium chloride and deltamethrin.

    Zhang, Tingting; Yang, Meiyi; Pan, Hongwei; Li, Shangge; Ren, Baigang; Ren, Zongming; Xing, Na; Qi, Luhuizi; Ren, Qing; Xu, Shiguo; Song, Jie; Ma, Jingchun


    In order to illustrate time difference in toxic effects of cadmium chloride (CdCl2) and deltamethrin (DM), AChE activities were measured in different tissues, liver, muscle, brain, and gill, of Zebra fish (Danio rerio) across different concentrations in this research. The average AChE activity decreased comparing to 0.0 TU with DM (82.81% in 0.1 TU, 56.14% in 1.0 TU and 44.68% in 2.0 TU) and with CdCl2 (74.68% in 0.1 TU, 52.05% in 1.0 TU and 50.14% in 2.0 TU) showed an overall decrease with the increase of exposure concentrations. According to Self-Organizing Map (SOM), the AChE activities were characterized in relation with experimental conditions, showing an inverse relationship with exposure time. As the exposure time was longer, the AChE activities were correspondingly lower. The AChE inhibition showed time delay in sublethal treatments (0.1 TU) in different tissues: the AChE was first inhibited in brain by chemicals followed by gill, muscle and liver (brain > gill > muscle > liver). The AChE activity was almost inhibited synchronously in higher environmental stress (1.0 TU and 2.0 TU). As the AChE inhibition can induce abnormal of behavior movement, these results will be helpful to the mechanism of stepwise behavior responses according to the time difference in different tissues rather than the whole body AChE activity.

  20. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

    Bryon Silva


    Full Text Available The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS, with an unconditioned stimulus (US. The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB, can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh receptors, while the US is encoded by biogenic amine (BA systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila.

  1. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

    Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano, Jorge M.


    The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID:26380118

  2. MRI of hyperacute stroke in the AChA territory

    Hamoir, Xavier L.; Grandin, Cecile B.; Cosnard, Guy; Duprez, Thierry [Department of Medical Imaging, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Peeters, Andre [Department of Neurology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Robert, Annie [Department of Epidemiology, Biostatistics Unit of the Public Health School, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium)


    The purpose of our study was to derive from the anatomical literature an easy-to-use map of the brain areas supplied by the anterior choroidal artery (AChA) and to assess the correspondence between damage within the putative AChA areas and clinical symptoms. A thorough review of the literature led to the recognition of 16 anatomical areas which could be delineated on routine diffusion-weighted MR images. A database of 138 consecutive ischemic stroke patients examined with MRI less than 6 h after symptoms onset was thereafter processed in a retrospective way. Patients presenting with at least one damaged AChA area were selected so as to assess the prevalence of AChA infarction and the clinical correlates of the condition. Fifteen patients (11%) had at least one damaged AChA area. Only two of them had ''pure'' AChA-restricted infarction. Contralateral hemiparesis and contralateral hemianesthesia were best predicted by lesions within the tail of the caudate nucleus with a sensitivity of 87% and 83%, respectively. Homonymous hemianopsia best correlated with lesions within the posterior limb of the internal capsule and within the retrolenticular part of the internal capsule, with a sensitivity of 100% and a specificity of 70% for both areas. We concluded that the clinical-radiological correlations did not match the neurophysiological standards, thereby highlighting the limitation of this study, which involved a cohort of acute stroke patients recruited from clinical practice and investigated the clinical impact of these brain lesions, even when documented with the most sensitive imaging modality. (orig.)

  3. Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms

    Spieker, Janine; Ackermann, Anica; Salfelder, Anika; Vogel-Höpker, Astrid; Layer, Paul G.


    Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS). Here, we first analyzed the expression of acetylcholinesterase (AChE) by IHC and of choline acetyltransferase (ChAT) by ISH in developing embryonic chicken limbs (stages HH17-37). AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB) and Alizarin red (AR) stainings, respectively. Both acetylcholine (ACh)- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein. PMID:27574787

  4. Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease.

    Zhou, An; Hu, Jianping; Wang, Lirong; Zhong, Guochen; Pan, Jian; Wu, Zeyu; Hui, Ailing


    Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).

  5. AChE and EROD activities in two echinoderms, Holothuria leucospilota and Holoturia atra (Holothuroidea), in a coral reef (Reunion Island, South-western Indian Ocean).

    Kolasinski, Joanna; Taddei, Dorothée; Cuet, Pascale; Frouin, Patrick


    AChE and EROD activities were investigated in two holothurian species, Holothuria leucospilota and Holoturia atra, from a tropical coral reef. These organisms were collected from 3 back-reef stations, where temperature and salinity were homogeneous. The activity levels of both AChE and EROD varied significantly between the two species, but were in the range of values determined in other echinoderm species. AChE activity levels were higher in the longitudinal muscle than in the tentacle tegument. Among the several tissues tested, the digestive tract wall exhibited higher EROD activity levels. Sex did not influence AChE and EROD activity levels in both species. Animal biomass and EROD activity levels were only correlated in the tegument tissue of H. atra, and we hypothesize a possible influence of age. EROD activity did not show intraspecific variability. A significant relationship was found between AChE activity and Cuvierian tubules time of expulsion in Holothuria leucospilota. Individuals collected at the southern site presented both lower AChE activity levels and Cuvierian tubules time of expulsion, indicating possible neural disturbance. More information on holothurians biology and physiology is needed to further assess biomarkers in these key species. This study is the first of its kind performed in the coastal waters of Reunion Island and data obtained represent reference values.

  6. Endosulfan exposure inhibits brain AChE activity and impairs swimming performance in adult zebrafish (Danio rerio).

    Pereira, Vanessa Maynart; Bortolotto, Josiane Woutheres; Kist, Luiza Wilges; Azevedo, Mariana Barbieri de; Fritsch, Rachel Seemann; Oliveira, Renata da Luz; Pereira, Talita Carneiro Brandão; Bonan, Carla Denise; Vianna, Monica Ryff; Bogo, Maurício Reis


    Endosulfan is a broad spectrum organochlorine pesticide that is still widely in use in many developing countries. Following application, endosulfan can get to watercourses through surface runoff from agricultural fields and disturb the non-target aquatic animals including freshwater fish species. Given that the activity of the enzyme acetylcholinesterase (AChE) is one of the most recurrently used biomarkers of exposure to pesticides and there are controversial results concerning the effects of endosulfan exposure and AChE activity in fish, the aim of the present study was to evaluate the effects of endosulfan in brain AChE activity and its gene expression pattern using adult zebrafish (Danio rerio) as an animal model. Moreover, we have analyzed the effects of endosulfan exposure in different parameters of zebrafish swimming activity and in long-term memory formation. After 96 h of exposition, fish in the 2.4 μg endosulfan/L group presented a significant decrease in AChE activity (9.44 ± 1.038 μmol SCh h(-1) mg protein(-1); p=0.0205) when compared to the control group (15.87 ± 1.768 μmol SCh h(-1) mg protein(-1); p=0.0205) which corresponds to approximately 40%. The down-regulation of brain AChE activity is not directly related with the transcriptional control as demonstrated by the RT-qPCR analysis. Our results reinforce AChE activity inhibition as a pathway of endosulfan-induced toxicity in brain of fish species. In addition, exposure to 2.4 μg endosulfan/L during 96 h impaired all exploratory parameters evaluated: decreased line crossings (≈21%, 273.7 ± 28.12 number of line crossings compared to the control group 344.6 ± 21.30, p=0.0483), traveled distance (≈20%, 23.44 ± 2.127 m compared to the control group 29.39 ± 1.585, p=0.0281), mean speed (≈25%, 0.03 ± 0.003 m/s compared to the control group 0.04 ± 0.002, p=0.0275) and body turn angle (≈21%, 69,940 ± 4871 absolute turn angle compared to the control group 88,010 ± 4560, p=0.0114). These

  7. Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease.

    Lemes, Laís Flávia Nunes; de Andrade Ramos, Giselle; de Oliveira, Andressa Souza; da Silva, Fernanda Motta R; de Castro Couto, Gina; da Silva Boni, Marina; Guimarães, Marcos Jorge R; Souza, Isis Nem O; Bartolini, Manuela; Andrisano, Vincenza; do Nascimento Nogueira, Patrícia Coelho; Silveira, Edilberto Rocha; Brand, Guilherme D; Soukup, Ondřej; Korábečný, Jan; Romeiro, Nelilma C; Castro, Newton G; Bolognesi, Maria Laura; Romeiro, Luiz Antonio Soares


    Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 μM, and a similar inhibition profile of the human isoform (IC50 = 5.7 μM). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 μM, which indicates drug-conform behavior. Also, compound 26 is capable of crossing the blood-brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti-Alzheimer drugs from CNSL is worth of further pursuit and development.

  8. The reactivation of tabun-inhibited mutant AChE with Ortho-7: steered molecular dynamics and quantum chemical studies.

    Lo, Rabindranath; Chandar, Nellore Bhanu; Ghosh, Shibaji; Ganguly, Bishwajit


    A highly toxic nerve agent, tabun, can inhibit acetylcholinesterase (AChE) at cholinergic sites, which leads to serious cardiovascular complications, respiratory compromise and death. We have examined the structural features of the tabun-conjugated AChE complex with an oxime reactivator, Ortho-7, to provide a strategy for designing new and efficient reactivators. Mutation of mAChE within the choline binding site by Y337A and F338A and its interaction with Ortho-7 has been investigated using steered molecular dynamics (SMD) and quantum chemical methods. The overall study shows that after mutagenesis (Y337A), the reactivator can approach more freely towards the phosphorylated active site of serine without any significant steric hindrance in the presence of tabun compared to the wild type and double mutant. Furthermore, the poor binding of Ortho-7 with the peripheral residues of mAChE in the case of the single mutant compared to that of the wild-type and double mutant (Y337A/F338A) can contribute to better efficacy in the former case. Ortho-7 has formed a greater number of hydrogen bonds with the active site surrounding residues His447 and Phe295 in the case of the single mutant (Y337A), and that stabilizes the drug molecule for an effective reactivation process. The DFT M05-2X/6-31+G(d) level of theory shows that the binding energy of Ortho-7 with the single mutant (Y337A) is energetically more preferred (-19.8 kcal mol(-1)) than the wild-type (-8.1 kcal mol(-1)) and double mutant (Y337A/F338A) (-16.0 kcal mol(-1)). The study reveals that both the orientation of the oxime reactivator for nucleophilic attack and the stabilization of the reactivator at the active site would be crucial for the design of an efficient reactivator.

  9. The Ache: Genocide Continues in Paraguay. IWGIA Document No. 17.

    Munzel, Mark

    In 1972, the Paraguayan Roman Catholic Church protested against the massacre of Indians in Paraguay. This was followed by further protests from Paraguayan intellectuals. These protests led to the removal of Jesus de Pereira, one of the executors of the official Ache policy. Thus, the critics were appeased. Since the beginning of 1973, new protests…

  10. Antimicrobial Activity of the Lichen Cetraria islandica (L.) Ach.

    Başaran DÜLGER; GÜCİN, Fahrettin


    In this study, extracts of Cetraria islandica (L.) Ach. were prepared with Ethyl acetate, Acetone, Chloroform and Ethanol and antimicrobial activities of these extracts were examined on test microorganisms as follows: Escherichia coli ATCC 11230, Enterobacter aerogenes CCM 2531, Staphylococcus aureus 6538P, Staphylococcus epidermidis, Bacillus subtilis La2114, Bacillus cereus var. mycoides, Bacillus sphaericus, Bacillus thurigiensis, Bacillus megaterium, Mycobacterium smegmatis RUT, Salmo...

  11. A mudança léxico-gramatical em propostas de redação de vestibular The lexical-grammatical change in the writing of instructional texts for university entrance exams

    Cibele Gadelha Bernardino


    Full Text Available Esta pesquisa tem como objetivo analisar as propostas de redação do vestibular da Universidade Federal do Ceará (UFC, referentes aos anos acadêmicos de 1990/1 e 2007, com o intuito de detectar os traços linguísticos indicadores de uma mudança nesses textos. Baseamos nossa interpretação na Análise Crítica do Discurso, em especial, na contribuição teórica de Norman Fairclough (2001 que discute a respeito das influências ideológicas para a formação discursiva, bem como para sua transformação. Nosso corpus constitui-se por 71 propostas de redação, as quais foram submetidas a uma análise dividida em dois níveis textuais: léxico e gramática. Os resultados obtidos demonstram que houve mudanças significativas em ambos os níveis.This research has the objective of analyzing writing instructional texts for the entrance exams of the Federal University of Ceará, Brazil, in what refers to the years of 1990/1 and 2007. Our aim was to identify which linguistic aspects may be responsible for changes in these writing instructional texts. We based our work on the Discourse Critical Analysis (FAIRCLOUGH, 2001 that regards the ideological influences for the discursive formation, as well as for its transformation. Our sequence corpus is constituted by 71 writing instructional texts which were submitted to an analysis divided into two textual levels: lexicon and grammar. The obtained results demonstrate that there were significant changes in both levels.

  12. Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker.

    Kuca, Kamil; Cabal, Jiri; Jun, Daniel; Musilek, Kamil; Soukup, Ondrej; Pohanka, Miroslav; Pejchal, Jaroslav; Oh, Kyung-Ae; Yang, Garp Yeol; Jung, Young-Sik


    Two newly developed AChE reactivators possessing two oxime groups in 4-position of the pyridinium rings with linkers CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) were tested for their potency to reactivate VX-inhibited AChE. Their reactivation potency was compared with currently available oximes such as pralidoxime, obidoxime and HI-6. Appropriate constants (affinity towards the intact and inhibited enzyme, reactivation rate) characterizing the reactivation process were determined. According to the data obtained, a new oxime with CH(2)O(CH(2))(2)OCH(2) linker reached as high reactivation potency as HI-6. The percentage of reactivation of the oxime with CH(2)O(CH(2))(2)OCH(2) linker was comparable to that of obidoxime at a concentration 10(-3)M. Hence, these oximes may be worthy of future development for the treatment of nerve agent intoxications, especially, with lipophilic agents such as soman and cyclosarin.

  13. A redação convergente e a produção de conteúdos para dispositivos móveis.

    Nair Moreira Silva


    Full Text Available As transformações no jornalismo, da última década, evidenciam, no interior da própria prática jornalística, mudanças inevitáveis na produção, nos meios humanos e nos formatos de distribuição de conteúdos. A crise económica que afeta o jornalismo, um pouco por todo o mundo, procura por soluções. Em Portugal, nunca como hoje se falou tanto em processos convergentes e, numa altura em que a imprensa reclama por um resgate económico, talvez a aliança às plataformas móveis seja a solução a ter em conta. A convergência de plataformas abriu as portas aos jornais na procura de novas audiências, não só ao criar novos espaços de organização de comunidades em torno de um meio de comunicação social, mas também ao oferecer a construção de produtos multimedia que sejam aliciantes para o internauta e que se movimentem na World Wide Web. Os aparelhos móveis, por seu lado, tornaram-se no acessório de bolso do leitor e do internauta no acesso à Web, na leitura e na partilha de conteúdos e converteram-se numa plataforma que carrega a mobilidade de uma cultura participativa. Para este artigo foi objetivo introduzir uma reflexão sobre as transformações dos dispositivos móveis e observar a dinâmica dessas transformações no jornal em papel. Para isso, e à luz do conceito de convergência, fizemos uma análise ao local onde as notícias são produzidas – a redação – de dois diários generalistas portugueses, de forma a analisar as potencialidades técnicas dos aparelhos, as suas implicações, os seus desafios e qual o papel reservado aos jornais. The transformation of journalism over the last decade highlights at the very core of the practice fundamental changes in the production process, human agency and the modes of content distribution. The economic crisis affecting journalism around the world has intensified the need to find solutions. In Portugal the process of convergence is more than ever sought as an answer

  14. 麦穗鱼脑乙酰胆碱酯酶(AChE)的纯化及其比较性研究%Purification of Brain Acetylcholinerase (AChE) from Topmouth Gudgeon and Comparative Study between Crude and Purified AChE

    谢显传; 李少南; 朱国念; 谭亚军


    用PEG2000双水相萃取、DEAE-Sephadex A-50和Sephadex G-200方法分离纯化麦穗鱼Pseudorasbora parva脑中的乙酰胆碱酯酶(AChE),然后比较分析纯酶液与粗酶液中鱼脑AChE 的动力学特性和抗抑制性,以便更直接地了解底物与酶以及毒剂与酶的反应关系.研究结果表明,经过一系列步骤的纯化,最后所得的AChE是纯度较高的酶液;通过对AChE的动力学研究发现,纯化后的麦穗鱼脑AChE与底物之间的亲和力和其在粗酶状态时没有显著的差别,而且纯化后的鱼脑AChE对底物抑制作用更敏感;抗抑制性研究发现,纯化后的麦穗鱼脑AChE对经溴水氧化的马拉硫磷(malathion)和三唑磷(triazophos)的敏感性显著高于粗酶状态的AChE,酶更易受抑制.

  15. Design, synthesis and evaluation of some N-methylenebenzenamine derivatives as selective acetylcholinesterase (AChE) inhibitor and antioxidant to enhance learning and memory.

    Shrivastava, Sushant K; Srivastava, Pavan; Upendra, T V R; Tripathi, Prabhash Nath; Sinha, Saurabh K


    Series of some 3,5-dimethoxy-N-methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N-methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4. The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 31 CFR 363.38 - What happens if my financial institution returns an ACH debit?


    ... TreasuryDirect § 363.38 What happens if my financial institution returns an ACH debit? If your designated financial institution returns an ACH debit, we reserve the right to reinitiate the debit at our option. We.... We are not responsible for any fees your financial institution may charge relating to returned ACH...

  17. Crystal structure of Lymnaea stagnalis AChBP complexed with the potent nAChR antagonist DHβE suggests a unique mode of antagonism.

    Azadeh Shahsavar

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed, activated (open, and desensitized (closed states. The acetylcholine binding protein (AChBP is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls in complex with dihydro-β-erythroidine (DHβE, which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

  18. AChE在Tn+人白血病Jurkat细胞中的表达状况研究%Study on the Expression Profile of AChE in Leukimia Cell Line Jurkat T Which is Tn Antigen Positive

    孙旭红; 于晓锋; 李乃坤; 杜镇镇; 李笑言; 胡涛


    通过研究Tn+人白血病Jurkat细胞中AChE的表达状况,可以分析Jurkat细胞AChE表达与Tn抗原表达水平的关系,从而为AChE用于肿瘤的预后判断或临床治疗提供实验依据.本论文利用ELISA、色度法试验在蛋白水平分析了AChE的表达状况,利用RT-PCR以及Real-time PCR试验在mRNA水平分析了AChE的表达状况.结果显示:Jurkat细胞中AChE的含量及活性明显低于Tn-的白血病细胞K562,且二者又均低于正常白细胞.由此认为,人白血病细胞中AChE的含量及活性低于正常细胞,AChE的表达与Tn抗原的表达水平呈负相关,为肿瘤的临床判断提供了有力的依据.

  19. 麦穗鱼脑AChE间接非竞争ELISA定量分析法的建立%Indirect and Non-competitive ELISA for Quantitative Analysis of the AChE from Topmouth Gudgeon

    李少南; 谢显传; 谭亚军; 朱国念


    用PEG2000双水相萃取、 DEAE-Sephadex A-50和Sephadex G-200方法分离纯化麦穗鱼Pseudorasbora parva脑中的乙酰胆碱酯酶(AChE), 并制备了兔抗麦穗鱼脑AChE抗血清.用兔抗麦穗鱼脑AChE抗体连接抗原, 建立了定量分析麦穗鱼脑AChE的间接非竞争酶联免疫吸附法(Indirect and non-competitive ELISA), 此法操作简便、灵敏度高, 适用于定量检测.该方法的建立有利于AChE在环境科学和农药学研究领域的进一步研究和应用.

  20. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

    Zheng, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Li, Juan [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Qiu, Zhuibai [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Xia, Zheng [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Li, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Yu, Lining; Chen, Hailin; Chen, Jianxing [NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Xie, Qiong, E-mail: [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Chen, Hongzhuan, E-mail: [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China)


    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

  1. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A


    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.

  2. In silico studies in probing the role of kinetic and structural effects of different drugs for the reactivation of tabun-inhibited AChE.

    Rabindranath Lo

    Full Text Available We have examined the reactivation mechanism of the tabun-conjugated AChE with various drugs using density functional theory (DFT and post-Hartree-Fock methods. The electronic environments and structural features of neutral oximes (deazapralidoxime and 3-hydroxy-2-pyridinealdoxime and charged monopyridinium oxime (2-PAM and bispyridinium oxime (Ortho-7 are different, hence their efficacy varies towards the reactivation process of tabun-conjugated AChE. The calculated potential energy surfaces suggest that a monopyridinium reactivator is less favorable for the reactivation of tabun-inhibited AChE compared to a bis-quaternary reactivator, which substantiates the experimental study. The rate determining barrier with neutral oximes was found to be ∼2.5 kcal/mol, which was ∼5.0 kcal/mol lower than charged oxime drugs such as Ortho-7. The structural analysis of the calculated geometries suggest that the charged oximes form strong O(…H and N(…H hydrogen bonding and C-H(…π non-bonding interaction with the tabun-inhibited enzyme to stabilize the reactant complex compared to separated reactants, which influences the activation barrier. The ability of neutral drugs to cross the blood-brain barrier was also found to be superior to charged antidotes, which corroborates the available experimental observations. The calculated activation barriers support the superiority of neutral oximes for the activation of tabun-inhibited AChE compared to charged oximes. However, they lack effective interactions with their peripheral sites. Docking studies revealed that the poor binding affinity of simple neutral oxime drugs such as 3-hydroxy-2-pyridinealdoxime inside the active-site gorge of AChE was significantly augmented with the addition of neutral peripheral units compared to conventional charged peripheral sites. The newly designed oxime drug 2 appears to be an attractive candidate as efficient antidote to kinetically and structurally reactivate the tabun

  3. In silico studies in probing the role of kinetic and structural effects of different drugs for the reactivation of tabun-inhibited AChE.

    Lo, Rabindranath; Chandar, Nellore Bhanu; Kesharwani, Manoj K; Jain, Aastha; Ganguly, Bishwajit


    We have examined the reactivation mechanism of the tabun-conjugated AChE with various drugs using density functional theory (DFT) and post-Hartree-Fock methods. The electronic environments and structural features of neutral oximes (deazapralidoxime and 3-hydroxy-2-pyridinealdoxime) and charged monopyridinium oxime (2-PAM) and bispyridinium oxime (Ortho-7) are different, hence their efficacy varies towards the reactivation process of tabun-conjugated AChE. The calculated potential energy surfaces suggest that a monopyridinium reactivator is less favorable for the reactivation of tabun-inhibited AChE compared to a bis-quaternary reactivator, which substantiates the experimental study. The rate determining barrier with neutral oximes was found to be ∼2.5 kcal/mol, which was ∼5.0 kcal/mol lower than charged oxime drugs such as Ortho-7. The structural analysis of the calculated geometries suggest that the charged oximes form strong O(…)H and N(…)H hydrogen bonding and C-H(…)π non-bonding interaction with the tabun-inhibited enzyme to stabilize the reactant complex compared to separated reactants, which influences the activation barrier. The ability of neutral drugs to cross the blood-brain barrier was also found to be superior to charged antidotes, which corroborates the available experimental observations. The calculated activation barriers support the superiority of neutral oximes for the activation of tabun-inhibited AChE compared to charged oximes. However, they lack effective interactions with their peripheral sites. Docking studies revealed that the poor binding affinity of simple neutral oxime drugs such as 3-hydroxy-2-pyridinealdoxime inside the active-site gorge of AChE was significantly augmented with the addition of neutral peripheral units compared to conventional charged peripheral sites. The newly designed oxime drug 2 appears to be an attractive candidate as efficient antidote to kinetically and structurally reactivate the tabun

  4. Distribution of NOS and AChE positive neurons in the neocortex of alligator sinensis%扬子鳄新皮质NOS、AChE阳性神经元的分布

    龚鑫; 熊克仁; 汪仁平


    目的 观察扬子鳄新皮质内一氧化氮合酶(nitric oxide synthase,NOS)和乙酰胆碱酯酶(acetylcholinesterase,AChE)阳性神经元的形态和分布,为扬子鳄脑的比较解剖学积累资料,为其机能研究提供形态学依据.方法 采用还原型尼克酰胺腺嘌呤二核苷酸黄递酶(NADPH-d)法和亚铁氰化酮法观察扬子鳄新皮质内NOS和AChE阳性神经元的分布和特征.结果 扬子鳄新皮质内有NOS和AChE阳性神经元分布,为大、中、小型细胞,以中小型细胞为主,胞体呈圆形、椭圆形、三角形和梭形.结论 扬子鳄新皮质内有NOS和AChE阳性神经元分布.%Objective To observe the distribution of nitric oxide synthase (NOS) and acetylcholinest-erase (AChE) positive neurons in the neocortex of Alligator sinensis. Therefore, to accumulate data for comparative anatomy of Alligator sinensis' brain, and to provide morphological foundation for its functional research. Methods The nicotinamide adenosine dinucleotide phosphate diaphorase (NADPH-d) and acetyl-cholinesterase histochemical technique were used to observe the distribution and morphology of NOS and AChE positive neurons in the neocortex of Alligator sinensis. Results The NOS and AChE positive neurons were observed in the neocortex of Alligator sinensis. They were large, middle or small sized cells, but most of them were middle and small. The cell bodies were round, oval, triangular or fusiform in shape. Conclusion The neocortex of Alligator sinensis contains NOS and AChE positive neurons.

  5. Leitura e redação entre universitários: avaliação de um programa de intervenção Reading and writing among undergraduates students: evaluation of a remedial program

    Isabel S. Sampaio


    Full Text Available Este trabalho avalia a aplicação de um programa de intervenção em leitura e redação realizado com alunos ingressantes de dois cursos da área de Negócios de uma universidade particular, período noturno, num total de 42 participantes. Os resultados obtidos indicam que as diferenças de desempenho não foram estatisticamente significativas entre o pré e o pós-teste, mas que houve mudanças qualitativas nas atitudes dos alunos em relação a esses temas. O estudo enfatiza a necessidade de incorporação de disciplinas especificas ou atividades de longa duração aos currículos dos cursos de graduação, destinadas a oferecer aos alunos a oportunidade de superarem deficiências da escolarização anterior.This work evaluates a remedial program focused in reading and writing skills developed with 42 freshmen of two undergraduate courses of Business area. Final results demonstrate that there wasn’t significative increasing in the performance of the participants (considering pre and post tests at reading and writing activities. A qualitative change was observed in their opinions and atitudes throughout these subjects. It’s suggested the inclusion of long duration disciplines or activities in the curricula of these courses, offering the freshmen the opportunity to overcome their difficulties.

  6. Escherichia coli Protein Expression System for Acetylcholine Binding Proteins (AChBPs.

    Nikita Abraham

    Full Text Available Nicotinic acetylcholine receptors (nAChR are ligand gated ion channels, identified as therapeutic targets for a range of human diseases. Drug design for nAChR related disorders is increasingly using structure-based approaches. Many of these structural insights for therapeutic lead development have been obtained from co-crystal structures of nAChR agonists and antagonists with the acetylcholine binding protein (AChBP. AChBP is a water soluble, structural and functional homolog of the extracellular, ligand-binding domain of nAChRs. Currently, AChBPs are recombinantly expressed in eukaryotic expression systems for structural and biophysical studies. Here, we report the establishment of an Escherichia coli (E. coli expression system that significantly reduces the cost and time of production compared to the existing expression systems. E. coli can efficiently express unglycosylated AChBP for crystallography and makes the expression of isotopically labelled forms feasible for NMR. We used a pHUE vector containing an N-terminal His-tagged ubiquitin fusion protein to facilitate AChBP expression in the soluble fractions, and thus avoid the need to recover protein from inclusion bodies. The purified protein yield obtained from the E. coli expression system is comparable to that obtained from existing AChBP expression systems. E. coli expressed AChBP bound nAChR agonists and antagonists with affinities matching those previously reported. Thus, the E. coli expression system significantly simplifies the expression and purification of functional AChBP for structural and biophysical studies.

  7. QSAR Models for the Reactivation of Sarin Inhibited AChE by Quaternary Pyridinium Oximes Based on Monte Carlo Method.

    Veselinović, Aleksandar M; Veselinović, Jovana B; Toropov, Andrey A; Toropova, Alla P; Nikolić, Goran M


    For three random splits, one-variable models of oximes reactivation of sarin inhibited acetylcholinesterase (logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M) have been calculated with CORAL software. The total number of considered oximes was 42. Simplified molecular input line entry system (SMILES) and hydrogen-suppressed graph (HSG) are used to represent the molecular structure. Using CORAL software by means of the calculation with Monte Carlo optimization of the so called correlation weights for the molecular fragments, optimal SMILES-based descriptors were defined, which are correlated with an endpoint for the training set. The predictability of these descriptors for an external test are estimated. In this study hybrid representation HSG together with SMILES was used. The "classic" scheme (i.e. split data into the training set and test set) of building up quantitative structure-activity relationships was employed. Computational experiments indicated that this approach can satisfactorily predict the desired endpoint. Best model had following statistical characteristics n=32, r2= 0.6012, s= 0.279, F= 45 for training and n=10, r2= 0.9301, s= 0.076, Rm2=0.9206 for test set.

  8. 吗啡依赖性大鼠海马CA1区AChE阳性反应物的变化%The alteration of AChE in CA1 of hippocampus in morphine dependent rats

    周郦楠; 王辛荑; 张广新; 李开明



  9. 早期营养不良对SD大鼠海马AchE和ChAT表达的影响%Effects of Perinatal Malnutrtition on AchE and ChAT of Hippocampus in Male Rat Offspring

    蒲亚岚; 王永红; 王小林; 金晶; 罗强


    Objective To explore the effects of perinatal malnutrtition on AchE and ChAT of hippocampus in the male rat offspring in the 21 days after birth.Methods In the food-restricted group(FR) ,females received 50% of the food-intake of control mothers(CM) ,which were not restricted with food,from pregant day 14 to postnatal day 21.Then,the male offspring were killed to measure the levels of hippocampal AchE and ChAT.Results The optical density of positive ChAT cells significantly reduced in the hippocampal CA3 layer of FS male offsping,compared to the CM( P <0.05 ) ,with no difference in the CA1 ( P >0.05 ).The optical density of positive AchE cells have no diffenrences in the CA1 and CA3 between the two groups( P >0.05 ).And the level of mRNA of AchE and ChAT were both singnificiantly reduced in FR rat offspring hippocampus( P <0.05 ).Conclusion Perinatal malnutrtion could prohibit the development of the hippocampus and central cholinergic system among male rats offspring,which would affect the lenarning and memory ability after they grown up.%目的探讨生命早期营养不良对21天雄性SD大鼠中枢AchE和ChAT的影响.方法从妊娠晚期到哺乳期末给予母鼠半量饲料,造成子鼠营养不良,取哺乳期末雄性子鼠脑海马组织进行测量.结果免疫组化结果示:实验组海马CA3区ChAT光密度低于对照组(P0.05);而两组间CA1和CA3区AchE光密度均无差异(P>0.05);RT-PCR示:实验组海马ChAT、AchE mRNA少于对照组(P<0.05).结论早期营养不良能导致子鼠海马及中枢胆碱能系统发育障碍,可能会影响成年后大鼠学习记忆能力.

  10. Mysterious a6-containing nAChRs: function, pharmacology, and pathophysiology

    Ke-chun YANGU; Guo-zhang JIN; Jie WU


    Neuronal nicotinic acetylcholine receptors (nAChRs) are the superfamily of ligand-gated ion channels and widely expressed throughout the central and peripheral nervous systems. nAChRs play crucial roles in modulating a wide range of higher cognitive functions by mediating presynaptic, postsynaptic, and extrasynaptic signaling. Thus far, nine alpha (a2-alO) and three beta ((32, (33, and (34) subunits have been identified in the CNS, and these subunits assemble to form a diversity of functional nAChRs. Although a4(32- and a7-nAChRs are the two major functional nAChR types in the CNS, a6*-nAChRs are abundantly expressed in the midbrain dopaminergic (DAergic) system, including mesocorticolimbic and nigrostriatal pathways, and particularly present in presynaptic nerve terminals. Recently, functional and pharmacological profiles of a6*-nAChRs have been assessed with the use of a6 subunit blockers such as a-conotoxin Mil and PIA, and also by using a6 subunit knockout mice. By modulating DA release in the nucleus accumbens (NAc) and modulating GABA release onto DAergic neurons in the ventral tegmental area (VTA), a6*-nAChRs may play important roles in the mediation of nicotine reward and addiction. Furthermore, a6*-nAChRs in the nigrostriatal DAergic system may be promising targets for selective preventative treatment of Parkinson's disease (PD). Thus, a6*-nAChRs may hold promise for future clinical treatment of human disorders, such as nicotine addiction and PD. In this review, we mainly focus on the recent advances in the understanding of ct6*-nAChR function, pharmacology and pathophysiology.

  11. Comparative functional expression of nAChR subtypes in rodent DRG neurons

    Nathan J. Smith


    Full Text Available We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: 1 neurons that express predominantly alpha3beta4 and alpha6beta4 nAChRs; 2 neurons that express predominantly alpha7 nAChRs; 3 neurons that express a combination of alpha3beta4/alpha6beta4 and alpha7 nAChRs; and 4 neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels and mitochondrial Ca2+ transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors (mAChRs and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  12. Prejunctional effects of the nicotinic ACh receptor agonist dimethylphenylpiperazinium at the rat neuromuscular junction.

    Singh, S; Prior, C


    1. We have studied the effects of the nicotinic acetylcholine (ACh) receptor agonist dimethylphenylpiperazinium (DMPP) on the evoked release of ACh from motor terminals in the rat isolated hemidiaphragm using an electrophysiological approach. 2. DMPP (1-4 microM) had no effect on the rate of spontaneous quantal ACh release but increased the number of quanta of ACh released per impulse during 50 Hz stimulation. The DMPP-induced increase in evoked ACh release was dependent on the frequency of stimulation, being absent when it was reduced to 0.5 Hz, but was not Ca2+ dependent, being unaffected at 50 Hz by a 4-fold decrease in the extracellular Ca2+ concentration. 3. The facilitation of evoked ACh release at 50 Hz by 2 microM DMPP was abolished by 10 microM of the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide hydrochloride) and, in the presence of W7, 2 microM DMPP depressed evoked ACh release at 0.5 Hz. The ability of the nicotinic ACh receptor antagonist vecuronium (1 microM) to depress evoked ACh release at 50 Hz was also abolished by 10 microM W7. 4. The present findings demonstrate, using an electrophysiological technique, that DMPP can produce changes in the evoked ACh release from rat motor nerve terminals that are consistent with the existence of facilitatory nicotinic ACh receptors on the motor nerve endings. Further, they indicate a role for calmodulin-dependent systems in this facilitatory effect of the compound.

  13. Exploration of the susceptibility of AChE from the poultry red mite Dermanyssus gallinae (Acari: Mesostigmata) to organophosphates in field isolates from France.

    Roy, Lise; Chauve, Claude; Delaporte, Jean; Inizan, Gilbert; Buronfosse, Thierry


    The red fowl mite Dermanyssus gallinae (De Geer, 1778) is a hematophagous mite species, which is very commonly found in layer facilities in Europe. The economic and animal health impact of this parasite is quite important. In laying hen houses, organophosphates are almost the only legally usable chemicals. Detecting a target resistance can be useful in order to limit the emergence of resistant populations. The acetylcholinesterase (AChE) activity and the enzyme sensitivity to paraoxon was investigated in 39 field samples and compared to a susceptible reference strain (SSK). Insensitivity factor values (expressed as IC50 ratio) obtained from field isolates compared to SSK revealed some polymorphism but not exceeding a 6-fold difference. The kinetic characteristics of AChE from some field samples showed some difference in KM values for acetylthiocholine and inhibition kinetics performed with diethyl paraoxon exhibited a 5.5-fold difference in the bimolecular rate constant in one field isolate. Taken together, these data suggested that differences in AChE susceptibility to organophosphates may exist in D. gallinae but no resistant population was found.

  14. Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis.

    Artursson, Elisabet; Akfur, Christine; Hörnberg, Andreas; Worek, Franz; Ekström, Fredrik


    The nerve agent tabun inhibits the essential enzyme acetylcholinesterase (AChE) by a rapid phosphoramidation of the catalytic serine residue. Oximes, such as K027 and HLö-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. To investigate HI-6, K027 and HLö-7, residues lining the active-site gorge of hAChE were substituted and the effects on kinetic parameters for reactivation were determined. None of the mutants (Asp74Asn, Asp74Glu, Tyr124Phe, Tyr337Ala, Tyr337Phe, Phe338Val and Tyr341Ala) were able to facilitate HI-6-mediated reactivation of tabun-hAChE. In contrast, Tyr124Phe and Tyr337Phe induce a 2-2.5-fold enhancement of the bimolecular rate constant for K027 and HLö-7. The largest effects on the dissociation constant (3.5-fold increase) and rate constant (20-fold decrease) were observed for Tyr341Ala and Asp74Asn, respectively. These findings demonstrate the importance of residues located distant from the conjugate during the reactivation of tabun-hAChE.


    Becerril, J; Gonzales, H; Saketkoo, L A


    An 80-year-old man presented with a complaint of three months of fatigue and aching of his shoulders and hips, as well as pain, swelling, and stiffness in bilateral fingers that was worse in the morning but improved with movement. Associated symptoms included worsening dry mouth and eyes, dysphagia, exertional dyspnea, and right foot drop. Physical exam was significant for edematous and tender bilateral proximal interphalangeal joints, metacarpophalangeal joints and wrists with decreased grip, extension and flexion, as well as bilateral pulmonary crackles. Laboratory analysis revealed Anti-Ro (SSA) and Anti-La (SSB) positivity with elevated erythrocyte sedimentation rate (70mm/hr) and C-reactive peptide (13mg/L). Pulmonary function testing was notable for a forced vital capacity (FVC) of 64% and carbon monoxide diffusing capacity (DLCO) of 44%. High resolution chest computed tomography demonstrated fibrotic changes consistent with nonspecific interstitial pneumonitis. The patient was started on mycophenolate mofetil, hydroxychloroquine, and prednisone for Sjögren's syndrome (SjS). Symptoms improved and repeat FVC revealed a 20 percent improvement, however subsequent tapering of prednisone resulted in worsening dyspnea and increase of FVC to 60 prcent. Prednisone was restarted and rituximab 2g divided in two doses was administered with overall symptom improvement. Symptoms and FVC continued to wax and wane over the following 18 months requiring re-dosing of rituximab with most recent FVC improved to 71 percent and DLCO 41 percent.

  16. High-Pressure Plasma Deposition of a-C:H Films by Dielectric-Barrier Discharge

    刘昌俊; 李阳; 杜海燕; 艾宝都


    The fabrication of a-C:H films from methane has been performed using dielectric-barrier discharges at atmospheric pressure. The effect of combined-feed gas, such as carbon dioxide,carbon monoxide or acetylene on the formation of a-C:H films has been investigated. It hasbeen demonstrated that the addition of carbon monoxide or acetylene into methane leads to aremarkable improvement in the fabrication of a-C:H films. The characterization of carbon filmobtained has been conducted using FT-IR, Raman and SEM.

  17. Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

    Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit


    Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

  18. AChR deficiency due to epsilon-subunit mutations : two common mutations in the Netherlands

    Faber, Catharina G.; Molenaar, Peter C.; Vles, Johannes S. H.; Bonifati, Domenic M.; Verschuuren, Jan J. G. M.; van Doorn, Pieter A.; Kuks, Jan B. M.; Wokke, John H. J.; Beeson, David; De Baets, Marc


    Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients

  19. AChR deficiency due to ε-subunit mutations: Two common mutations in the Netherlands

    C.G. Faber (Carin); P.C. Molenaar (Peter); J.S.H. Vles (Johannes); D.M. Bonifati (Domenic); J.J. Verschuuren (Jan); P.A. van Doorn (Pieter); J.B.M. Kuks (Jan); J.H.J. Wokke (John); D. Beeson (David); M.H. de Baets (Marc)


    textabstractCongenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine

  20. Remarkably increased resistin levels in anti-AChR antibody-positive myasthenia gravis.

    Zhang, Da-Qi; Wang, Rong; Li, Ting; Li, Xin; Qi, Yuan; Wang, Jing; Yang, Li


    Resistin is a pro-inflammatory cytokine involved in the pathogenesis of autoimmune diseases. To investigate serum resistin levels in patients with myasthenia gravis (MG) and determine if there are associations between resistin levels and disease severity, we measured serum resistin levels in 102 patients with anti-acetylcholine receptor antibody-positive MG (AChR-MG). We further analyzed associations between serum resistin levels and clinical variables in patients with MG. Our findings demonstrate that serum resistin levels are elevated in patients with AChR-generalized MG and AChR-MG with thymoma and are correlated with disease severity. Resistin has potential as a useful serum biomarker for inflammation in AChR-MG.

  1. AChR deficiency due to ε-subunit mutations: Two common mutations in the Netherlands

    C.G. Faber (Carin); P.C. Molenaar (Peter); J.S.H. Vles (Johannes); D.M. Bonifati (Domenic); J.J. Verschuuren (Jan); P.A. van Doorn (Pieter); J.B.M. Kuks (Jan); J.H.J. Wokke (John); D. Beeson (David); M.H. de Baets (Marc)


    textabstractCongenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patie

  2. AChR deficiency due to epsilon-subunit mutations : two common mutations in the Netherlands

    Faber, Catharina G.; Molenaar, Peter C.; Vles, Johannes S. H.; Bonifati, Domenic M.; Verschuuren, Jan J. G. M.; van Doorn, Pieter A.; Kuks, Jan B. M.; Wokke, John H. J.; Beeson, David; De Baets, Marc


    Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients (s

  3. AChR deficiency due to epsilon-subunit mutations : two common mutations in the Netherlands

    Faber, Catharina G.; Molenaar, Peter C.; Vles, Johannes S. H.; Bonifati, Domenic M.; Verschuuren, Jan J. G. M.; van Doorn, Pieter A.; Kuks, Jan B. M.; Wokke, John H. J.; Beeson, David; De Baets, Marc


    Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) epsilon-subunit gene underlying congenital myasthenic syndromes in nine patients (s

  4. Synthesis, biological evaluation, and computational studies of Tri- and tetracyclic nitrogen-bridgehead compounds as potent dual-acting AChE inhibitors and hH3 receptor antagonists.

    Darras, Fouad H; Pockes, Steffen; Huang, Guozheng; Wehle, Sarah; Strasser, Andrea; Wittmann, Hans-Joachim; Nimczick, Martin; Sotriffer, Christoph A; Decker, Michael


    Combination of AChE inhibiting and histamine H3 receptor antagonizing properties in a single molecule might show synergistic effects to improve cognitive deficits in Alzheimer's disease, since both pharmacological actions are able to enhance cholinergic neurotransmission in the cortex. However, whereas AChE inhibitors prevent hydrolysis of acetylcholine also peripherally, histamine H3 antagonists will raise acetylcholine levels mostly in the brain due to predominant occurrence of the receptor in the central nervous system. In this work, we designed and synthesized two novel classes of tri- and tetracyclic nitrogen-bridgehead compounds acting as dual AChE inhibitors and histamine H3 antagonists by combining the nitrogen-bridgehead moiety of novel AChE inhibitors with a second N-basic fragment based on the piperidinylpropoxy pharmacophore with different spacer lengths. Intensive structure-activity relationships (SARs) with regard to both biological targets led to compound 41 which showed balanced affinities as hAChE inhibitor with IC50 = 33.9 nM, and hH3R antagonism with Ki = 76.2 nM with greater than 200-fold selectivity over the other histamine receptor subtypes. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds and molecular dynamics studies to explain high affinity at the hH3R.

  5. Modulation of presynaptic nAChRs on postsynaptic GABA receptor in optictectum of juvenile Xenopus


    Using the blind patch-clamp technique with the whole-cell mode, we have studied the modulation of presynaptic receptor on postsynaptic γ-aminobutyric acid (GABA) receptor measuring miniature inhibitory postsynaptic currents (mIPSCs) in optic tectum of Xenopus during critical peroid. It was demonstrated that compared with mature neurons, mIPSCs recorded from immature neurons had smaller amplitude and longer decay time. mIPSCs are mediated by GABAa receptor. The nicotinic acetylcholine receptor agonists (carbachol, cytisine, nicotine, DMPP and so on) could increase the frequency of mIPSCs. The enhancement of mIPSCs frequency induced by nAChR agonists was calcium-dependent. However, the choline, a product of hydrolyzed acetylcholine, could not increase the frequency of mIPSCs. DH-β-E, a competitive antagonist of nAChR, blocked the increase of mIPSCs frequency induced by carbachol. Mecamyllamine, an α3β4 subtype of nAChR antagonist, also blocked the carbachol-induced enhancement of mIPSCs. On the other hand, MLA, α7 subtype of nAChR antagonist, had no effect on it. Thus, it seems that nAChR could presynaptically modulate the mIPSCs and α3β4 subtype of nAChR might be involved. But α7 nAChR subtype of nAChR would not be involved. The modulation is calcium- dependent. Meanwhile, we found that Ca2+-free solution could elicit giant PSCs. The frequency of mIPSCs also is related with the level of HP.

  6. Acetylcholinesterase Inhibitors (AChEI's for the treatment of visual hallucinations in schizophrenia: a case report

    Patel Sachin S


    Full Text Available Abstract Background Visual hallucinations are commonly seen in various neurological and psychiatric disorders including schizophrenia. Current models of visual processing and studies in diseases including Parkinsons Disease and Lewy Body Dementia propose that Acetylcholine (Ach plays a pivotal role in our ability to accurately interpret visual stimuli. Depletion of Ach is thought to be associated with visual hallucination generation. AchEI's have been used in the targeted treatment of visual hallucinations in dementia and Parkinson's Disease patients. In Schizophrenia, it is thought that a similar Ach depletion leads to visual hallucinations and may provide a target for drug treatment Case Presentation We present a case of a patient with Schizophrenia presenting with treatment resistant and significantly distressing visual hallucinations. After optimising treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to treat her symptoms successfully. Conclusions This case is the first to illustrate this novel use of an AchEI in the targeted treatment of visual hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can be considered in challenging cases although more evidence is required in this field.

  7. Crystal Structure of Lymnaea stagnalis AChBP Complexed with the Potent nAChR Antagonist DHßE Suggests a Unique Mode of Antagonism

    Shahsavar, Azadeh; Kastrup, Jette S; Nielsen, Elsebet Ø.;


    Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed), activated (open), and desensitized (closed) states...

  8. Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

    Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia


    Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

  9. Atomic interactions of neonicotinoid agonists with AChBP: Molecular recognition of the distinctive electronegative pharmacophore

    Talley, Todd T.; Harel, Michal; Hibbs, Ryan E.; Radi, Zoran; Tomizawa, Motohiro; Casida, John E.; Taylor, Palmer (UCB); (UCSD)


    Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 {angstrom} in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids.

  10. Acetylshikonin, a Novel AChE Inhibitor, Inhibits Apoptosis via Upregulation of Heme Oxygenase-1 Expression in SH-SY5Y Cells

    Yan Wang


    Full Text Available Acetylcholinesterase inhibitors are prominent alternative in current clinical treatment for AD patients. Therefore, there is a continued need to search for novel AChEIs with good clinical efficacy and less side effects. By using our in-house natural product database and AutoDock Vina as a tool in docking study, we have identified twelve phytochemicals (emodin, aloe-emodin, chrysophanol, and rhein in Rhei Radix Et Rhizoma; xanthotoxin, phellopterin, alloisoimperatorin, and imperatorin in Angelicae dahuricae Radix; shikonin, acetylshikonin, isovalerylshikonin, and β,β-dimethylacrylshikonin in Arnebiae Radix as candidates of AChEIs that were not previously reported in the literature. In addition to AChEI activity, a series of cell-based experiments were conducted for the investigation of their neuroprotective activities. We found that acetylshikonin and its derivatives prevented apoptotic cell death induced by hydrogen peroxide in human and rat neuronal SH-SY5Y and PC12 cells at 10 μM. We showed that acetylshikonin exhibited the most potent antiapoptosis activity through the inhibition of the generation of reactive oxygen species as well as protection of the loss of mitochondria membrane potential. Furthermore, we identified for the first time that the upregulation of heme oxygenase 1 by acetylshikonin is a key step mediating its antiapoptotic activity from oxidative stress in SH-SY5Y cells.

  11. In silico pharmacophore modeling on known pyridinium oxime reactivators of cyclosarin (GF) inhibited AChE to Aid discovery of potential, more efficacious novel non-oxime reactivators.

    Bhattacharjee, Apurba K; Musilek, Kamil; Kuca, Kamil


    Cyclohexyl methylphosphonofluoridate (cyclosarin, cyclosin, GF) is a highly toxic organophosphorus (OP) nerve agent considered as potential warfare threats and known to be resistant to conventional oxime antidotal therapy. To aid discovery of novel antidotes for GF toxicity, a three-dimensional in silico pharmacophore model for reactivation efficacy against GF intoxication is presented. The model was generated from published experimental percentage reactivation data on oximes as changes of AChE/BuChE activities in the whole blood after cyclosarin intoxication and administration. The generated pharmacophore model was found to contain a hydrogen bond donor site and two ring aromatic sites as necessary optimal features for reactivation of GF intoxication. Stereo-electronic features of oximes reported by us earlier provided guidance to develop the model and were found to be consistent with the reported structure activity data. Furthermore, from virtual screening of two commercial databases, Maybridge and ChemNavigator using map-fitting of the model led us to identify two new non-oxime compounds showing reactivation efficacy within 10-fold range of 2-PAM for DFP-inhibited AChE. Since GF is a G simulator like DFP (diisopropylfluorophosphate), the model should have the potential for discovery of novel reactivators against GF intoxication.

  12. Neurochemical mechanism of the gastrointestinal interdigestive migrating motor complex in rats with acute inflammatory stomach ache

    Xiaoli Xu; Qin Li; Lv Zhou; Liqiang Ru


    The normal gastrointestinal interdigestive migrating motor complex cycle was interrupted, and paroxysmal contraction appeared after formaldehyde-induced stomach ache. Activities of nitric oxide synthase, acetylcholinesterase and vasoactive intestinal peptide neurons were significantly reduced, whereas activities of calcitonin gene-related peptide neurons were significantly increased in the pyloric sphincter muscular layer, myenteric nerve plexus and submucous nerve plexus. Electroacupuncture at Zusanli (ST36) suppressed paroxysmal contraction in rats with formaldehyde-induced stomach ache, and neurons in the enteric nervous system were normal. These results indicated that nitrergic neurons, cholinergic neurons, vasoactive intestinal peptide neurons and calcitonin gene-related peptide neurons in the enteric nervous system may be involved in changes to the gastrointestinal interdigestive migrating motor complex following stomach ache, and that electroacupuncture can regulate this process.

  13. Etude théorique de la réactivation de l'AChE inhibée par le tabun

    Kwasnieski, Ophélie


    Research of efficient reactivation agents of inhibited AChE is still challenging as dysfunction of AChE due to inhibition by organophosphorus (OP) compound is a major threat. We choose to look at tabun since it is one of the more potent nerve agents, and the AChE-tabun complex is very difficult to reactivate. In order to study the interaction between AChE and tabun from a theoretical point of view, we used a QM/MM methodology. First, we defined our model on acetylcholine which is the natural ...

  14. Presencia de hifas de Evernia prunastri (L.) Ach. en los tejidos caulinares de Betula alba L

    Monsó Senabre, María Andrea; Solas Alados, María Teresa; Fernández Ruiz, Benjamín


    [ES] En el presente trabajo se estudia el mecanismo y alcance de la penetración de las hifas de un liquen epífito, Evernia prunastri (L.) Ach., en ramas de Betula alba L. Se pretende averiguar la relación entre el ataque químico de las substancias liquénicas con el metabolismo foliar. [EN] The present research describes the results of the mechanisms and reach penetration study of an epiphytic lichen, Evernia prunastri (L.) Ach. into the branches of Betula alba L. It's a question of to disc...

  15. The Effects of Dimethoate on HSP70 Expression and AChE Activity in Glioma U87 Cells%乐果对U87细胞HSP70表达及AChE活性的影响

    谢芳; 周志俊; 吴强恩; 吴同俊


    [目的]研究乐果对神经胶质瘤细胞U87热应激蛋白70(HSP70)表达的影响规律,比较HSP70与乙酰胆碱酯酶(AChE)对乐果的敏感性.[方法]以不同浓度乐果(100、10、1、0.1、0.01、0 μmol/L)对体外培养的U87细胞分别进行2、4、8、16和24h染毒,再分别用Western-blot法和DTNB法检测各组细胞HSP70表达和AChE活性的变化,比较这两个指标变化的幅度以及引起此变化所需乐果浓度和染毒时间的差异.[结果]乐果染毒2 h即可引起HSP70表达的显著增高(P<0.01),这一变化在染毒4 h时出现于各剂量组,并可持续至染毒16 h.在染毒2 h和4 h,HSP70表达的变化与乐果剂量之间存在相关关系(Pearson相关系数分别为0.916和0.989,P<0.01).AChE活性的显著降低出现在染毒4 h,且仅出现在剂量较高的3个组,变化幅度也较小.[结论]乐果可以在相对较短时间内以较低剂量引起U87细胞HSP70表达的显著变化,并存在一定的剂量-反应关系.HSP70比AChE对乐果更为敏感.

  16. Effect of Fipronil on Malathion-inhibited Topmouth Gudgeon (Pseudorasbora parva) Brain AChE Recovery at Different Temperatures%不同温度下锐劲特对受马拉硫磷抑制的麦穗鱼AChE活性恢复的影响

    顾晓军; 李少南; 樊德方


    研究了15~17 ℃、20~22 ℃下,0.01 mg/L锐劲特对被1 mg/L马拉硫磷抑制的麦穗鱼(Pseudorasbora parva)脑乙酰胆碱酯酶(AChE)活性恢复的影响.结果表明:在15~17 ℃,经48 h抑制, AChE被抑制了40%,恢复144 h后,处理组与无锐劲特对照都恢复到了空白对照的80%以上.在此温度下锐劲特对AChE活性恢复的影响不明显;而在20~22 ℃下,经相同的处理时间,AChE被抑制了70%,恢复240 h后,处理组与无锐劲特对照都只恢复到了对照的70%.其间于144、192 h, AChE活性差异达显著水平(P<0.05),说明了在此温度下锐劲特对AChE活性恢复的影响.文中还讨论了恢复研究的意义.%Effect of 0.01 mg/L fipronil on 1 mg/L malathion-inhibited topmouth gudgeon (Pseudorasbora parva) acetylcholinesterase (AChE) recovery at 15~17 ℃ and 20~22 ℃ respectively was studied. AChE was inhibited by 40 percent in both treatment and control without fipronil after 48 h exposure and recovered to over 80 percent after 144 h recovery at 15~17 ℃. At this temperature, effect of fipronil on AChE recovery was not discernible. However, after same exposure period, AChE in both treatment and control without fipronil was inhibited by 70 percent and recovered only to 70 percent after 240 h at 20~22 ℃. The difference between treatment and control without fipronil was significant at 144 h and 192 h respectively(P<0.05), which indicated the effect of fipronil on AChE recovery at this temperature. The importance of recovery study was also discussed.

  17. [Cation ions modulate the ACh-sensitive current in type II vestibular hair cells of guinea pigs].

    Guo, Chang-Kai; Zhang, Song; Kong, Wei-Jia; Li, Qing-Tian; Li, Zhi-Wang


    Molecular biological studies and electrophysiological data have demonstrated that acetylcholine (ACh) is the principal cochlear and vestibular efferent neurotransmitter among mammalians. However, the functional roles of ACh in type II vestibular hair cells among mammalians are still unclear, with the exception of the well-known alpha9-containing nicotinic ACh receptor (alpha9-nAChR) in cochlear hair cells and frog saccular hair cells. In this study, the properties of the ACh-sensitive current were investigated by whole-cell patch clamp technique in isolated type II vestibular hair cells of guinea pigs. The direct effect of extracellular ACh was to induce a hyperpolarization effect in type II vestibular hair cells. Type II vestibular hair cells displayed a sustained outward current in response to the perfusion of ACh. It took about 60 s for the ACh-sensitive current to get a complete re-activation. The reversal potential of the ACh-sensitive current was (-66 +/- 8) mV, which indicated that potassium ion was the main carrier of this current. The blocking effect by the submillimolar concentration of tetraethylammonium (TEA) further indicated that extracellular ACh stimulated the calcium-dependent potassium current. Following replacement of the compartment of NaCl in the normal external solution with TrisCl, LiCl or saccharose respectively, the amplitude of the ACh-sensitive current was not affected. Blocking of the release of intracellular Ca(2+) stores by intracellular application of heparin failed to inhibit the ACh-sensitive current. Therefore, extracellular Na(+)and the inositol 1,4,5-trisphosphate (IP(3))-dependent intracellular Ca(2+)release were not involved in the activation of the ACh-sensitive current. However, the ACh-sensitive current was strongly affected by the concentration of the extracellular K(+), extracellular Ca(2+) and intracellular Mg(2+). The amplitude of the ACh- sensitive current was strongly inhibited by high concentration of extracellular K

  18. nAChR agonist-induced cognition enhancement: integration of cognitive and neuronal mechanisms.

    Sarter, Martin; Parikh, Vinay; Howe, William M


    The identification and characterization of drugs for the treatment of cognitive disorders has been hampered by the absence of comprehensive hypotheses. Such hypotheses consist of (a) a precisely defined cognitive operation that fundamentally underlies a range of cognitive abilities and capacities and, if impaired, contributes to the manifestation of diverse cognitive symptoms; (b) defined neuronal mechanisms proposed to mediate the cognitive operation of interest; (c) evidence indicating that the putative cognition enhancer facilitates these neuronal mechanisms; (d) and evidence indicating that the cognition enhancer facilitates cognitive performance by modulating these underlying neuronal mechanisms. The evidence on the neuronal and attentional effects of nAChR agonists, specifically agonists selective for alpha4beta2* nAChRs, has begun to support such a hypothesis. nAChR agonists facilitate the detection of signals by augmenting the transient increases in prefrontal cholinergic activity that are necessary for a signal to gain control over behavior in attentional contexts. The prefrontal microcircuitry mediating these effects include alpha4beta2* nAChRs situated on the terminals of thalamic inputs and the glutamatergic stimulation of cholinergic terminals via ionotropic glutamate receptors. Collectively, this evidence forms the basis for hypothesis-guided development and characterization of cognition enhancers.

  19. M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses.

    Pancani, Tristano; Bolarinwa, Caroline; Smith, Yoland; Lindsley, Craig W; Conn, P Jeffrey; Xiang, Zixiu


    The striatum is the main input station of the basal ganglia and is extensively involved in the modulation of motivated behavior. The information conveyed to this subcortical structure through glutamatergic projections from the cerebral cortex and thalamus is processed by the activity of several striatal neuromodulatory systems including the cholinergic system. Acetylcholine potently modulates glutamate signaling in the striatum via activation of muscarinic receptors (mAChRs). It is, however, unclear which mAChR subtype is responsible for this modulatory effect. Here, by using electrophysiological, optogenetic, and immunoelectron microscopic approaches in conjunction with a novel, highly selective M4 positive allosteric modulator VU0152100 (ML108) and M4 knockout mice, we show that M4 is a major mAChR subtype mediating the cholinergic inhibition of corticostriatal glutamatergic input on both striatonigral and striatopallidal medium spiny neurons (MSNs). This effect is due to activation of presynaptic M4 receptors, which, in turn, leads to a decrease in glutamate release from corticostriatal terminals. The findings of the present study raise the interesting possibility that M4 mAChR could be a novel therapeutic target for the treatment of neurological and neuropsychiatric disorders involving hyper-glutamatergic transmission at corticostriatal synapses.

  20. Genome Sequence of the Mycorrhiza Helper Bacterium Streptomyces sp. Strain AcH 505.

    Tarkka, M T; Feldhahn, L; Buscot, F; Wubet, T


    A draft genome sequence of Streptomyces sp. strain AcH 505 is presented here. The genome encodes 22 secondary metabolite gene clusters and a large arsenal of secreted proteins, and their comparative and functional analyses will help to advance our knowledge of symbiotic interactions and fungal and plant biomass degradation.

  1. Preparation and comparison of a-C:H coatings using reactive sputter techniques

    Keunecke, M., E-mail: martin.keunecke@ist.fraunhofer.d [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Weigel, K.; Bewilogua, K. [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Cremer, R.; Fuss, H.-G. [CemeCon AG, Wuerselen (Germany)


    Amorphous hydrogenated carbon (a-C:H) coatings are widely used in several industrial applications. These coatings commonly will be prepared by plasma activated chemical vapor deposition (PACVD). The main method used to prepare a-C:H coating in industrial scale is based on a glow discharge in a hydrocarbon gas like acetylene or methane using a substrate electrode powered with medium frequency (m.f. - some 10 to 300 kHz). Some aims of further development are adhesion improvement, increase of hardness and high coating quality on complex geometries. A relatively new and promising technique to fulfil these requirements is the deposition of a-C:H coatings by a reactive d.c. magnetron sputter deposition from a graphite target with acetylene as reactive gas. An advancement of this technique is the deposition in a pulsed magnetron sputter process. Using these three mentioned techniques a-C:H coatings were prepared in the same deposition machine. For adhesion improvement different interlayer systems were applied. The effect of different substrate bias voltages (d.c. and d.c. pulse) was investigated. By applying the magnetron sputter technique in the d.c. pulse mode, plastic hardness values up to 40 GPa could be reached. Besides hardness other mechanical properties like resistance against abrasive wear were measured and compared. Cross sectional SEM images showed the growth structure of the coatings.

  2. Measurement of p-nitrophenyl acetate esterase activity (EA), total antioxidant capacity (TAC), total oxidant status (TOS) and acetylcholinesterase (AChE) in gills and digestive gland of Mytilus galloprovincialis exposed to binary mixtures of Pb, Cd and Cu.

    Franco-Martinez, Lorena; Romero, Diego; García-Navarro, José A; Tecles, Fernando; Teles, Mariana; Tvarijonaviciute, Asta


    The aims of the present work were (1) to evaluate oxidative stress biomarkers and AChE in two tissues of wild mussel (Mytilus galloprovincialis) of high biochemical activity and accumulation capacity (gills and digestive gland) and (2) to study the behaviour of these biomarkers in presence of heavy metals. For this, EA, TOS, TAC and AChE were measured in tissues of mussels exposed to binary combination of Pb, Cd and Cu. Mussels (n = 36) were exposed to one of the binary mixtures of Pb (1000 μg L(-1)), Cd (100 μg L(-1)) and Cu (100 μg L(-1)) for 7 days, under controlled conditions. Gills and digestive gland were extracted and frozen at -80 °C until analysis. The automatic methods employed for the measurement of EA, TAC, TOS and AChE in M. galloprovincialis revealed higher levels of these biomarkers in digestive gland than gills. Study results suggest that gills would be the tissue of election for study oxidative stress markers, whereas digestive tissue should be selected for AChE measurements in case of evaluation of combined metal toxicity in mussels.

  3. 家蝇乙酰胆碱酯酶基因的克隆与序列分析%Cloning and sequence analysis of AChE gene from Housefly (Musca domestica)

    方晓东; 黄俊生


    目的克隆家蝇Ace基因并进行表达,并对家蝇AChE序列进行分析,为利用基因工程进行酶改造提供必要的参考. 方法结合已有的文献资料,利用生物信息学方法对家蝇AChE的序列进行分析,包括密码子偏爱性、系统发生、三维结构预测等. 结果成功克隆家蝇Ace基因,并利用同源模建方法获得了家蝇AChE的三维结构,以果蝇AChE为参考,判断了家蝇AChE应属于AChE 2家族. 结论根据所得家蝇AChE的三维模型从理论上分析了因AChE中一个氨基酸突变导致家蝇产生有机磷抗性的可能原因,并为半理性改造家蝇乙酰胆碱酯酶提供了三维模型.

  4. Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: discovery of quinoxaline-based hybrid compounds with AChE, H₃R and BACE 1 inhibitory activities.

    Huang, Wenhai; Tang, Li; Shi, Ying; Huang, Shufang; Xu, Lei; Sheng, Rong; Wu, Peng; Li, Jia; Zhou, Naiming; Hu, Yongzhou


    A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H(3)R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H(3)R/AChE/BACE 1 (H(3)R antagonism, IC(50)=280.0 ± 98.0 nM; H(3)R inverse agonism, IC(50)=189.3 ± 95.7 nM; AChE, IC(50)=483 ± 5 nM; BACE 1, 46.64±2.55% inhibitory rate at 20 μM) and high selectivity over H(1)R/H(2)R/H(4)R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes.

  5. Dexamethasone reduces tachykinin but not ACh airway hyperreactivity after O[sub 3

    Murlas, C.G.; Lang, Z.; Chodimella, V. (Rush Univ., Chicago, IL (United States))


    We investigated whether dexamethasone pretreatment affected the acute increase in airway reactivity produced by high-level ozone exposure. Reactivity to intravenous IV substance P (SP), IV acetylcholine (ACh), or aerosolized capsaicin (CAP) before and 1 hr after ozone exposure (3 ppm for 2 hr) was determined by measuring specific airway resistance in anesthetized, spontaneously breathing guinea pigs, half of whom had been pretreated for 2 days pre-ozone with dexamethasone (2 mg/kg intramuscularly [IM] daily). The amount of IV SP, IV ACh, or inhaled capsaicin necessary to increase baseline specific airway resistance by 100% (ED200ACh or ED200SP) or 35% (ED135CAP) was determined by interpolation from dose-response curves. Compared to their pre-ozone status on the day of exposure, we found that dexamethasone-pretreated animals manifested significantly less of an increase in airway reactivity postozone to IV SP or inhaled CAP than did untreated animals. Changes in logEDs of the pretreated group were 0.18 +/- 0.03 (mean +/- SE) for SP and 2.20 +/- 0.11 for CAP compared to 0.27 +/- 0.04 and 3.38 +/- 0.34, respectively, for the untreated groups post-ozone (p < 0.05 and n = 4 for each). In contrast, dexamethasone pretreatment had no effect on IV ACh reactivity postozone: changes in logED200ACh were 0.27 +/- 0.08 and 0.28 +/- 0.04 for the pretreated and untreated groups, respectively (n = 4). In animals pretreated with captopril to block possible dexamethasone stimulation of angiotensin-converting enzyme synthesis that could influence tachykinin reactivity, we found that the corticosteroid effect on post-ozone SP reactivity was as marked as that seen in animals without captopril (n = 4). These reactivity studies were consistent with the possibility that dexamethasone may ameliorate ozone-induced, tachykinin hyperreactivity by stimulating airway neutral endopeptidase (NEP).

  6. Deposition of a-C:H films on a nanotrench pattern by bipolar PBII&D

    Hirata, Yuki; Nakahara, Yuya; Nagato, Keisuke; Choi, Junho


    In this study, hydrogenated amorphous carbon (a-C:H) films were deposited on a nanotrench pattern (300 nm pitch, aspect ratio: 2.0) by bipolar-type plasma based ion implantation and deposition technique (bipolar PBII&D), and the effects of bipolar pulse on the film properties were investigated. Moreover, the behaviour of ions and radicals surrounding the nanotrench was analyzed to clarify the coating mechanism and properties of the a-C:H films on the nanotrench. Further, thermal nanoimprint lithography was carried out using the nanotrench pattern coated with a-C:H films as the mold, and the mold release properties were evaluated. All nanotrench surfaces were successfully coated with the a-C:H films, but the film thickness on the top, sidewall, and bottom surfaces of the trench were not uniform. The surface roughness of the a-C:H films was found to decrease at a higher positive voltage; this happens due to the higher electron temperature around the nanotrench because of the surface migration of plasma particles arrived on the trench. The effects of the negative voltage on the behaviour of ions and radicals near the sidewall of the nanotrench are quite similar to those near the microtrench reported previously (Park et al 2014 J. Phys. D: Appl. Phys. 47 335306). However, the positive pulse voltage was also found to affect the behaviour of ions and radicals near the sidewall surface. The incident angles of ions on the sidewall surface increased with the positive pulse voltage because the energy of incoming ions on the trench decreases with increasing positive voltage. Moreover, the incident ion flux on the sidewall is affected by the positive voltage history. Further, the radical flux decreases with increasing positive voltage. It can be concluded that a higher positive voltage at a lower negative voltage condition is good to obtain better film properties and higher film thickness on the sidewall surface. Pattern transfer properties for the nanoimprint formed by

  7. Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies.

    Lo, Rabindranath; Ganguly, Bishwajit


    Organophosphorus nerve agents are highly toxic compounds which strongly inhibit acetylcholinesterase (AChE) in the blood and in the central nervous system (CNS). Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. The reactivation mechanism of tabun-conjugated AChE with various drugs has been examined with density functional theory and ab initio quantum chemical calculations. The presence of a lone-pair located on the amidic group resists the nucleophilic attack at the phosphorus center of the tabun-conjugated AChE. We have shown that the newly designed drug candidate N-(pyridin-2-yl)hydroxylamine, at the MP2/6-31+G*//M05-2X/6-31G* level in the aqueous phase with the polarizable continuum solvation model (PCM), is more effective in reactivating the tabun-conjugated AChE than typical oxime drugs. The rate determining activation barrier with N-(pyridin-2-yl)hydroxylamine was found to be ∼1.7 kcal mol(-1), which is 7.2 kcal mol(-1) lower than the charged oxime trimedoxime (one of the most efficient reactivators in tabun poisonings). The greater nucleophilicity index (ω(-)) and higher CHelpG charge of pyridinylhydroxylamine compared to TMB4 support this observation. Furthermore, we have also examined the reactivation process of tabun-inhibited AChE with some other bis-quaternary oxime drug candidates such as methoxime (MMB4) and obidoxime. The docking analysis suggests that charged bis-quaternary pyridinium oximes have greater binding affinity inside the active-site gorge of AChE compared to the neutral pyridinylhydroxylamine. The peripheral ligand attached to the neutral pyridinylhydroxylamine enhanced the binding with the aromatic residues in the active-site gorge of AChE through effective π-π interactions. Steered molecular dynamics (SMD) simulations have also been performed with the charged oxime (TMB4) and the neutral hydroxylamine. From protein-drug interaction

  8. Muscle aches

    ... plenty of sleep and try to reduce stress. Yoga and meditation are excellent ways to help you sleep and relax. If home measures aren't working, your health care provider may prescribe medicine or physical therapy, ...

  9. Microdemographic Determinants of Population Recovery among the Northern Aché.

    Baker, Jack D; Hill, Kim; Hurtado, A Magdalena; Alcantara, Adelamar; Hunsinger, Eddie; Sprague, Webb


    A pattern of population crash and rapid recovery is a common feature of the pacification and settlement experience of the indigenous peoples of tropical South America. Despite the obvious importance of these events to the demographic and anthropological sciences as a whole, as well as their significant practical implications, little is known about the microdemographic determinants of these paired phenomena. Using methods of asymptotic and stochastic demographic analysis, we reconstructed the microdemographic drivers of this history among one indigenous population: the Northern Aché of eastern Paraguay. This article explores the implications of these relationships for understanding the overall demographic turnaround observed within similar groups, as well as for the future trajectory of the Northern Aché in particular.

  10. Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay.

    Bribiescas, Richard G; Hill, Kim R


    Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age-related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age-associated variation in testosterone, it was hypothesized that Ache men would not show age-related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18-64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = -0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40-49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within-individual analyses of diurnal variation capture age-related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context.

  11. Evidence for aging theories from the study of a hunter-gatherer people (Ache of Paraguay).

    Libertini, G


    In the late seventies, a small tribal population of Paraguay, the Ache, living under natural conditions, was studied. Data from this population turn out to be useful for considerations about evolutionary hypotheses on the aging phenomenon. 1) Ache show an age-related increasing mortality, which strongly limits the mean duration of life, as observed in other studies on mammal and bird species. 2) According to current theories on aging, in the wild very few or no individual reach old age and, so, aging cannot be directly influenced by natural selection. However, data from our population show that a significant proportion of the population reaches in the wild 60 and 70 years of age. 3) Data from Ache are also in agreement with the observation about an inverse correlation between extrinsic mortality and deaths due to the age-related increasing mortality. 4) For many gerontologists, the age-related decline of vital functions is a consequence of the gradual decline of cell turnover, genetically determined and regulated by the declining duplication capacities of stem cells. The current interpretation is that these restrictions are a general defense against the proliferation of any tumoral mass. However, among wild Ache cancer is virtually unknown in non-elderly subjects, and only among older individuals are there deaths attributable to oncological diseases. Moreover, fitness decline begins long before oncological diseases have fatal effects in significant numbers. This completely disproves the current hypothesis, because a supposed defense against a deadly disease cannot exterminate a population before the disease begins to kill. These data are consistent with similar data from other species studied under natural conditions, and they bring new arguments against the non-adaptive interpretation of aging and in support of the adaptive interpretation.

  12. Modeling nicotinic neuromodulation from global functional and network levels to nAChR based mechanisms

    Michael GRAUPNER; Boris GUTKIN


    Neuromodulator action has received increasing attention in theoretical neuroscience. Yet models involving both neuronal populations dynamics at the circuit level and detailed receptor properties are only now being developed. Here we review recent computational approaches to neuromodulation, focusing specifically on acetylcholine (ACh) and nicotine. We dis-cuss illustrative examples of models ranging from functional top-down to neurodynamical bottom-up. In the top-down approach, a computational theory views ACh as encoding the uncertainty expected in an environment. A different line of models accounts for neural population dynamics treating ACh as toggling neuronal networks between read-in of informa-tion and recall of memory. Building on the neurodynamics idea we discuss two models of nicotine's action with increasing degree of biological realism. Both consider explicitly receptor-level mechanisms but with different scales of detail. The first is a large-scale model of nicotine-dependent modulation of dopaminergic signaling that is capable of simulating nicotine self-administration. The second is a novel approach where circuit-level neurodynamics of the ventral tegmental area (VTA) are combined with explicit models of the dynamics of specific nicotinic ACh receptor subtypes. We show how the model is constructed based on local anatomy, electrophysiology and receptor properties and provide an illustration of its potential. In particular, we show how the model can shed light on the specific mechanisms by which nicotine controls dopaminergic neurotransmission in the VTA. This model serves us to conclude that detailed accounts for neuromodulator action at the basis of behavioral and cognitive models are crucial to understand how neuromodulators mediate their functional proper-ties.

  13. Acetylcholinesterase Inhibitors (AChEI's for the treatment of visual hallucinations in schizophrenia: A review of the literature

    Patel Sachin S


    Full Text Available Abstract Background Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition. Methods A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia. Results No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group. Discussion Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly. Conclusions We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

  14. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    Schaal, Courtney [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States); Padmanabhan, Jaya [Department of Molecular Medicine and USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL 33612 (United States); Chellappan, Srikumar, E-mail: [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States)


    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer.

  15. Selective activation of α7 nicotinic acetylcholine receptor (nAChRα7) inhibits muscular degeneration in mdx dystrophic mice.

    Leite, Paulo Emílio Correa; Gandía, Luís; de Pascual, Ricardo; Nanclares, Carmen; Colmena, Inés; Santos, Wilson C; Lagrota-Candido, Jussara; Quirico-Santos, Thereza


    Amount evidence indicates that α7 nicotinic acetylcholine receptor (nAChRα7) activation reduces production of inflammatory mediators. This work aimed to verify the influence of endogenous nAChRα7 activation on the regulation of full-blown muscular inflammation in mdx mouse with Duchenne muscular dystrophy. We used mdx mice with 3 weeks-old at the height myonecrosis, and C57 nAChRα7(+/+) wild-type and nAChRα7(-/-) knockout mice with muscular injury induced with 60µL 0.5% bupivacaine (bp) in the gastrocnemius muscle. Pharmacological treatment included selective nAChRα7 agonist PNU282987 (0.3mg/kg and 1.0mg/kg) and the antagonist methyllycaconitine (MLA at 1.0mg/kg) injected intraperitoneally for 7 days. Selective nAChRα7 activation of mdx mice with PNU282987 reduced circulating levels of lactate dehydrogenase (LDH, a marker of cell death by necrosis) and the area of perivascular inflammatory infiltrate, and production of inflammatory mediators TNFα and metalloprotease MMP-9 activity. Conversely, PNU282987 treatment increased MMP-2 activity, an indication of muscular tissue remodeling associated with regeneration, in both mdx mice and WTα7 mice with bp-induced muscular lesion. Treatment with PNU282987 had no effect on α7KO, and MLA abolished the nAChRα7 agonist-induced anti-inflammatory effect in both mdx and WT. In conclusion, nAChRα7 activation inhibits muscular inflammation and activates tissue remodeling by increasing muscular regeneration. These effects were not accompanied with fibrosis and/or deposition of non-functional collagen. The nAChRα7 activation may be considered as a potential target for pharmacological strategies to reduce inflammation and activate mechanisms of muscular regeneration.

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

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


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

  17. Mutations in congenital myasthenic syndromes reveal an epsilon subunit C-terminal cysteine, C470, crucial for maturation and surface expression of adult AChR

    Ealing, J; Webster, R; Brownlow, S; Abdelgany, A; Oosterhuis, H; Muntoni, F; Vaux, DJ; Vincent, A; Beeson, D


    Many congenital myasthenic syndromes (CMS) are associated with mutations in the genes encoding the acetylcholine receptor (AChR), an oligomeric protein with the structure alpha(2)betadeltaepsilon. AChR deficiency is frequently due to homozygous or heteroallelic mutations in the AChR epsilon subunit,

  18. The dual-acting H3 receptor antagonist and AChE inhibitor UW-MD-71 dose-dependently enhances memory retrieval and reverses dizocilpine-induced memory impairment in rats.

    Khan, Nadia; Saad, Ali; Nurulain, Syed M; Darras, Fouad H; Decker, Michael; Sadek, Bassem


    Both the histamine H3 receptor (H3R) and acetylcholine esterase (AChE) are involved in the regulation of release and metabolism of acetylcholine and several other central neurotransmitters. Therefore, dual-active H3R antagonists and AChE inhibitors (AChEIs) have shown in several studies to hold promise to treat cognitive disorders like Alzheimer's disease (AD). The novel dual-acting H3R antagonist and AChEI 7-(3-(piperidin-1-yl)propoxy)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline (UW-MD-71) with excellent selectivity profiles over both the three other HRs as well as the AChE's isoenzyme butyrylcholinesterase (BChE) shows high and balanced in vitro affinities at both H3R and AChE with IC50 of 33.9nM and hH3R antagonism with Ki of 76.2nM, respectively. In the present study, the effects of UW-MD-71 (1.25-5mg/kg, i.p.) on acquisition, consolidation, and retrieval in a one-trial inhibitory avoidance task in male rats were investigated applying donepezil (DOZ) and pitolisant (PIT) as reference drugs. Furthermore, the effects of UW-MD-71 on memory deficits induced by the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (DIZ) were tested. Our results indicate that administration of UW-MD-71 before the test session dose-dependently increased performance and enhanced procognitive effect on retrieval. However neither pre- nor post-training acute systemic administration of UW-MD-71 facilitated acquisition or consolidation. More importantly, UW-MD-71 (2.5mg/kg, i.p.) ameliorated the DIZ-induced amnesic effects. Furthermore, the procognitive activity of UW-MD-71 in retrieval was completely reversed and partly abrogated in DIZ-induced amnesia when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL), but not with the CNS penetrant H1R antagonist pyrilamine (PYR). These results demonstrate the procognitive effects of UW-MD-71 in two in vivo memory models, and are to our knowledge the first demonstration in vivo that a potent dual

  19. Docking studies of benzylidene anabaseine interactions with α7 nicotinic acetylcholine receptor (nAChR) and acetylcholine binding proteins (AChBPs): application to the design of related α7 selective ligands.

    Kombo, David C; Mazurov, Anatoly; Tallapragada, Kartik; Hammond, Philip S; Chewning, Joseph; Hauser, Terry A; Vasquez-Valdivieso, Montserrat; Yohannes, Daniel; Talley, Todd T; Taylor, Palmer; Caldwell, William S


    AChBPs isolated from Lymnaea stagnalis (Ls), Aplysia californica (Ac) and Bulinus truncatus (Bt) have been extensively used as structural prototypes to understand the molecular mechanisms that underlie ligand-interactions with nAChRs [1]. Here, we describe docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR. Results reveal that docking of these compounds using Glide software accurately reproduces experimentally-observed binding modes of DMXBA and of its active metabolite, in the binding pocket of Ac. In addition to the well-known nicotinic pharmacophore (positive charge, hydrogen-bond acceptor, and hydrophobic aromatic groups), a hydrogen-bond donor feature contributes to binding of these compounds to Ac, Bt, and the α7 nAChR. This is consistent with benzylidene anabaseine analogs with OH and NH(2) functional groups showing the highest binding affinity of these congeners, and the position of the ligand shown in previous X-ray crystallographic studies of ligand-Ac complexes. In the predicted ligand-Ls complex, by contrast, the ligand OH group acts as hydrogen-bond acceptor. We have applied our structural findings to optimizing the design of novel spirodiazepine and spiroimidazoline quinuclidine series. Binding and functional studies revealed that these hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype and demonstrate partial agonism. The gain in affinity is also due to conformational restriction, tighter hydrophobic enclosures, and stronger cation-π interactions. The use of AChBPs structure as a surrogate to predict binding affinity to α7 nAChR has also been investigated. On the whole, we found that molecular docking into Ls binding site generally scores better than when a α7 homology model, Bt or Ac crystal structure is used. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

    Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan


    Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity.

  1. Uma nova maneira de avaliar as competências escritoras na redação do ENEM Un nuevo modo de evaluar las competencias escritoras en la redacción del ENEM A new way to evaluate the writing skills in ENEM's compositions

    Ruben Klein


    Full Text Available O artigo apresenta um estudo realizado com a correção da redação do ENEM 2008 adotando-se uma nova forma de avaliar o domínio das competências escritoras do exame. Cada competência e seus critérios de correção foram tratados como 5 itens polítomos com ordenação de resposta de 1 a 7 . Essa metodologia possibilita que se obtenha para cada competência/item polítomo as estatísticas clássicas, percentuais de resposta por categoria, coeficientes ponto-polisseriais e ponto-bisseriais por categoria de resposta. Permite também o uso da Teoria da Resposta ao Item-Tri para obter-se uma escala de proficiências de Redação no ENEM. A adoção de metodologia de interpretação de escalas permite descrever as competências e habilidades dominadas pelos candidatos nos diferentes níveis da escala, possibilitando definir os pontos nos quais as categorias de resposta das competências são dominadas. O uso dessa metodologia pode aperfeiçoar a apresentação dos resultados do ENEM e ser útil para maior aprofundamento dos resultados da redação. Com esse trabalho os autores pretendem introduzir uma discussão do uso da TRI na correção da redação do ENEM.El artículo presenta estudio realizado en la a corrección de la redacción del ENEM 2008 adoptándose nova forma de evaluar el dominio de las competencias escritoras de los candidatos. Cada competencia y sus criterios de corrección fueran tratados como 5 itens polítomos con ordenación de respuesta de 1 a 7. Esa metodología posibilita que se obtenga para cada competencia/item polítomo las estadísticas clásicas, porcentuales de respuesta por categoría, coeficientes punto-poliseriales e punto-biseriales por categoría de respuesta. Permite también el uso de la Teoría de la Respuesta al Ítem-Tri para obtenerse una escala de resultados proficientes con la Redacción del ENEM. La adopción de metodología de interpretación de escalas permite describir las competencias y habilidades

  2. UMA DELICADA RELAÇÃO NO JORNALISMO: O encontro do conteúdo e da produção nos sistemas de gerenciamento de conteúdos. Um estudo comparativo da sistemática de trabalho das redações no Brasil e Estados Unidos.

    Amy Schmitz Weiss


    Full Text Available Este estudo comparativo documenta como salas de redaçãocom diferentes sistemáticas e culturas compartilham questõessemelhantes no que tange aos sistemas para a publicação deconteúdos. Argumenta-se que os desafios encontrados pelosciberjornalistas muitas vezes ocorrem em função dos sistemasterem sido criados não objetivando os leitores ou mesmo o trabalho jornalístico, mas sim a lógica própria dos desenvolvedores. Por fim, os resultados são apresentados de forma a se procurar compreender como a estrutura dos Sistemas de Gerenciamento de Conteúdos (CMS influencia a apresentação das matérias, bem como a qualidade do jornalismo produzido. As autoras discutem as implicações dos resultados e como formatos alternativos, tais como os dos sistemas abertos de publicação de conteúdos, podemdeterminar um novo nível para o jornalismo nesta delicada relação entre o conteúdo e a produção. Também são indicadas áreas para possíveis investigações futuras.

  3. Age-related changes in functional postsynaptic nAChR subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction

    Christensen, Mark Holm; Kohlmeier, Kristi Anne


    by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within...... that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny...

  4. Mycorrhiza helper bacterium Streptomyces AcH 505 induces differential gene expression in the ectomycorrhizal fungus Amanita muscaria.

    Schrey, Silvia D; Schellhammer, Michael; Ecke, Margret; Hampp, Rüdiger; Tarkka, Mika T


    The interaction between the mycorrhiza helper bacteria Streptomyces nov. sp. 505 (AcH 505) and Streptomyces annulatus 1003 (AcH 1003) with fly agaric (Amanita muscaria) and spruce (Picea abies) was investigated. The effects of both bacteria on the mycelial growth of different ectomycorrhizal fungi, on ectomycorrhiza formation, and on fungal gene expression in dual culture with AcH 505 were determined. The fungus specificities of the streptomycetes were similar. Both bacterial species showed the strongest effect on the growth of mycelia at 9 wk of dual culture. The effect of AcH 505 on gene expression of A. muscaria was examined using the suppressive subtractive hybridization approach. The responsive fungal genes included those involved in signalling pathways, metabolism, cell structure, and the cell growth response. These results suggest that AcH 505 and AcH 1003 enhance mycorrhiza formation mainly as a result of promotion of fungal growth, leading to changes in fungal gene expression. Differential A. muscaria transcript accumulation in dual culture may result from a direct response to bacterial substances.

  5. In Vitro Anti-AChE, Anti-BuChE, and Antioxidant Activity of 12 Extracts of Eleutherococcus Species


    Neurodegenerative diseases are one of the most occurring diseases in developed and developing countries. The aim of this work focused on the screening of the natural inhibitors of AChE and BuChE and antioxidants in Eleutherococcus species. We found that the ethanol extracts of E. setchuenensis and E. sessiliflorus showed the strongest inhibition towards AChE (IC50: 0.3 and 0.3 mg/mL, resp.). Among chloroform extracts, the most active appeared to be E. gracilistylus (IC50: 0.37 mg/mL). In turn, the ethanol extract of E. henryi inhibited the strongest BuChE with IC50 value of 0.13 mg/mL. Among chloroform extracts, E. gracilistylus, E. setchuenensis, and E. sessiliflorus appeared to be the strongest with IC50 values of 0.12, 0.18, and 0.19 mg/mL. HPTLC screening confirmed the presence of inhibitors in extracts. All extracts exhibited anti-DPPH⁎ activity and single antioxidants have been identified. To the best of our knowledge, no information was available on this activity of compounds in Eleutherococcus. These studies provide a biochemical basis for the regulation of AChE and BuChE and encourage us to continue isolation of active compounds. PMID:27803761

  6. Pirenzepine block of ACh-induced mucus secretion in tracheal submucosal gland cells

    Farley, J.M.; Dwyer, T.M. (Univ. of Mississippi Medical Center, Jackson (USA))


    Muscarinic stimulation of mucus secretion, as measured by the release of ({sup 3}H)glycoprotein, was studied in explants from the tracheal epithelium of weanling swine. The mucus glycoprotein secretion was transient, ceasing within the first 10 min of a continuous exposure to 100 {mu}M ACh. Increasing the solutions' osmotic pressure did not alter basal mucus glycoprotein secretion. Mucus glycoprotein secretion was inhibited by 2-10 {mu}M PZP, indicting that the M{sub 3} muscarinic receptors mediate cholinergic stimulation of mucus production.

  7. Age-dependency in hunting ability among the Ache of eastern Paraguay.

    Walker, Robert; Hill, Kim; Kaplan, Hillard; McMillan, Garnett


    This paper examines changes in hunting ability across the lifespan for the Ache of eastern Paraguay. Hunting ability is decomposed into two components-finding prey and probability of kill upon encounter- and analyzed for important prey species. Results support the argument that skill acquisition is an important aspect of the human foraging niche with hunting outcome variables reaching peaks surprisingly late in life, significantly after peaks in strength. The implications of this study are important for modeling the role of the human foraging niche in the co-evolution of various outstanding human life history characteristics such as large brains, long lifespans, and extended juvenile periods.

  8. Kinetics of Hydrocarbon formation in a-C:H film deposition plasmas

    De la Cal, E.; Tabares, F.L.


    The formation of C{sub 2} and C{sub 3} hydrocarbons during the PACVD of a-C-H films from admixtures of methane with H{sub 2} and He has been investigated by mass espectrometry under several deposition condition. The time evolution of the observed species indicates that the formation mechanism of ethylene and acetylene are sensitive to the conditions of the wall during the growing of the film. Acetylene are sensitive to the conditions of the wall during the growing of the carburized metal. (Author)

  9. Extracellular polysaccharidases synthesized by the epiphytic lichen Evernia prunastri (L.) Ach.

    Yagüe, E; Orus, M I; Estevez, M P


    Evernia prunastri Ach., an epiphytic lichen growing on Quercus rotundifolia Lam., produces a β-1,4-glucanase (EC and a polygalacturonase (EC The activity of these polysaccharidases increases as a response to incubation of the lichen with carboxymethylcellulose or sodium polygalacturonate, respectively. This increase in activity is thought to be the result of enzyme induction because it is inhibited by both cycloheximide and 8-azaguanine. Both polysaccharide-degrading enzymes are partially secreted into the incubation media.

  10. Preliminary Geological Maps of the Ac-H-10 Rongo and Ac-H-15 Zadeni Quadrangles: An integrated Mapping Study Using Dawn Spacecraft Data

    Platz, T.; Nathues, A.; Crown, D. A.; Mest, S. C.; Williams, D. A.; Hoffmann, M.; Schäfer, M.; Sizemore, H. G.; Yingst, R. A.; Ruesch, O.; Buczkowski, D.; Kneissl, T.; Schmedemann, N.; Hughson, K.; Preusker, F.; Russell, C. T.


    We used geologic mapping applied to Dawn spacecraft data as a tool to understand the geologic history of the Ac-H-10 Rongo and Ac-H-15 Zadeni quadrangles of dwarf planet Ceres. These regions, Rongo and Zadeni, are located between 22°S-22°N and 288°-360°E and 65-90°S and 0°-360°E, respectively. The Rongo Quadrangle hosts a number of features: 1) the southwest portion is dissected by curvilinear structures likely caused by Yalode basin formation; 2) the central part is marked by dome-like constructs up to 100 km across; 3) a peculiar bright, c.4 km tall, conical structure informally known as the 'pyramid'; 4) impact craters of various diameters appear moderately to highly degraded or are partially buried; and 5) bright material is primarily exposed in the central portion and often associated with craters. Rongo crater (68 km across) exhibits a central peak and scalloped walls indicative of its degraded appearance. The Zadeni Quadrangle is characterised by impact craters up to 130 km in diameter of which Zadeni crater is the largest. Impact craters across all sizes exhibit fresh to highly degraded morphologies or are partially buried. Many craters developed central peaks. Inter-crater plains are generally hummocky with isolated regions of smooth-textured surfaces. The south pole area (85-90°S) is poorly illuminated and may host a large impact structure. At the time of this writing geologic mapping was performed on Framing Camera (FC) mosaics from Approach (1.3 km/px) and Survey (415 m/px) orbits, including clear filter and colour images and digital terrain models derived from stereo images. In Fall 2015 images from the High Altitude Mapping Orbit (140 m/px) will be used to refine the mapping, followed by Low Altitude Mapping Orbit (35 m/px) starting in December 2015. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA through the Dawn project, and from the German and Italian Space Agencies.

  11. 健脑增智饮对遗忘型轻度认知损害患者认知功能及AchE的影响%The effect of Jiannao Zengzhi Yin on the cognitive function and AchE of patients with amnestic mild cognitive impairment

    王成银; 梁妍霞; 邝仰东; 吕金丹; 梁洁; 刘健红; 何子意; 黄德弘


    目的:观察健脑增智饮对遗忘型轻度认知损害(aMCI)患者认知功能的改善情况及AchE水平的影响。方法:将70例aMCI患者随机分为治疗组和对照组各35例,治疗组给予健脑增智饮(熟地、茯苓、巴戟天、山茱萸、石斛、肉苁蓉、麦冬、石菖蒲、远志、川芎、丹参、赤芍、五味子、生姜、大枣)治疗,对照组给予脑复康片(吡拉西坦片)治疗,两组疗程均为16周。两组患者在治疗前、治疗8周后、治疗16周后分别进行神经心理学测试,包括CMS、ADL、MMSE、CDT,抽血查AchE活性变化。另设健康组20例,只进行神经心理学测试及抽血查AchE水平,不进行治疗。结果:治疗组CMS指标、MMSE评分、血清AchE含量治疗8周后及治疗16周后明显改善(P<0.05,P<0.01),且显著优于对照组(P<0.01)。结论:健脑增智饮能提高aMCI患者记忆功能,CMS评分及MMSE评分均明显改善,降低胆碱酯酶的活性,AchE水平明显降低,提示健脑增智饮有显著提高智能的作用。%Objective:To observe the effect of Jiannao Zengzhi Yin on improvement of the cognitive function and AchE of patients with amnestic mild cognitive impairment (aMCI). Methods:70 aMCI patients were randomly divided into the control group and the treatment group, with 35 cases in each group. The control group was treated with Naofukang Tablets (Piracetam Tablets) while the observation group was treated with Jiannao Zengzhi Yin (composed of Rehmannia, Poria, Morinda officinalis, dogwood, Dendrobium, Cistanche, ophiopogon root, calamus, Polygala, Rhizoma Chuanxiong, Salvia miltiorrhiza, radix paeoniae rubra, Schisandra, ginger, jujube), the treatment of both groups lasted 16 weeks. Neuropsychological test which contains test of CMS, ADL, MMSE and CDT of was given to patients in two groups 8 weeks before and after treatment, 16 weeks after treatment respectively, changes of AchE activity in

  12. The significance of aches/pains among workers in an electronics factory.

    Ho, S F; Phoon, W H


    Three hundred and fifteen female workers with at least three months' employment history in a factory manufacturing disk drives were studied. Each worker completed a self-administered questionnaire on their personal particulars, hours of work, opinion on the work and the workplace and the presence and severity of aches/pains experienced over the past one month. One hundred and forty one (44.8%) of the workers had complaints of aches/pains. Of these, 81 (57.5%) reported an improvement in their symptoms during their off-days. 59 (41.8%) had symptoms affecting two or more sites. The most commonly affected sites were the hands and shoulders, followed by the head and back. There was no significant difference in the prevalence of symptoms between workers from the different work stations. Ninety four (66.7%) of these workers reported that the pains that were severe enough to affect their activities. 76 (53.9%) had to seek some form of medical treatment while 33 (23.4%) had to be on medical leave. However, the physical examinations of this group of workers were normal. The symptoms appeared to be influenced by their attitude towards work. A significantly higher number of workers with symptoms expressed dissatisfaction with work and had complaints of a noisy and cold environment. The study showed that workers' morale and the quality of the work environment may play an important role in improving their general well-being.

  13. Methadone's effect on nAChRs--a link between methadone use and smoking?

    Talka, Reeta; Tuominen, Raimo K; Salminen, Outi


    Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone. Nevertheless, methadone maintenance patients are willing to quit smoking although their quit rates are low. Studies on nicotine-methadone interactions provide an example of the bedside-to-bench approach, i.e., observations in clinical settings have been studied experimentally in vivo and in vitro. In vivo studies have revealed the interplay between nicotine and the endogenous opioid system. At the receptor level, methadone has been shown to be an agonist of human α7 nAChRs and a non-competitive antagonist of human α4β2 and α3* nAChRs. These drugs do not have significant interactions at the level of drug metabolism, and thus the interaction is most likely pharmacodynamic. The net effect of the interaction may depend on individual characteristics because pharmacogenetic factors influence the disposition of both methadone and nicotine.

  14. Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.

    Murthy, Vidya; Taranda, Julián; Elgoyhen, A Belén; Vetter, Douglas E


    Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) alpha9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR alpha9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in alpha9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the alpha9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult alpha9 null mice. Finally, by using mice expressing the nondesensitizing alpha9 L9'T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation.

  15. H2 formation via the UV photo-processing of a-C:H nano-particles

    Jones, A P


    Context. The photolysis of hydrogenated amorphous carbon, a-C(:H), dust by UV photon-irradiation in the laboratory leads to the release of H2 as well as other molecules and radicals. This same process is also likely to be important in the interstellar medium. Aims. To investigate molecule formation arising from the photo-dissociatively-driven, regenerative processing of a-C(:H) dust. Methods. We explore the mechanism of a-C(:H) grain photolysis leading to the formation of H2 and other molecules/radicals. Results. The rate constant for the photon-driven formation of H2 from a-C(:H) grains is estimated to be 2x10^-17 cm^3 s^-1. In intense radiation fields photon-driven grain decomposition will lead to fragmentation into daughter species rather than H2 formation. Conclusions. The cyclic re-structuring of arophatic a-C(:H) nano-particles appears to be a viable route to formation of H2 for low to moderate radiation field intensities (1 < G_0 < 10^2), even when the dust is warm (T ~ 50 - 100 K).

  16. The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats.

    Sadek, Bassem; Khan, Nadia; Darras, Fouad H; Pockes, Steffen; Decker, Michael


    Both the acetylcholine esterase (AChE) and the histamine H3 receptor (H3R) are involved in the metabolism and modulation of acetylcholine release and numerous other centrally acting neurotransmitters. Hence, dual-active AChE inhibitors (AChEIs) and H3R antagonists hold potential to treat cognitive disorders like Alzheimer's disease (AD). The novel dual-acting AChEI and H3R antagonist 7-(3-(piperidin-1-yl)propoxy)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (UW-MD-72) shows excellent selectivity profiles over the AChE's isoenzyme butyrylcholinesterase (BChE) as well as high and balanced in-vitro affinities at both AChE and hH3R with IC50 of 5.4μM on hAChE and hH3R antagonism with Ki of 2.54μM, respectively. In the current study, the effects of UW-MD-72 (1.25, 2.5, and 5mg/kg, i.p.) on memory deficits induced by the muscarinic cholinergic antagonist scopolamine (SCO) and the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (DIZ) were investigated in a step-through type passive avoidance paradigm in adult male rats applying donepezil (DOZ) and pitolisant (PIT) as reference drugs. The results observed show that SCO (2mg/kg, i.p.) and DIZ (0.1mg/kg, i.p.) significantly impaired learning and memory in rats. However, acute systemic administration of UW-MD-72 significantly ameliorated the SCO- and DIZ-induced amnesic effects. Furthermore, the ameliorating activity of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10mg/kg, i.p.). Moreover, ameliorative effect of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was strongly reversed when rats were pretreated with a combination of ZOL (10mg/kg, i.p.) and SCO (1.0mg/kg, i.p.), indicating that these memory enhancing effects were, in addition to other neural circuits, observed through histaminergic H2R as well as

  17. Activation of volume-regulated Cl− channels by ACh and ATP in Xenopus follicles

    Pérez-Samartín, Alberto L; Miledi, Ricardo; Arellano, Rogelio O


    Osmolarity-dependent ionic currents from follicle-enclosed Xenopus oocytes (follicles) were studied using electrophysiological techniques. Whole follicle currents were monitored using a two-electrode voltage clamp and single-channel activity was measured using the patch-clamp technique.In follicles held at -60 mV two chloride currents were activated in external hyposmotic solutions. One was the habitual volume-regulated current elicited by external hyposmolarity (ICl,swell), and the second was a slow and smooth current (Sin) generated by ACh or ATP application.In follicles, the permeability ratios for different anions with respect to Cl− were similar for both ICl,swell and Sin, with a sequence of: SCN− > I− > Br−≥ NO3−≥ Cl− > gluconate ≥ cyclamate > acetate > SO42−.Extracellular ATP blocked the outward component of Sin. Also, extracellular pH modulated the inactivation kinetics of Sin elicited by ACh; e.g. inactivation at +80 mV was ∼100% slower at pH 8.0 compared with that at pH 6.0.Lanthanides inhibited ICl,swell and Sin. La3+ completely inhibited ICl,swell with a half-maximal inhibitory concentration (IC50) of 17 ± 1.9 μm, while Sin was blocked up to 55% with an apparent IC50 of 36 ± 2.6 μm.Patch-clamp recordings in follicular cells showed that hyposmotic challenge opened inward single-channel currents. The single channel conductance (4.7 ± 0.4 pS) had a linear current-voltage relationship with a reversal membrane potential close to −20 mV. This single-channel activity was increased by application of ACh or ATP.The ICl,swell generation was not affected by pirenzepine or metoctramine, and did not affect the purinergic activation of the chloride current named Fin. Thus, ICl,swell was not generated via neurotransmitters released during cellular swelling.All together, equal discrimination for different anions, similar modulatory effects by extracellular pH, the blocking effects by ATP and La3+, and the same single-channel activity

  18. Isenção de Tributos Estaduais para aquisição de veículo automotor para portador(es de deficiência(s: Proposta de um novo olhar e nova redação sobre a legislação vigente no RS

    Sergio Carvalho


    Full Text Available Têm-se como objetivos: propor um novo olhar sobre a legislação estadual que trata de isenções fiscais para aquisição de veículo automotor por portador de deficiência tomando-se como referência a Instrução Normativa da Secretaria da Receita Federal de nº 442 de 12 de agosto de 2004, que reconhece a isenção de tributo federal (IPI às pessoas portadoras de deficiência física, visual, mental severa ou profunda, ou autistas diretamente ou por intermédio de seu representante legal; propor nova redação à Lei 8.820/89 (ICMS, Decreto nº. 32144/85 e Lei 8.115/85 (IPVA, Decreto n. º 37.699/97 similarizando-as àquela emanada pelo Ministério da Fazenda, Secretaria da Receita Federal. Sustenta-se tal proposta no entendimento de que ainda que os direitos fundamentais de cidadania estejam preservados na Constituição Federal, nem sempre a transferência destes para o cotidiano das pessoas é uma ação pacífica. Principalmente aqueles que de nascimento ou de circunstância acidental se tornaram, ao longo da vida, dependentes dos cuidados de terceiros legais. O Estado gaúcho fere os direitos individuais do cidadão e contraria frontalmente sua Constituição ao reconhecer somente os deficientes físicos e paraplégicos condutores e proprietários de veículos automotores como beneficiários de tais isenções.Palavras-chave: Deficientes. Dignidade Humana. Direitos Fundamentais. Legislação Estadual.

  19. Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology

    Luis F. Padilla-Morales


    Full Text Available The presented data provides additional information about the assessment of affinity purified nicotinic acetylcholine receptor (nAChR rich membrane solubilized with long chain (16 saturated carbons lysophospholipid with glycerol headgroup (LFG-16. The assessment of stability and functionality of solubilized membrane protein is a critical step prior to further crystallization trails. One of the key factors for this task is the appropriate choice of a detergent that can support nAChR activity and stability comparable to the crude membranes. The stability of the nAChR-LFG-16 complex incorporated into lipid cubic phase (LCP was monitored for a period of 30 days by means of fluorescence recovery after photobleaching (FRAP and the functionality was evaluated after its incorporation into Xenopus oocyte by means of the two electrode voltage clamp technique.

  20. Auger electron spectroscopy, secondary ion mass spectroscopy and optical characterization of a-C-H and BN films

    Pouch, J. J.; Alterovitz, S. A.; Warner, J. D.


    The amorphous dielectrics a-C:H and BN were deposited on III-V semiconductors. Optical band gaps as high as 3 eV were measured for a-C:H generated by C4H10 plasmas; a comparison was made with bad gaps obtained from films prepared by CH4 glow discharges. The ion beam deposited BN films exhibited amorphous behavior with band gaps on the order of 5 eV. Film compositions were studied by Auger electron spectroscopy (AES), x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The optical properties were characterized by ellipsometry, UV/VIS absorption, and IR reflection and transmission. Etching rates of a-C:H subjected to O2 dicharges were determined.

  1. Drift mobility measurements in a-C:H films by time-resolved electroluminescence

    Foulani, A


    Carrier transport mechanism has been studied in thin insulating hydrogenated amorphous carbon (a-C:H) films. The layers were prepared by plasma polymerization of methane (CH{sub 4}) at a frequency of 20 kHz. Electron mobility was derived from time-resolved luminescence experiments. Between the application of a rectangular voltage pulse and the first appearance of electroluminescence (EL) a time lag exists, which depends on the pulse height. Transit times are in the order of 10{sup -3} to {approx}10{sup -6} s in a voltage rabetween 10 and 25 V. And the estimated electron mobility varies accordingly from 8x10{sup -8} to {approx}10{sup -6} cm{sup 2}/(V s). The field dependence of the carriers mobility is characteristic of Poole-Frenkel-detrapping conduction model, and thus confirms the results obtained by dc experimental data.

  2. Deposition of a-C:H films on inner surface of high-aspect-ratio microchannel

    Hirata, Yuki; Choi, Junho


    Hydrogenated amorphous carbon (a-C:H) films were prepared on inner surface of 100-μm-width microchannel by using a bipolar-type plasma based ion implantation and deposition. The microchannel was fabricated using a silicon plate, and two kinds of microchannels were prepared, namely, with a bottom layer (open at one end) and without a bottom layer (open at both ends). The distribution of thickness and hardness of films was evaluated by SEM and nanoindentation measurements, respectively, and the microstructures of films were evaluated by Raman spectroscopy. Furthermore, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision and Direct Simulation Monte Carlo to investigate the coating mechanism for the microchannel. It was found that the film thickness decreased as the depth of the coating position increased in the microchannels where it is open at one end. The uniformity of the film thickness improved by increasing the negative pulse voltage because ions can arrive at the deeper part of the microchannel. In addition, the hardness increased as the depth of the coating position increased. This is because the radicals do not arrive at the deeper part of the microchannel, and the incident proportion of ions relative to that of radicals increases, resulting in a high hardness due to the amorphization of the film. The opening area of the microchannel where the aspect ratio is very small, radicals dominate the incident flux, whereas ions prevail over radicals above an aspect ratio of about 7.5. On the other hand, in the microchannels that are open at both ends, there were great improvements in uniformity of the film thickness, hardness, and the film structure. The a-C:H films were successfully deposited on the entire inner surface of a microchannel with an aspect ratio of 20.

  3. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Vuslat Yilmaz

    Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

  4. 氯吡嘧磺隆对斑马鱼肝脏抗氧化酶·ATP酶和AchE酶活性的影响%Effect of Halosulfuron-methy on the Antioxidant Enzyme, ATPase and AchE Activities of Zebra Fish Liver

    张洪; 何建昇; 康乐; 刘慧平


    [目的]研究氯吡嘧磺隆对斑马鱼肝脏中抗氧化酶、ATP酶和AchE酶活性的影响.[方法]通过化学品半静态式鱼类静态试验研究斑马鱼肝脏中CAT、SOD、GSTs、Na+K+、Ca2+ Mg2+-ATPase、AchE酶的活性和MDA含量.[结果]在低浓度处理中,氯吡嘧磺隆对CAT、SOD和GSTs起到诱导作用;高浓度组中氯吡嘧磺隆对CAT、SOD、GSTs、ATPase、AchE酶均起到抑制作用.[结论]亚致死剂量氯吡嘧磺隆会对斑马鱼肝脏造成损伤.

  5. Semisynthetic analogues of toxiferine I and their pharmacological properties at α7 nAChRs, muscle-type nAChRs, and the allosteric binding site of muscarinic M2 receptors

    Zlotos, D.P.; Tränkle, C; Holzgrabe, U;


    , saturation of the exocyclic double bonds, and various N-substituents (methyl, allyl, 4-nitrobenzyl). At the muscle-type nAChRs, most ligands showed similar binding to the muscle relaxant alcuronium, indicating neuromuscular blocking activity, with the nonhydroxylated analogues 3b (Ki = 75 nM) and 3c (Ki = 82...

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

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


    The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target...


    龚鑫; 熊克仁; 汪仁平


    目的 观察扬子鳄梨状皮质内一氧化氮合酶(nitric oxide synthase,NOS)和乙酰胆碱酯酶(acetylcholinesterase,AChE)阳性神经元的形态和分布,为扬子鳄脑的比较解剖学积累资料,为其机能研究提供形态学依据.方法 采用还原型尼克酰胺腺嘌呤二核苷酸黄递酶(NADPH-d)法和亚铁氰化酮法观察扬子鳄梨状皮质内NOS和AChE阳性神经元的分布和特征.结果 扬子鳄梨状皮质内有NOS和AChE阳性神经元分布,为大、中、小型细胞,以中小型细胞为主,胞体呈圆形、椭圆形、三角形和梭形.结论 扬子鳄梨状皮质内有NOS和AChE阳性神经元分布.

  8. Recovery of malathion-inhibited topmouth qudqeon ( Pseudorasbora parva ) brain AChE%受马拉硫磷抑制的麦穗鱼(Pseudorasbora parua)脑乙酰胆碱酯酶(AChE)的恢复

    顾晓军; 李少南; 樊德方; 田素芬


    研究了受亚致死剂量马拉硫磷抑制的麦穗鱼(Pseudorasbora parva)脑乙酰胆碱酯酶(AChE)的活性恢复.马拉硫磷处理浓度分别为0.5 mg/L、1.0 mg/L、2.0 mg/L,约为LC50的1/20、1/10、1/5.处理48h后,AChE抑制率随浓度升高而增加,分别为33.76%、57.89%、63.05%.恢复120h后,0.5 mg/L处理过的鱼AChE恢复到了对照的80%以上(80%被认为是鱼的安全限);1.0 mg/L处理过的鱼经288h也恢复到了对照的80%以上;而2.0 mg/L处理过的鱼恢复360h还低于对照的60%.恢复期间后两个处理鱼AChE活性差异加大.这些结果表明恢复研究能够提供更多信息.

  9. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors

    Brejc, K.; Dijk, van W.J.; Klaassen, R.V.; Schuurmans, M.; Oost, van der J.; Smit, A.B.; Sixma, T.K.


    Pentameric ligand gated ion-channels, or Cys-loop receptors, mediate rapid chemical transmission of signals. This superfamily of allosteric transmembrane proteins includes the nicotinic acetylcholine (nAChR), serotonin 5-HT3, -aminobutyric-acid (GABAA and GABAC) and glycine receptors. Biochemical an

  10. Geological Mapping of the Ac-H-9 Occator Quadrangle of Ceres from NASA Dawn Mission

    Buczkowski, Debra; Williams, David; Scully, Jennifer; Mest, Scott; Crown, David; Aileen Yingst, R.; Schenk, Paul; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Platz, Thomas; Nathues, Andreas; Hoffmann, Martin; Schaefer, Michael; Marchi, Simone; De Sanctis, M. Cristina; Raymond, Carol; Russell, Chris


    As was done at Vesta [1], the Dawn Science Team is conducting a geological mapping cam-paign at Ceres during the nominal mission, including iterative mapping using data obtained dur-ing each orbital phase. We are using geological mapping as a method to identify the geologic processes that have modified the surface of dwarf planet Ceres. We here present the geology of the Ac-H-9 Occator quadrangle, located between 22°S-22°N and 216-288°E. The Ac-H-9 map area is completely within the topographically high region on Ceres named Erntedank Planum. It is one of two longitudinally distinct regions where ESA Herschel space telescope data suggested a release of water vapor [2]. The quadrangle includes several other notable features, including those discussed below. Occator is the 92 km diameter crater that hosts the "Bright Spot 5" that was identified in Hubble Space Telescope data [3], which is actually comprised of multiple bright spots on the crater floor. The floor of Occator is cut by linear fractures, while circumferential fractures are found in the ejecta and on the crater walls. The bright spots are noticeably associated with the floor fractures, although the brightest spot is associated with a central pit [4]. Multiple lobate flows are observed on the crater floor; these appear to be sourced from the center of the crater. The crater has a scalloped rim that is cut by regional linear structures, displaying a cross-section of one structure in the crater wall. Color data show that the Occator ejecta have multiple colors, generally related to changes in morphology. Azacca is a 50 km diameter crater that has a central peak and bright spots on its floor and within its ejecta. Like Occator, Azacca has both floor fractures and circumferential fractures in its ejecta and crater walls. Also like Occator, the Azacca ejecta is multi-colored with variable morphology. Linear structures - including grooves, pit crater chains, fractures and troughs - cross much of the eastern

  11. 锐劲特对麦穗鱼脑乙酰胆碱酯酶活性、敏感性及恢复的影响%Effect of Fipronil on Topmouth Gudgeon (Pseudorasbora parva) Brain AChE Activity, Sensitivity and Recovery

    顾晓军; 樊德方; 田素芬; 李少南


    The effect of fipronil on topmouth gudgeon (Pseudorasbora parva) brain AChE activ-ity, sensitivity and recovery was studied. The results showed that under sublethal dosages (0.0125, 0.025, 0.05 and 0.1 mg/L respectively), AChE activity of treated fish had no significant change, which indicates that fipronil does not affect fish AChE activity. It also had no further effect on AChE sensitivity to malathion (5 mg/L), proved by the fish which were pretreated with fipronil at sublethal dosages (0.0125, 0.025, 0.05 and 0.1 mg/L respectively) for 48 h. Compared with single 2 mg/L malathion treated fish, the mixture of 2 mg/L malathion and fipronil at different dosages treated fish AChE recovered a little slowlier and after 168 h, the difference was significant (P<0.05). It suggests fipronil affects inhibited AChE recovery, but the relationship between the effect and fipronil concentration is not obvious. Interaction between pesticides on environmental organism fitness should be paid more attention.%研究了锐劲特对麦穗鱼(Pseudorasbora parva)脑AChE活性、敏感性、恢复的影响。结果表明: 分别以0.0125、0.025、0.05、0.1 mg/L 锐劲特处理麦穗鱼96 h后,AChE活性均无显著变化,说明锐劲特不影响AChE活性;同样地,以上述浓度锐劲特预处理试鱼48 h,也不影响AChE对5 mg/L马拉硫磷敏感性;但与单独的2 mg/L浓度的马拉硫磷相比,以不同浓度锐劲特与马拉硫磷混合物处理过的试鱼AChE恢复较慢,且168 h后,差异显著(P<0.05),说明锐劲特影响被抑制AChE的恢复, 但是影响程度与锐劲特浓度关系不明显。应该重视农药相互作用对环境生物适合性的影响。

  12. Inhibition of ACh release at an Aplysia synapse by neurotoxic phospholipases A2: specific receptors and mechanisms of action.

    Fossier, P; Lambeau, G; Lazdunski, M; Baux, G


    1. Monochain (OS2) and multichain (taipoxin) neurotoxic phospholipases A2 (PLA2), purified from taipan snake venom, both inhibited ACh release at a concentration of 20 nM (90% inhibition in 2 h) at an identified synapse from buccal ganglion of Aplysia californica. 2. The Na+ current was unchanged upon application of either OS2 or taipoxin. Conversely, presynaptic K+ currents (IA and IK) were increased by taipoxin but not by OS2. In addition, OS2 induced a significant decrease of the presynaptic Ca2+ current (30%) while taipoxin increased this latter current by 20-30%. 3. Bee venom PLA2, another monochain neurotoxic PLA2, also inhibited ACh release while non-toxic enzymatically active PLA2s like OS1 (also purified from taipan snake venom) or porcine pancreatic PLA2 elicited a much weaker inhibition of ACh release, suggesting a specific action of neurotoxic PLA2s versus non-toxic PLA2s on ACh release. 4. Using iodinated OS2, specific high affinity binding sites with molecular masses of 140 and 18 kDa have been identified on Aplysia ganglia. The maximal binding capacities were 55 and 300-400 fmol (mg protein)-1 for membrane preparations from whole and buccal ganglia, respectively. These binding sites are of high affinity for neurotoxic PLA2s (Kd values, 100-800 pM) and of very low affinity for non-toxic PLA2s (Kd values in the micromolar range), thus indicating that these binding sites are presumably involved in the blockade of ACh release by neurotoxic PLA2s. Images Figure 8 Figure 9 PMID:8583413

  13. Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

    McPherson, D.W.; Luo, H.; Knapp, F.F. Jr.


    Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

  14. Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands.

    Imming, P; Klaperski, P; Stubbs, M T; Seitz, G; Gündisch, D


    We have developed one-step syntheses of halogenated derivatives of (-)-cytisine featuring a halogen substituent at positions 3, 5 or 3 and 5 of the 2-pyridone fragment, and prepared the novel bioisosteric thiocytisine by oxygen-sulphur exchange. The affinities of these pyridone-modified analogs of (-)-cytisine for (alpha 4)(2)(beta 2)(3) and alpha 7* nAChRs in rat forebrain membranes were determined by competition with (+/-)-[(3)H]epibatidine and [(3)H]MLA, respectively. The 3-halocytisines 7 possess subnanomolar affinities for (alpha 4)(2)(beta 2)(3) nAChRs, higher than those found for (-)-cytisine as well as for the 5-halocytisines 8 and 3,5-dihalocytisines 6. In contrast to the parent alkaloid the 3-halogenated species display much a higher affinity for the alpha 7* nAChR subtype. The most potent molecule was 3-bromocytisine (7b) with preferential selectivity (200-fold) for the (alpha 4)(2)(beta 2)(3) subtype [K(i)=10 pM (alpha 4 beta 2) and 2.0 nM (alpha 7*)]. Replacement of the lactam with a thiolactam pharmacophore to thiocytisine (12) resulted in a subnanomolar affinity for the (alpha 4)(2)(beta 2)(3) nAChR subtype (K(i)=0.832 nM), but in a drastic decrease of affinity for the alpha 7* subtype; thiocytisine (12) has a K(i) value of 4000 nM (alpha 7*), giving a selectivity of 4800-fold for the neuronal (alpha 4)(2)(beta 2)(3)-nAChR and thus displaying the best affinity-selectivity profile in the series under consideration.

  15. Binding of long-chain α-neurotoxin would stabilize the resting state of nAChR: A comparative study with α-conotoxin

    Naderi-Manesh Hossein


    Full Text Available Abstract Background The details of interaction in a complex between potent antagonists such as long chain α-neurotoxins and α-conotoxins with nicotinic acetylcholine receptor (nAChR, and conformational changes induced by these antagonists, are not yet clear. Modeling In order to uncover some of these critical structural features, we conducted a docking simulation and a molecular dynamics simulation (MD of a model of the ligand binding domain of nAChR in complex with a long-chain α-neurotoxin and an α-conotoxin. Results Our docking results confirm the claim that T.nAChR is in the basal or resting state, which favors binding to the alpha-neurotoxins. Moreover, more correct "hits" for the α/γ interface upon docking for conotoxin-nAChR confirm the preference of conotoxin GI for the α/γ interface. More importantly, upon binding of α-neurotoxin, ligand-bonded nAChR is less dynamic in certain domains than the apo form of the conotoxin-AChR complex. Some critical interactions in the binding site such as the salt bridge formed between K145/D200 in the neurotoxin-nAChR complex is further stabilized during the MD simulation, while it is obviously more labile in the apo form. Conclusion These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state.

  16. Effects of sublethal dose of metaldehyde on the activities of AchE, GSTs and MFO in Pomacea canaliculata%四聚乙醛亚致死剂量对福寿螺AchE、GSTs 和MFO 活性的影响

    张文领; 牟希东; 韦慧; 杨叶欣; 徐猛; 罗渡; 胡隐昌


    为了解亚致死剂量四聚乙醛对福寿螺的主要靶标酶和解毒酶活性的影响,研究了0.50 mg/L 的四聚乙醛处理不同时间后福寿螺不同组织中乙酰胆碱酯酶(AchE)、谷胱甘肽 S-转移酶(GSTs)和多功能氧化酶(MFO)的活力变化。结果显示,四聚乙醛对福寿螺具有良好的杀灭效果,96 h LC50为3.856 mg/L,安全浓度为0.039 mg/L;在用0.50 mg/L 的四聚乙醛处理的24 h 内,福寿螺鳃和腹足内 AchE 酶活力分别升高到未处理时的1.565和1.481倍而后下降,肝和肠组织内AchE 酶活力分别下降为未处理时的0.132、0.282倍而后升高;不同组织中 GSTs 酶活力均呈现为“降低—升高—降低”的趋势;不同组织内 MFO 酶活力均为先下降后上升的趋势。研究表明0.50 mg/L 的四聚乙醛能诱导 AchE、MFO和 GST 活性不同程度的增加,解毒酶 MFO 和 GSTs 可能在四聚乙醛的代谢中起着一定作用。%To explore the sublethal effect of metaldehyde exposure on main target enzymes and detoxification en-zymes in Pomacea canaliculata ,the activity dynamics of AchE,GSTs and MFO were measured under sublethal concentrations of metaldehyde.The results showed that metaldehyde could significantly kill P .canaliculata ,and 96 h LC50 and the safe concentration were 3.856 mg/L and 0.039 mg/L,respectively.Under 0.50 mg/L metalde-hyde stress,AchE enzyme activity in gills and pleopod increased to 1.565 and 1.481 times as that of the control group,respectively,while the AchE activity in liver and intestine decreased to 0.132 and 0.282 times as that of the control group,respectively,but increased subsequently.GSTs activities were presented as a trend of “de-crease-increase-decrease”;MFO activities decreased at the beginning and then were induced to increase to differ-ent extents.The results indicated that the activities of AchE,MFO and GSTs were induced to enhance to some ex-tent during

  17. Spectroscopic Study of Plasma Polymerized a-C:H Films Deposited by a Dielectric Barrier Discharge

    Thejaswini Halethimmanahally Chandrashekaraiah


    Full Text Available Plasma polymerized a-C:H thin films have been deposited on Si (100 and aluminum coated glass substrates by a dielectric barrier discharge (DBD operated at medium pressure using C2Hm/Ar (m = 2, 4, 6 gas mixtures. The deposited films were characterized by Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS, Raman spectroscopy, and ellipsometry. FT-IRRAS revealed the presence of sp3 and sp2 C–H stretching and C–H bending vibrations of bonds in the films. The presence of D and G bands was confirmed by Raman spectroscopy. Thin films obtained from C2H4/Ar and C2H6/Ar gas mixtures have ID/IG ratios of 0.45 and 0.3, respectively. The refractive indices were 2.8 and 3.1 for C2H4/Ar and C2H6/Ar films, respectively, at a photon energy of 2 eV.

  18. Biocompatible Silver-containing a-C:H and a-C coatings: AComparative Study

    Endrino, Jose Luis; Allen, Matthew; Escobar Galindo, Ramon; Zhang, Hanshen; Anders, Andre; Albella, Jose Maria


    Hydrogenated diamond-like-carbon (a-C:H) and hydrogen-free amorphous carbon (a-C) coatings are known to be biocompatible and have good chemical inertness. For this reason, both of these materials are strong candidates to be used as a matrix that embeds metallic elements with antimicrobial effect. In this comparative study, we have incorporated silver into diamond-like carbon (DLC) coatings by plasma based ion implantation and deposition (PBII&D) using methane (CH4) plasma and simultaneously depositing Ag from a pulsed cathodic arc source. In addition, we have grown amorphous carbon - silver composite coatings using a dual-cathode pulsed filtered cathodic-arc (FCA) source. The silver atomic content of the deposited samples was analyzed using glow discharge optical spectroscopy (GDOES). In both cases, the arc pulse frequency of the silver cathode was adjusted in order to obtain samples with approximately 5 at.% of Ag. Surface hardness of the deposited films was analyzed using the nanoindentation technique. Cell viability for both a-C:H/Ag and a-C:/Ag samples deposited on 24-well tissue culture plates has been evaluated.

  19. Advanced structure-activity relationships applied to Mentha spicata L. subsp. spicata essential oil compounds as AChE and NMDA ligands, in comparison with donepezil, galantamine and memantine - new approach in brain disorders pharmacology.

    Avram, Speranta; Maria, Mernea; Bagci, Eyup; Hritcu, Lucian; Borcan, Livia-Cristina; Mihailescu, Dan


    Alzheimer's disease (AD) therapy is based on several natural and synthetic compounds that act as acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands that have limited efficiency in relieving AD symptoms. Recent studies show that inhibitors isolated from Mentha spicata L. subsp. spicata are promising for AD therapy. We aimed to identify novel and more potent phytopharmaceutical compounds for AD treatment by taking into account the compounds from Mentha spicata L. subsp. spicata essential oil. We generated structure-activity relationship (SAR) models that predict the biological activities of 14 Mentha spicata L. subsp. spicata compounds on AChE and NMDA by comparing their molecular features with those of the three conventional ligands: donepezil, galantamine and memantine. The most relevant descriptors for predicting the biological activities of considered compounds are solvent accessible area and their subdivided, hydrophobicity, energy of frontier molecular orbitals and counts of the aromatic ring and rotatable bounds. 1,8-cineole, the main compound from Mentha spicata L. subsp. spicata essential oil, resulted to be similar with memantine and dissimilar with donepezil in respect to hidrophobicity (logP1,8-cineole=2.95, logPmemantine=2.81, logPdonepezil=4.11), the energy of LUMO (eLUMO1,8-cineole=3.01 eV, eLUMOmemantine=3.35 eV, eLUMOdonepezil=-0.35 eV) and the solvent accessible surface areas over all hydrophobic (SA_H1,8-cineole= 350 Å2, SA_Hmemantine= 358 Å2, SA_Hdonepezil= 655 Å2) or polar atoms (SA_P1,8-cineole= 4 Å2, SA_Pmemantine=10 Å2, SA_Pdonepezil=44.62 Å2). Our results point towards 1,8-cineole as a good candidate for NMDA antagonism, with a weaker AChE inhibitory effect. Our results may be useful in establishing new therapeutic strategies for neurological disorders.

  20. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    Hirata, Yuki; Choi, Junho, E-mail: [Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)


    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a

  1. Toxicity of Total Alkaloid from Tripterygium wilfordii Hook against Mythimna separata (Walker)and Its Effects of on AChE and Ach%雷公藤总生物碱对粘虫幼虫的毒力及对乙酰胆碱酯酶和乙酰胆碱的影响



    雷公藤生物碱是雷公藤Tripterygium wilfordii Hook中的主要杀虫活性物质.为进一步阐明雷公藤总生物碱的杀虫活性及杀虫作用机理提供线索和依据,研究采用载毒叶片法测定了雷公藤总生物碱对粘虫(Mythimna separata (Walker))三龄幼虫的胃毒毒力,观察了粘虫五龄幼虫的中毒症状,并测定了其对不同中毒阶段粘虫五龄幼虫头部乙酰胆碱酯酶(AChE)活性和乙酰胆碱(ACh)含量的影响.结果表明,雷公藤总生物碱对粘虫三龄幼虫48,72,96,120 h的胃毒LC50分别为306.39,216.12,157.18,129.92 mg/L;试虫中毒后行动迟缓,停止取食,继而软瘫麻痹(即麻醉),后复苏(或死亡),复苏试虫可再次取食、麻醉、复苏(或死亡),如此反复,直止死亡;雷公藤总生物碱对各中毒期试虫AChE无明显的抑制或激活作用;麻醉期试虫体内ACh的相对含量与同期对照无显著差异,复苏期有所下降.%Alkaloid is the main insecticidal composition in Tripterygium wilfordii Hook,a famous insecticidal plant. In order to study its insecticidal activites and mechanism ,the stomach toxicity of the total alkaloid against larvae of Mythimna separata Walker was tested, their toxicity symptoms were observed, and its effects on the activities of AChE and the content of ACh of larval heads in different toxicity stages were assayed. The results showed the stomach toxicity LD50 values of the total alkaloid against the 3rd instar larvae of M. separata in 24,48,96 and 120 h post treatment were 306.39,216.12,157.18 and 129. 92 mg/L. In vivo toxicity symptoms were characterized by a definite sequence of events, starting with moving slowly,stopping feeding, flaccid paralysis and recovering or death. Anabiotic insects started feeding ,were paralyzed, recovered or died again and up to death. It was presumed the total alkaloid from T. wilfordii influenced the nerve system of insects. AChE was not strongly inhibited or activated by the total alkaloid.ACh

  2. In silico studies on the role of mutant Y337A to reactivate tabun inhibited mAChE with K048.

    Chandar, Nellore Bhanu; Ghosh, Shibaji; Lo, Rabindranath; Banjo, Semire; Ganguly, Bishwajit


    Organophosphorus compound (OP) tabun is resistant to reactivate by many oxime drugs after the formation of OP-conjugate with AChE. The reactivation of tabun-inhibited mAChE and site-directed mutants by bispyridinium oxime, K048 (N-[4-(4-hydroxyiminomethylpyridinio)butyl]-4-carbamoylpyridinium dibromide) showed that the mutations significantly poor the overall reactivation efficacy of K048. We have unravelled the lowered efficacy of K048 with the tabun-mutant mAChE(Y337A) using docking and steered molecular dynamics (SMD) simulations. The computed results showed some interesting features for the interaction of drug molecule K048 with tabun-mAChE(wild-type) and tabun-mutant mAChE(Y337A). The SMD simulations showed that the active pyridinium ring of K048 is directed towards the phosphorus atom conjugated to the active serine (SUN203) of tabun-mAChE(wild-type). The cradle shaped residues Tyr337-Phe338 present in the choline binding site stabilize the active pyridinium ring of K048 with π-π interaction and the residue Trp86 involved in T-shaped cation-π interaction. However, in the case of tabun-mutant mAChE(Y337A).K048 conjugate, the replacement of aromatic Tyr337 with the aliphatic alanine unit in the choline binding site, however, loses one of the π-π interaction between the active pyridinium ring of K048 and the Tyr337. The placement of aliphatic alanine unit resulted in the displacement of the side chain of Phe338 towards the His447. Such displacement is causing the inaccessibility of the drug towards the phosphorus atom conjugated to the active serine (SUN203) of tabun-mutant mAChE(Y337A). Furthermore, the unbinding of the K048 with SMD studies showed that the active pyridinium ring of the drug undergoes a complete turn along the gorge axis and is directed away from the phosphorus atom conjugated to the active serine of the tabun-mutant mAChE(Y337A). Such effects inside the gorge of tabun-mutant mAChE(Y337A) would lower the efficacy of the drug molecule (K048

  3. Geological Mapping of the Ac-H-12 Toharu Quadrangle of Ceres from NASA Dawn Mission

    Mest, Scott; Williams, David; Crown, David; Yingst, Aileen; Buczkowski, Debra; Scully, Jennifer; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Nathues, Andres; Hoffmann, Martin; Schaefer, Michael; Raymond, Carol; Russell, Christopher


    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the surface geology and geologic evolution of the Ac-H-12 Toharu Quadrangle (21-66°S, 90-180°E). At the time of this writing LAMO images (35 m/pixel) are just becoming available. The current geologic map of Ac-H-12 was produced using ArcGIS software, and is based on HAMO images (140 m/pixel) and Survey (400 m/pixel) digital terrain models (for topographic information). Dawn Framing Camera (FC) color images were also used to provide context for map unit identification. The map (to be presented as a poster) will be updated from analyses of LAMO images. The Toharu Quadrangle is named after crater Toharu (86 km diameter; 48.3°S, 156°E), and is dominated by smooth terrain in the north, and more heavily cratered terrain in the south. The quad exhibits ~9 km of relief, with the highest elevations (~3.5-4.6 km) found among the western plateau and eastern crater rims, and the lowest elevation found on the floor of crater Chaminuka. Preliminary geologic mapping has defined three regional units (smooth material, smooth Kerwan floor material, and cratered terrain) that dominate the quadrangle, as well as a series of impact crater material units. Smooth materials form nearly flat-lying plains in the northwest part of the quad, and overlies hummocky materials in some areas. These smooth materials extend over a much broader area outside of the quad, and appear to contain some of the lowest crater densities on Ceres. Cratered terrain forms much of the map area and contains rugged surfaces formed largely by the structures and deposits of impact features. In addition to geologic units, a number of geologic features - including crater rims, furrows, scarps, troughs, and impact

  4. Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

    Drew H Bailey

    Full Text Available The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110 and other-reports (n = 66 on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132 revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS, allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

  5. Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

    Bailey, Drew H; Walker, Robert S; Blomquist, Gregory E; Hill, Kim R; Hurtado, A Magdalena; Geary, David C


    The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

  6. Metal extraction from Cetraria islandica (L. Ach. lichen using low pH solutions



    Full Text Available Extraction of metals (K, Al, Ca, Mg, Fe, Cu, Ba, Zn, Mn and Sr from dry Cetraria islandica (L. Ach. lichen was performed using solutions similar to acid rain (solution A – H2SO4–HNO3–(NH42SO4 and solution B – H2SO4–HNO3–(NH42SO4–NH4NO3. The pH values of these solutions were 2.00, 2.58, 2.87, 3.28, and 3.75. Five consecutive extractions were performed with each solution. In all solutions, the extracted metal content, except Cu and Ca, was the highest in the first extract. The highest percentage of the metals desorbed in the first extraction was obtained using solutions with low pH values, 2.00, 2.58, and 2.87. The lowest percentage in the first extraction was obtained using solutions with pH 3.28 and 3.75, indicating influence of the H+ ion on the extraction. According to the results obtained, the investigated metals form two groups. The first group includes K, Al, Ca, Mg, and Fe. They were extracted in each of the five extractions at each of the pH values. The second group includes Ba, Zn, Mn, Cu, and Sr, which were not all extracted at each pH value. The first group yielded three types of extraction curves when the logarithms of extracted metal amounts were plotted as a function of the number of successive extractions. These effects indicate that three different positions (centres of metal ion accumulation exist in the lichen (due to sorption, complex formation, or other processes present in the tissues.

  7. [Children's and adolescent's use of medicine for aches and psychological problems: secular trends from 1988 to 2006.

    Holstein, Bjørn; Andersen, Anette; Due, Pernille


    INTRODUCTION: Medicine use for aches and psychological problems is common among adolescents. Medicines are toxic and may have harmful side effects. It is therefore important to study change over time and patterns of medicine use. The objective of this paper is to describe self-reported medicine use...... for headaches, stomach-aches, difficulties in falling asleep, and nervousness among 11-, 13-, and 15-year-old boys and girls from 1968 to 2006. MATERIAL AND METHODS: The data material is 6 comparable and representative cross-sectional studies of 11-, 13-, and 15-year-olds from 1988, 1991, 1994, 1998, 2002......, and 2006, total n = 23,871. Data were collected by a validated self-report method for medicine use and prevalence of the corresponding complaints. RESULTS: The proportion of students who used medicine for headaches within the previous month increased from 24.6% in 1988 to 42.0% in 2002 and 41.5% in 2006...

  8. Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.

    Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R; McIntosh, J Michael; Brunzell, Darlene H; Cannon, Jason R; Drenan, Ryan M


    α6β2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. © 2013 International Society for Neurochemistry.

  9. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Bopanna I Kalappa

    Full Text Available BACKGROUND: The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596. METHODOLOGY/PRINCIPAL FINDINGS: An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the

  10. Synthesis of the possible receptor ligand [{sup 131}I]-3-iodo-cytisine for in vivo imaging of the nAChReceptor

    Oezbolat, A.; Guhlke, S. [Bonn Univ. (Germany). Dept. of Nuclear Medicine; Munoz, L.; Guendisch, D. [Bonn Univ. (Germany). Dept. of Pharmaceutical Chemistry; Wuellner, U. [Bonn Univ. (Germany). Dept. of Neurology; Schmaljohann, J. [Bonn Univ. (Germany). Dept. of Nuclear Medicine]|[Bonn Univ. (Germany). Dept. of Neurology


    In-vivo labeling of the nicotinic acetylcholine receptors (nAChRs) could be a useful tool for early diagnosis and evaluating therapies of neurodegenerative disorders. Although central nAChRs contribute to a variety of brain functions, relatively few data are available on their physiological functions and their potential role in neurological diseases. No data have yet been available on the regulation of nAChRs in the disease process of Alzheimer's disease or other neurodegenerative disorders in living patients. 2-[{sup 18}F]-A85380 is the first radiotracer to visualize the distribution of nAChR in human brain in vivo. This PET ligand has a high affinity and subtype selectivity for {alpha}4{beta}2 nAchR. A reduction of different nAChR subtypes has been reported in post-mortem brains of patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). 3-Iodo-cytisine displays a high affinity for neuronal nAChRs and subtype selectivity for {alpha}4{beta}2 and thus for the radiolabeled analog a high potential can be expected for its clinical use in the diagnostic of neurodegenerative disorders. Here, we report on an optimized labeling of cytisine with iodine-131 by electrophilic substitution. (orig.)

  11. Enantiopure Cyclopropane-Bearing Pyridyldiazabicyclo[3.3.0]octanes as Selective α4β2-nAChR Ligands.

    Onajole, Oluseye K; Eaton, J Brek; Lukas, Ronald J; Brunner, Dani; Thiede, Lucinda; Caldarone, Barbara J; Kozikowski, Alan P


    We report the synthesis and characterization of a series of enantiopure 5-cyclopropane-bearing pyridyldiazabicyclo[3.3.0]octanes that display low nanomolar binding affinities and act as functional agonists at α4β2-nicotinic acetylcholine receptor (nAChR) subtype. Structure-activity relationship studies revealed that incorporation of a cyclopropane-containing side chain at the 5-position of the pyridine ring provides ligands with improved subtype selectivity for nAChR β2 subunit-containing nAChR subtypes (β2*-nAChRs) over β4*-nAChRs compared to the parent compound 4. Compound 15 exhibited subnanomolar binding affinity for α4β2- and α4β2*-nAChRs with negligible interaction. Functional assays confirm selectivity for α4β2-nAChRs. Furthermore, using the SmartCube assay system, this ligand showed antidepressant, anxiolytic, and antipsychotic features, while mouse forced-swim assay further confirm the antidepressant-like property of 15.

  12. Effect of calcium on nicotine-induced current expressed by an atypical alpha-bungarotoxin-insensitive nAChR2.

    Thany, Steeve H; Courjaret, Raphael; Lapied, Bruno


    Two distinct native alpha-bungarotoxin (alpha-Bgt)-insensitive nicotinic acetylcholine receptors (nAChRs), named nAChR1 and nAChR2, were identified in the cockroach Periplaneta americana dorsal unpaired median (DUM) neurons. They differed in their electrophysiological, pharmacological properties and intracellular regulation pathways. nAChR2 being an atypical nicotinic receptor closed upon agonist application and its current-voltage relationship resulted from a reduction in potassium conductance. In this study, using whole-cell patch-clamp technique, we demonstrated that calcium modulated nAChR2-mediated nicotine response. Under 0.5 microM alpha-Bgt and 20 mM d-tubocurarine, the nicotine-induced inward current amplitude was strongly reduced in the presence of intracellularly applied BAPTA or bath application of calcium-free solution. In addition, using cadmium chloride, we showed that nicotine response was modulated by extracellular calcium through plasma membrane calcium channels. Moreover, extracellular application of caffeine and thapsigargin reduced nAChR2-mediated response. Together these experiments revealed a complex calcium-dependent regulation of nAChR2.

  13. Fabrication of a Highly-sensitive Acetylcholine Sensor Based on AChOx Immobilized Smart-chips

    M. M. RAHMAN


    Full Text Available Acetylcholine (ACh sensor based on acetylcholine oxidase (AChOx on EDC activated thioglycolic acid self-assembled monolayer (TGA-SAM using smart-chip has been developed. The simple cyclic voltammetry (CV, at 0.1 V/s technique is performed in total investigation, where 0.5M K3Fe(CN6 is utilized as a standard mediator in phosphate buffer solution (PBS, 0.1M. The ACh sensor exhibited a lower detection limit (DL, 0.1392 ± 0.005 nM, a wide linear dynamic range (LDR, 1.0 nM to 1.0 mM, good linearity (R=0.9951, and higher sensitivity (7.3543 ± 0.2 μAμM-1cm-2, and required small sample volume (70.0 μL as well as good stability and reproducibility. The smart-chip system employed a simple and efficient approach to the immobilization of enzymes onto active sensitive surface, which can enhance sensor performances to a large group of bio-molecules for wide range of biomedical applications in health care fields.

  14. Contribution of α4β2 nAChR in nicotine-induced intracellular calcium response and excitability of MSDB neurons.

    Wang, Jiangang; Wang, Yali; Wang, Yang; Wang, Ran; Zhang, Yunpeng; Zhang, Qian; Lu, Chengbiao


    The neurons of medial septal diagonal band of broca (MSDB) project to hippocampus and play an important role in MSDB-hippocampal synaptic transmission, plasticity and network oscillation. Nicotinic acetylcholine receptor (nAChR) subunits, α4β2 and α7 nAChRs, are expressed in MSDB neurons and permeable to calcium ions, which may modulate the function of MSDB neurons. The aims of this study are to determine the roles of selective nAChR activation on the calcium responses and membrane currents in MSDB neurons. Our results showed that nicotine increased calcium responses in the majority of MSDB neurons, pre-treatment of MSDB slices with a α4β2 nAChR antagonist, DhβE but not a α7 nAChR antagonist, MLA prevented nicotine-induced calcium responses. The whole cell patch clamp recordings showed that nicotine-induced inward current and acetylcholine (ACh) induced-firing activity can be largely reduced or prevented by DhβE in MSDB neurons. Surprisingly, post-treatment of α4β2 or α7 nAChR antagonists failed to block nicotine׳s role, they increased calcium responses instead. Application of calcium chelator EGTA reduced calcium responses in all neurons tested. These results suggest that there was a subtype specific modulation of nAChRs on calcium signaling and membrane currents in MSDB neurons and nAChR antagonists were also able to induce calcium responses involving a distinct mechanism.

  15. Efficient expression of functional (α6β22β3 AChRs in Xenopus oocytes from free subunits using slightly modified α6 subunits.

    Carson Kai-Kwong Ley

    Full Text Available Human (α6β2(α4β2β3 nicotinic acetylcholine receptors (AChRs are essential for addiction to nicotine and a target for drug development for smoking cessation. Expressing this complex AChR is difficult, but has been achieved using subunit concatamers. In order to determine what limits expression of α6* AChRs and to efficiently express α6* AChRs using free subunits, we investigated expression of the simpler (α6β22β3 AChR. The concatameric form of this AChR assembles well, but is transported to the cell surface inefficiently. Various chimeras of α6 with the closely related α3 subunit increased expression efficiency with free subunits and produced pharmacologically equivalent functional AChRs. A chimera in which the large cytoplasmic domain of α6 was replaced with that of α3 increased assembly with β2 subunits and transport of AChRs to the oocyte surface. Another chimera replacing the unique methionine 211 of α6 with leucine found at this position in transmembrane domain 1 of α3 and other α subunits increased assembly of mature subunits containing β3 subunits within oocytes. Combining both α3 sequences in an α6 chimera increased expression of functional (α6β22β3 AChRs to 12-fold more than with concatamers. This is pragmatically useful, and provides insights on features of α6 subunit structure that limit its expression in transfected cells.

  16. HLA class II diversity in seven Amerindian populations. Clues about the origins of the Aché.

    Tsuneto, L T; Probst, C M; Hutz, M H; Salzano, F M; Rodriguez-Delfin, L A; Zago, M A; Hill, K; Hurtado, A M; Ribeiro-dos-Santos, A K C; Petzl-Erler, M L


    The study of the HLA variability of Native American populations revealed several alleles specific to one or more of the Latin American indigenous populations. The analysis of Amerindian groups distributed all over the continent might inform about the area of origin and the dispersal of these alleles and shed light on the evolution of this remarkable polymorphism. Moreover, HLA alleles and haplotypes are excellent markers to understand the genetic relationships between populations. For these reasons, we characterized the HLA class II polymorphism in seven South American Amerindian populations and compared the results with those previously reported for other Amerindian groups. The Guarani-Kaiowá (n = 160) and Guarani-Nandeva (n = 87) were from the Brazilian state of Mato Grosso do Sul, the Guarani-M'byá (n = 93) and Kaingang (n = 235) from Paraná state, the Aché (n = 89) from eastern Paraguay, the Quechua (n = 44) from Andean Peru. From Amazonia, a heterogeneous group was analyzed (n = 45). The most frequent alleles and haplotypes are common also in other Amerindian populations. Each HLA-DRB1 allele was typically found in combination with just one DQA1-DQB1 haplotype, most likely as a result of some form of random genetic drift and reduced gene flow from non-Amerindians. The frequency distribution differed significantly among all populations, although differences were less pronounced between the Guarani subgroups. Marker alleles allowed an estimate of European and sub-Saharan African gene flow into these populations: Quechua 23%, Guarani-Nandeva 14%, Kaingang 7%, Guarani-M'byá 4%, Guarani-Kaiowá, Amazonia, and Aché 0%. Interestingly, the DRB1*1413 allele, previously found only among the Guarani-M'byá (frequency 15%), appeared in the Aché (8%). The relationship of the Aché to other Amerindian populations is unclear, and this finding reveals a link with the Guarani. On the basis of genetic distance and the HLA allele/haplotype set, we propose that the Ach

  17. Aging of oxygen and hydrogen plasma discharge treated a-C:H and ta-C coatings

    Bachmann, Svenja [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Schulze, Marcus [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Morasch, Jan [Institute of Materials Science, Technische Universität Darmstadt, Surface Science Division, Jovanka-Bonschits-Straße 2, 64287 Darmstadt (Germany); Hesse, Sabine [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Hussein, Laith [Eduard-Zintl-Institut, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 12, 64287, Darmstadt (Germany); Krell, Lisa; Schnagl, Johann [BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Stark, Robert W. [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); and others


    Highlights: • The water CA of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C changes from hydrophillic to hydrophobic on aging. • XPS study indicates that the decrease in surface energy of plasma treated a-C:H and ta-C could be due to adsorption of organic component from air. • The COFLFM of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C decreased upon aging. • The COF of glycerol lubricated ta-C showed no sign of change upon aging. - Abstract: Surface modification with gas plasma is an efficient and easy way to improve the surface energy and the tribological behavior of diamond-like carbon (DLC) coatings, e.g., in biomedical implants or as protective coatings. However, the long-term performance of the plasma treated DLC coatings is not fully clear. We thus studied the long-term stability of two kinds of DLC coatings, namely (a) hydrogenated amorphous carbon (a-C:H) and (b) tetrahedral amorphous carbon (ta-C) treated at different radio frequency (RF) power and time of oxygen (O{sub 2}) and hydrogen (H{sub 2}) plasma. Their surface properties, e.g. surface wettability, structure and tribological behavior, were studied at regular intervals for a period of two months using contact angle goniometer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), lateral force microscopy (LFM) and ball on disc apparatus. The surface energy of both the coatings decreased upon aging. The higher the RF power and time of treatment, the higher was the hydrophobicity upon aging. XPS analysis showed that the increase in hydrophobicity could be due to adsorption of unavoidable volatile organic components in the atmosphere. The H{sub 2} plasma treated ta-C was capable of rearranging its structural bonds upon aging. The nano-friction measurements by LFM showed that the coefficient of friction of plasma treated a-C:H and ta-C decreased upon aging. The results indicate that the surface properties of plasma treated a‐C:H and ta‐C are not stable on long-term and are

  18. When the Earth has a Belly-Ache: Young Seismologists at School

    Burrato, P.; Nostro, C.; Tertulliani, A.; Winkler, A.; Casale, P.; Marsili, A.; Castellano, C.; Cultrera, G.; Scarlato, P.; Alfonsi, L.; Ciaccio, M.; Frepoli, A.


    The INGV cohoperates with schools of different grades to promote Earth science programs and geophysical knowledge. This is particularly important in areas prone to seismic and volcanic hazards, like Italy. The E&O Group organizes every year school visits to the scientific laboratories of the INGV center of Rome, during which more than 4,000 students interact with scientists and learn about the dynamic Earth. Besides that the E&O Group brings on the road educational activities, carring out projects with schools and partecipating to science festivals. In March 2000 a small size earthquake hit the towns of Subiaco and Agosta, near Rome. This event was strongly felt by teachers and students of the local primary schools, and sprang the idea of a project focused on earthquakes. The aim of the project was to gain knowledge of what causes earthquakes and to familiarize with a phenomenon considered random and unforeseeable. Another goal was to train students and teachers to behave properly during the occurrence of an earthquake. The project was developed starting from the personal experience of the students, with theoretical lessons and practical experiments. The INGV researchers partecipated giving talks and producing educational materials. During the talks they showed that earthquakes are not phenomena so rare and random as thought by most people. They also showed the instruments used to register seismicity, and encouraged kids to produce their own earthquakes jumping close to a portable seismometer. In a second phase the students were divided in groups that investigated different topics of the seismic event, giving a talk to their school mates at the end of the research. The teachers used a cooperative learning approach to stimulate the ability of the kids to team up and work in cooperation. At the end of the project the kids published a book (When the Earth has a belly-ache) and a calendar, that tell about earthquakes using the kid's original drawings. The book

  19. Geological Mapping of the Ac-H-11 Sintana Quadrangle of Ceres from NASA's Dawn Mission.

    Schulzeck, Franziska; Krohn, Katrin; Jaumann, Ralf; Williams, David A.; Buczkowski, Debra L.; Mest, Scott C.; Scully, Jennifer E. C.; Gathen, Isabel v. d.; Kersten, Elke; Matz, Klaus-Dieter; Naß, Andrea; Otto, Katharina; Pieters, Carle M.; Preusker, Frank; Roatsch, Thomas; De Sanctis, Maria C.; Schenk, Paul; Schröder, Stefanus; Stephan, Katrin; Wagner, Roland


    In December 2015, the Dawn spacecraft delivered the first images of the Low Altitude Mapping Orbit (LAMO) of the dwarf planet Ceres at a resolution of 35 m/pixel. This data will be used to finish the geological mapping of Ceres' surface in order to identify composition and surface forming processes. Mapping was already done using Survey Orbit and High Altitude Mapping Orbit (HAMO) data. With the new images, an updated map will be presented. To this point, the data material consists of a HAMO clear-filter mosaic (140 m/pixel) [1], a digital elevation model (DTM) [2] derived from Survey orbit (415 m/pixel) data, color-filter ratios and photometrically corrected images. Ceres' surface has been divided into 15 mapping quadrangles. The Ac-H-11 Sintana quadrangle is located in the southern hemisphere of Ceres between 21 66°S and 0 90°E. Geological units identified so far are cratered terrain, which covers most of the area, and a younger unit of relatively smooth material. The latter is characterized by a low crater density. Material of the same unit was found in adjacent quadrangles as well. Interest is taken in the diversity of crater shapes. Many craters show different forms of asymmetries. One and the same crater for instance displays different stages of rim degradation and some crater walls are partly terraced and their slopes' steepness is varying alongside the crater rim. Several mass wasting features, which partly cause the observed asymmetries, have been identified. Next to the multiple collapsed rims, landslides due to later cratering on the primary crater rim are observed. Whereas collapse structures are mostly blocky, single landslides are characterized by lobate margins. Occurrence and type of mass wasting feature might hint to subsurface differences. Further, there is a diversity of inner crater structures, like relaxed crater floors, ridges, central peaks, mounds and smooth plains. Processes like mass wasting and relaxation have modified many craters

  20. Geological Mapping of the Ac-H-13 Urvara Quadrangle of Ceres from NASA's Dawn Mission

    Sizemore, Hanna; Williams, David; Platz, Thomas; Mest, Scott; Yingst, Aileen; Crown, David; O'Brien, David; Buczkowski, Debra; Schenk, Paul; Scully, Jennifer; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Nathues, Andreas; De Sanctis, Maria Cristina; Russell, Christopher; Raymond, Carol


    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map, and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the geologic evolution of the Ac-H-13 Urvara Quadrangle. At the time of this writing LAMO images (35 m/pixel) are just becoming available. Thus, our geologic maps are based on HAMO images (140 m/pixel) and Survey (400 m/pixel) digital ter-rain models (for topographic information). Dawn Framing Camera (FC) color images are also used to provide context for map unit identification. The maps to be presented as posters will be updated from analyses of LAMO images. The Urvara Quadrangle is dominated by the 170-km diameter impact basin Urvara (46.4°S, 248.6°E) and includes cratered terrain to the west. Named features include the impact craters Meanderi (40.9°S, 193.7°E, 103 km diameter), Sekhet (66.4°S, 254.9°E, 41 km diameter), and Fluusa (31.5°S, 277.9°E), as well as the crater chains Gerber Catena (38.1°S, 214.8°E) and Sam-hain Catena (19.6°S, 210.3°E). Based on preliminary geologic mapping [3,4], we interpret the two prominent catenae as pit craters associated with large scale tectonism rather than secondary impacts. We interpret two large curvilinear depressions near the eastern quadrangle boundary as secondary crater chains resulting from the Urvara impact. Textural and morphological asymme-tries in crater materials within the quadrangle indicate heterogeneities in subsurface composition and volatile content. Features on the Urvara basin floor are consistent with impact fluidization of target materials; post impact extrusion of volatile rich material may have also played a minor role. References: [1] Williams D.A. et al. (2014) Icarus, 244, 1-12. [2] Yingst R.A. et al. (2014) PSS, 103, 2-23. [3] Sizemore et al. (2015) GSA Abstracts with Program

  1. Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the a7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells

    Yong-Hua Yang


    Full Text Available Background: Excessive activation of matrix metalloproteinase 9 (MMP-9 has been found in several inflammatory diseases. Previous studies have shown that acetylcholine (ACh reduced the levels of pro-inflammatory cytokines and decreased tissue damage. Therefore, this study was designed to explore the potential effects and mechanisms of ACh on MMP-9 production and cell migration in response to lipopolysaccharide (LPS stimulation in RAW264.7 cells. Methods: MMP-9 expression and activity were induced by LPS in RAW264.7 cells, and examined by real-time PCR, western blotting and gelatin zymography, respectively. ELISA was used to determine the changes in MMP-9 secretion among the groups. Macrophage migration was evaluated using transwell migration assay. Knockdown of a7 nicotinic acetylcholine receptor (a7 nAChR expression was performed using siRNA transfection. Results: Pre-treatment with ACh inhibited LPS-induced MMP-9 production and macrophage migration in RAW264.7 cells. These effects were abolished by the a7 nAChR antagonist methyllycaconitine (MLA and a7 nAChR siRNA. The a7 nAChR agonist PNU282987 was found to have an effect similar to that of ACh. Moreover, ACh enhanced the expression of JAK2 and STAT3, and the JAK2 inhibitor AG490 and the STAT3 inhibitor static restored the effect of ACh. Meanwhile, ACh decreased the phosphorylation and nuclear translocation of NF-κB, and this effect was abrogated in the presence of MLA. In addition, the JAK2 and STAT3 inhibitor abolished the inhibitory effects of ACh on phosphorylation of NF-κB. Conclusions: Activation of a7 nAChR by ACh inhibited LPS-induced MMP-9 production and macrophage migration through the JAK2/STAT3 signaling pathway. These results provide novel insights into the anti-inflammatory effects and mechanisms of ACh.

  2. 苏云金杆菌和灭幼脲混剂对美国白蛾幼虫2种酶活性的影响%Effects of the Activity of Midgut Chitinase,Cuticle AChE on 4th Instar Larvae of Hyphantria cunea by the Treatment of Different Concentration of the Mixture of Bt and Chlorbenzuron

    徐明; 徐福元; 吴小芹


    通过室内外毒力测定和防治试验发现,苏云金杆菌(Bt)+灭幼脲混剂对美国白蛾2~3代4龄幼虫有较强增效作用,在此基础上分析该混剂对白蛾4龄幼虫体内中肠几丁质酶和乙酰胆碱脂酶(AChE)活力的影响。结果表明:5种浓度的 Bt、灭幼脲及其混剂对白蛾4龄幼虫体内中肠几丁质酶活力的影响随处理浓度增高和处理时间延长抑制作用越明显,且差异极显著,说明 Bt +灭幼脲混剂均有抑制白蛾4龄幼虫中肠几丁质酶活力的作用,是该混剂对白蛾4龄幼虫提高毒杀效果的原因;5种浓度 Bt +灭幼脲及其混剂处理对白蛾4龄幼虫体壁 AChE 活性的影响随处理时间的增加有先升高后降低的趋势,36~96 h 具诱导幼虫体壁 AChE 活性逐渐增强的趋势,96 h 后活性明显减弱,AChE 活性减低后白蛾4龄幼虫很快死亡,对 AChE 活性抑制率为20.13%~90.00%,为Bt +灭幼脲混剂增效关键作用的另一个原因。%Based on the indoor virulence and field control test results showed that the mixture of Bacillus thuringiensis(Bt)and chlorbenzuron had strong synergism to the second and third generation of the larvae of Hyphantria cunea.This paper analyzed the influence on the activity of midgut chitinase and cuticle AChE on the 4th instar larvae of Hyphantria cunea the result as following:As the concentration increased and treatment time pro-longed 5 concentrations of the mixture of Bt and chlorbenzuron treated,the midgut chitinase activity of the 4th instar larvae of Hyphantria cunea showed inhibitory effect more obvious and got significant differences (P <0.01).It in-dicated that Bt +chlorbenzuron mixture could improved the effect to the 4th instar larvae of Hyphantria cunea.As the treatment time increased 5 concentrations of the mixture of Bt and chlorbenzuron treated,the cuticle AChE ac-tivity of the 4th instar larvae of Hyphantria cunea increased first and then

  3. The linoleic acid derivative DCP-LA increases membrane surface localization of the α7 ACh receptor in a protein 4.1N-dependent manner.

    Kanno, Takeshi; Tsuchiya, Ayako; Tanaka, Akito; Nishizaki, Tomoyuki


    In yeast two-hybrid screening, protein 4.1N, a scaffolding protein, was identified as a binding partner of the α7 ACh (acetylcholine) receptor. For rat hippocampal slices, the linoleic acid derivative DCP-LA {8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid} increased the association of the α7 ACh receptor with 4.1N, and the effect was inhibited by GF109203X, an inhibitor of PKC (protein kinase C), although DCP-LA did not induce PKC phosphorylation of 4.1N. For PC-12 cells, the presence of the α7 ACh receptor in the plasma membrane fraction was significantly suppressed by knocking down 4.1N. DCP-LA increased the presence of the α7 ACh receptor in the plasma membrane fraction, and the effect was still inhibited by knocking down 4.1N. In the monitoring of α7 ACh receptor mobilization, DCP-LA enhanced signal intensities for the α7 ACh receptor at the membrane surface in PC-12 cells, which was clearly prevented by knocking down 4.1N. Taken together, the results of the present study show that 4.1N interacts with the α7 ACh receptor and participates in the receptor tethering to the plasma membrane. The results also indicate that DCP-LA increases membrane surface localization of the α7 ACh receptor in a 4.1N-dependent manner under the control of PKC, but without phosphorylating 4.1N.

  4. [Capacitative Ca²⁺ entry is involved in ACh-induced distal colon smooth muscle contraction in rats].

    Kong, De-Hu; Zhou, Hua; Song, Jie; Ke, Dao-Ping; Hu, Jin-Lan; Li, Zhong-Wen; Ma, Rong


    Contraction of smooth muscle cells is triggered by an increase in cytosolic Ca(2+) upon agonist stimulation. Ca(2+) influx across the plasma membrane constitutes a major component of the agonist-induced response in smooth muscle cells. Traditionally, voltage-operated Ca(2+) channel (VOCC) is considered as the channel mediating the Ca(2+) entry. However, this view has been challenged by recent discoveries, which demonstrated that other types of ion channels, such as store-operated and/or receptor-operated Ca(2+) channels (SOCC and/or ROCC), also participate in Ca(2+) response induced by agonists in smooth muscle cells. SOCC is defined as the channel activated in response to the depletion of the internal Ca(2+) stores, an event secondary to G protein coupled receptor or receptor tyrosine kinase stimulation. The Ca(2+) flow mediated by SOCC is termed as capacitative Ca(2+) entry (CCE). Previous study from other group has demonstrated that VOCC played a predominant role in ACh-induced contraction of distal colon smooth muscle in guinea pig. However, whether SOCC participates in the agonist-induced contractile response in this particular tissue is unknown. The present study was performed to investigate the role of CCE in ACh-induced mechanical activity of distal colon smooth muscle in rats. The contractile function of the smooth muscle was assessed by measuring isometric force of isolated rat distal colon rings. We showed that both high extracellular K(+) (40 mmol/L) and ACh (5 mumol/L) evoked striking contraction of the smooth muscle. The contractile responses were almost abolished by removal of extracellular Ca(2+) with ethylene glycol-bis(2-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), suggesting a critical contribution of extracellular source of Ca(2+) to the contraction. Verapamil (5 mumol/L), an L-type VOCC blocker, significantly attenuated, but didn't completely eliminate the high K(+)- and ACh-induced contraction (74% and 41% for high K(+) and ACh

  5. Geological Mapping of the Ac-H-14 Yalode Quadrangle of Ceres from NASA's Dawn Mission

    Crown, David; Yingst, Aileen; Mest, Scott; Platz, Thomas; Sizemore, Hanna; Berman, Daniel; Williams, David; Roatsch, Thomas; Preusker, Frank; Nathues, Andreas; Hoffman, Martin; Schäfer, Michael; Raymond, Carol; Russell, Christopher


    The Dawn Science Team is conducting a geologic mapping campaign for Ceres that includes production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the surface geology and geologic evolution of the Ac-H-14 Yalode Quadrangle (21-66°S, 270-360°E). The current geologic map was produced using ArcGIS software based on HAMO images (140 m/pixel) for surface morphology and stratigraphic relationships, Survey (400 m/pixel) digital terrain models for topographic information, and Dawn Framing Camera (FC) color images as context for map unit identification. The map will be updated through analysis of LAMO images (35 m/pixel) that are just becoming available. The Yalode Quadrangle is dominated by the 260-km diameter impact basin Yalode (42.3°S, 293.6°E) and includes rugged and smooth terrains to the east. Preliminary geologic mapping defined two regional units (cratered terrain and smooth material), which dominate the quadrangle, as well as a series of impact crater material units. Mapped geologic features include crater rims, graben, ridges, troughs, scarp, lineaments, and impact crater chains. Geologic contacts are typically not distinct in Survey and HAMO images. Impact craters in Yalode Quadrangle display a range of preservation states. Degraded features, including Yalode basin and numerous smaller craters, exhibit subdued rims, lack discrete ejecta deposits, and have infilled interiors. More pristine features (including Mondamin, Besua, Lono and craters on the Yalode basin floor) have well-defined, quasi-circular forms with prominent rims and in some cases discernible ejecta. Some of these craters have bowl-shaped interiors, and others contain hills or mounds on their floors that are interpreted as central peaks. Yalode basin has a variably preserved rim, which is continuous and sharply defined to the north/northwest and is irregular or degraded

  6. Geological Mapping of the Ac-H-5 Fejokoo Quadrangle of Ceres from NASA's Dawn Mission

    Hughson, Kynan; Russell, Christopher; Williams, David; Buczkowski, Debra; Mest, Scott; Scully, Jennifer; Kneissl, Thomas; Ruesch, Ottaviano; Frigeri, Alessandro; Combe, Jean-Philippe; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Platz, Thomas; Nathues, Andreas; Hoffmann, Martin; Schaefer, Michael; Park, Ryan; Marchi, Simone; Raymond, Carol


    NASA's Dawn spacecraft arrived at Ceres on March 6, 2015, and has been studying the dwarf planet through a series of successively lower orbits, obtaining morphological & topographical image, mineralogical, elemental abundance, and gravity data. Ceres is the largest object in the asteroid belt with a mean diameter of ~950 km. The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for the asteroid Vesta [1, 2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map, and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we present the LAMO-based geologic map of the Ac-H-5 Fejokoo quadrangle (21-66 °N and 270-360 °E) and discuss its geologic evolution. At the time of this writing LAMO images (35 m/pixel) are just becoming available. Thus, our geologic maps are based on HAMO images (~140 m/pixel) and Survey (~400 m/pixel) digital terrain models (for topographic information) [3, 4]. Dawn Framing Camera (FC) color images are also used to provide context for map unit identification. The maps to be presented as posters will be updated from analyses of LAMO images (~35 m/pixel). The Fejokoo quadrangle hosts six primary geologic features: (1) the centrally located, ~80 km diameter, distinctly hexagonal impact crater Fejokoo; (2) Victa crater with its large exterior dark lobate flow feature, and interior lobate and furrowed deposits; (3) Abellio crater, which exhibits a well formed ejecta blanket and has an arcuately textured infilled floor whose morphology is similar to those of homologously sized craters on some of the icy Saturnian satellites [5]; (4) Cozobi crater, whose floor is filled with an unusually bulbous and smooth deposit, thin sheeted multi-lobed flow-like features that are reminiscent of fluidized ejecta as seen on Mars are also observed to be emanating outwards from the N and S rims of this crater [6]; (5) the peculiar Oxo crater on the eastern

  7. Geological Mapping of the Ac-H-3 Dantu Quadrangle of Ceres from NASA's Dawn Mission.

    Kneissl, Thomas; Schmedemann, Nico; Neesemann, Adrian; Williams, David A.; Crown, David A.; Mest, Scott C.; Buczkowski, Debra L.; Scully, Jennifer E. C.; Frigeri, Allessandro; Ruesch, Ottaviano; Hiesinger, Harald; Walter, Sebastian H. G.; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Kersten, Elke; Naß, Andrea; Nathues, Andreas; Platz, Thomas; Russell, Chistopher T.


    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the geologic evolution of the Ac-H-3 Dantu Quadrangle. The current map is based on a Framing Camera (FC) clear-filter image mosaic from HAMO data (~140 m/px) as well as a digital terrain model (DTM) derived from imagery of the Survey phase [3]. Albedo variations were identified and mapped using a mosaic of photometrically corrected HAMO images provided by DLR. FC color images provided further context for map unit identification. LAMO images (35m/pixel), which have just become available at the time of writing, will be used to update the map to be presented as a poster. The quadrangle is located between 21-66°N and 90-180°E in a large-scale depression north of the impact basin Kerwan. The northern and southeastern parts of the quadrangle are characterized by cratered terrain while the south and southwest are dominated by the partially smooth ejecta blankets of craters Dantu and Gaue. East-west oriented pit/crater chains in the southern half of the quadrangle might be related to tectonic processes [4,5]. Dantu crater (d=~126 km) is a complex impact crater showing slump terraces and a partially smooth crater floor with concentric and radial fractures. Furthermore, Dantu shows a central pit structure with pitted terrain on its floor as well as several bright spots in the interior and exterior of the crater. High-resolution measurements of crater size-frequency distributions (CSFDs) superposed on Dantu indicate a formation/modification age of ~200 - 700 Ma. Most of the ejecta appear to be relatively bright and correspond to parts of the #2 high albedo region observed with the Hubble Space Telescope [6]. However, the southwestern portion of the ejecta blanket is

  8. The identification and restitution of human remains from an Aché girl named "Damiana": an interdisciplinary approach.

    Koel-Abt, Katrin; Winkelmann, Andreas


    In June 2010, the postcranial skeleton of an adolescent girl was returned by the Natural History Museum of La Plata, Argentina, to the Aché community in Paraguay. In March 2011 the missing skull was identified in the anatomical collection of Charité in Berlin. We initiated a historical and anthropological investigation to confirm the identity of the human remains and to reconstruct the fate of the individual in question in its historical context. Anthropological publications from Argentina had indicated that the girl named "Damiana" was abducted by colonising settlers in Southern Paraguay in 1897 at the age of 3-4 years, later taken to La Plata in Argentina where she grew up as a "maidservant", and died in 1907 of "galloping consumption". In accordance with these reports, the present palaeopathological investigation confirms tuberculous meningitis as a likely cause of death. It also demonstrates some markers of "stress", the nature of which, however, is difficult to determine. Surviving letters and publications by Berlin anatomist Hans Virchow reveal that the girl's preserved head was sent from La Plata to Berlin in January 1908 for comparative investigations in the context of the racial theories of the time. We were convinced that the justified wishes of the Aché community to bury these remains alongside those restituted in 2010 outweighed any future scientific interest in these remains. In April 2012, the skull and two related specimens were returned from the Charité to the Aché community, mediated by the Paraguayan ambassador in Berlin. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Nicotinic acetylcholine receptors (nAChRs) at zebrafish red and white muscle show different properties during development.

    Ahmed, Kazi T; Ali, Declan W


    Nicotinic acetylcholine receptors (nAChRs) are highly expressed at the vertebrate neuromuscular junction (NMJ) where they are required for muscle activation. Understanding the factors that underlie NMJ development is critical for a full understanding of muscle function. In this study we performed whole cell and outside-out patch clamp recordings, and single-cell RT-qPCR from zebrafish red and white muscle to examine the properties of nAChRs during the first 5 days of development. In red fibers miniature endplate currents (mEPCs) exhibit single exponential time courses at 1.5 days postfertilization (dpf) and double exponential time courses from 2 dpf onwards. In white fibers, mEPCs decay relatively slowly, with a single exponential component at 1.5 dpf. By 2 and 3 dpf, mEPC kinetics speed up, and decay with a double exponential component, and by 4 dpf the exponential decay reverts back to a single component. Single channel recordings confirm the presence of two main conductance classes of nAChRs (∼45 pS and ∼65 pS) in red fibers with multiple time courses. Two main conductance classes are also present in white fibers (∼55 pS and ∼73 pS), but they exhibit shorter mean open times by 5 dpf compared with red muscle. RT-qPCR of mRNA for nicotinic receptor subunits supports a switch from γ to ε subunits in white fibers but not in red. Our findings provide a developmental profile of mEPC properties from red and white fibers in embryonic and larval zebrafish, and reveal previously unknown differences between the NMJs of these muscle fibers.© 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 916-936, 2016.

  10. Diamond-like a-C:H coatings deposited in a non-self-sustained discharge with plasma cathode

    Gavrilov, N. V.; Mamaev, A. S.; Kaĭigorodov, A. S.


    Hydrogenated amorphous carbon (a-C:H) coatings have been obtained by means of acetylene decomposition in a non-self-sustained periodic pulse discharge (2A, 50 kHz, 10 μs) with hollow cathode. The discharge operation was maintained by plasma cathode emission with grid stabilization based on dc glow discharge. Using the proposed method, it is possible to control the deposition conditions (total pressure of the Ar + C2H2 mixture, partial pressure of C2H2, ion current density, carbon ion energy) within broad limits, to apply a-C:H coatings onto large-area articles, and to perform deposition in one technological cycle with ion etching and ion implantation treatments aimed at improving the adhesion of coatings to substrates (Ti, Al, stainless steel, VK8 hard alloy) at temperatures below 150°C. Results of determining the deposition rate (1-8 μm), the nanohardness of coatings (up to 70 GPa), and the fraction of sp 3 bonds (25-70%) in the diamond-like coating material are presented.

  11. Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

    Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio


    Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

  12. Gentamicin Blocks the ACh-Induced BK Current in Guinea Pig Type II Vestibular Hair Cells by Competing with Ca2+ at the l-Type Calcium Channel

    Hong Yu


    Full Text Available Type II vestibular hair cells (VHCs II contain big-conductance Ca2+-dependent K+ channels (BK and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh evoked the BK current by triggering the influx of Ca2+ ions through l-type Ca2+ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs. Aminoglycoside antibiotics, such as gentamicin (GM, are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC50 value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca2+ concentration ([Ca2+]o could antagonize it. Moreover, 50 µM GM potently blocked Ca2+ currents activated by (--Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca2+ at the l-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  13. The interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) in mouse corpus cavernosum.

    Aydinoglu, Fatma; Dalkir, Fatma Tugce; Demirbag, Hatice Oruc; Ogulener, Nuran


    The aim of this study was to investigate the possible interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) in the mouse corpus cavernosum (CC). l-cysteine (endogenous H2S substrate; 10(-6)-10(-3) M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10(-6)-10(-3) M) and acetylcholine (10(-9)-10(-4) M) produced concentration-dependent relaxation in isolated mouse CC tissues. Relaxations to endogenous and exogenous H2S were reduced by non-selective mAChR antagonist atropine (5 × 10(-5) M), selective M1 mAChR antagonist pirenzepine (5 × 10(-5) M) and selective M3 mAChR antagonist 4-DAMP (10(-7) M) but not by selective M2 mAChR antagonist AF-DX 116 (10(-6) M). Also, acetylcholine-induced relaxations were reduced by atropine, pirenzepine, 4-DAMP and AF-DX 116, confirming the selective effects of mAChR antagonists. Furthermore, acetylcholine-induced relaxations were attenuated by cystathionine-gamma-lyase (CSE) inhibitor d,l-propargylglycine (PAG, 10(-2) M) and cystathionine-β-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10(-3) M). l-nitroarginine, nitric oxide synthase inhibitor, augmented the inhibitory effects of mAChR antagonists and H2S enzyme inhibitors on acetylcholine-induced relaxations. In addition, the existence and localization of CSE, CBS and 3-MST were demonstrated in mouse CC. Furthermore, tissue acetylcholine release was significantly increased by l-cysteine but not by exogenous H2S. The increase in acetylcholine level was completely inhibited by AOAA and PAG. These results suggest that M1 and M3 mAChRs contributes to relaxant effect mediated by endogenous H2S but at same time l-cysteine triggers acetylcholine release from cavernosal tissue. Also, the role of NO in the interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) could not be excluded. Copyright © 2017. Published by Elsevier Inc.

  14. Influence of surgical and chemical orchidectomy on weight and distribution of AChE-nerve fibres in thymuses of adult rats

    F. Dorko


    Full Text Available The thymus is a crossroad between the immune and neuroendocrine systems. As such, it is innervated by acetylcholinesterase (AChE-positive fibres of the vagus, the recurrent laryngeal and the phrenic nerves. It is well know, that the innervations density of the thymus increases with age. In our study, adult rats were orchidectomized (surgically and chemically by the application of a luteinizing hormone-releasing hormone. The density of AChE-positive nerve fibres in thymuses, as well as the weight of thymuses was examined. The authors found that both surgical and chemical orchidectomy result in macroscopic and microscopic regeneration of the atrophied thymuses. In regenerated rat’s thymuses after orchidectomy the density of AChE-positive nerve fibres was markedly higher in comparison with the control animals. The distribution, as well as the density of AChE-positive nerve fibres in regenerated thymuses after orchidectomy evokes the images of its innervations like in young animals before age-related involution. The authors also found a markedly higher weight of thymuses of orchidectomized rats in comparison with the control groups. In recent study the authors proved that after 8 weeks surgical orchidectomy leads to the regeneration of thymic AChE-positive innervation and chemical orchidectomy by administration of luteinizing hormone-releasing hormone after 4 weeks of adult rats.

  15. Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity.

    Yu, Li-Fang; Tückmantel, Werner; Eaton, J Brek; Caldarone, Barbara; Fedolak, Allison; Hanania, Taleen; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P


    There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.

  16. 3D MI-DRAGON: new model for the reconstruction of US FDA drug- target network and theoretical-experimental studies of inhibitors of rasagiline derivatives for AChE.

    Prado-Prado, Francisco; García-Mera, Xerardo; Escobar, Manuel; Alonso, Nerea; Caamaño, Olga; Yañez, Matilde; González-Díaz, Humberto


    The number of neurodegenerative diseases has been increasing in recent years. Many of the drug candidates to be used in the treatment of neurodegenerative diseases present specific 3D structural features. An important protein in this sense is the acetylcholinesterase (AChE), which is the target of many Alzheimer's dementia drugs. Consequently, the prediction of Drug-Protein Interactions (DPIs/nDPIs) between new drug candidates and specific 3D structure and targets is of major importance. To this end, we can use Quantitative Structure-Activity Relationships (QSAR) models to carry out a rational DPIs prediction. Unfortunately, many previous QSAR models developed to predict DPIs take into consideration only 2D structural information and codify the activity against only one target. To solve this problem we can develop some 3D multi-target QSAR (3D mt-QSAR) models. In this study, using the 3D MI-DRAGON technique, we have introduced a new predictor for DPIs based on two different well-known software. We have used the MARCH-INSIDE (MI) and DRAGON software to calculate 3D structural parameters for drugs and targets respectively. Both classes of 3D parameters were used as input to train Artificial Neuronal Network (ANN) algorithms using as benchmark dataset the complex network (CN) made up of all DPIs between US FDA approved drugs and their targets. The entire dataset was downloaded from the DrugBank database. The best 3D mt-QSAR predictor found was an ANN of Multi-Layer Perceptron-type (MLP) with profile MLP 37:37-24-1:1. This MLP classifies correctly 274 out of 321 DPIs (Sensitivity = 85.35%) and 1041 out of 1190 nDPIs (Specificity = 87.48%), corresponding to training Accuracy = 87.03%. We have validated the model with external predicting series with Sensitivity = 84.16% (542/644 DPIs; Specificity = 87.51% (2039/2330 nDPIs) and Accuracy = 86.78%. The new CNs of DPIs reconstructed from US FDA can be used to explore large DPI databases in order to discover both new drugs

  17. Thin films of hydrogenated amorphous carbon (a-C:H) obtained through chemical vapor deposition assisted by plasma; Peliculas delgadas de carbono amorfo hidrogenado (a-C:H) obtenidas mediante deposito quimico de vapores asistido por plasma

    Mejia H, J.A.; Camps C, E.E.; Escobar A, L.; Romero H, S.; Chirino O, S. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Muhl S, S. [IIM-UNAM, 04510 Mexico D.F. (Mexico)


    Films of hydrogenated amorphous carbon (a-C:H) were deposited using one source of microwave plasma with magnetic field (type ECR), using mixtures of H{sub 2}/CH{sub 4} in relationship of 80/20 and 95/05 as precursory gases, with work pressures of 4X10{sup -4} to 6x10{sup -4} Torr and an incident power of the discharge of microwaves with a constant value of 400 W. It was analyzed the influence among the properties of the films, as the deposit rate, the composition and the bonding types, and the deposit conditions, such as the flow rates of the precursory gases and the polarization voltage of the sample holders. (Author)

  18. Targeting α4β2 nAChRs in CNS disorders: Perspectives on positive allosteric modulation as a therapeutic approach

    Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.;


    The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders...... be used as a treatment approach in various CNS disorders. As subtype-selective agonists and other cholinergic ligands have only shown limited therapeutic success, the focus of recent drug development endeavours has largely shifted to positive allosteric modulators (PAMs). By potentiating the action...

  19. Biophysical characterization of inwardly rectifying potassium currents (I(K1) I(K,ACh), I(K,Ca)) using sinus rhythm or atrial fibrillation action potential waveforms

    Tang, Chuyi; Skibsbye, Lasse; Yuan, Lei


    to voltage protocols adapted from atrial action potentials recorded in human tissue at 1 and 3 Hz. The current recordings were performed in the HEK-293 heterologous cell system expressing either I(K1), I(K,ACh) or I(K,Ca) to establish the individual contribution of each of these currents during the voltage...... changes of atrial action potential waveforms. I(K1) primarily contributes to the atrial electrophysiology at the latter part of repolarization and during the diastolic phase, while both I(K,Ca) under high [Ca2+]i and I(K,ACh) contribute relatively most during repolarization.......Although several physiological, pathophysiological and regulatory properties of classical inward rectifier K+ current I(K1), G-protein coupled inwardly-rectifying K+ current I(K,ACh) and the small-conductance Ca2+ activated K+ current I(K,Ca) have been identified, quantitative biophysical details...

  20. Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by regulating α7AChR, ERK, HIF-1α and VEGF/PEDF signaling.

    Dingbo Shi

    Full Text Available Nicotine, the major component in cigarette smoke, can promote tumor growth and angiogenesis, but the precise mechanisms involved remain largely unknown. Here, we investigated the mechanism of action of nicotine in human nasopharyngeal carcinoma (NPC cells. Nicotine significantly promoted cell proliferation in a dose and time-dependent manner in human NPC cells. The mechanism studies showed that the observed stimulation of proliferation was accompanied by the nicotine-mediated simultaneous modulation of α7AChR, HIF-1α, ERK and VEGF/PEDF signaling. Treatment of NPC cells with nicotine markedly upregulated the expression of α7AChR and HIF-1α proteins. Transfection with a α7AChR or HIF-1α-specific siRNA or a α7AChR-selective inhibitor significantly attenuated the nicotine-mediated promotion of NPC cell proliferation. Nicotine also promoted the phosphorylation of ERK1/2 but not JNK and p38 proteins, thereby induced the activation of ERK/MAPK signaling pathway. Pretreatment with an ERK-selective inhibitor effectively reduced the nicotine-induced proliferation of NPC cells. Moreover, nicotine upregulated the expression of VEGF but suppressed the expression of PEDF at mRNA and protein levels, leading to a significant increase of the ratio of VEGF/PEDF in NPC cells. Pretreatment with a α7AChR or ERK-selective inhibitor or transfection with a HIF-1α-specific siRNA in NPC cells significantly inhibited the nicotine-induced HIF-1α expression and VEGF/PEDF ratio. These results therefore indicate that nicotine promotes proliferation of human NPC cells in vitro through simultaneous modulation of α7AChR, HIF-1α, ERK and VEGF/PEDF signaling and suggest that the related molecules such as HIF-1α might be the potential therapeutic targets for tobacco-associated diseases such as nasopharyngeal carcinomas.

  1. Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex.

    Gigout, S; Wierschke, S; Dehnicke, C; Deisz, R A


    Cholinergic transmission plays a pivotal role in learning, memory and cognition, and disturbances of cholinergic transmission have been implicated in neurological disorders including Alzheimer's disease, epilepsy and schizophrenia. Pharmacological alleviation of these diseases by drugs including N-desmethylclozapine (NDMC), promising in animal models, often fails in patients. We therefore compared the effects of NDMC on glutamatergic and GABAergic transmission in slices from rat and human neocortex. We used carbachol (CCh; an established agonist at metabotropic muscarinic acetylcholine (ACh) receptors (mAChRs)) as a reference. Standard electrophysiological methods including intracellular and field potential recordings were used. In the rat neocortex, NDMC prevented the CCh-induced decrease of GABAA and GABAB receptor-mediated responses but not the CCh-induced increase of the paired-pulse depression. NDMC reduced neither the amplitude of the excitatory postsynaptic potentials (EPSP) nor antagonized the CCh-induced depression of EPSP. In the human neocortex, however, NDMC failed to prevent CCh-induced decrease of the GABAB responses and directly reduced the amplitude of EPSP. These data suggest distinct effects of NDMC in rat and human at M2 and M4 mAChRs underlying presynaptic modulation of GABA and glutamate release, respectively. In particular, NDMC might be a M2 mAChR antagonist in the rat but has no activity at this receptor in human neocortex. However, NDMC has an agonistic effect at M4 mAChR in the human but no such effect in the rat neocortex. The present study confirms that pharmacology at mAChRs can differ between species and emphasizes the need of studies in human tissue.

  2. Surface morphology and grain analysis of successively industrially grown amorphous hydrogenated carbon films (a-C:H) on silicon

    Catena, Alberto [Department of Physics, University of Koblenz-Landau, 56070 Koblenz (Germany); McJunkin, Thomas [Department of Physics, The Ohio State University, 43210 Columbus, Ohio (United States); Agnello, Simonpietro; Gelardi, Franco M. [Department of Physics and Chemistry, University of Palermo, 90100 Palermo (Italy); Wehner, Stefan [Department of Physics, University of Koblenz-Landau, 56070 Koblenz (Germany); Fischer, Christian B., E-mail: [Department of Physics, University of Koblenz-Landau, 56070 Koblenz (Germany)


    Graphical abstract: - Highlights: • Two different a-C:H coatings in various thicknesses on Si (1 0 0) have been studied. • For both types no significant difference in surface morphology is detectable. • The grain number with respect to their height appears randomly distributed. • In average no grain higher than 14 nm and larger than 0.05 μm{sup 2} was observed. • A height to area correlation confines all detected grains to a limited region. - Abstract: Silicon (1 0 0) has been gradually covered by amorphous hydrogenated carbon (a-C:H) films via an industrial process. Two types of these diamond-like carbon (DLC) coatings, one more flexible (f-DLC) and one more robust (r-DLC), have been investigated. Both types have been grown by a radio frequency plasma-enhanced chemical vapor deposition (RF-PECVD) technique with acetylene plasma. Surface morphologies have been studied in detail by atomic force microscopy (AFM) and Raman spectroscopy has been used to investigate the DLC structure. Both types appeared to have very similar morphology and sp{sup 2} carbon arrangement. The average height and area for single grains have been analyzed for all depositions. A random distribution of grain heights was found for both types. The individual grain structures between the f- and r-type revealed differences: the shape for the f-DLC grains is steeper than for the r-DLC grains. By correlating the average grain heights to the average grain areas for all depositions a limited region is identified, suggesting a certain regularity during the DLC deposition mechanisms that confines both values. A growth of the sp{sup 2} carbon entities for high r-DLC depositions is revealed and connected to a structural rearrangement of carbon atom hybridizations and hydrogen content in the DLC structure.

  3. Up-scaling the production of modified a-C:H coatings in the framework of plasma polymerization processes

    Corbella, C.; Bialuch, I.; Kleinschmidt, M.; Bewilogua, K.


    Hydrogenated amorphous carbon (a-C:H) films with silicon and oxygen additions, which exhibit mechanical, tribological and wetting properties adequate for protective coating performance, have been synthesized at room temperature in a small- (0.1 m 3) and a large-scale (1 m 3) coaters by low-pressure Plasma-Activated Chemical Vapour Deposition (PACVD). Hence, a-C:H:Si and a-C:H:Si:O coatings were produced in atmospheres of tetramethylsilane (TMS) and hexamethyldisiloxane (HMDSO), respectively, excited either by radiofrequency (RF - small scale) or by pulsed-DC power (large scale). Argon was employed as a carrier gas to stabilize the glow discharge. Several series of 2-5 μm thick coatings have been prepared at different mass deposition rates, Rm, by varying total gas flow, F, and input power, W. Arrhenius-type plots of Rm/ F vs. ( W/ F) -1 show linear behaviours for both plasma reactors, as expected for plasma polymerization processes at moderated energies. The calculation of apparent activation energy, Ea, in each series permitted us to define the regimes of energy-deficient and monomer-deficient PACVD processes as a function of the key parameter W/ F. Moreover, surface properties of the modified a-C:H coatings, such as contact angle, abrasive wear rate and hardness, appear also correlated to this parameter. This work shows an efficient methodology to scale up PACVD processes from small, lab-scale plasma machines to industrial plants by the unique evaluation of macroscopic parameters of deposition.

  4. Electron energy-loss spectroscopy analysis of low-temperature plasma-enhanced chemically vapor deposited a-C:H films

    Nelson, A.J.; Benson, D.K.; Tracy, C.E.; Kazmerski, L.L.; Wager, J.F.


    Electron energy-loss spectroscopy (EELS) has been applied to the analysis of a-C:H films grown on various substrates by a unique low-temperature (<100 /sup 0/C) plasma-enhanced chemical vapor deposition (PECVD) process using ethylene and hydrogen gases. EELS data are used to characterize the relative amounts of fourfold coordinated sp/sup 3/ carbon bonding to threefold coordinated sp/sup 2/ carbon bonding as well as the relative order/disorder due to substrate effects. Ellipsometric and transmission measurements provide optical constants for the PECVD a-C:H films.

  5. Tolerance to a self-peptide of acetylcholine receptor induces myasthenia gravis%重症肌无力的AChR自身耐受研究进展

    徐秀娟; 黄志


    重症肌无力(myasthenia gravis,MG)是抗乙酰胆碱受体(acetycholine receptor,AChR)抗体介导、细胞免疫依赖性、补体参与的神经-肌肉接头处的自身免疫性疾病,是神经肌肉接头处最常见的疾病,其发生的关键在于机体针对AChR所产生的免疫应答异常。



    Este trabalho visou o desenvolvimento de uma metodologia analítica para a determinação de metomil em solos através da inibição da enzima acetilcolinesterase (AChE), abordando a influência dos parâmetros de fertilidade do solo. As amostras de solos foram coletadas em áreas agrícolas da microbacia do Córrego de São Lourenço, município de Nova Friburgo, RJ, visando contemplar diferentes categorias de solos e de manejo da região, que é uma das principais ...

  7. Selection of replicon variants resistant to ACH-806, a novel hepatitis C virus inhibitor with no cross-resistance to NS3 protease and NS5B polymerase inhibitors.

    Yang, Wengang; Zhao, Yongsen; Fabrycki, Joanne; Hou, Xiaohong; Nie, Xingtie; Sanchez, Amy; Phadke, Avinash; Deshpande, Milind; Agarwal, Atul; Huang, Mingjun


    We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells. The leading compound in the series, ACH-806 (GS-9132), is a potent and specific inhibitor of HCV. The selection of resistance replicon variants against ACH-806 was performed to map the mutations conferring resistance to ACH-806 and to determine cross-resistance profiles with other classes of HCV inhibitors. Several clones emerged after the addition of ACH-806 to HCV replicon cells at frequencies and durations similar to that observed with NS3 protease inhibitors and NS5B polymerase inhibitors. Phenotypic analyses of these clones revealed that they are resistant to ACH-806 but remain sensitive to other classes of HCV inhibitors. Moreover, no significant change in the susceptibility to ACH-806 was found when the replicon cellular clones resistant to NS3 protease inhibitors and NS5B polymerase inhibitors were examined. Sequencing of the entire coding region of ACH-806-resistant replicon variants yielded several consensus mutations. Reverse genetics identified two single mutations in NS3, a cysteine-to-serine mutation at amino acid 16 and an alanine-to-valine mutation at amino acid 39, that are responsible for the resistance of the replicon variants to ACH-806. Both mutations are located at the N terminus of NS3 where extensive interactions with the central hydrophobic region of NS4A exist. These data provide evidence that ACH-806 inhibits HCV replication by a novel mechanism.

  8. Susceptibility of Three Housefly(Musca domestica L.) Populations and Their AchE to Insecticides%3个家蝇(Musca domestica L.)种群及其乙酰胆碱酯酶对杀虫剂的敏感性研究

    魏辉; 沈晋良; 吴玮; 赵建伟


    采用药膜法测定了3个家蝇(Musca domestica L.)种群对12种有机磷和氨基甲酸酯类杀虫剂的敏感性,采用酶动力学方法测定了不同杀虫剂对家蝇乙酰胆碱酯酶(acetylcholinesterase,AChE)的体外抑制作用.结果表明,Org种群对抗蚜威(LC50=18.654 mg·L-1)、速灭威(LC50=17.387 mg·L-1)比FAAS种群(LC50分别为26.011、26.632 mg·L-1)更为敏感,FAAS种群对仲丁威(LC50=8.271 mg·L-1)比Org种群(LC50=12.539 mg·L-1)更为敏感;除了与乙酰甲胺磷无显著差异外,FZ种群对其他供试杀虫剂的敏感性均显著低于Org种群和FAAS种群(95% CI没有重叠).Org种群AChE对二嗪磷(IC50=0.025 mg·L-1)比FAAS种群AChE(IC50=0.048 mg·L-1)更为敏感,FAAS种群AChE对辛硫磷(IC50=0.021 mg·L-1)比Org种群AChE(IC50=0.026 mg·L-1)更为敏感;FZ种群AChE对所有供试杀虫剂的敏感性均显著低于Org种群和FAAS种群AChE(95% CI没有重叠).

  9. Auxofuran, a Novel Metabolite That Stimulates the Growth of Fly Agaric, Is Produced by the Mycorrhiza Helper Bacterium Streptomyces Strain AcH 505†

    Riedlinger, Julia; Schrey, Silvia D.; Tarkka, Mika T.; Hampp, Rüdiger; Kapur, Manmohan; Fiedler, Hans-Peter


    The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 μM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 μM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce. PMID:16672502

  10. Auxofuran, a novel metabolite that stimulates the growth of fly agaric, is produced by the mycorrhiza helper bacterium Streptomyces strain AcH 505.

    Riedlinger, Julia; Schrey, Silvia D; Tarkka, Mika T; Hampp, Rüdiger; Kapur, Manmohan; Fiedler, Hans-Peter


    The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 microM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 microM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce.

  11. Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors

    Mellor, I R; Brier, T J; Pluteanu, F


    Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isox...

  12. 乙酰胆碱酯酶抑制剂Territrem B类似物的合成新方法%The New Method for the Preparation of Territrem B Analogues as AChE Inhibitors

    赵金浩; 程敬丽; 赵锋; 朱国念; 王彦广; 赵昱



  13. Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model.

    Takeshi Yamamoto

    Full Text Available The prevalence of food allergy (FA has increased in developed countries over the past few decades. However, no effective drug therapies are currently available. Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory system to ameliorate disrupted mucosal immune homeostasis in the gut based on the pathophysiological elucidation of mucosal mast cells (MMCs in a murine FA model. BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the development of FA. FA mice developed severe allergic diarrhea and exhibited enhanced type 2 helper T (Th2 cell immune responses in both systemic immunity and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were localized primarily in the strategic position of the mucosal epithelium. Furthermore, the allergic symptoms did not develop in p85α disrupted phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR agonists (nicotine and α7 nAChR agonist GTS-21 alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.

  14. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    Machaalani, R., E-mail: [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Ghazavi, E. [Bosch Institute, The University of Sydney, NSW 2006 (Australia); School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Hinton, T. [School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Waters, K.A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Hennessy, A. [School of Medicine, University of Western Sydney, NSW 2751 (Australia); Heart Research Institute, 7 Eliza St Newtown, NSW 2042 (Australia)


    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

  15. Effect of middle cerebral artery occlusion on AChE of anterior horn motor neurons in rat%大鼠大脑中动脉栓塞对脊髓前角运动神经元乙酰胆碱酯酶的影响

    曲英杰; 李颖; 薛景凤


    目的:探讨大鼠大脑中动脉栓塞(MCAO)对脊髓前角运动神经元外侧核群乙酰胆碱酯酶(AChE)的影响.方法:20只雄性SD大鼠随机分为4组,均采用线栓法建立一侧大鼠MCAO致脑缺血模型,术后大鼠分别存活1、2、4、8周,取脊髓颈膨大.采用亚铁氰化铜法显示AChE,Image-Pro Plus 6.0图像分析软件对脊髓前角运动神经元外侧核群AChE反应阳性区域的累积光密度(IOD)进行定量分析.结果:MCAO 1周组实验侧脊髓前角运动神经元外侧核群AChE的IOD值高于对照侧,MCAO 2周组开始低于对照侧,且病程越长此变化更为明显.结论:大鼠MCAO可导致脊髓前角运动神经元外侧核群AChE的含量发生改变.

  16. Electrical characterization of a-C:H as a dielectric material in metal/insulator/metal structures

    Zuniga-I., C.; Kosarev, A.; Torres-J., A.; Rosales-Q., P.; Calleja-A., W.; Hidalga-W., F.J. de la; Malik, O. [Electronic' s Department, National Institute for Astrophysics, Optics, and Electronics, INAOE, Puebla (Mexico)


    The fabrication and electrical characterization of Metal-Insulator-Metal (MIM) structures, using a-C:H films as the insulating material, are presented in this work. These PECVD carbon films show a very low dielectric constant and a very high resistivity. The current conduction mechanisms were analyzed before and after the post deposition annealing in pure argon ambient at 400 C. For as-deposited films, the experimental J -U curves showed that under low biasing regime (vertical stroke U vertical stroke <8 V) the space charge limited current conduction is the main transport mechanism, whereas under higher biasing regime (vertical stroke U vertical stroke >8 V) the current transport is dominated by the Schottky mechanism. For annealed structures, under low and high biasing the ohmic and Schottky mechanisms were identified as the main processes for the electrical transport. Finally, we found that both parameters, the dielectric constant and resistivity, decrease slightly after the thermal annealing. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  17. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase

    Chen, Yun; Zhang, Yiming; Siewers, Verena;


    Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast Saccha...... mitochondria and the cytosol. These results will increase our fundamental understanding of intracellular transport of acetyl units, and also help to develop microbial cell factories for many kinds of acetyl-CoA derived products.......Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast......-fermentative yeast strain. We found that mitochondrial Ach1 can convert acetyl-CoA in this compartment into acetate, which crosses the mitochondrial membrane before being converted into acetyl-CoA in the cytosol. Based on our finding we propose a model in which acetate can be used to exchange acetyl units between...

  18. Self-Reported Ache, Pain, or Numbness in Feet and Use of Computers amongst Working-Age Finns

    Leena Korpinen


    Full Text Available The use of the computers and other technical devices has increased. The aim of our work was to study the possible relation between self-reported foot symptoms and use of computers and cell phones using a questionnaire. The study was carried out as a cross-sectional study by posting a questionnaire to 15,000 working-age Finns. A total of 6121 responded, and 7.1% of respondents reported that they very often experienced pain, numbness, and aches in the feet. They also often experienced other symptoms: 52.3% had symptoms in the neck, 53.5% in had problems in the hip and lower back, and 14.6% often had sleeping disorders/disturbances. Only 11.2% of the respondents thought that their symptoms were connected to the use of desktop computers. We found that persons with symptoms in the feet quite often, or more often, had additional physical and mental symptoms. In future studies, it is important to take into account that the persons with symptoms in the feet may very often have other symptoms, and the use of computers can influence these symptoms.

  19. AChE activity inhibiting in neutral system of diabetic mouse%胆碱酯酶抑制剂对糖尿病小鼠中枢胆碱酯酶活力的影响

    李大军; 沈明浩



  20. Application of Taguchi Method to the Optimization of a-C:H Coatings Deposited Using Ion Beam Assisted Physical Vapor Deposition

    W. H. Kao


    Full Text Available The Taguchi design method is used to optimize the adhesion, hardness, and wear resistance properties of a-C:H coatings deposited on AISI M2 steel substrates using the ion beam assisted physical vapor deposition method. The adhesion strength of the coatings is evaluated by means of scratch tests, while the hardness is measured using a nanoindentation tester. Finally, the wear resistance is evaluated by performing cyclic ball-on-disc wear tests. The Taguchi experimental results show that the optimal deposition parameters are as follows: a substrate bias voltage of 90 V, an ion beam voltage of 1 kV, an acetylene flow rate of 21 sccm, and a working distance of 7 cm. Given these optimal processing conditions, the a-C:H coating has a critical load of 99.8 N, a hardness of 25.5 GPa, and a wear rate of 0.4 × 10−6 mm3/Nm.

  1. Discovery of Isoxazole Analogs of Sazetidine-A as Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists for the Treatment of Depression

    Liu, Jianhua; Yu, Li-Fang; Eaton, J. Brek; Caldarone, Barbara; Cavino, Katie; Ruiz, Christina; Terry, Matthew; Fedolak, Allison; Wang, DaGuang; Ghavami, Afshin; Lowe, David A; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P.


    Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenalin are not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogs that interact with α4β2-nAChR as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selectiv...

  2. Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production.

    Dong, Miao-Wu; Li, Ming; Chen, Jie; Fu, Tong-Tong; Lin, Ke-Zhi; Ye, Guang-Hua; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao; Yu, Lin-Sheng; Fan, Yan-Yan


    Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages.

  3. Ramalina farinacea (L.) Ach. ve Usnea intermedia (A.Massal.) Jatta Likenlerinin Antimikrobiyal Aktiviteleri Üzerine Araştırmalar

    ŞİRİN, Neslihan; Başaran DÜLGER


    In this study,Ramalina farinacea (L.) Ach. and Usnea intermedia (A Massal.) Jatta lichens which were collected from The National Park around Bursa-Uludağ were investigated antimicrobial activity against the bacterial cultures; Bacillus cereus ATCC 7064, Bacillus licheniformis ATCC 14580, Citrobacter freundii ATCC 8090, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25992, Klebsiella oxytoca ATCC 8724, Listeria innocua ATCC 33090, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATC...

  4. Induction of long-term oscillations in the γ frequency band by nAChR activation in rat hippocampal CA3 area.

    Zhang, X; Ge, X Y; Wang, J G; Wang, Y L; Wang, Y; Yu, Y; Li, P P; Lu, C B


    The hippocampal neuronal network oscillation at γ frequency band (γ oscillation) is generated by the precise interaction between interneurons and principle cells. γ oscillation is associated with attention, learning and memory and is impaired in the diseased conditions such as Alzheimer's disease (AD) and schizophrenia. Nicotinic acetylcholine receptor (nAChR) plays an important role in the regulation of hippocampal neurotransmission and network activity. It is not known whether nicotine modulates plasticity of network activity at γ oscillations in the hippocampus. In this study we investigated the effects of nicotine on the long-term changes of KA-induced γ oscillations. We found that hippocampal γ oscillations can be enhanced by a low concentration of nicotine (1μM), such an enhancement lasts for hours after washing out of nicotine, suggesting a form of synaptic plasticity, named as long-term oscillation at γ frequency band (LTOγ). Nicotine-induced LTOγ was mimicked by the selective α4β2 but not by α7 nAChR agonist and was involved in N-methyl-d-aspartate (NMDA) receptor activation as well as depended on excitatory and inhibitory neurotransmission. Our results indicate that nAChR activation induced plasticity in γ oscillation, which may be beneficial for the improvement of cognitive deficiency in AD and schizophrenia.

  5. Interaction with mycorrhiza helper bacterium Streptomyces sp. AcH 505 modifies organisation of actin cytoskeleton in the ectomycorrhizal fungus Amanita muscaria (fly agaric).

    Schrey, Silvia D; Salo, Vanamo; Raudaskoski, Marjatta; Hampp, Rüdiger; Nehls, Uwe; Tarkka, Mika T


    The actin cytoskeleton (AC) of fungal hyphae is a major determinant of hyphal shape and morphogenesis, implicated in controlling tip structure and secretory vesicle delivery. Hyphal growth of the ectomycorrhizal fungus Amanita muscaria and symbiosis formation with spruce are promoted by the mycorrhiza helper bacterium Streptomyces sp. AcH 505 (AcH 505). To investigate structural requirements of growth promotion, the effect of AcH 505 on A. muscaria hyphal morphology, AC and actin gene expression were studied. Hyphal diameter and mycelial density decreased during dual culture (DC), and indirect immunofluorescence microscopy revealed that the dense and polarised actin cap in hyphal tips of axenic A. muscaria changes to a loosened and dispersed structure in DC. Supplementation of growth medium with cell-free bacterial supernatant confirmed that reduction in hyphal diameter and AC changes occurred at the same stage of growth. Transcript levels of both actin genes isolated from A. muscaria remained unaltered, indicating that AC changes are regulated by reorganisation of the existing actin pool. In conclusion, the AC reorganisation appears to result in altered hyphal morphology and faster apical extension. The thus improved spreading of hyphae and increased probability to encounter plant roots highlights a mechanism behind the mycorrhiza helper effect.

  6. Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating.

    Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G


    We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.

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

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


    Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Influência da redação da prescrição médica na administração de medicamentos em horários diferentes do prescrito Influencia de la redación de la prescripción médica en la administración de medicamentos en horarios diferentes al prescripto Influence of the writing of the medical orders on the administration of medications at the wrong schedule time

    Fernanda Raphael Escobar Gimenes


    Full Text Available OBJETIVO: Analisar a influência da redação da prescrição médica na administração de medicamentos em horários diferentes do prescrito ocorridas em unidades de clínica médica de cinco hospitais brasileiros. MÉTODOS: Trata-se de estudo descritivo que utilizou dados secundários obtidos de uma pesquisa multicêntrica realizada em 2005. A amostra foi composta por 1084 doses de medicamentos administradas em horários diferentes do prescrito. RESULTADOS: Do total analisado, 96,2% apresentavam siglas e/ou abreviaturas; 7,8% apresentavam o registro do horário de administração incompleto e 4,8% destes registros estavam rasurados. Ainda, faltou o horário e/ou a freqüência de administração em 1,9% das prescrições. CONCLUSÃO: Com a implantação do sistema computadorizado de prescrições, associada à prática da educação permanente será possível minimizar a administração de medicamentos em horários diferentes do prescrito.OBJETIVO: Analizar la influencia de la redacción de la prescripción médica en la administración de medicamentos en horarios diferentes al prescripto ocurridas en unidades de clínica médica de cinco hospitales brasileños. MÉTODOS: Se trata de un estudio descriptivo que utilizó datos secundarios obtenidos de una investigación multicéntrica realizada en el 2005. La muestra estuvo compuesta por 1084 dosis de medicamentos administradas en horarios diferentes al prescripto. RESULTADOS: Del total analizado, el 96,2% presentaba siglas y/o abreviaturas; el 7,8% presentaba el registro del horario de administración incompleto y el 4,8% de estos registros estaban borrados. Aun más, faltó el horario y/o la frecuencia de administración en el 1,9% de las prescripciones. CONCLUSIÓN: Con la implantación del sistema computarizado de prescripciones, asociada a la práctica de la educación permanente será posible minimizar la administración de medicamentos en horarios diferentes al prescripto.OBJECTIVE: To

  9. De la escena ritual a la teatral en una obra de teatro indígena prehispánico: Rabinal Achí o Danza del Tun From Ritual to Theatre Stage in a Pre-Hispanic Indigenous Drama: Rabinal Achí or Danza del Tun

    Patricia Henríquez Puentes


    El Rabinal Achí o Danza del Tun es arte escénico fundacional del teatro latinoamericano y clave para el proceso de desarrollo del teatro occidental del siglo XX, en tanto cifra ese momento en el que rito y teatro...

  10. Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury

    XIONG Jun; YUAN Yu-jing; XUE Fu-shan; WANG Qiang; LI Shan; LIAO Xu; LIU Jian-hua; CHEN Yi; LI Rui-ping


    Background Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury (IRI).Ischemia postconditioning (IPOC) can protect the heart against IRI by inhibiting inflammation,but its cardioprotection is weaker than that of ischemia preconditioning.Recently,the α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist has shown anti-infiammatory effects in many diseases related to inflammation.This randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial IRI.Methods Fifty Sprague-Dawley rats were randomly divided into five equal groups:sham group,control group,IPOC group,α7nAChR agonist postconditioning group (APOC group) and combined postconditioning with IPOC and α7nAChR agonist group (combined group).Hemodynamic parameters were recorded during the periods of ischemia and reperfusion.Serum concentrations of troponin I (Tnl),tumor necrosis factor α (TNF-α) and high-mobility group box 1 (HMGB-1) at 180 minutes after reperfusion were assayed in all groups.At the end of the experiment,the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride staining.Results As compared to the sham group,the infarct size in the other four groups was significantly increased,serum levels of Tnl,TNF-α and HMGB1 in the control group and TNF-α,HMGB1 in the IPOC group were significantly increased.The infarct size and serum concentrations of TNF-α,HMGB1 and Tnl in the IPOC,APOC and combined groups were significantly lower than those in the control group.As compared to the IPOC group,the infarct size in the combined group was significantly decreased,serum concentrations of Tnl,TNF-α and HMGB1 in the APOC and combined groups were significantly reduced.Although the infarct size was significantly smaller in the combined group than in the APOC group

  11. 不同训练方式对大鼠腓肠肌乙酰胆碱和烟碱型乙酰胆碱受体含量的影响%The Effect of Different Training Modes on the Contents of ACh and nAChR in Rat Gastrocnemius

    周思红; 王艳春


    目的:观察离心训练和向心训练对大鼠腓肠肌乙酰胆碱( ACh)、烟碱型乙酰胆碱受体(nAChR)含量的影响,探讨不同训练方式对大鼠神经肌肉适应性的影响.方法:雄性SD大鼠30只,随机分为离心训练组、向心训练组和对照组.离心训练组采用-14°的下坡跑训练,每天进行1次速度为17~21 m/min、总时间25~40 min的训练;向心训练组采用4°上坡跑训练,每天进行1次速度为19~23 rn/min、总时间为25~40 min的训练.两组大鼠均持续训练8周.对照组不参加训练,正常饮食.在训练组最后一次运动结束24小时,麻醉3组大鼠并取材,采用Elisa技术检测大鼠左侧下肢腓肠肌ACh、nAChR含量.结果:离心训练组和向心训练组ACh含量均显著高于对照组.离心组nAChR含量显著高于对照组.结论:离心训练和向心训练对大鼠神经肌肉适应性产生不同影响,离心训练影响更显著.%Objective The purpose of this study is to investigate the neuromuscular adaptation of rats to eccentric training and concentric training through the changes in the content of Ach (acetylcho-line) , and nAChR (nicotinic acetylcholine receptors) . Methods Thirty male SD rats were randomly divided into the eccentric training group (EE group) , concentric training group (CE group) and control group. -14° downhill running was applied for EE group (25-40 minute at a speed of 17-21 m/min, once a day) . 4° uphill running was applied for CE group (25~40 minute at the speed of 19-23 ml min, once a day) . They were continuously trained for 8 weeks. Within 24 hours of ending the training protocol, rats in three groups were simultaneously harvested under anesthesia. The gastrocnemius muscle of the rats was removed and Ach and nAChR in the muscle were tested by Elisa techniques. Results The content of Ach in both exercise groups was significantly higher than that in the control group, and the content of nAChR in EE group was significantly higher

  12. Role of ERK signaling pathway in up-regulation of γ-AChR during development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats%ERK信号通路在烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时γ-AChR上调中的作用

    靳天; 王宏; 吴进; 李士通


    Objective To evaluate the role of ERK signaling pathway in up-regulation of fetal gamma-acetylcholine receptor (μ-AChR) during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.Methods Thirty adult male SPF Sprague-Dawley rats,weighing 230-250 g,aged 9-10 weeks,were randomly divided into 3 groups (n=10 each) using a random number table:control group (C group),burn group (B group) and ERK1/2 inhibitor U0126 group (U group).The surface area of bilateral hindlimbs was shaved,and the tibialis anterior muscle of the right hiudlimb was exposed to 95 ℃ copper for 12 s in anesthetized rats.At 1.5 h after burn,15 mg/kg U0126 was injected intraperitoneally in group U,and the equal volume of dimethyl sulfoxide was given in C and B groups.The tibialis anterior muscle was obtained on 7th day after establishment of the model for determination of the expression of μ-AChR and adult epsilon-AChR (ε-AChR) mRNA in skeletal muscle cells using real-time polymerase chain reaction.The concentration-effect curve of rocuronium was drawn using muscular tension experiment,and the half inhibitory concentration (IC50) and 95% confidence interval were calculated.Resuits Compared with group C,the expression of μ-AChR mRNA in skeletal muscle cells was significantly up-regulated,and the IC50 was significantly increased in group B (P<0.05).Compared with group B,the expression of γ-AChR mRNA in skeletal muscle cells was significantly down-regulated,and the IC50 was significantly decreased in group U (P<0.05).There was no significant difference in the expression of ε-AChR in skeletal muscle cells between the three groups (P>0.05).Conclusion Up-regulation of μ,-AChR is dependent on activation of ERK signaling pathway during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.%目的 评价细胞外信号调节激酶(ERK)信号通路在烧伤大鼠骨骼肌对非去极化肌松药

  13. 阿仑膦酸钠对绝经后骨质疏松性骨痛的疗效分析%Effect analysis of alendronate on postmenopausal osteoporosis with bone ache


    @@ Background: Osteoporosis is a metabolic bone disease characterized by low bone component and regeneration of the microstructure of bone tissues, osteoporosis occurs in postmenopausal women for decreased estrogen level. Those women with osteoporosis often suffer from bone ache, such as pain at low back, back, knees and heels. In severe cases, there may be crookback or non- violent fracture. Objective: To discuss treatment effect of the Alendronate on 56 postmenopausal women with bone ache caused by osteoporosis. Unit: 210 Hospital of PLA.

  14. The first trimester human trophoblast cell line ACH-3P: A novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations – TNF-α stimulates MMP15 expression

    Knöfler Martin


    Full Text Available Abstract Background The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P by fusion of primary human first trimester trophoblasts (week 12 of gestation with a human choriocarcinoma cell line (AC1-1. Results Expression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases, invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts. Conclusion We conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-α on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

  15. Nicotine reduces TNF-α expression through a α7 nAChR/MyD88/NF-ĸB pathway in HBE16 airway epithelial cells.

    Li, Qi; Zhou, Xiang-Dong; Kolosov, Victor P; Perelman, Juliy M


    To explore the signaling mechanism associated with the inhibitory effect of nicotine on tumor necrosis factor (TNF)- α expression in human airway epithelial cells. HBE16 airway epithelial cells were cultured and incubated with either nicotine or cigarette smoke extract (CE). Cells were then transfected with α1, α5, or α7 nicotinic acetylcholine receptor (nAChR)-specific small interfering RNAs (siRNAs). The effects of nicotine on the production of proinflammatory factors TNF-α, in transfected cells were analyzed. Furthermore, we assayed the expression levels of myeloid differentiation primary response gene 88 (MyD88) protein, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 protein, NF-κB activity and NF-κB inhibitor alpha (I-κBα) expression in cells after treatment with nicotine or α7 nAChR inhibitor, α -bungarotoxin (α-BTX). The production of TNF-α was lower in cells pretreated with nicotine before lipopolysaccharide (LPS) stimulation, compared with LPS-only-treated cells. In contrast, in α7 siRNA-transfected cells incubated with nicotine and LPS, TNF-α expression was higher than that in non-transfected cells or in α1 or α5 siRNA-transfected cells. Addition of MyD88 siRNA or the NF-κB inhibitor pyridine-2,6-dithiocarboxylic acid (PDTC) also reduced TNF-α expression. Furthermore, we found that nicotine decreased MyD88 protein, NF-κB p65 protein, NF-κB activity and phospho-I-κBα expression induced by CE or LPS. The inhibitor α-BTX could reverse these effects. Nicotine reduces TNF-α expression in HBE16 airway epithelial cells, mainly through an α7 nAChR/MyD88/NF-κB pathway. Copyright © 2011 S. Karger AG, Basel.

  16. Identification of the Chemical Bonding Prompting Adhesion of a-C:H Thin Films on Ferrous Alloy Intermediated by a SiCx:H Buffer Layer.

    Cemin, F; Bim, L T; Leidens, L M; Morales, M; Baumvol, I J R; Alvarez, F; Figueroa, C A


    Amorphous carbon (a-C) and several related materials (DLCs) may have ultralow friction coefficients that can be used for saving-energy applications. However, poor chemical bonding of a-C/DLC films on metallic alloys is expected, due to the stability of carbon-carbon bonds. Silicon-based intermediate layers are employed to enhance the adherence of a-C:H films on ferrous alloys, although the role of such buffer layers is not yet fully understood in chemical terms. The chemical bonding of a-C:H thin films on ferrous alloy intermediated by a nanometric SiCx:H buffer layer was analyzed by X-ray photoelectron spectroscopy (XPS). The chemical profile was inspected by glow discharge optical emission spectroscopy (GDOES), and the chemical structure was evaluated by Raman and Fourier transform infrared spectroscopy techniques. The nature of adhesion is discussed by analyzing the chemical bonding at the interfaces of the a-C:H/SiCx:H/ferrous alloy sandwich structure. The adhesion phenomenon is ascribed to specifically chemical bonding character at the buffer layer. Whereas carbon-carbon (C-C) and carbon-silicon (C-Si) bonds are formed at the outermost interface, the innermost interface is constituted mainly by silicon-iron (Si-Fe) bonds. The oxygen presence degrades the adhesion up to totally delaminate the a-C:H thin films. The SiCx:H deposition temperature determines the type of chemical bonding and the amount of oxygen contained in the buffer layer.

  17. Deposition and characterisation of multilayer hard coatings. Ti/TiN{delta}/TiC{sub x}N{sub y}/(TiC) a-C:H/(Ti) a-C:H

    Burinprakhon, T


    Multilayer hard coatings containing Ti, TiN{delta}, TiC{sub x}N{sub y}, (TiC{sub m}) a-C:H, (TiC{sub n}) a-C:H, and (Ti) a-C:H were deposited on commercially pure titanium substrates by using an asymmetric bipolar pulsed-dc reactive magnetron sputtering of a titanium target, with Ar, Ar+N{sub 2}, Ar+N{sub 2}+CH{sub 4}, and Ar+CH{sub 4} gas mixtures. The microstructures, elemental compositions and bonding states of the interlayers and the coating surfaces were studied by using cross-sectional transmission electron microscopy (XTEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The microstructure development of the multilayer coating was strongly influenced by target poisoning. As a result of the complete poisoning of the titanium target during the deposition of TiN{delta} and TiC{sub x}N{sub y} interlayers, the a-C:H interlayers containing graded titanium and nitrogen contents were found to develop successively to the TiC{sub x}N{sub y} interlayer without the formation of near-stoichiometric TiC. The (TiC{sub m}) a-C:H interlayer consisted of nano-particles of distorted fcc crystal structure embedded in the a-C:H matrix. The (TiC{sub n}) a-C:H and (Ti) a-C:H top layers were found to be a-C:H matrix without nano-particles. In the (Ti) a-C:H top layer there was no measurable amount of Ti observed, regardless of the variation of CH{sub 4} concentration between 37.5 and 60 % flow rate in Ar+-CH4 gas mixture. The top layer (Ti) a-C:H was found to contain approximately 10 atomic % nitrogen, due to N{sub 2} contamination during deposition caused by low conductance of N{sub 2} through the nominally closed valve of the mass flow controller. The change of the CH{sub 4} concentration during deposition of the top layer (Ti) a-C:H, however, showed a strong influence on the hydrogen content. The comparison of the fluorescence background of the Raman spectra revealed that hydrogen-less (Ti) a-C:H

  18. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats.

    Fen Sun

    Full Text Available In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II of α7 nicotinic acetylcholine receptors (nAChRs, as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min middle cerebral artery occlusion (MCAO. Animals were then subdivided into two groups and injected intravenously (i.v. 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group or vehicle only (untreated group. Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke.

  19. 口虾蛄口胃神经系统AChE的组织化学与免疫组织化学定位



    本文同时采用了组织化学和免疫组织化学的方法去探索AChE在口虾蛄(Oratosquilla oratoria)口胃神经系统(stomatogastric nervous system, STNs)的分布.结果显示:在STG巾,AChE在口胃神经节(stomatogastric ganglion, STG)腹侧胞体区神经元的细胞膜及细胞间隙神经纤维和中央神经纤维网中标记为阳性;在食道神经节(oesophageal ganglion, OG)的腹侧中央偏右有一个大的神经元周围的神经突起呈强阳性反应,并且在紧靠该神经元的一侧还有一个神经元周围的神经纤维也呈阳性反应,另外在神经纤维网也有Ach阳性反应分布.结论:实验证明乙酰胆碱在口胃神经节和食道神经节都有分布,主要分布在神经纤维网和神经元的细胞膜及神经元间隙.

  20. Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

    Rekosh David


    Full Text Available Abstract AIDS-associated, CCR5-tropic (R5 HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

  1. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    DuRant, Sarah E. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States); University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States); Hopkins, William A. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States) and University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail:; Talent, Larry G. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States)


    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 {mu}g/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards.

  2. The influence of the nitrogen substitution in three cytisine derivatives as ligands for the neuronal nAChRs: a structural and theoretical study.

    Bombieri, Gabriella; Meneghetti, Fiorella; Artali, Roberto; Tasso, Bruno; Canu Boido, Caterina; Sparatore, Fabio


    Three cytisine derivatives, (-)-(7R,9S)-1-phenyl-3-(cytisin-12-yl)propan-1-one (1), (-)-(7R,9S)-1-phenyl-2-(cytisin-12-yl)ethane (2), and (-)-(7R,9S)-1,2-bis(cytisin-12-yl)ethane (3), with different electronic and steric features have been characterized by X-ray analysis and theoretical calculations in order to evaluate how structural modulations affect the intrinsic binding affinity at the neuronal nicotinic receptors (nAChRs). The crystal structures of 1 and 2, which display comparable affinities, are characterized by the same conformation of the cytisine moiety with different orientations of the substituent at N2. In 3, two independent molecules have the pyridinone rings diversely oriented. This compound has a lower affinity with respect to 1 and 2, but it increases the expression of neuronal nAChRs. Compounds 1, 2, and 3 retain the key prerequisite of the classical pharmacophoric models, with sp(3)-N-atom--HBA distances close to the expected value, both in solid state and in solution (theoretical calculations), where, in contrast with the extended in the crystal state, a curled-up conformation has been found, though maintaining the N-substituent in equatorial position.

  3. Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

    Olivieri, Kevin C; Scoggins, Robert M; Broderick, Brooks; Powell, Maria LC; Alexander, Melissa A; Hammarskjöld, Marie-Louise; Rekosh, David; Camerini, David


    AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors [1]. In contrast to other reports [1-3], this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone. PMID:18510766

  4. Synthesis and biological evaluation of novel hybrids of highly potent and selective α4β2-Nicotinic acetylcholine receptor (nAChR) partial agonists.

    Zhang, Han-Kun; Eaton, J Brek; Fedolak, Allison; Gunosewoyo, Hendra; Onajole, Oluseye K; Brunner, Dani; Lukas, Ronald J; Yu, Li-Fang; Kozikowski, Alan P


    We previously reported the cyclopropylpyridine and isoxazolylpyridine ether scaffolds to be versatile building blocks for creating potent α4β2 nicotinic acetylcholine receptor (nAChR) partial agonists with excellent selectivity over the α3β4 subtype. In our continued efforts to develop therapeutic nicotinic ligands, seven novel hybrid compounds were rationally designed, synthesized, and evaluated in [(3)H]epibatidine binding competition studies. Incorporation of a cyclopropane- or isoxazole-containing side chain onto the 5-position of 1-(pyridin-3-yl)-1,4-diazepane or 2-(pyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane led to highly potent and selective α4β2* nAChR partial agonists with Ki values of 0.5-51.4 nM for α4β2 and negligible affinities for α3β4 and α7. Moreover, compounds 21, 25, and 30 maintained the functional profiles (EC50 and IC50 values of 15-50 nM) of the parent azetidine-containing compounds 3 and 4 in the (86)Rb(+) ion flux assays. In vivo efficacy of the most promising compound 21 was confirmed in the mouse SmartCube(®) platform and classical forced swim tests, supporting the potential use of α4β2 partial agonists for treatment of depression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Sub-micro a-C:H patterning of silicon surfaces assisted by atmospheric-pressure plasma-enhanced chemical vapor deposition

    Boileau, Alexis; Gries, Thomas; Noël, Cédric; Perito Cardoso, Rodrigo; Belmonte, Thierry


    Micro and nano-patterning of surfaces is an increasingly popular challenge in the field of the miniaturization of devices assembled via top-down approaches. This study demonstrates the possibility of depositing sub-micrometric localized coatings—spots, lines or even more complex shapes—made of amorphous hydrogenated carbon (a-C:H) thanks to a moving XY stage. Deposition was performed on silicon substrates using chemical vapor deposition assisted by an argon atmospheric-pressure plasma jet. Acetylene was injected into the post-discharge region as a precursor by means of a glass capillary with a sub-micrometric diameter. A parametric study was carried out to study the influence of the geometric configurations (capillary diameter and capillary-plasma distance) on the deposited coating. Thus, the patterns formed were investigated by scanning electron microscopy and atomic force microscopy. Furthermore, the chemical composition of large coated areas was investigated by Fourier transform infrared spectroscopy according to the chosen atmospheric environment. The observed chemical bonds show that reactions of the gaseous precursor in the discharge region and both chemical and morphological stability of the patterns after treatment are strongly dependent on the surrounding gas. Various sub-micrometric a-C:H shapes were successfully deposited under controlled atmospheric conditions using argon as inerting gas. Overall, this new process of micro-scale additive manufacturing by atmospheric plasma offers unusually high-resolution at low cost.

  6. Synthesis and in-vitro reactivation screening of imidazolium aldoximes as reactivators of sarin and VX-inhibited human acetylcholinesterase (hAChE).

    Sharma, Rahul; Gupta, Bhanushree; Sahu, Arvind Kumar; Acharya, Jyotiranjan; Satnami, Manmohan L; Ghosh, Kallol K


    Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole ring resulted in substantial increase in the reactivation strength of prepared reactivator. Physicochemical properties of synthesized reactivators have also been evaluated.

  7. M1/M2 muscarinic receptor selectivity using potassium (K/sup +/)-stimulated release of (/sup 3/H)-dopamine (DA) and (/sup 14/C)-acetyl-choline (ACH) in striatum

    DeHaven, D.L.; Steranka, L.R.


    Raiteri et al have suggested that muscarinic receptor subtypes can be differentiated in striatal synaptosomes by the release of DA (M1) or ACh (M2). The authors attempted to replicate this finding and to characterize responses of selective and non-selective cholinergic agonists and antagonists using K+-stimulated release of transmitters from rat striatal slices. The non-selective agonists ACh, carbachol and oxotremorine stimulated release of (/sup 3/H)-DA and inhibited release of (/sup 14/C)-ACh with EC50 values of 10.6, 9.2 and 4.2 (DA) and 1.2, 0.77 and 0.43 (ACh), respectively. The M1 agonist McN-A-343-11 selectively inhibited release of DA with an EC50 value of 4.8 Pilocarpine was ineffective in this system. The M1 antagonist pirenzepine reversed the effects of 10/sup -4/ M carbachol on release with an eight-fold selectivity for release of (/sup 3/H)-DA (IC50 = 0.77 vs (/sup 14/C)-ACh (IC50 = 6.3 These results suggest that although this system can determine relative subtype selectivities, the results obtained in this assay do not always correlate with those obtained from phosphatidyl inositol turnover or adenylate cyclase activity.

  8. Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α1(2)βγδ nAChRs.

    Bourne, Yves; Sulzenbacher, Gerlind; Radić, Zoran; Aráoz, Rómulo; Reynaud, Morgane; Benoit, Evelyne; Zakarian, Armen; Servent, Denis; Molgó, Jordi; Taylor, Palmer; Marchot, Pascale


    Pinnatoxins are macrocyclic imine phycotoxins associated with algal blooms and shellfish toxicity. Functional analysis of pinnatoxin A and pinnatoxin G by binding and voltage-clamp electrophysiology on membrane-embedded neuronal α7, α4β2, α3β2, and muscle-type α12βγδ nicotinic acetylcholine receptors (nAChRs) reveals high-affinity binding and potent antagonism for the α7 and α12βγδ subtypes. The toxins also bind to the nAChR surrogate, acetylcholine-binding protein (AChBP), with low Kd values reflecting slow dissociation. Crystal structures of pinnatoxin-AChBP complexes (1.9-2.2 Å resolution) show the multiple anchoring points of the hydrophobic portion, the cyclic imine, and the substituted bis-spiroketal and cyclohexene ring systems of the pinnatoxins that dictate tight binding between the opposing loops C and F at the receptor subunit interface, as observed for the 13-desmethyl-spirolide C and gymnodimine A congeners. Uniquely, however, the bulky bridged EF-ketal ring specific to the pinnatoxins extends radially from the interfacial-binding pocket to interact with the sequence-variable loop F and govern nAChR subtype selectivity and central neurotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Regulation of CD11b transcription by decreasing PRC2 and increased acH4 level during ATRA-induced HL-60 differentiation

    Huarong Tang; Fangping Chen; Qian Tan; Sanqin Tan; Linxin Liu; Fan Zhang


    Polycomb repressive complex 2 (PRC2),which mediates trimethylation of lysine 27 on histone H3 (K27me3),plays an important role in many types of stem cell differentiation.Here,we try to reveal how PRC2,PRC2-mediated repressive histone marker H3K27me3,and active histone marker histone H4 acetylation (acH4) regulate the CD11b transcription during all-trans retinoic acid (ATRA)-induced HL-60 leukemia cell differentiation.By using quantitative real-time polymerase chain reaction (qPCR) and western blot analysis,we found that the mRNA and protein expression levels of two members of PRC2 were decreased during ATRA-induced HL-60 differentiation,respectively.When treated with ATRA for 72 h,the EZH2 and SUZ12 mRNA levels were decreased to 35% and 38% of the control group,respectively.At the same time,the granulocytic mature surface marker CD11b expression was increased significantly at mRNA level detected by qPCR and protein level detected by flow cytometry.By using chromatin immunoprecipita-tion assay,we compared the local changes in SUZ12 binding and PRC2-mediated H3K27me3 at the promo-ter of CD11b during ATRA-induced HL-60 differ-entiation.Both the levels of SUZ12 binding and PRC2-mediated H3K27me3 at the promoter of CD11b were decreased for 4.1 and 3.8 folds,respectively.And we also found the increase in the acH4 level up to 4 folds after 72 h of ATRA treatment.These results suggested that the histone modification including PRC2-mediated repressive histone marker H3K27me3 and active histone marker acH4 may involve in CD11b transcription during HL-60 leukemia cells reprogram-ming to terminal differentiation.

  10. Estimation and Test of Interaction Parameters in the UNIFAC Model of Group—OCOO—with Group—CH3,ACH, CH3OH and CH3COO—

    方云进; 钱俊明


    Isobaric vapor-liquid equilibria (VLE) are experimentally measured for the binary systems of dimethyl carbonate (DMC)+ ethylene carbonate and methanol + ethylene carbonate at 101.325kPa. The thermodynamic consistency of these experimental data is tested with an available statistic method. Interaction parameters of the carbonate group —OCOO— with the group —CH3, ACH, CH3OH and CHACO0— in UNIFAC model are determined using the experimental and literature VLE data. The results show that the calculated VLE data using the new UNIFAG parameters agree excellently with the experimental data in this work and in literature. These results are useful in the research on DMG and diphenyl carbonate synthesis by transesterification in design of reactor and distillation tower.

  11. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

    Munro, G; Hansen, Rikke Rie; Erichsen, Hk


    -120596 attenuated the carrageenan-induced increase in levels of TNF-α and IL-6 within the hind paw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by carrageenan or CFA was also partially reversed by compound B and PNU-120596. However, diclofenac......ACh receptor agonist compound B with the positive allosteric modulator (PAM) PNU-120596 and the standard non-steroidal anti-inflammatory drug (NSAID), diclofenac, in rats with hind paw inflammation induced by either formalin, carrageenan or complete Freund's adjuvant (CFA). KEY RESULTS: When administered...... before carrageenan, both diclofenac (30 mg·kg(-1) ) and PNU-120596 (30 mg·kg(-1) ) significantly reduced mechanical hyperalgesia and weight-bearing deficits for up to 4 h. Compound B (30 mg·kg(-1) ) also attenuated both measures of pain-like behaviour, albeit less robustly. Whereas compound B and PNU...

  12. Inadvertent injection of potassium chloride instead of sodium chloride during treatment of chronic low back ache with epidural injection leading to paraplegia

    Rahul Ranjan


    Full Text Available Epidural injection of steroid is given for back pain resistant to other conservative management. Normal saline (NS is used as diluent in 80 mg methylprednisolone and a local anesthetic. Due to a similar looking ampoule of NS and potassium chloride (KCl, there is a probability of accidental use of KCl instead of NS. We present a case of a 50 year old male patient having low back ache refractory to other conservative treatments. Epidural injection of steroid was given, but accidently KCl was mixed with methylprednisolone instead of NS. He developed severe cramps in the lower limbs, pruritus, and sweating, and finally paraplegia. Electrocardiography and blood showed features suggestive of hyperkalemia. He was given calcium gluconate and potassium chelating agent along with supportive measures. The patient recovered within 8 h. It is concluded that calcium gluconate and potassium chelating agent can be used if accidentally KCl is injected in epidural space.

  13. Identification of key amino acid differences contributing to neonicotinoid sensitivity between two nAChR α subunits from Pardosa pseudoannulata.

    Meng, Xiangkun; Zhang, Yixi; Guo, Beina; Sun, Huahua; Liu, Chuanjun; Liu, Zewen


    Chemical insecticides are still primary methods to control rice planthoppers in China, which not only cause environmental pollution, insecticide residue and insecticide resistance, but also have negative effects on natural enemies, such as Pardosa pseudoannulata (the pond wolf spider), an important predatory enemy of rice planthoppers. Neonicotinoids insecticides, such as imidacloprid and thiacloprid, are insect-selective nAChRs agonists that are used extensively in the areas of crop protection and animal health, but have hypotoxicity to P. pseudoannulata. In the present study, two nAChR α subunits, Ppα1 or Ppα8, were found to be successfully expressed with rβ2 in Xenopus oocytes, but with much different sensitivity to imidacloprid and thiacloprid on two recombinant receptors Ppα1/rβ2 and Ppα8/rβ2. Key amino acid differences were found in and between the important loops for ligand binding. In order to well understand the relationship between the amino acid differences and neonicotinoid sensitivities, different segments in Ppα8 or Ppα1 with key amino acid differences were introduced into the corresponding regions of Ppα1 or Ppα8 to construct chimeras and then co-expressed with rβ2 subunit in Xenopus oocytes. The results from chimeras of both Ppα8 and Ppα1 showed that segments Δ5, Δ6, and Δ7 contributed to neonicotinoid sensitivities directly between two receptors. Although the segment Δ4 including all loop B region had no direct influences on neonicotinoid sensitivities, it could more remarkably influence neonicotinoid sensitivities when co-introductions with Δ5, Δ6 or Δ7. So, key amino acid differences in these four segments were important to neonicotinoid sensitivities, but the difference in Δ4 was likely ignored because of its indirect effects.

  14. A nootropic effect of Moringa oleifera on Ach and ChAT activity in colchicine induced experimental rat model of Alzheimer’s disease: Possible involvement of antioxidants

    Chandan Roy


    Full Text Available Context: The fruit and leaf of Moringa oleifera (MO is an important ingredient of ‘Kusmanda lehyam’ (Ayurvedic medicine, which is widely used, in nervous disorders. Objective: To determine the cognition facilitating effect of MO leaf extract in colchicine induced experimental rat model of AD and to investigate the role of central cholinergic system in the nootropic effect of MO leaf extract with the possible involvement of antioxidant enzymes. Materials and methods: The behavior study, Acetylcholine concentration, cholineacetyl transferase activity, antioxidant level such as, superoxide dismutase (SOD, catalase (CAT, reduced glutathione (GSH and lipid peroxidation (LPO level were studied in different parts of the brain such as frontal cortex (FC and hippocampus (HPC in colchicine induced experimental Alzheimer rat model before and after treatment with MO. Results: MO (250 mg/kg p.o. induced statistically significant reversal of colchicine induced cognitive deficits. MO (250 mg/kg p.o. markedly induced frontal, cortical and hippocampal concentrations of Ach and ChAt activity, the effects being statistically significant on days 7, 14 and 21 respectively. Moreover, MO significantly increased SOD, CAT, GSH activities and significantly decreased LPO level on day 7, 14 and 21 respectively. Discussion and conclusion: The aqueous pulp extract of MO (250 mg/kg body weight containing vit- A, C, E results significant protection in the level of antioxidant status in frontal cortex and hippocampus after a certain period of co administration on colchicine induced oxidative stress without causing any general and metabolic toxicity and possibly thereby induced frontal cortical and hippocampal concentration of Ach and ChAT activity.

  15. Nicotine analogues as potential therapeutic agents in Parkinson’s disease by targeting nicotinic acetylcholine receptors (nAChRs in astrocytes

    Valentina Echeverria Moran


    Full Text Available Parkinson’s disease (PD is a relatively common disorder of the Central Nervous System (CNS, whose etiology is characterized by a selective and progressive degeneration of dopaminergic neurons, and the presence of Lewy bodies in the pars compacta of the substantia nigra, thus dopamine depletion in the striatum. Patients with this disease suffer from tremors, slowness of movements, gait instability, rigidity, and may also present functional disability, reduced quality of life, and rapid cognitive decline. The prevalence of this disease is in a range of 107-187 per 100,000 inhabitants. Previous studies have shown that nicotine exerts beneficial effects in patients with PD and in in vitro and in vivo models of this disease. Astrocytes have an important role in the immune system, and that nicotine might be able to reduce inflammation-induced activation of pro-apoptotic signaling in PD. Nicotine might exert its effect through activation of α7 nicotinic acetylcholine receptors (α7-nAChRs expressed in glial cells. Moreover, nicotine administration can protect dopaminergic neurons against degeneration by inhibiting astrocytes activation in the substantia nigra pars compacta (SNpc and therefore reducing inflammation. Besides this beneficial effect of nicotine, its continuing use can induce toxicity and cause dependency. To counteract this effect, nicotine analogues have risen as an important therapeutic approach to maintain nicotine´s beneficial effects, but avoid its toxicity. Since astrocytes might drive chronic inflammatory processes in PD, therefore increasing neuronal vulnerability to damage, the administration of nicotine analogues in astrocytes is of interest to diminish neuronal death. In this work, we assess the role of different nicotine analogues in astrocytes following rotenone stimuli, and determine whether the possible beneficial effects of nicotine are via activation of α7-nAChRs.

  16. In Vitro Activity of ACH-702, a New Isothiazoloquinolone, against Nocardia brasiliensis Compared with Econazole and the Carbapenems Imipenem and Meropenem Alone or in Combination with Clavulanic Acid ▿

    Vera-Cabrera, Lucio; Campos-Rivera, Mayra Paola; Escalante-Fuentes, Wendy G.; Pucci, Michael J.; Ocampo-Candiani, Jorge; Welsh, Oliverio


    The in vitro activities of ACH-702 and other antimicrobials against 30 Nocardia brasiliensis isolates were tested. The MIC50 (MIC for 50% of the strains tested) and MIC90 values of ACH-702 were 0.125 and 0.5 μg/ml. The same values for econazole were 2 and 4 μg/ml. The MIC50 and MIC90 values of imipenem and meropenem were 64 and >64 μg/ml and 2 and 8 μg/ml, respectively; the addition of clavulanic acid to the carbapenems had no effect. PMID:20308390

  17. The Relationship between AChR-Ab and the Post-thymectomy Clinical Outcome of Generalized Myasthenia Gravis%乙酰胆碱受体抗体与全身型重症肌无力手术预后的关系

    刘天芳; 任明山; 吴元波; 杨毅


    Aim To compare the clinical outcome of the post-thymectomy between generalized myasthenia gravis (gMG) with acetylcholine receptor antibody (AChR-Ab) positive and AChR-Ab negative. Methods124 cases of gMG who were retrospectively reviewed had received video-assisted thoracoscopic thymectomy in the thoracic surgery. According to the type of the serum antibodies, the patients were divided in to AChR-Ab-positive group and AChR-Ab-negative group. The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients in the two groups.ResultsThere were 81 patients in the AChR-Ab positive group, and 43 patients in AChR-Ab-negative group, there was no signiifcant difference among the three groups regarding sex, age at onset and disease duration, and thymus pathology. One case in AChR-Ab-positive group was lost, two cases in AChR-Ab-negative group were lost. Until the deadline of follow-up time of Sep. 2014, a total of 121 patients were followed, including 80 cases in AChR-Ab-positive group, 41 cases in AChR-Ab-negative group. Follow-up time was 15 to 84 months, mean (44.9±19.9) months in AchR-Ab positive group, mean (48.2±20.3) months in AChR-Ab-negative group. The complete stable remission rate (CSR) in AChR-Ab-positive group was 48.8%, in the AChR-Ab-negative group theP vaule was 26.8%. The CSR in the AChR-Ab-positive group was higer than that in the AChR-Ab-negative group [(χ2=5.372,P=0.020)]. The overall remission rate in the AChR-Ab-positive group was 85.1%, and 73.2% in the AChR-Ab-negative. There was no signiifcant difference in the overall remission rate between the two group. By Kaplan–Meier analysis, there was signiifcant difference in CSR rates between AChR-Ab-positive group and AChR-Ab-negative group (P=0.03).Conclusion Long-term post-thymectomy clinical outcome was better in AChR-Ab-positive group than in AChR-Ab-negative group, but our results showed no differences in the overall remission rate.%目的:比较乙酰

  18. REDA 重燃艺术和传统的远古渊源


    <正>世界著名高级男装羊毛织品制造商,同时又是诸多国际知名男装设计师供应商的REDA公司,日前在全球范围推出其最新广告计划,体现了其对于艺术及传统的重新思考。由已故意大利著名艺术家卢西奥·冯塔那(Lucio Fontana)先生等众多欧洲当代艺术大师作品激发灵感而诞生的广告设计,着重突出的主题

  19. Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).

    Karade, Hitendra N; Raviraju, G; Acharya, B N; Valiveti, Aditya Kapil; Bhalerao, Uma; Acharya, Jyotiranjan


    Previously (Karade et al., 2014), we have reported the synthesis and in vitro evaluation of bis-pyridinium derivatives of pyridine-3-yl-(2-hydroxyimino acetamide), as reactivators of sarin and VX inhibited hAChE. Few of the molecules showed superior in vivo protection efficacy (mice model) (Kumar et al., 2014; Swami et al., 2016) in comparison to 2-PAM against DFP and sarin poisoning. Encouraged by these results, herein we report the synthesis and in vitro evaluation of isonicotinamide derivatives of pyridine-3-yl-(2-hydroxyimino acetamide) (4a-4d) against sarin and VX inhibited erythrocyte ghost hAChE. Reactivation kinetics of these compounds was studied and the determined kinetic parameters were compared with that of commercial reactivators viz. 2-PAM and obidoxime. In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential.


    司银楚; 朱培纯



  1. Role of α7- and α4β2-nAChRs in the neuroprotective effect of nicotine in stress-induced impairment of hippocampus-dependent memory.

    Alzoubi, Karem H; Srivareerat, Marisa; Tran, Trinh T; Alkadhi, Karim A


    We have previously shown that nicotine prevents stress-induced memory impairment. In this study, we have investigated the role of α7- and α4β2-nicotinic acetylcholine receptors (nAChRs) in the protective effect of nicotine during chronic stress conditions. Chronic psychosocial stress was induced using a form of rat intruder model. During stress, specific antagonist for either α7-nAChRs [methyllycaconitine (MLA)] or α4β2-nAChRs [dihydro-β-erythroidine (DHβE)] was infused into the hippocampus using a 4-wk osmotic pump at a rate of 82 μg/side.d and 41 μg/side.d, respectively. Three weeks after the start of infusion, all rats were subjected to a series of cognitive tests in the radial arm water maze (RAWM) for six consecutive days or until the animal reached days to criterion (DTC) in the fourth acquisition trial and in all memory tests. DTC is defined as the number of days the animal takes to make no more than one error in three consecutive days. In the short-term memory test, MLA-infused stressed/nicotine-treated rats made similar errors to those of stress and significantly more errors compared to those of stress/nicotine, nicotine or control groups. This finding was supported by the DTC values for the short memory tests. Thus, MLA treatment blocked the neuroprotective effect of nicotine during chronic stress. In contrast, DHβE infusion did not affect the RAWM performance of stress/nicotine animals. These results strongly suggest the involvement of α7-nAChRs, but not α4β2-nAChRs, in the neuroprotective effect of chronic nicotine treatment during chronic stress conditions.

  2. The α3β4 nAChR partial agonist AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats.

    Yuan, Menglu; Malagon, Ariana M; Yasuda, Dennis; Belluzzi, James D; Leslie, Frances M; Zaveri, Nurulain T


    The strong reinforcing effects of nicotine and the negative symptoms such as anxiety experienced during a quit attempt often lead to relapse and low success rates for smoking cessation. Treatments that not only block the reinforcing effects of nicotine but also attenuate the motivation to relapse are needed to improve cessation rates. Recent genetic and preclinical studies have highlighted the involvement of the α3, β4, and α5 nicotinic acetylcholine receptor (nAChR) subunits and the α3β4 nAChR subtype in nicotine dependence and withdrawal. However, the involvement of these nAChR in relapse is not fully understood. We previously reported that the α3β4 nAChR partial agonist AT-1001 selectively decreases nicotine self-administration in rats without affecting food responding. In the present experiments, we examined the efficacy of AT-1001 in attenuating reinstatement of nicotine-seeking behavior in a model of stress-induced relapse. Rats extinguished from nicotine self-administration were treated with the pharmacological stressor yohimbine prior to AT-1001 treatment and reinstatement testing. We also examined whether AT-1001 produced any withdrawal-related effects when administered to nicotine-dependent rats. We found that AT-1001 dose-dependently reduced yohimbine stress-induced reinstatement of nicotine seeking. When administered to nicotine-dependent rats at the dose that significantly blocked nicotine reinstatement, AT-1001 elicited minimal somatic withdrawal signs in comparison to the nicotinic antagonist mecamylamine, which is known to produce robust withdrawal. Our data suggest that α3β4 nAChR-targeted compounds may be a promising approach for nicotine addiction treatment because they can not only block nicotine's reinforcing effects, but also decrease motivation to relapse without producing significant withdrawal effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Influence of Applied Bias Voltage on the Composition, Structure, and Properties of Ti:Si-Codoped a-C:H Films Prepared by Magnetron Sputtering

    Jinlong Jiang


    Full Text Available The titanium- and silicon-codoped a-C:H films were prepared at different applied bias voltage by magnetron sputtering TiSi target in argon and methane mixture atmosphere. The influence of the applied bias voltage on the composition, surface morphology, structure, and mechanical properties of the films was investigated by XPS, AFM, Raman, FTIR spectroscopy, and nanoindenter. The tribological properties of the films were characterized on an UMT-2MT tribometer. The results demonstrated that the film became smoother and denser with increasing the applied bias voltage up to −200 V, whereas surface roughness increased due to the enhancement of ion bombardment as the applied bias voltage further increased. The sp3 carbon fraction in the films monotonously decreased with increasing the applied bias voltage. The film exhibited moderate hardness and the superior tribological properties at the applied bias voltage of −100 V. The tribological behaviors are correlated to the H/E or H3/E2 ratio of the films.

  4. Preliminary Geological Map of the Ac-H-13 Urvara Quadrangle of Ceres: An Integrated Mapping Study Using Dawn Spacecraft Data

    Williams, D. A.; Sizemore, H. G.; Platz, T.; O'Brien, D. P.; Mest, S. C.; Yingst, R. A.; Crown, D. A.; Buczkowski, D.; Schenk, P.; Scully, J. E. C.; Jaumann, R.; Roatsch, T.; Preusker, F.; Nathues, A.; De Sanctis, M. C.; Russell, C. T.; Raymond, C. A.


    We used geologic mapping applied to Dawn spacecraft data as a tool to understand the geologic history of the Ac-H-13 Urvara Quadrangle of dwarf planet Ceres. This region, located between 21˚S-66˚S and 180-270˚E, is dominated by the Urvara basin in the east and cratered plains in the west. The elevation of the cratered plains is intermediate between the identified "highland" and "lowland" units of Ceres. Plains in the SW corner of the quadrangle are hummocky and heavily cratered, while the NW corner is smoother and less densely cratered. Features of note include 1) the 200 km diameter Urvara basin, which includes a degraded northern rim and smooth interior and exterior material that hosts a significantly lower impact crater density than most of the rest of Ceres' surface; 2) semi-radial curvilinear structures extending to the east and west of Urvara; 3) two large-scale dome structures 10s of km in diameter exterior to Urvara; and 4) numerous small-scale domical structures (digital terrain models derived from stereo images. In Fall 2015 images from the High Altitude Mapping Orbit (140 m/px) will be used to refine the mapping, followed by Low Altitude Mapping Orbit (35 m/px) images starting in December 2015. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA, the Max Planck Society and from the German and Italian Space Agencies.

  5. Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs?

    Kara, Yusuf; Doguc, Duygu Kumbul; Kulac, Esin; Gultekin, Fatih


    Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChRα7, α4 and β2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin+ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin+ascorbic acid group (p acid group as compared to the control group (p acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process.

  6. Effects of Chlorpyrifos on Food Utilization and Detoxifying Enzymes and Acetylcholinesterase of Lymantria dispar%毒死蜱对舞毒蛾食物利用和解毒酶及AChE活性的影响

    李慧; 严善春; 王志英; 葛士林; 曹传旺


    采用质量法和酶活性测定法研究了毒死蜱对舞毒蛾(Lymantria dispar)3龄幼虫食物利用的影响,并测定了其毒力及解毒酶、乙酰胆碱酯酶(AChE)的活性.用亚致死浓度(1.5 mg·L-1)毒死蜱处理小黑杨叶片,饲喂舞毒蛾3龄幼虫,其幼虫生长率(RGR)、食物利用率(ECI)和食物转化率(ECD)均显著低于对照,而近似消化率(AD)显著高于对照,相对取食量(RCR)处理和对照间差异不显著.毒死蜱对舞毒蛾幼虫24 h致死中浓度(LC50)为5.86 mg·L-1,其毒力低于三氟氯氰菊酯而高于氧化乐果.毒死蜱对舞毒蛾3龄幼虫体内羧酸酯酶(CarE)、谷胱甘肽S-转移酶(GSTs)和AChE均有抑制作用,抑制程度为CarE>AChE>GSTs.毒死蜱通过影响舞毒蛾食物利用和抑制酶活性而表现出杀虫活性,为一种有效防治舞毒蛾的有机磷杀虫剂.%The effects of sublethal dose of chlorpyrifos (CPF) on food utilization of gypsy moth, Lymantria dispar,as well as CPF toxicity and enzyme activities of carboxylesterase ( CarE ), glutathione S-transferases (GSTs) and acetylcholinesterase (AChE) were evaluated in the 3rd-instar gypsy moth larvae using gravimetric method and measuring enzyme activities. Relative growth rate (RGR), efficiency of the conversion of ingested food (ECI) and efficiency of the conversion of digested food (ECD) of 3rd-instar larvae fed on poplar leaves treated by sublethal concentration of CPF were significantly lower than thosc fed on normal polar leaves. However, approximate digestibility (AD) of the treatment was significantly higher than that of control. The relative consumption rate (RCR) of the treatment and control groups were not significantly different. The 24 h LC50 of CPF to the gypsy moth 3rd-instar larvae was 5.86 mg · L-1, which was higher than that of omethoate but lower than that of cyhalothrin. In vitro inhibition assay indicated that the activities of AChE, CarE and GSTs were inhibited by CPF depended on concentrations

  7. 柴胡疏肝散对抑郁模型大鼠海马乙酰胆碱代谢的影响%Effect of Chaihu Shugan Powderon metabolism of ach in brain hippocampus tissue of depressive rats

    董海影; 张晓杰


    Objective: To observe the changes of acetylcholine metabolism of hippocampal of depression models on rats and the effect of Chaihu Shugan Powder on it.Method: 60 male Sprague-Dawley rats of 4 - 5 month were randomly divided into four groups and 15 rats in 4 groups: normal control group, model group, western medicine group and Chinese medicine group.The depressed modle was reduced by single feed combined with CUMS.After twenty-one days,behavior changes in rats were detected through open-field test, sugar consumption test and body weight;expression changes of acetylcholine transferase and acetylcholinesterase in hippocampus of rats brain were observed with immunochemistry method; ChAT mRNA expression was detected with RT-PCR; the activity of AChE in hippocampus of rats brain tissue was measured with colorimetric method.Results:On the 21st day of model replication, compared with normal control group, the scores of horizontal activity and vertical activity,weight and sugar preference degrees in model group decreased significantly (P<0.01-0.001); Compared with model group,western medicine group and Chinese medicine group got significantly higher scores of horizontal activity and vertical activity, weight and sugar preference degrees (P<0.05-0.001).The results of immunochemistry staining showed that ChAT, AChEprotein expression was significantly increased in hippocampus of model group compared with that of normal control group (P<0.05);Compared with model group, western medicine group and Chinese medicine group had significantly lower ChAT, AChE protein expression in hippocampus (P<0.05).RT-PCR results showed that expression levels of ChAT mRNA in hippocampus of rats of model group were significantly raised compared with those of normal control group (P<0.05); Compared with those of model group,expression levels of ChAT mRNA in hippocampus of rats of western medicine group and Chinese medicine group was significantly reduced (P<0.05); The results of

  8. Electronic structure calculations toward new potentially AChE inhibitors

    de Paula, A. A. N.; Martins, J. B. L.; Gargano, R.; dos Santos, M. L.; Romeiro, L. A. S.


    The main purpose of this study was the use of natural non-isoprenoid phenolic lipid of cashew nut shell liquid from Anacardium occidentale as lead material for generating new potentially candidates of acetylcholinesterase inhibitors. Therefore, we studied the electronic structure of 15 molecules derivatives from the cardanol using the following groups: methyl, acetyl, N, N-dimethylcarbamoyl, N, N-dimethylamine, N, N-diethylamine, piperidine, pyrrolidine, and N-benzylamine. The calculations were performed at RHF level using 6-31G, 6-31G(d), 6-31+G(d) and 6-311G(d,p) basis functions. Among the proposed compounds we found that the structures with substitution by acetyl, N, N-dimethylcarbamoyl, N, N-dimethylamine, and pyrrolidine groups were better correlated to rivastigmine indicating possible activity.

  9. 基于UNIFAC模型的基团-OCOO-与-CH3,ACH,CH3OH和CH3COO-的交互作用参数估算与验证%Estimation and Test of Interaction Parameters in the UNIFAC Model of Group-OCOO-with Group-CH3,ACH, CH3OH and CH3COO-

    方云进; 钱俊明


    Isobaric vapor-liquid equilibria (VLE) are experimentally measured for the binary systems of dimethyl carbonate (DMC)+ ethylene carbonate and methanol + ethylene carbonate at 101.325 kPa. The t hermodynamic consistency of these experimental data is tested with an available statistic method. Interaction parameters of the carbonate group -OCOO- with the group -CH3, ACH, CH3OH and CHaCOO- in UNIFAC model are determined using the experimental and literature VLE data. The results show that the calculated VLE data using the new UNIFAC parameters agree excellently with the experimental data in this work and in literature. These results are useful in the research on DMC and diphenyl carbonate synthesis by transesterification in design of reactor and distillation tower.

  10. Aches and pains during pregnancy

    ... is normal and will go away after you give birth (it may take a few weeks to months). You may also have numbness or tingling in your fingers and hands. You may ... after you give birth, though, again, not always right away. If ...

  11. LWH & ACH Helmet Hardware Study


    testing included dimensional measurements, Rockwell hardness and Vicker’s microhardness measurements, metallographic examination of the grain... microhardness measurements (ASTM E384 Standard Test Method for Microindentation Hardness of Materials) were made on the exterior surfaces of screws...hardware as reference values. However, we do not recommend use of surface Vicker’s microhardness testing for characterizing the nuts, because, as

  12. [Back ache in helicopter pilots].

    Colak, S; Jovelić, S; Manojlović, J


    Due to low back pain (LBP) and harmful effects of flying, questionnaires were sent to 71 helicopter pilots of the experimental group, 22 mechanics helicopter flyers and to the control group of 28 air-traffic controllers. The prevalence of LBP was the highest in helicopter pilots, then in helicomechanics and air-traffic controllers (53%, 50% and 36%). Effects of exposure to vibration, body posture and working load have not contributed significantly to the occurrence of LBP. LBP has not lead to an important difference in the strength of the back musculature, body mass index and spondylosis, that is, scoliosis. The necessity of further study of LBP and maintaining of specific preventive measures are indicated.

  13. A prescrição médica eletrônica em um hospital universitário: falhas de redação e opiniões de usuários La prescripción médica electrónica en un hospital universitario: fallas en la redacción y opinión de los usuarios Computerized physician order entry in a university hospital: writing failure and users´ opinions

    Silvia Helena de Bortoli Cassiani


    Full Text Available Este estudo analisou as falhas de redação da prescrição médica eletrônica e opiniões dos usuários acerca das suas vantagens e desvantagens. Foram analisadas 1.351 prescrições médicas de um hospital universitário e entrevistados 84 profissionais da área da enfermagem e medicina. Os resultados indicaram que 17,7% das prescrições apresentavam rasuras, em 16,8 % havia medicamentos suspensos, em 28,2% havia informações que podiam deixar os profissionais em dúvida e em 25% havia medicamentos prescritos manualmente. Os profissionais indicaram as seguintes vantagens: facilidade de leitura dos dados e rapidez com que a prescrição é feita e liberada e como desvantagens: repetição de prescrições de dias anteriores sem revisão e informações digitadas de forma incorreta. Conclui-se que apesar de ser uma estratégia importante na redução de erros, é preciso revisão desse sistema e educação dos profissionais na sua utilização.Este estudio tuvo por objetivo identificar las fallas en la redacción de la prescripción médica electrónica y las opiniones de los usuarios sobre sus ventajas y desventajas. Fueron analizadas 1351 prescripciones médicas de un hospital universitario y entrevistados 84 profesionales de las áreas de enfermería y medicina. Los resultados indicaron que el 17,7% de las prescripciones presentaban rasgaduras, en el 16,8% habían medicamentos suspendidos, en el 28,2% habían informaciones que podían dejar a los profesionales en duda y en el 25% habían medicamentos prescriptos manualmente. Los profesionales indicaron algunas ventajas como: facilidad para leer los datos y rapidez con que la prescripción es realizada y liberada, entre otras, y como desventajas: repetición de prescripciones de días anteriores sin revisión e informaciones digitadas incorrectamente. Se concluye que a pesar de ser una estrategia importante para la reducción de errores, es necesario una revisión de ese sistema y educaci

  14. Developmental plasticity in fat patterning of Ache children in response to variation in interbirth intervals: a preliminary test of the roles of external environment and maternal reproductive strategies.

    Baker, Jack; Hurtado, Ana Magdalena; Pearson, Osbjorn M; Hill, Kim R; Jones, Troy; Frey, M Anderson


    A firm link between small size at birth and later more centralized fat patterning has been established in previous research. Relationships between shortened interbirth intervals and small size at birth suggest that maternal energetic prioritization may be an important, but unexplored determinant of offspring fat patterning. Potential adaptive advantages to centralized fat storage (Baker et al., 2008: In: Trevathan W, McKenna J, Smith EO, editors. Evolutionary Medicine and Health: New Perspectives. New York: Oxford) suggest that relationships with interbirth intervals may reflect adaptive responses to variation in patterns of maternal reproductive effort. Kuzawa (2005: Am J Hum Biol 17:5-21; 2008: In: Trevathan W, McKenna J, Smith EO, editors. Evolutionary Medicine and Health: New Perspectives. New York: Oxford) has argued that maternal mediation of the energetic quality of the environment is a necessary component of developmental plasticity models invoking predictive adaptive responses (Gluckman and Hanson 2004: Trends Endocrinol Metab 15:183-187). This study tested the general hypothesis that shortened interbirth intervals would predict more centralized fat patterning in offspring. If long-term maternally mediated signals are important determinants of offspring responses, then we expected to observe a relationship between the average interbirth interval of mothers and offspring adiposity, with no relationship with the preceding interval. Such a finding would suggest that maternal, endogenous resource allocation decisions are related to offspring physiology in a manner consistent with Kuzawa's description. We observed exactly such a relationship among the Ache of Paraguay, suggesting that maternally mediated in utero signals of postnatal environments may be important determinants of later physiology. The implications of these findings are reviewed in light of life history and developmental plasticity theories and ourability to generalize the results to other

  15. Uridine stimulate laxative effect in the loperamide-induced constipation of SD rats through regulation of the mAChRs signaling pathway and mucin secretion.

    Kim, Ji Eun; Go, Jun; Sung, Ji Eun; Lee, Hyun Ah; Yun, Woo Bin; Hong, Jin Tae; Hwang, Dae Youn


    Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation. The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd. The number, weight and water contents of stools were significantly higher in the Lop + Urd treated group than the Lop + Vehicle treated group, while food intake and water consumption of the same group were maintained at a constant level. The thickness of the mucosa layer, muscle and flat luminal surface, as well as the number of goblet cells, paneth cells and lipid droplets were enhanced in the Lop + Urd treated group. Furthermore, the expression of the muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) at the transcriptional and translational level was recovered in the Lop + Urd treated group, while some markers such as Gα and inositol triphosphate (IP3) in their downstream signaling pathway were completely recovered by Urd treatment. Moreover, the ability for mucin secretion and the expression of membrane water channel (aquaporine 8, AQP8) were increased significantly in the Lop + Urd treated group compared with Lop + Vehicle treated group. Finally, the activity of Urd was confirmed in primary smooth muscle of rat intestine cells (pRISMC) based on Gα expression and IP3 concentration. The results of the present study provide the first strong evidence that Urd can be considered an important candidate for improving chronic constipation induced by Lop treatment in animal models.

  16. Preliminary Geological Map of the Ac-H-9 Occator Quadrangle of Ceres: An Integrated Mapping Study Using Dawn Spacecraft Data

    Buczkowski, D.; Yingst, R. A.; Williams, D. A.; Mest, S. C.; Scully, J. E. C.; Crown, D. A.; Schenk, P.; Jaumann, R.; Roatsch, T.; Preusker, F.; Platz, T.; Nathues, A.; Hoffmann, M.; Schäfer, M.; Marchi, S.; De Sanctis, M. C.; Raymond, C. A.; Russell, C. T.


    We used geologic mapping applied to Dawn spacecraft data as a tool to understand the geologic history of the Ac-H-9 Occator quadrangle of dwarf planet Ceres. This region, located between 22˚S-22˚N and 216-288˚E, is one of two longitudinally distinct regions on Ceres where ESA Herschel space telescope data suggested a release of water vapor [1] and hosts: 1) the 92 km diameter impact crater Occator in the NW of the quadrangle, whose rim is scalloped and whose interior encompasses Hubble "Bright Spot 5"; 2) the 115 km diameter crater Kirnis, a degraded crater that contains a large dome-like feature on the western half of its floor; and 3) regional linear structures, that both cut crater rims (including Occator and Kirnis) and affect crater shapes. Key goals of the ongoing mapping are to 1) determine the source of the bright spots in Occator; 2) determine if the dome-like feature in Kirnis resulted from a mass-wasting or is a product of uplift; and 3) assess the relationships between linear structural features and impact craters, including the effects of surface stress regimes on crater formation and modification. At the time of this writing geologic mapping was performed on Framing Camera (FC) mosaics from late Approach (1.3 km/px) and Survey (415 m/px) orbits, including clear filter and color images and digital terrain models derived from stereo images. In Fall 2015 images from the High Altitude Mapping Orbit (140 m/px) will be used to refine the mapping, followed by Low Altitude Mapping Orbit (35 m/px) images starting in December 2015. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA through the Dawn project, and from the German and Italian Space Agencies. Reference: [1] Küppers, M., et al. (2014). Nature, v. 505, 525-527.

  17. Nitrogen uptake in relation to excess supply and its effects on the lichens Evernia prunastri (L.) Ach and Xanthoria parietina (L.) Th. Fr.

    Gaio-Oliveira, Gisela; Dahlman, Lena; Palmqvist, Kristin; Martins-Loução, Maria Amélia; Máguas, Cristina


    The aim of this study was to compare the physiological responses to increased nitrogen (N) supply between the nitrophytic lichen Xanthoria parietina (L.) Th. Fr. and the acidophytic lichen Evernia prunastri (L.) Ach. The two lichens were exposed to a weekly dosage of 0.05, 0.1, 0.2, 0.6 or 2.4 g N m(-2) for 2 months, administered as NH(4)NO(3) dissolved in artificial rainwater (1 l m(-2)). After the treatments, in vivo chlorophyll a fluorescence was determined to assess vitality; concentrations of total N, ammonium, nitrate and dominant amino acids, including glutamate, glutamine and arginine, were quantified in order to follow changes in N status; and the polyols ribitol, arabitol and mannitol were quantified to follow changes in the lichens' carbon (C) status. The uptake of N was quantified by labelling the fertiliser with (15)N in the ammonium position; chlorophyll a was used as an indirect marker for algal activity, and ergosterol as an indirect marker of fungal activity. Nitrogen uptake was higher in E. prunastri than in X. parietina, although the latter species may have used the mannitol reserves to obtain C skeletons and energy for N assimilation. Chlorophyll a and ergosterol concentrations remained unaltered in X. parietina irrespective of N dosage while ergosterol decreased with increasing N uptake in E. prunastri. The latter species had accumulated a large pool of ammonium at the highest N dosage, whilst in X. parietina a significant nitrate pool was instead observed. Taken together, these short-term responses to high N supply observed in the two lichens, and the differences between them, can partly explain the higher tolerance of X. parietina towards increased atmospheric N levels.

  18. Nicotine Induces the Production of IL-1ß and IL-8 via the a7 nAChR/NF-κB Pathway in Human Periodontal Ligament Cells: an in Vitro Study

    Lizheng Wu


    Full Text Available Background/Aims: Tobacco smoking is a major risk factor for the occurrence and progression of periodontitis. We previously demonstrated that nicotine could induce the expression of a7 nicotinic acetylcholine receptors (a7 nAChR in human and rat periodontal tissues. To further examine the signal pathways mediated by a7 nAChR in periodontal ligament (PDL cells, we investigated whether nicotine affects interleukin-1ß (IL-1ß and interleukin-8 (IL-8 via the a7 nAChR/NF-κB pathway in human PDL cells. Methods: Human PDL cells were pre-incubated with alpha-bungarotoxin (a-BTX or pyrrolidine dithiocarbamate (PDTC, then cultured with nicotine. Then, we used western blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme-linked immunoassay to assess expression of the NF-κB p65 subunit, NF-κB activity and production of IL-1ß and IL-8 in human PDL cells. Results: Compared with the control group, nicotine could significantly induce production of IL-1ß and IL-8 in human PDL cells and cause the similar effects on the expression of the NF-κB p65 subunit and NF-κB activity. Conclusion: This study demonstrates that nicotine could induce production of IL-1ß and IL-8 via the a7 nAChR/NF-κB pathway in human PDL cells, providing data for a better understanding of the relationships among smoking, nicotine, and periodontitis.

  19. Nicotine induces the production of IL-1β and IL-8 via the α7 nAChR/NF-κB pathway in human periodontal ligament cells: an in vitro study.

    Wu, Lizheng; Zhou, Yongchuan; Zhou, Zhifei; Liu, Yingfeng; Bai, Yudi; Xing, Xianghui; Wang, Xiaojing


    Tobacco smoking is a major risk factor for the occurrence and progression of periodontitis. We previously demonstrated that nicotine could induce the expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in human and rat periodontal tissues. To further examine the signal pathways mediated by α7 nAChR in periodontal ligament (PDL) cells, we investigated whether nicotine affects interleukin-1β (IL-1β) and interleukin-8 (IL-8) via the α7 nAChR/NF-κB pathway in human PDL cells. Human PDL cells were pre-incubated with alpha-bungarotoxin (α-BTX) or pyrrolidine dithiocarbamate (PDTC), then cultured with nicotine. Then, we used western blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme-linked immunoassay to assess expression of the NF-κB p65 subunit, NF-κB activity and production of IL-1β and IL-8 in human PDL cells. Compared with the control group, nicotine could significantly induce production of IL-1β and IL-8 in human PDL cells and cause the similar effects on the expression of the NF-κB p65 subunit and NF-κB activity. This study demonstrates that nicotine could induce production of IL-1β and IL-8 via the α7 nAChR/NF-κB pathway in human PDL cells, providing data for a better understanding of the relationships among smoking, nicotine, and periodontitis. © 2014 S. Karger AG, Basel.

  20. 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


    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...

  1. Tela zuo qin in treatment of chronic prostatitis/chronic pelvis ache syndrame%特拉唑嗪治疗慢性前列腺炎/慢性骨盆疼痛综合征疗效观察



    Objective The discussion teffective treatment of chronic prostatitis/chronie pelvis ache syndrome.Methods Tela Zuo qin,in combination with traditional Chinese medicine,was used for treatment of 126 patients with chronic prostatitis/chronic pelvis ache syndrome.Results In 126 patients 82(65%)were cured,30(23.8%)alleviated,14(11.2%)invalid,with total effective rate being 88.8%.Conclusion Tela ZUO qin in combination with traditional Chinese medicine is effective in the treatment of chronic prostatitis/chronic pelvis ache syndrome.%目的 探讨治疗慢性前列腺炎/慢性骨盆疼痛综合征的有效治疗方法.方法 采用特拉唑嗪,辅助用药为活血化瘀中药组方治疗慢性前列腺炎/慢性骨盆疼痛综合征126例.结果 126例中治愈82例(65%),好转30例(23.8%),无效14例(11.2%),总有效率为88.8%.结论 特拉唑嗪配合中药治疗慢性前列腺炎/慢性骨盆疼痛综合征临床效果显著.

  2. 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

    Leonardo Pisani


    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.

  3. 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.

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


    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.

  4. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

    Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela


    3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Tribological properties of amorphous hydrogenated (a-C:H) and hydrogen-free tetrahedral (ta-C) diamond-like carbon coatings under jatropha biodegradable lubricating oil at different temperatures

    Mobarak, H.M., E-mail:; Masjuki, H.H.; Mohamad, E. Niza, E-mail:; Kalam, M.A.; Rashedul, H.K.; Rashed, M.M.; Habibullah, M.


    Highlights: • We tested a-C:H and ta-C DLC coatings as a function of temperature. • Jatropha oil contains large amounts of polar components that enhanced the lubricity of coatings. • CoF decreases with increasing temperature for both contacts. • Wear rate increases with increasing temperature in a-C:H and decreases in ta-C DLC. • At high temperature, ta-C coatings confer more protection than a-C:H coatings. - Abstract: The application of diamond-like carbon (DLC) coatings on automotive components is emerging as a favorable strategy to address the recent challenges in the industry. DLC coatings can effectively lower the coefficient of friction (CoF) and wear rate of engine components, thereby improving their fuel efficiency and durability. The lubrication of ferrous materials can be enhanced by a large amount of unsaturated and polar components of oils. Therefore, the interaction between nonferrous coatings (e.g., DLC) and vegetable oil should be investigated. A ball-on-plate tribotester was used to run the experiments. Stainless steel plates coated with amorphous hydrogenated (a-C:H) DLC and hydrogen-free tetrahedral (ta-C) DLC that slide against 440C stainless steel ball were used to create a ball-on-plate tribotester. The wear track was investigated through scanning electron microscopy. Energy dispersive and X-ray photoelectron spectroscopies were used to analyze the tribofilm inside the wear track. Raman analysis was performed to investigate the structural changes in the coatings. At high temperatures, the CoF in both coatings decreased. The wear rate, however, increased in the a-C:H but decreased in the ta-C DLC-coated plates. The CoF and the wear rate (coated layer and counter surface) were primarily influenced by the graphitization of the coating. Tribochemical films, such as polyphosphate glass, were formed in ta-C and acted as protective layers. Therefore, the wear rate of the ta-C DLC was lower than that of the-C:H DLC.

  6. Keele Aches and Pains Study protocol: validity, acceptability, and feasibility of the Keele STarT MSK tool for subgrouping musculoskeletal patients in primary care

    Campbell P


    Full Text Available Paul Campbell,1 Jonathan C Hill,1 Joanne Protheroe,1 Ebenezer K Afolabi,1 Martyn Lewis,1 Ruth Beardmore,1 Elaine M Hay,1 Christian D Mallen,1 Bernadette Bartlam,1 Benjamin Saunders,1 Danielle A van der Windt,1 Sue Jowett,2 Nadine E Foster,1 Kate M Dunn1 1Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Keele, 2Health Economics Unit, University of Birmingham, Birmingham, UK Abstract: Musculoskeletal conditions represent a considerable burden worldwide, and are predominantly managed in primary care. Evidence suggests that many musculoskeletal conditions share similar prognostic factors. Systematically assessing patient’s prognosis and matching treatments based on prognostic subgroups (stratified care has been shown to be both clinically effective and cost-effective. This study (Keele Aches and Pains Study aims to refine and examine the validity of a brief questionnaire (Keele STarT MSK tool designed to enable risk stratification of primary care patients with the five most common musculoskeletal pain presentations. We also describe the subgroups of patients, and explore the acceptability and feasibility of using the tool and how the tool is best implemented in clinical practice. The study design is mixed methods: a prospective, quantitative observational cohort study with a linked qualitative focus group and interview study. Patients who have consulted their GP or health care practitioner about a relevant musculoskeletal condition will be recruited from general practice. Participating patients will complete a baseline questionnaire (shortly after consultation, plus questionnaires 2 and 6 months later. A subsample of patients, along with participating GPs and health care practitioners, will be invited to take part in qualitative focus groups and interviews. The Keele STarT MSK tool will be refined based on face, discriminant, construct, and predictive validity at baseline and 2

  7. Przyczynek do obrazu szlachty Inflant Polskich w łotewskich źródłach i opracowaniach historycznych początku XX w.

    Beata Biesiadowska-Magdziarz


    Full Text Available A contribution to the image of Polish Livonia nobility in the Latvian historical sources and studies of the early Twentieth Century Polish literature devoted to the role of the Poles in shaping Latvian culture presents unanimity as far as the positive role and results of this influence are concerned. However diametrically opposite Latvian perspective particularly clear in the first years of the existence of independent Latvia needs to be highlighted here. Contacts between the Latvians and Poles and their cultures  differed in different parts of Latvia since the beginning of the Polish presence in this country. The period called ‘the Polish times in Latvia’ in Latvian historical sources lasted the longest in Latgale (1561-1772, i.e. in the so called Polish Livonia. The Polish influence on Latvian folk culture was the strongest there. This period, especially the scale of the influence of Polish culture on Latvian native culture as well as general development of this region, was strongly criticized by numerous Latvian historians. The interest of the Polish noblemen in developing Latgale was subjected to criticism, too. Considering these lands as their own the Poles were not interested in propagating national ideas among  local village people who, according to the Polish nobles, were to succumb to complete polonisation. Great influence of the Polish nobility on culture, economy and creating the national identity of the Latgalian Latvians, the policy of the Polish clergy and polonisation of the local people resulted in a negative opinion of the Polish influence in the Latvian lands. The study is an attempt to outline the issue which Polish researchers have not paid attention to so far. Nevertheless, regarding rich material it needs detailed research on a large scale.   Przyczynek do obrazu szlachty Inflant Polskich w łotewskich źródłach i opracowaniach historycznych początku XX w. W literaturze polskiej poświęconej roli Polaków w kszta

  8. α7nAChR的激活通过抑制TNF-α表达促进糖尿病小鼠伤口愈合%Activation of a7nAChR promotes wound healing in diabetic mice by suppressing TNF-a expression

    范琰琰; 叶光华; 林刻智; 董缪武; 冯相平; 韩军鸽; 李兴彪; 喻林升


    AIM:To explore the role of α7 nicotinic acetylcholine receptor (α7nAChR)-specific agonist PNU-282987 in promoting wound healing in diabetic mice by suppressing the expression of tumor necrosis factor α (TNF-α).METHODS:A model of incised wound was established in diabetic mice or normoglycaemic mice (control).Skin samples were taken on 1 d,3 d,5 d,10 d,14 d and 21 d post-injury (5 mice in each posttraumatic interval).The numbers of macrophages and fibroblasts,the expression of TNF-α and the deposition of collagen were detected by the methods of immunohistochemistry,Western blotting and Masson staining,respectively.After incised wound was performed in the diabetic mice,PNU-282987 was applied by intraperitoneal injection at suitable posttraumatic interval.The above indexes were investigated again.RESULTS:Compared with control group,the diabetic mice presented delayed wound healing.In diabetic mice,the infiltration of macrophages and the expression of TNF-α were significantly reduced in the early phase during wound healing,while they were significantly increased from 5 d post-injury.Besides,from 5 d to 21 d post-injury,the wounds in diabetic mice showed decreased number of fibroblasts and deposition of collagen.From 5 d post-injury,PNU282987 was applied to diabetic mice,which significantly down-regulated the expression of TNF-α,and increased the number of fibroblasts and the content of collagen in the wounds,eventually promoted wound healing.CONCLUSION:Inflammatory reactions delay wound healing in diabetic mice.Activation of α7nAChR promotes wound healing in diabetic mice by suppressing the expression of TNF-α.%目的:观察糖尿病小鼠伤口愈合期间巨噬细胞浸润及肿瘤坏死因子α(TNF-α)表达特征,探讨α7烟碱型乙酰胆碱受体(α7nAChR)特异性激动剂PNU-282987是否可通过抑制TNF-α表达促进糖尿病小鼠伤口的愈合.方法:(1)制作糖尿病小鼠切创模型(糖尿病组),正常小鼠在相同部位制作相同大小

  9. Role of up-regulated expression of α7nAChR in skeletal muscle in decrease in sensitivity to vecuronium in mice%骨骼肌α7nAChR表达上调在小鼠维库溴铵敏感性降低中的作用

    刘力; 刘雪茹; 白毅平; 伍佳丽; 莫丽群; 吴刚明; 周军; 王晓斌


    目的 评价骨骼肌α7烟碱型乙酰胆碱受体(α7nAChR)表达上调在小鼠维库溴铵敏感性降低中的作用.方法 健康雄性野生型C57BL/6J小鼠18只,10~ 12周龄,体重22~ 30 g,采用随机数字表法分为3组(n=6):对照组(C组)、假手术组(S组)和关节制动组(Ⅰ组).健康雄性Chrna7LM1Bay/J敲除小鼠18只,10~ 12周龄,体重22~ 30 g,采用随机数字表法分为3组(n=6):对照组(α7(+)C组)、假手术组(α7(+)-S组)和关节制动组(α7(+)Ⅰ组).Ⅰ组和α7(+)Ⅰ组采用外塑铸件固定法制备小鼠关节制动模型.分别于建模前和建模后14 d时记录体重.建模后14 d时解除铸件,取固定侧和对侧腓肠肌,计算固定侧与对侧腓肠肌湿重比值和干重比值.建模后14 d时,以0.1 Hz的频率给予坐骨神经单次超强刺激,采用累积剂量法静脉注射维库溴铵,初始剂量为0.1 mg/kg,以0.05mg/kg递增,最大剂量为0.8 mg/kg,计算维库溴铵最大肌颤搐抑制率,并拟合量效关系曲线,计算半数有效抑制浓度(IC50)及其50%可信区间和希尔系数.结果与C组和S组比较,Ⅰ组造模后14 d时体重减轻,腓肠肌湿重比值和干重比值降低,IC50升高,希尔系数降低(P<0.05);与α7(+)C组和α7(+)S组比较,α7(+)Ⅰ组造模后14d时体重减轻,腓肠肌湿重比值和干重比值降低,IC50和希尔系数升高(P<0.05).与Ⅰ组比较,α7(+)-Ⅰ组IC50降低,希尔系数升高(P<0.05);C组和S组间、α7(+)C组和α7(7+)S组间上述各指标比较差异无统计学意义(P>0.05).结论 骨骼肌α7nAchR表达上调参与了维库溴铵敏感性的降低.%Objective To evaluate the role of up-regulated expression of α7 nicotinic acetylcholine receptor (α7nAChR) in the skeletal muscle in the decrease in sensitivity to vecuronium in mice.Methods Eighteen healthy male wild-type C57BL/6J mice,aged 10-12 weeks,weighing 22-30 g,were randomly divided into 3 groups (n=6 each) using a random number table:control group (group

  10. Transcriptional Changes in nAChRs, Interactive Proteins and P450s in Locusta migratoria manilensis (Orthoptera: Acrididae) CNS in Response to High and Low Oral Doses of Imidacloprid.

    Wang, Xin; Sun, Huahua; Zhang, Yixi; Liu, Chuanjun; Liu, Zewen


    The insect central nervous system (CNS) is the target for many insecticides, and changes in transcript levels could be expected after insecticide applications. In this study, differentially expressed genes in the locust (Locusta migratoria manilensis) CNS in response to imidacloprid treatments at low dose (LD, 10% mortality) and high dose (HD, 80% mortality) were identified. Two nicotine acetylcholine receptor (nAChR) subunits genes and 18 interacting protein genes were regulated at LD, and only one nAChR subunit gene and 11 interacting proteins were regulated at HD. Among the 110 annotated P450 unigenes, 43 unigenes were regulated at LD and 34 unigenes were regulated at HD. Most of the differentially expressed P450 unigenes were mapped to CYP4, in which most unigenes were upregulated at LD, but downregulated at HD. Totally, the numbers and regulation levels of the regulated genes were more at LD than that at HD. Seventeen unigenes were selected to test their expression changes following insecticide treatments by qRT-PCR, in which the changes in more than half of the selected genes were verified. The results revealed the variation in the response of locusts to different insecticide pressure, such as different doses.

  11. Słownictwo kulinarne w chorwackich przysłowiach, porzekadłach, frazeologizmach, przyśpiewkach, formach żargonalnych i ludowych

    Adrianna Słabińska


    Full Text Available Culinary lexis in Croatian proverbs, sayings, idioms, songs, and jargon and dialectal forms Dishes and food products – the way they are made, their complexity, taste and appearance – are all part of culture and tradition that are created by people feasting at the table. While discussing various everyday issues, they also talk about food – they praise it, complain about it and criticize it. Eating meals with friends and family both in everyday situations and on special occasions creates a special mood. It creates an occasion for confessions, advice, jokes, memories and reflections about life. Various sayings and proverbs, which enrich the culture of a given country or region are brought to life on these occasions. Croatia is not an exception in this regard. Many proverbs and sayings connected with local culinary traditions exist in Croatian. Some of them are known widely throughout the country, others only in certain territories. Numerous proverbs are known throughout Croatia, albeit with a slightly changed imagery. The proverbs presented in my article are found in a dictionary by Josip Kekez, a renowned Croatian paremiologist. It is worth noting that they comprise selected material, which does not cover information present in internet dictionaries. Further in the paper I describe regional proverbs and songs, which are an important element presenting the diversity of Croatian dialects. Each Croatian phrase is accompanied by my Polish translation, which clarifies its meaning. Additionally, I quote other language variants like jargonisms and foreign lexis in culinary vocabulary with a view to present the extraordinary abundance and diversity of Croatian culinary lexis.   Słownictwo kulinarne w chorwackich przysłowiach, porzekadłach, frazeologizmach, przyśpiewkach, formach żargonalnych i ludowych Potrawy i artykuły spożywcze, sposób ich sporządzania, złożoność, smak i wygląd są częścią kultury i tradycji, którą tworz

  12. Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

    Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi


    Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9% NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

  13. 豚鼠Ⅱ型前庭毛细胞乙酰胆碱敏感性大电导钙依赖性钾通道与L型钙通道共存%Co-location of Ach-sensitive BK channels and L-type calcium channels in type Ⅱ vestibular hair cells of guinea pig

    郭长凯; 李冠乔; 孔维佳; 张松; 吴婷婷; 李家荔; 李擎天


    Objective To explore the mechanisms of the influx of calcium ions during the activation of Ach-sensitive BK channel(big conductance,calcium-dependent potassium channel)in type Ⅱ vestibular hair cells of guinea pigs. Methods Type Ⅱ vestibular hair cells were isolated by collagenase type IA.Under the whole-cell patch mode,the sensitivity of Ach-sensitive BK current to the calcium channels blockers was investigated,the pharmacological property of L-type calcium channel activator-sensitive current and Ach-sensitive BK current was compared. Results Following application of Ach, type Ⅱ vestibular hair cells displayed a sustained outward potassium current,with a reversal potential of(-70.5±10.6)mV(-x±s,n=10). At the holding potential of -50 mV, the current amplitude of Ach-sensitive potassium current activated by 100 μmol/L Ach was(267±106) pA(n=11). Ach-sensitive potassium current was potently sensitive to the BK current blocker, IBTX(iberiotoxin, 200 nmol/L). Apamin,the well-known small conductance, calcium-dependent potassium current blocker, failed to inhibit the amplitude of Ach-sensitive potassium current at a dose of 1 μmol/L. Ach-sensitive BK current was sensitive to NiCl2 and potently inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with a half inhibitionmaximal response of(135.5±18.5)μmol/L(n=7) and (23.4±2.6) μmol/L(n=7). The L-type calcium channel activator,(-)-Bay-K 8644(10 μmol/L),mimicked the role of Ach and activated the IBTX-sensitive outward current. Conclusion Ach-sensitive BK and L-type calcium channels are co-located in type Ⅱ vestibular hair cells of guinea pigs.%目的 研究豚鼠Ⅱ型前庭毛细胞乙酰胆碱(acetylcholine,ACh)敏感性大电导钙依赖性钾通道(big conductance,calcium-dependent potassium channel,BK)激活过程中的钙离子内流机制.方法 健康杂色豚鼠52只,断头后取出前庭终器,经胶原酶IA消化后获取Ⅱ型前庭毛细胞.采用全细胞膜片钳技术

  14. Is Patch It® better than placebo in alleviating swelling and ache in the lower legs and feet? A randomized, placebo-controlled, double blind, crossover, sequential trial

    Shakeel A


    Full Text Available Aliya Shakeel1, Hoong Keong Hui2, Chetan S Patil3, Manojkumar V Chaudhari4, Yogesh D Kadam5, Shrikant V Pensalwar6, Suhas G Erande7, Rajesh M Kewalramani81Vedic Lifesciences Pvt Ltd, Mumbai, Maharashtra, India; 2Nutriworks Limited, Kowloon, Hong Kong; 3Muktai Hospital, Nasik, 4Bhagirathi Medical Foundation, 5Poona Diabetes Center, 6Balaji Clinic, Mumbai, 7Akshay Hospital, Pune, 8Shanti Niketan, Kandar Pada, Dahisar, Mumbai, Maharashtra, IndiaBackground: Existing therapeutic measures for swelling, aching and discomfort in the lower limbs, which include compression stockings and leg elevation, are difficult to use and inconvenient. Patch It®, a proprietary herbomineral patch is an easy-to-use alternative therapy. This trial was conducted to compare it's efficacy against that of a placebo in swollen and aching lower legs and feet.Methods: This randomized, placebo-controlled, double blind, crossover, sequential trial was conducted in the private clinics of physicians. A total of 100 patients (24 men and 76 women, aged 25 to 60 years, with recurring swelling in the feet and (optionally up to two more related complaints, having an average visual analog score (VAS of at least 60 (scale 0–100 for each complaint were recruited into the study. Patches (active or placebo were applied to both soles overnight for 8 weeks: 4 consecutive weeks each with active or placebo in randomized sequence. Outcome measures included the average VAS score (baseline to week 4, and week 5 to week 8, preference for either patch (difference of >5 mm in average VAS score reduction, ankle figure-of-eight measures, investigator's global assessment (good, fair, poor, patient's willingness to continue using the patch after the trial (yes, no, and adverse events.Results: Out of 100 patients, 86 completed the trial, while ten were excluded for noncompliance, three withdrew, and one was lost to follow-up. The active placebo boundary of the sequential chart was crossed when 82

  15. Upravljanje frekvencijom i radnom snagom mikro hidroelektrana kliznim režimom rada i redukcijom reda modela sustava

    Qian, Dianwei; Tong, Shiwen; Liu, Xiangjie


    Mikro hidroelektrane smatraju se jednim od glavnih obnovljivih izvora energije. Ovakve elektrane su poglavito zanimljive pošto izbjegavaju dileme vezane za iseljavanje ljudi i utjecaj na okoliš. Međutim, njihov učinak na indeks frekvencije energetskih sustava može biti negativan zbog naglih manjih promijena u opterećenju i nesigurnosti parametara. Kako bi se unaprijedila učinkovitost, javlja se problem regulacije frekvencije i radne snage. Projektiranje regulatora po varijablama stanja sustav...

  16. α4β2亚型烟碱受体激动抑制SH-EP1-α4β2 nAChR-hAPP695细胞BACE1基因启动子活性

    聂惠贞; 李佐青; 赵文娟; 郭凌晨; 殷明


    目的:为了在构建的共表达α4β2烟碱亚型受体(nAChR)基因和淀粉样蛋白前体蛋白(APP695)基因的SH-EP1-α4β2 nAChR—hAPP695细胞模型进行高通量药物筛选,探索用基因启动子活性分析作为在此细胞模型进行亚型特异性药物筛选的简捷节省的方法。方法:用荧光定量PCR的方法,探测在SH-EP1-α4β2 nAChR-hAPP695细胞模型α4β2 nAChR激动对BACE1和PSEN1 mRNA水平的影响;

  17. 抚触和非营养性吸吮对新生儿足跟采血时疼痛程度的影响研究%The observation of caresses touches and the non-trophism suction alleviate the ache degree when sampling the blood to the newborn heel

    张伟青; 黄凌雁; 张舒梅; 邓彩英


    Objective:The observation of caresses touches and the non - trophism suction picks when sampling the blood to the newborn heel,what influence to the heart rate and the ache degree, the exploration alleviates the newborn ache effectively the method.Methods: 150 example in hospital newborn were randomly divided into 3 groups: The control group,non -trophism suction group and touches group, each group of 50 examples.To observe the heel picks when the blood each group of heart rate change, and using the newborn ache meter ( Neonatal Infant Pain Scale, NIPS ) carries on ache degree grading.Results : When finally the heel picks the blood, each group of newborn's heart rate obviously speeds up, compares with the control group, the non - trophism suction and caresses touches the intervention measure to be possible to alleviate the heart rate and the grading change which the ache stimulation causes, the difference has the significance ( P <0.01 ).Conclusion: Different intervention method to will alleviate the newborn ache the short - term effect to be different, the non -trophism suction alleviation ache effect will surpass caresses touches the group.%目的:观察抚触和非营养性吸吮对新生儿足跟采血时心率和疼痛程度的影响,探索有效缓解新生儿疼痛的方法.方法:将150例住院新生儿随机分为3组:对照组、应用非营养性吸吮组和抚触组,每组50例,观察足跟采血时各组心率的变化,并应用新生儿疼痛量表进行疼痛程度评分.结果:足跟采血时,各组新生儿的心率均显著加快,与对照组比较,非营养性吸吮和抚触干预措施均可缓解疼痛刺激引起的心率和评分变化,差异有显著性意义(P<0.01).结论:不同的干预方法对缓解新生儿疼痛的近期效果不同,非营养性吸吮缓解疼痛效果优于抚触组.

  18. Inhibitory effect of botulinum toxin type A against exogenous ACh-and substance P-induced contraction of rat lower esophageal sphincter in vitro%A型肉毒毒素抑制外源性乙酰胆碱及P物质引发的大鼠离体食管下括约肌收缩增强

    李超彦; 于海英; 周媛媛; 任亮; 楚宪襄


    Objective To study whether botulinum toxin type A (BTX-A) can inhibit the spontaneous and acetylcholine (ACh)- or substance P (SP)-induced contraction of rat lower esophageal sphincter in vitro, and to discuss the related mechanism. Methods The lower esophagus muscle strips were taken from Sprague-Dawley rats and were randomly divided into control group, BTX-A group, ACh group, ACh+BTX-A group, ACh+Atropine group, SP group, SP+APTL-SP group and SP+BTX-A group. The contractile graph of the muscle strips was recorded by physiological experimental system Biolap-420E. Results BTX-A significantly decreased the spontaneous contractile tension and amplitude in the lower esophageal sphincter(P< 0. 05). ACh significantly enhanced the contractile tension and amplitude in the lower esophageal sphincter (F<0. 01), which could be significantly inhibited by both BTX-A and Atropine (P<0. 01). SP significantly enhanced the contractile tension in the lower esophageal sphincter (P<0. 01), which could be significantly inhibited by both BTX-A and APTL-SP (P<0. 01). Conclusion ACh and SP can enhance the spontaneous contractility of lower esophageal sphincter. BTX-A can inhibit ACh- and SP-induced enhancement of lower esophageal sphincter contraction.%目的 观察A型肉毒毒素(BTX-A)对大鼠食管下括约肌离体肌条自发性收缩及乙酰胆碱(ACh)、P物质(SP)引发的收缩增强是否存在抑制作用,并探讨其作用机制.方法 剪取食管下括约肌制备肌条并随机分为对照组、BTX-A组、ACh组、ACh+ BTX-A组、ACh+阿托品组、SP组、SP-+NK1受体拮抗剂(APTL)-SP组、SP+ BTX-A组,采用Biolap420E生物机能实验系统记录肌条在不同条件下的收缩变化.结果 BTX-A降低食管下括约肌自发性收缩张力及振幅(P<0.05);ACh可增强食管下括约肌收缩张力及振幅(P<0.01),而BTX-A、阿托品均可抑制ACh的增强效应(P<0.01);SP可增强食管下括约肌收缩张力(P<0.01),其增强效应

  19. 强脉冲噪声暴露豚鼠耳蜗传出神经乙酰胆碱酯酶(AChE)活性的定量分析%Quantitative analysis of the acetylcholinesterase activities of cochlear efferent nerve in the guinea pig after the exposure of intensive impulse noise

    孙建和; 李兴启; 胡吟燕


    目的强脉冲噪声暴露后,豚鼠耳蜗听神经复合动作电位(Cochlear action potential,CAP)阀值提高,按不同的阈移分为五组:0~5 dB(6只);10~15 dB(5只);20~25 dB(11只);30~35 dB(7只);55~60dB(5只)以及正常对照组6只豚鼠.方法用Image-pro plus图象分析软件,人机交互对话方式对各组耳蜗铺片观察耳蜗传出神经末梢处病变的长度、传出神经末梢数目以及乙酰胆碱酯酶(AChE)活性(以灰度表示)进行测量.结果不同阈移组间耳蜗病变长度差异均有显著性或极显著性;各实验组耳蜗传出神经末梢计数随阈移增大而减少,与对照组相比差异均有显著性;AChE灰度值变化多集中在第二圈,第二圈传出神经末梢个数与该圈AChE活性呈正相关(r=+0.75);第二圈AChE灰度值变化与CAP阈移相关,即CAP阈移愈大,AChE灰度值愈大(活性降低),反之亦然.结论生理的变化与形态学计量的变化是相一致的.

  20. Discovery of highly potent and selective α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists containing an isoxazolylpyridine ether scaffold that demonstrate antidepressant-like activity. Part II.

    Yu, Li-Fang; Eaton, J Brek; Fedolak, Allison; Zhang, Han-Kun; Hanania, Taleen; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P


    In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [(3)H]epibatidine binding studies together with functional assays based on (86)Rb(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.

  1. LWH and ACH Helmet Hardware Study


    testing included dimensional measurements, Rockwell hardness and Vicker’s microhardness measurements, metallographic examination of the grain... microhardness measurements (ASTM E384 Standard Test Method for Microindentation Hardness of Materials) were made on the exterior surfaces of screws...hardware as reference values. However, we do not recommend use of surface Vicker’s microhardness testing for characterizing the nuts, because, as

  2. LWH and ACH Helmet Hardware Study


    hardness and Vicker’s microhardness measurements, metallographic examination of the grain microstructure, basic chemical composition , tensile...examination and dimensional measurements; intermediate property screening tests are surface hardness , grain microstructure examination, cross...upon simple measures such as hardness , tensile strength, composition , or grain structure. However, there tends to be enough of a correlation that if

  3. Escherichia coli ehl1 Gene-Positive Serotype O18ac:H31 Associated with an Outbreak of Diarrhea in a Neonatal Nursery in Neuquén City, Argentina

    Chinen, Isabel; Rivas, Marta; Soriano, Viviana; Miliwebsky, Elizabeth; Fernández Galvez, Gabriel; Chillemi, Germán; Baschkier, Ariela; Wang, Gehua; Caldeira, Richard; Woodward, David L.; Rodgers, Frank G.


    Between 9 October and 12 November 1996, an outbreak of bloody diarrhea occurred in the neonatal nursery ward of the Policlínico Neuquén, in Neuquén, a city in the southwestern region of Argentina. Seven patients of the intermediate care unit were affected. Isolates of Escherichia coli O18ac:H31 that were non-lactose and -sorbitol fermenting were recovered from outbreak cases. Although the strains were negative for a number of virulence factors typically found in diarrheagenic groups of E. coli, all isolates from the present neonatal outbreak possessed the enterohemolysin gene, ehl1. All isolates showed resistance to the antibiotics ampicillin and chloramphenicol. These isolates showed a low adherence property in HeLa cells without any recognizable pattern. In order to evaluate the outbreak dissemination in the neonatology ward, a prevalence study was conducted on 13 November. Stool specimens were obtained from 16 neonates hospitalized in the sector and from 33 medical staff members. E. coli isolates with identical biochemical characteristics of the outbreak strain were recovered from 11 of 16 inpatients and from 4 of 33 staff members during the prevalence study. A total of 15 E. coli strains recovered both from the outbreak and the prevalence study were processed by random amplified polymorphic DNA (RAPD)-PCR and pulsed-field gel electrophoresis (PFGE). By RAPD-PCR 14 of 15 strains showed patterns with 85 to 100% similarity, and by PFGE these strains were identical, each showing a unique pattern with 15 bands between 40 and 400 kb. One strain isolated from a nurse during the prevalence study presented a pattern not related to the others, and this was characterized as E. coli O81:HNM resistant to ampicillin only and negative for all the virulence factors studied. This outbreak occurred despite strict regulations in place to prevent cross-infection in the hospital. Postoutbreak prevalence studies were performed weekly thereafter without detecting new cases. PMID

  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.

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


    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. 模拟船舱环境对红细胞乙酰胆碱酯酶活性和抗运动病能力变化的影响%Effects on the RBC-AchE and anti-seasickness capacity in cabin environment

    张瑞萍; 孙学川; 张波



  6. A型肉毒素抑制电场刺激及乙酰胆碱引发的大鼠胃体胃底离体平滑肌收缩%Inhibitory Effect of Botulinum Toxin Type A on Gastric Body and Gastric Fundus Smooth Muscle Contractility Induced by EFS and ACh-induced in Rats in vitro

    周媛媛; 李超彦; 侯一平


    Objective: To observe the effect of botulinum toxin type A ( BTX-A) , electrical field stimulation (EFS) and acetylcholine ( ACh) on spontaneous contractility in gastric body and gastric fundus smooth muscle. Method; Muscle strips in gastric body and gastric fundus were prepared, and subdivided randomly into control group, EFS group, BTX-A (10 U -mL-1) group, BTX-A (10 U -mL-1) + EFS group, ACh (100 Ixmol-L-1) group, ACh (100 (xmol-L-1) + BTX-A (10 U -mL-1) group, Ach (100 μmol - L-1) + Atropine (1 (μ.mol -L-1) group. The data were recorded by physiological experimental system of BL-420. Result: EFS enhanced the tension ( P < 0. 05 ) and amplitude ( P < 0. 01 ) in gastric body contractility, and similar results was observed in gastric fundus contractility; BTX-A decreased spontaneous contractile tension and amplitude (P <0. 01) in gastric body and tension ( P < 0. 05 ) in gastric fundus; BTX-A inhibited EFS-induced smooth muscle contractility including tension and amplitude ( P < 0. 01 ) in gastric body, tension (P < 0. 01 ) and amplitude ( P < 0. 05 ) in gastric fundus, BTX-A inhibited ACh-induced smooth muscle contractility including tension and amplitude (P <0. 01) in gastric body and gastric fundus. Conclusion; EFS enhances smooth muscle spontaneous contractility in gastric body and gastric fundus; BTX-A inhibits gastric body and gastric fundus smooth muscle spontaneous contractility; BTX-A inhibits EFS and ACh-induced smooth muscle contractility in gastric body and gastric fundus.%目的:观察大鼠胃体、胃底离体平滑肌条自发性收缩及电场刺激( EFS)、乙酰胆碱(ACh)和A型肉毒素( BTX-A)对肌条收缩的影响,并探讨其机制.方法:取大鼠胃体胃底平滑肌制备肌条,肌条随机分为对照组、EFS组、BTX-A(10 U·mL-1)组、BTX-A(10 U·mL-1)+ EFS组、ACh(100 μmol· L-1)组、ACh(100 μmol·L-1)+BTX-A(10 U·mL-1)组、ACh(100 μmol· L-1)+阿托品(1 μmol· L-)组,采用Biolap 420E生物机能实验系统记录肌

  7. ACh-evoked membrane hyperpolarization in smooth muscle cells of rat vas deferens in vitro: Involvement of K+ channels and NO%一氧化氮和K+通道参与乙酰胆碱引起的大鼠离体输精管平滑肌细胞超极化

    范平; 李丽; 刘政江; 司军强; 张志琴; 赵磊; 马克涛


    To explore the underlying mechanism of acetylcholine (Ach)-evoked membrane hyperpolarizing response in isolated rat vas deferens smooth muscle cells (SMCs), intracellular microelectrode recording technique and intracellular microelectrophoresis fluorescent staining technique were used to study Ach-evoked membrane hyperpolarizing response in SMCs freshly isolated from Wistar rat vas deferens. By using microelectrodes containing fluorescent dye 0.1% propidium iodide (PI), 37 and 17 cells were identified as SMCs in outer longitudinal and inner circular muscular layers, respectively. The resting membrane potentials of SMCs were (–53.56±3.88) mV and (–51.62±4.27) mV, respectively. The membrane input resistances were (2 245.60±372.50) MΩ and (2 101.50±513.50) MΩ , respectively. Ach evoked membrane hyperpolarizing response in a concentration-dependent manner with an of 36 μmol/L. This action of Ach was abolished by both a non-sepcific muscarinic (M) receptor antagonist atropine (1 μmol/L) and a selective M 3 receptor antagonist diphenylacetoxy-N-methylpiperidine-methiodide (DAMP, 100 nmol/L). Ach-evoked membrane hyperpolarization was also abolished by a nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 300 μmol/L) and suppressed by an ATP-sensitive potassium (K ATP ) channel blocker glipizide (5 μmol/L) and an inward rectifier potassium (K ir ) channel inhibitor bariumion (50 μmol/L). A combination of glipizide and bariumion abolished Ach-evoked membrane hyperpolarizing response. The results suggest that Ach-evoked membrane hyperpolarization in rat vas deferens SMCs is mediated by M 3 receptor followed with activation of K ATP channels, K ir channels, and NO release.%本文旨在探讨大鼠新鲜离体输精管平滑肌细胞中乙酰胆碱(acetylcholine,Ach)引起超极化反应的机制,采用细胞内微电极记录技术和细胞内荧光标记技术研究Ach对大鼠输精管不同走行方向平滑肌细

  8. Detection significance of AchR antibody,Titin antibody and MuSK antibody in myasthenia gravis combined with thymic lesion%重症肌无力合并胸腺病变患者血清乙酰胆碱受体抗体、肌联蛋白抗体和肌肉特异性酪氨酸激酶抗体的检测意义

    刘岚剑; 杨文娟


    目的:探究对重症肌无力合并胸腺病变的患者血清中乙酰胆碱受体(acetylcholine receptors,AchR)抗体、肌联蛋白(Titin)抗体和肌肉特异性酪氨酸激酶(muscle specific tyrosine kinase,MuSK)抗体的检测意义。方法选取我院收治的80例重症肌无力患者,根据是否存在胸腺病变分为胸腺病变组48例和非胸腺病变组32例,另取80例健康个体作为对照组,通过免疫酶联吸附试验对3组成员血清中 AchR 抗体、Titin 抗体和 MuSK 抗体进行检测并比较。结果重症肌无力患者血清 AchR 抗体和 Titin 抗体阳性率(76.3%,52.5%)均明显高于对照组(11.3%,5.0%)(P <0.05);重症肌无力组及对照组患者血清 MuSK 抗体阳性率均为0,但前者血清中 MuSK 抗体水平明显高于后者(P <0.05);AchR,Titin 两种抗体联合检测可明显提高检测重症肌无力的灵敏度;AchR 和 Titin 抗体在胸腺病变组中的阳性率明显高于非胸腺病变组(P <0.05);全身型重症肌无力患者的血清 AchR 抗体和 Titin 抗体阳性率明显高于眼肌型(P <0.05)。结论 AchR 抗体和 Titin 抗体的阳性率与重症肌无力患者的病情相关,病情严重或合并胸腺病变可明显提高两者的阳性率,此外两者联合检测可提高诊断的灵敏度。而 MuSK 抗体在我国重症肌无力患者中的阳性率较低。%ABSTRACT:Objective To explore the significance of AchR antibody,Titin antibody and MuSK antibody in myasthenia gravis patients combined with thymic lesion.Methods A total 80 cases of myasthenia gravis patients treated in our hospital were selected.They were divided into thymic lesion group(n =48)and no-thymic lesion group (n = 32 ).Another 80 cases of healthy individuals were selected as control group.The positive rates of AchR antibody,Titin antibody and MuSK antibody were compared among three groups and different Osserman types. Results The positive rates of AchR antibody and Titin antibody of myasthenia gravis

  9. bFGF对慢性应激小鼠学习记忆及海马Ach含量的影响%Effects of bFGF on Learning-Memory Ability and the Content of Ach in Hippocampus in Chronic Stress Mice

    李春颖; 曲娴


    目的探讨碱性成纤维细胞生长因子(Basic fibroblast growth factor,bFGF)对慢性应激模型小鼠学习记忆的影响及海马内Ach含量的变化.方法利用不确定应激方法建立慢性应激动物模型,共4周;应激第15天开始每日应激前腹腔注射bFGF,持续15 d;应用跳台法和避暗法观察bFGF对慢性应激小鼠学习记忆的作用;碱羟胺比色法检测乙酰胆碱(Ach)含量.结果 bFGF组小鼠学习记忆能力提高,海马Ach含量增高.结论 bFGF通过增加海马内胆碱能功能,改善慢性应激小鼠学习记忆能力.%Objective To investigate effects of basic fibroblast growth factor(bFGF)on the ability of learning and memory,and the content of Ach in hippocampus in chronic stress mice.Method An uncertain stress method was used for four weeks to establish the chronic stress model in mice.bFGF was injected intraperitoneally for 15 days on 15th day of the stress.The step-down test and darkness avoidance test were used to observe the effect of bFGF on learning-memory ability in the chronic stress mice.The change of Ach levels was tested with the hydroxylamine colorimetric assay.Results The results showed that the learning-memory abilities of mice in bFGF group were improved and contents of Ach in hippocampus increased.Conclusion bFGF can improve the learning-memory ability of chronic stress mice through improving the cholinergic function in hippocampus.

  10. Cognitive function and expression of α7 nAChR in the amygdala kindling model of epilepsy%杏仁核电点燃大鼠认知功能及海马α7型神经烟碱胆碱能受体的表达

    苗珍花; 王峰; 刘庆祝; 孙涛


    Objective:To investigate cognitive function and emotional deficits in the amygdala kindling model of epilepsy and the expression of the α7 nicotinic acetylcholine receptors(α7 nAChR)in hippocampus. Methods:The 40 male SD rats were randomly divided into 1-and 2-week control groups (C1 and C2 groups, n=8) and 1-and 2-week kindling groups (K1 and K2 groups, n=12). The kindling group that had been evoked for 5 consecutive stage V seizures were established by the electrical stimulation fully-kindled amygdala seizures. Then emotional deficits were tested by open field test, learning and memory abilities were tested by Morris water maze, and the expression level of α7 nAChR in hippocampus was determined by immu-nohistochemical techniques and Western blotting. Results:In the open-field exploratory maze, compared with the control group, the numbers of grids(Flu, = 24. 77, Pla, = 0. 00, F2lu = 42. 86, P2u,=0. 00) and standing time(F1w, = 56. 18, P1w= 0. 00, F2w, = 42. 25, P2w = 0.00) of K1 and K2 groups were all obviously decreased,while the numbers of feces(F1w, = 10.08, P1w = 0.01, F2w = 31.22, P2w = 0.00) of K1 and K2 groups were increased, and compared with C1 and C2 groups, the difference between the escape latency(F1w=3.139, P1w, = 0.095; F2w = 0.884, P2w = 0.361) and the time in the platform quad-rant(F1w = l.907, P1w = 0.185, F2w = 0.446, P2w=0.513) of K1 and K2 groups were not significant, and the expressions of α7 nAChR of K1 and K2 groups were all increased (E1w = 15. 70, P1w = 0.02, F2w= 24.61, P2w = 0.01). Contusion:Kindling might differentially result in emotional deficits, and at the same time the expression level of α7 nAChR was significant increased in the hippocampus of the rat amygdale electrical kindling epilepsy model. But its learning and memory abilities did not change, which may be correlated to the age of onset, duration and type of seizures, seizure frequency and medication.%目的:本研究旨在探讨杏仁核电点燃大鼠恐惧状况、

  11. α7nAChR agonist postconditioning attenuates rat myocardia ischemia reperfusion injury in vivo%α7烟碱样乙酰胆碱受体激动剂后处理对大鼠在体心肌缺血/再灌注损伤的影响

    熊军; 薛富善; 袁玉静; 王强; 廖旭; 李杉; 王卫利; 张雁鸣; 刘建华


    目的 观察α7烟碱样乙酰胆碱受体(α7 nicotinic acetylcholine receptor,α7nAChR)激动剂后处理对大鼠在体心肌缺血/再灌注损伤(ischemia reperfusion injurv,IRI)的影响.方法 将40只SD大鼠采用计算机产生随机数法平均分为假手术组(S组)、缺血/再灌注组(IR组)、缺血预处理组(IPC组)和α7nAChR激动剂后处理组(PNU组),每组10只.实验中记录缺血期和再灌注初期心律失常,测定冉灌注30 min和180 min时的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)、高迁移率组蛋白1(high mobilitv group box 1 protein,HMGB1)和肌钙蛋白Ⅰ(troponin Ⅰ,TnI)血清浓度,实验结束取心脏,采用伊文思蓝和1%TTC双重染色法测量心肌梗死面积.结果 IR组,IPC组和PNU组的心肌梗死面积值分别为(78.4±16.1)%、(35.3±9.4)%和(60.4±7.0)%,且3组的TnI血清浓度分别为(1.02±0.12)μg/L,(0.25±0.03)μg/L和(0.17±0.04)μg/L与IR组相比,IPC组和PNU组心肌梗死面积(infarct size,IS%)显著减小、TnI血清浓度显著降低,IPC组灌注30min时TNF-α、IL-6血清浓度以及再灌注180 min时TNF-α和HMCB1血清浓度显著降低,PNU组再灌注30 min和180 min时TNF-α、IL-6和再灌注180 min时HMCB1血清浓度显著降低.与IPC组相比,PNU组IS%显著增大,但血清TnI浓度显著降低,冉灌注30 min时TNF-α血清浓度以及再灌注180 min时TNF-α、IL-6和HMCB1血清浓度显著降低,但再灌注30 min时IL-6血清浓度显著升高.结论 在大鼠在体心肌缺血/冉灌注损伤模型,α7nAChR激动剂后处理可通过抑制炎症反应获得心肌保护效应、但其心肌保护效应较缺血预处理弱.%Objective To observe the cardioprotective effects of α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning on myocardial ischemia reperfusion injury (IRI) in rat models in vivo. Methods Forty SD rats were randomly divided into four groups (n=10): sham group( S group), ischemia

  12. α7亚基烟碱能乙酰胆碱受体激动剂后处理减轻大鼠在体心肌缺血/再灌注损伤最佳干预时间的实验研究%The hest interventional time of α7nAChR agonist postconditioning attenuating myocardial ischemia/reperfusion injury in rats

    熊军; 薛富善; 袁玉静; 王强; 廖旭; 李杉; 王卫利; 张雁鸣; 刘建华


    Objective To determine the best interventional time of α7nAChR agonist postconditioning for attenuating myocardial ischemia reperfusion injury in rat in vivo model. Methods Sixty SD rats were randomly divided into six groups(n=10):sham group (S group), ischemia/reperfusion group (I/R group ), α7nAChR agonist postconditioning at onset of reperfusion group( P0group), α7nAChR agonist postconditioning at 30, 60 and 90 min of reperfusion group(P30, P60 and P90 groups). Serum concentrations of TnI, TNF-α and HMGB1 were assayed at 180 min after reperfusion. At the end of experiment, infarction sizes were assessed from excised hearts by Evans blue and triphenyltetrazolium chloride(TTC) staining. Results The infarct sizes(IS%) were (78±16)% in IR group, (60±7)% in P0 group, (49±17)% in P30 group, (54±12)% in P60 group and (64±15)% in P90 group, respectively. Serum concentrations of TnI were ( 1.016±0.121 ), (0.168±0.037), (0.156±0.019), (0.194±0.041) and(0.138±0.029) μg/L in these groups respectively. As compared to the S group, serum concentrations of TNF-α in the I/R and P30 groups were significantly increased,TNF-α in the P0 group was significantly reduced. Serum concentration of HMGB1 was significantly higher in the I/R group than that in the S group, but that of all α7nAChR agonist postconditioning groups was significantly lower. As compared with the I/R group, infarct size and serum concentrations of TnI, TNF-α and HMGB1 in all α7nAChR agonist postconditioning groups were significantly reduced. As compared with the P0group, serum concentrations of TNF-α and HMGB1 in the P30, P60 and P90 groups were significantly increased. As compared with the P90 group, in the P30 group, serum concentrations of TNF-α and HMGB1 were significantly increased and IS% significantly decreased. Conclusion In rat in vivo models of myocardial ischemia reperfusion injury, α7nAChR agonist postconditioning at 30 min of reperfusion could produce the strongest

  13. 一清胶囊对痤疮丙酸杆菌及表皮葡萄球菌的体外抑菌作用研究%Bacteriostatic Action of Yiqing Capsule against Propionibacterium Aches and Staphylococcus Epidermidis in vitro

    蒋献; 何燕; 李利


    OBJECTIVE: To study the bacteriostatic action of Yiqing capsule against propionibacterium acnes and staphyl-ococcus epiderrnidis in vitro. METHODS: Propionibacterium aches and staphylococcus epidermidis were cultured by mi-croplating method and routine plating, and the bacteriostatic action of different concentration of Yiqing capsule and its main components against propionibacterium aches and staphylococcus epidermidis were determined by measuring their MICs. RE-SULTS: The MICs of Yiqing capsule and Scutellaria baicalensis extractum against propionibacterium acnes and staphylococ-cus epiderrnidis were 0.98 mg·mL~(-1) and 1 mg·mL~(-1),respectively, whereas the MICs of Radix et Rhizoma Rhei and Rhizoma Coptidis Scutellaria extractum against propionibacterium acnes and staphylococcus epidermidis were 1.96 mg·mL~(-1) and 1 mg·mL~(-1),respectively. CONCLUSION: Yiqing capsule showed satisfactory bacteriostatic action against the major pathogenic bacteria of acne.%目的:研究一清胶囊对痤疮丙酸杆菌及表皮葡萄球菌的体外抑菌作用.方法:采用微量板、常规平皿法分别对痤疮丙酸杆菌、表皮葡萄球菌进行培养并观察不同浓度一清胶囊及其主要成分的抑菌效果,分别求出其最小抑菌浓度(MIC).结果:一清胶囊对痤疮丙酸杆菌及表皮葡萄球菌的MIC分别为0.98、1 mg·mL~(-1),黄芩浸膏的MIC分别为0.98、1 mg·mL~(-1),而大黄黄连浸膏的MIC分别为1.96、1 mg·mL~(-1).结论:一清胶囊对痤疮主要致病菌有较好的体外抑菌效果.

  14. Effects of ethology,TChE and Ach activities in rat model of Middle cerebral artery occlusion administrated by human um- bilical cord-derived Mesenchymal stem cells%脐带间充质干细胞对脑梗死大鼠行为学及胆碱能的影响

    贾芙蓉; 张贯石; 王辉; 潘洪涛; 何欣; 张东; 丁冬梅


    Objective To observe the effects of intravenous administration of human umbilical cord-derived mesen-chymal stem cells(UC-MSCs)after middle cerebral artery occlusion(MCAO)in adult rats.Methods Adult male SD rats were administrated by MCAO.Functional outcome measurements using Beam walking Test(BWT)were performed at 24 hour of MCAO group and 10 days of UC-MSCs treatment group respectively.TTC staining ,TChE and Ach activity array were also used.Results There was significant neurological function improvement in rats treated with MSC com-paring with that of control groups(P <0.05),and also Ach and TChE activity (P <0.05).Conclusion Intravenous ad-ministration of UC-MSCs promotes the neurological function in rat MCAO model.UC-MSCs play an advantageous function on cholinergic neurotransmitters in the case of lesion.%目的:观察脑梗死大鼠经人脐带间充质干细胞(umbilical cord-derived mesenchymal stem cells,UC-MSCs)治疗后,行为学的恢复情况,2,3,5-氯化三苯基四氮唑(triphenyl tetrazolium chloride,TTC)染色以及胆碱能的变化。方法制备脑梗死大鼠大脑中动脉闭塞(Middle cerebral artery occlusion,MCAO)模型,将 UC-MSCs 注入脑梗死大鼠体内,对大鼠运动功能进行评分,比较 TTC 染色显示的脑梗死区域所占比例,测定脑组织和血浆中乙酰胆碱酯酶(True choline esterase,TChE)活性和乙酰胆碱(Acetylcholine,Ach)浓度。结果与模型组相比,UC-MSCs 组大鼠行为学恢复明显(P <0.05),UC-MSCs 组大鼠脑组织和血浆乙酰胆碱酯酶(TChE)和乙酰胆碱(Ach)活性显著增强(P<0.05)。结论UC-MSCs 经尾静脉移植可促进脑梗死后神经功能恢复,增强大鼠胆碱能系统活性。

  15. Effects of MCT1 Inhibitor p-CMB on Ach Induced Pancreatic Exocrine Secretions in Rats%MCT1抑制剂p-CMB对乙酰胆碱诱导的大鼠胰液分泌的影响



    采用在体试验方法研究单羧酸转运蛋白第1亚型(monocarboxylate transporter 1,MCT1)抑制剂(p-chloromercuribenzene sulfonate,p-CMB)对乙酰胆碱(acetylcholine,Ach)诱导的大鼠胰液分泌的影响.Sprague-Dwley (SD)雄性大鼠,体重180 g~210 g,分6组,每组5只,试验前禁食24 h,自由饮水.动物麻醉后经外科手术后,每隔10 min收集一次胰液,采用Lowry 法测定胰液蛋白量,Bernfeld法测定胰酶.结果对照组(-p-CMB)和实验组(+p-CMB),在注射1、5 、10 ìg/kg的Ach后对胰液分泌量、胰蛋白分泌量以及胰淀粉酶分泌量都呈现增加作用,注射后1 h内达到峰值,之后逐渐降低.然而,试验组的胰液分泌各项指标比对照组的显著减少(P<0.01).表明MCT1抑制剂p-CMB减弱了Ach增加大鼠胰液分泌的作用.

  16. Study on Deposition of a-C:H Film by Reactive DC Magnetron Sputtering and Its Surface Roughness%直流反应磁控溅射制备a-C:H薄膜及其表面粗糙度研究

    张艳茹; 杭凌侠; 郭峰; 宁晓阳


    The -CH3 atoms methane gas was filled to study the preparation and performance of the hydrogen-containing DLC(a-C:H) thin film. At different CH4/Ar flow ratio condition, the a-C:H was deposited on the N type silicon substrate. By means of ellipsometer, the non-contact white light interferometer as well as the laser wave interferometer, the deposition rate and surface roughness were lucubrated. Experiment results show that the deposition rate of the diamond-like carbon thin film is enhanced by the addition of the hydrogen-containing carbon gas and the surface flatness is also improved.%为研究含氢类金刚石(a-C:H)薄膜的制备及性能,充入含-CH3原子团的CH4气体,在不同CH4/Ar流量比条件下于N型硅基底上沉积a-C:H薄膜,并借助椭偏仪、非接触式白光干涉仪及激光波面干涉仪对薄膜的沉积速率及表面粗糙度进行测定.结果表明,含氢碳源气体的加入提高了类金刚石薄膜的沉积速率,改善了表面平整度.

  17. dātu ša šarri. La « loi du roi »dans la Babylonie achéménide et séleucide dātu ša šarri, The “Law of the King” in Achaemenid and Seleucid Babylonia

    Sophie Démare-Lafont


    Full Text Available Cet article examine le champ sémantique de l’expression dātu ša šarri, « loi du roi », formée sur un terme d’origine vieux-perse (data. La dizaine d’occurrences d’époques achéménide et séleucide montre que la « loi du roi »désigne un mode d’élaboration de la norme issu de la pratique judiciaire du souverain, progressivement compilée pour former un corps de règles invoquées dans les contrats. Ce procédé de création de la loi et de fabrication des recueils législatifs rappelle celui du rescrit romain.This article investigates the meaning of the formula dātu ša šarri, “law of the king”, using the akkadian dātu based on the old Persian word dāta. The ten Achaemenid and Seleucid occurrences of this formula suggest a process of creation of legal rules comparable to the Roman rescript: the legal standard dātu ša šarri derives from the judicial practice of the king, whose decisions were progressively compiled in order to create a body of regulations which were invoked in contracts.

  18. A physical model of nicotinic ACh receptor kinetics

    Nurowska, Ewa; Bratiichuk, Mykola; Dworakowska, Beata; Nowak, Roman J.


    We present a new approach to nicotinic receptor kinetics and a new model explaining random variabilities in the duration of open events. The model gives new interpretation on brief and long receptor openings and predicts (for two identical binding sites) the presence of three components in the open time distribution: two brief and a long. We also present the physical model of the receptor block. This picture naturally and universally explains receptor desensitization, the phenomenon of centra...

  19. Pneumococcal Meningitis in an Adolescent with Fever and Foot Ache

    Catarina Dias


    Full Text Available Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement.

  20. Teatro Maya: Rabinal Achí o Danza del Tun

    Patricia Henríquez Puentes


    ... revela una forma de escribir con el cuerpo que articula danza, música y poesía, y representa ese momento en la historia del teatro en que el arte de la representación y rito compartían la misma escena...

  1. Insect nicotinic acetylcholine receptors (nAChRs): Important amino ...



    Dec 29, 2008 ... neonicotinoid insecticides selectivity and resistance. Zewen Liu*, Xiangmei Yao and Yixi Zhang. Key Laboratory of Monitoring and Management of Plant Disease and Insect, ..... residue, should change the electrostatic properties of the .... resistance patterns and possible mechanisms, Pest. Manage. Sci. 59:.

  2. The ReACH Collaborative--improving quality home care.

    Boyce, Patricia Simino; Pace, Karen B; Lauder, Bonnie; Solomon, Debra A


    Research on quality of care has shown that vigorous leadership, clear goals, and compatible incentive systems are critical factors in influencing successful change (Institute of Medicine, 2001). Quality improvement is a complex process, and clinical quality improvement applications are more likely to be effective in organizations that are ready for change and have strong leaders, who are committed to creating and reinforcing a work environment that supports quality goals (Shortell, 1998). Key leadership roles include providing clear and sustained direction, articulating a coherent set of values and incentives to guide group and individual activities, aligning and integrating improvement efforts into organizational priorities, obtaining or freeing up resources to implement improvement activities, and creating a culture of "continuous improvement" that encourages and rewards the pursuit and achievement of shared quality aims (Institute of Medicine, 2001, 70-71). In summary, home health care is a significant and growing sector of the health care system that provides care to millions of vulnerable patients. There seems little doubt that home health agencies want to focus on quality of care issues and provide optimal care to home-based patients. Furthermore, there is a growing awareness of the value for adapting innovative, effective models for improving the culture of home care practice. This awareness stems from the notion that some agencies see quality improvement activities as a way for them to distinguish themselves not only to regulators and customers, but also to meet the cultural and transformational needs to remain viable in a constantly evolving and competitive health care industry.

  3. ACH Double Pull Issues: Designing with Client Constraints

    Suzanne Marie Fortner


    Full Text Available The Customer Service Center of a large Midwestern insurance company requested training to research and prevent double payments from being deducted from their customers’ bank accounts. This issue was costing the customer service center between $9,000 and $13,000 per month and resulted in dissatisfied customers. The instructional designer was assigned to this project and faced challenges such as corporate politics, tight timeframes for development, and lack of content knowledge. This design case describes the project history, the design process, the design challenges, and the resulting design decisions.

  4. The Effects of Repeated Sub-Toxic Sarin Exposure on Behavior, EEG and Blood and Brain AChE Activity


    in rats. Pharmacol Biochem Behav. 1984; 21: 133-136. (13) Deurveilher S, Iroudayanadin SD, Hars B, Breton P and Hennevin E. Chronic, low-level...New York: McGraw-Hill, 1981, pp. 426-441. (16) Ellman GL, Courtney KD, Andres V Jr and Featherstone RM. A new and rapid colorimetric

  5. Practical use of technology for exploring obstacles and soil collapse state around shield machine using underground radar; Chichu reda wo mochiita shirudo ki shuhen no shogaibutsu to dosha hokai jotai tansa gijutsu no jitsuyoka

    Tanimoto, K. [Mitsubishi Heavy Industries Ltd., Tokyo (Japan)


    A report is made on the outline and the used result of a newly developed `underground radar.` The objects for underground exploration in shield tunneling methods are divided broadly into obstacles, state of the peripheral ground, and geological change in the working place. Electromagnetic method is employed for the exploration method of this system which can explore the ground conditions very accurately and in real time although the explorable distance is a little limited. As to antennas, there are two types, i.e. the separate transmitter and receiver antenna and the integrated transceiver antenna. The antennas are mounted at the side of cutter face, at the shield machine fixed side, and at the front of the cutter face. The system configuration varies according to the type of antenna and the displaying location of the explored result. The system introduced in this report consists of a radar antenna, antenna control device, slip ring, measurement control computer, and monitoring computer. A report is made on the condition of an existing buried pipe found accidentally during drilling with a shield machine. 12 figs., 1 tab.

  6. Enzymological differences of AChE and diazinon hepatic metabolism: correlation of in vitro data with the selective toxicity of diazinon to fish species.

    Keizer, J; D'Agostino, G; Nagel, R; Volpe, T; Gnemi, P; Vittozzi, L


    The in vitro hepatic metabolism of diazinon, as well as the sensitivity of the brain acetylcholine esterase, to diazoxon inhibitory action have been studied in order to explain the different toxicity of diazinon to Oncorhynchus mykiss (rainbow trout), Poecilia reticulata (guppy), Brachydanio rerio (zebra fish) and Cyprinus carpio (carp). In spite of a very sensitive acetylcholine esterase the carp is very resistant to diazinon toxicity because of its very low rate of bioactivation and relatively high activity of detoxicating enzymes. The trout is very sensitive towards diazinon in spite of its low activity of bioactivation, because of its lack of detoxicating enzymes and a very sensitive acetylcholine esterase. Diazinon is very toxic for the guppy, because this fish combines a relatively sensitive acetylcholine esterase with a high rate of bioactivation. The zebra fish has the most insensitive acetylcholine esterase, associated with a limited activation rate, thus resulting a rather resistant species. The results obtained indicate that diazinon toxicity differences among the fish species studied can largely be explained in relation to metabolic balances in the liver and with the features of the target enzyme.

  7. Progressing With Passion


    Twenty-two years ago, Fran?ois Vanvi joined Air Canada as an air steward. But to him, air stewarding was just a job, not a career. Two years later, he came to Hong Kong, where his mother was born. A French national, Vanvi was born in Paris and moved to Hong Kong when he was a teenage.

  8. The aching surgeon: a survey of physical discomfort and symptoms following open, laparoscopic, and robotic surgery.

    Plerhoples, Timothy A; Hernandez-Boussard, Tina; Wren, Sherry M


    There is increasing interest in understanding the toll that operating takes on a surgeon's body. The effect of robotic surgery on surgeon discomfort has not been studied. We sought to document the discomfort of robotic surgery compared with open and laparoscopic surgery and to investigate the factors that affect the risk of physical symptoms. Nineteen-thousand eight-hundred and sixty-eight surgeons from all specialties trained in the use of robots were sent a 26-question online survey and 1,407 responded. One-thousand two-hundred and fifteen surgeons who practiced all three approaches were used in the analysis. Eight-hundred and seventy-one surgeons had physical discomfort or symptoms attributable to operating. Of those with symptoms, 55.4% attributed most of the symptoms to laparoscopic surgery, 36.3% to open surgery, and 8.3% to robotic surgery. A higher case load was predictive of increased symptoms for open and laparoscopic surgery, but not for robotic surgery. Robotic surgery was less likely than open or laparoscopic surgery to lead to neck, back, hip, knee, ankle, foot, and shoulder pain and less likely than laparoscopic surgery to lead to elbow and wrist pain. Robotic surgery was more likely than either open or laparoscopic surgery to lead to eye pain, and more likely than open surgery to lead to finger pain. Nearly a third (30.3%) of surgeons admit to giving consideration to their own discomfort when choosing an operative modality. Robotic surgery has promise in reducing the risk of physical discomfort for the operator. This is important as more surgeons consider their own health when choosing a surgical modality.

  9. Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection

    Zhou Xiao-Nong


    Full Text Available Abstract Blastocystis is a prevalent enteric protozoan that infects a variety of vertebrates. Infection with Blastocystis in humans has been associated with abdominal pain, diarrhea, constipation, fatigue, skin rash, and other symptoms. Researchers using different methods and examining different patient groups have reported asymptomatic infection, acute symptomatic infection, and chronic symptomatic infection. The variation in accounts has lead to disagreements concerning the role of Blastocystis in human disease, and the importance of treating it. A better understanding of the number of species of Blastocystis that can infect humans, along with realization of the limitations of the existing clinical laboratory diagnostic techniques may account for much of the disagreement. The possibility that disagreement was caused by the emergence of particular pathogenic variants of Blastocystis is discussed, along with the potential role of Blastocystis infection in irritable bowel syndrome (IBS. Findings are discussed concerning the role of protease-activated receptor-2 in enteric disease which may account for the presence of abdominal pain and diffuse symptoms in Blastocystis infection, even in the absence of fever and endoscopic findings. The availability of better diagnostic techniques and treatments for Blastocystis infection may be of value in understanding chronic gastrointestinal illness of unknown etiology.

  10. Georges Perec et le deuil de l’achèvement

    Daniele Carluccio


    What is modern reading? Walter Benjamin defines the modern man, and thus the modern reader, as a “traumatophilic type”. Jules de Gaultier, the theoretician of bovarism, compares Mrs Bovary, the famous Flaubertian reading hero, to an artist constrained to incompletion, who fails to bring the ideal she finds in books to life. In this article, I explore the case of Georges Perec as reader of Raymond Roussel in an essay entitled Roussel and Venice. Outline of a Melancholic Geography. Secondly, I focus on Perec as both author and reader of W, an incomplete fiction included in an autobiographical context which reveals its traumatic origin. I attempt to show that the work of Perec is for a reader who is similar to him: a modern, melancholic reader who mourns for completion.

  11. Structural and mechanical properties of nanocrystalline Zr co-sputtered a-C(:H) amorphous films

    Escudeiro, A., E-mail: [SEG-CEMUC DEM University of Coimbra, Coimbra (Portugal); Figueiredo, N.M. [SEG-CEMUC DEM University of Coimbra, Coimbra (Portugal); Polcar, T. [Engineering Materials, Faculty of Engineering and the Environment, University of Southampton, SO17 1BJ (United Kingdom); Department of Control Engineering, Czech Technical University in Prague, Technicka 2, Prague 6 (Czech Republic); Cavaleiro, A. [SEG-CEMUC DEM University of Coimbra, Coimbra (Portugal)


    Highlights: • The incorporation of Zr led to formation of nanocrystalline ZrC embedded into C-matrix. • The incorporation of Zr and H decreased the typical columnar microstructure of a-C films. • The hardness was independent on Zr content but increased with the introduction of H. - Abstract: The aim of this study was to investigate the effect of Zr as alloying element to carbon films, particularly in respect to film structure and mechanical properties. The films were deposited by magnetron sputtering in reactive (Ar + CH{sub 4}) and non-reactive (Ar) atmosphere with different Zr contents (from 0 to 14 at.%) in order to achieve a nanocomposite based films. With an increase of Zr content a broad peak was observed in X-ray diffraction spectra suggesting the presence of nanocrystalline (nc) ZrC phase for the coatings with Zr content higher than 4 at.%. The application of Scherrer formula yielded a grain sizes with a dimension of 1.0–2.2 nm. These results were supported by X-ray photoelectron spectroscopy showing typical charge transfer at Zr-C nanograins and carbon matrix interface. The nc-ZrC phase was also observed by transmission electron microscopy. The hardness of the coatings was approximately independent of Zr content. However, the Young modulus increased linearly. The residual stress of the coatings was strongly improved by the presence of nc-ZrC phase embedded in the a-C matrix. Finally, the incorporation of H into the matrix led to denser and harder films.

  12. Estación depuradora de aguas de Achères III Francia

    Editorial, Equipo


    Full Text Available The article describes the works and installations designed to unite in one single plant all the purification plants that serve the capital of the country and its sorrounding district, with a capacity of approximately 3,000,000 m^/day, serving a population of about 8 millions. The construction complex comprises 5 phases out of which 3 are completed, one is in operation, and the last one in its beginning, developing the whole process of: pretreatment, primary decantation, biological purification, digestion, power station, control post —^with an extremely complete computer— relief of the treated liquid and drying of the sludges. The majority of the pipes are subterranean passing below high buildings, highways and the river Seine. Due to the fact that the ground that the complex occupies is situated close to a housing area, the compression and ventilator halls have been equipped to avoid disturbing noises.En el artículo se describen las obras e instalaciones destinadas a reunir en una sola todas las plantas depuradoras que sirven a la capital del país y su alfoz, con capacidad para unos 3.000.000 de metros cúbicos/día, atendiendo a unos ocho millones de habitantes. El conjunto de construcciones comprende cinco fases, de las que tres están realizadas, una en marcha y la última en sus comienzos, desarrollando todo el proceso de: pretratamiento, decantación primaria, depuración biológica, digestión, central energética, puesto de mando —con ordenador completísimo—, relevo del líquido tratado y secado de fangos. Gran parte de las conducciones son subterráneas, pasando bajo edificios de gran altura, de autopistas y del Sena. Como el terreno que ocupan está próximo a una zona de viviendas, las naves de compresores y sopladores se han acondicionado para evitar ruidos molestos.

  13. Effects of fufang yimucao oral liquid on acute ache model mice

    Fengjie Wang; Mingsan Miao; Yulin Zhang; Jingjing Shi; Yalei Yang; Huili Liu


    BACKGROUND: Fufang yimucao oral liquid has markedly effects on ameliorating circulation, restraining uterine constriction induced by oxytocin, alleviating dysmenorrhea, as a traditional medicine on promoting blood circulation by removing blood stasis, yimucao could ameliorate abnormal hemorrheological when hemorrhagic shock happens, enhance the hemoperfusion of organs and actively react on the result of hemorrhagic shock. OBJECTIVE: To investigate the abirritation of fufang yimucao oral liquid on pain model mice induced by hot board method and acetic acid twist body method and dysmenorrhea model mice induced by estradiol. DESIGN: Entirely randomly grouping and control experiment.SETTING: Pharmacological Laboratory, Henan College of Traditional Chinese Medicine. MATERIALS: A total of 200 female Kunming genus mice of grade 2 and weighing 18-21 g were collected. Fufang yimucao oral liquid, mainly consist of yimucao, danggui, chuanxiong, muxiang, and so on, was produced by Henan Joyline&Joysun Pharmaceutical Stock Co., Ltd. (batch number: 050701); yimucao oral liquid was produced by Shangqiu Lvyuan Pharmaceutical Co., Ltd. (batch number: 050108); estradiol slice by Shanghai Xinyi Kangjie Pharmaceutical Co., Ltd. (batch number: 050301); YSL-6A intelligence hot plate instrument by Shandong Equipments Station of the Medical Science.METHODS:The experiment was carried out in the Animal Experiment Center of the Henan College of Traditional Chinese Medicine from August to November 2005. The high-, middle- and low-dosage fufang yimucao oral liquid in the experiment was 1, 0.5 and 0.25 in volume fraction, respectively, and yimucao oral liquid was 0.5.①Among 80 mice, 60 mice were eligible in pain threshold tested by hot plate, and randomly dividing into 5 groups with 12 in each group. Mice in the high-, middle- and low-dose fufang yimucao oral liquid groups were perfused with 1 mL, 0.5 mL and 0.25 mL/mL fufang yimucao, and mice in the yimucao group and saline group were perfused with the same volume yimucao oral liquid and saline, respectively, once a day for 3 successive days. Half an hour and one hour after administration for the last tune, the range of pain was tested in hot plate and the increasing numerical value was counted.②Another 60 mice were randomly divided into 5 groups. The grouping ways, numbers of animal and administration were as the same as those mentioned above. Forty minutes after administration for the last time, mice were given the celiac injecting with the fresh acetic acid, then observed and registered the delitescence of turned body and the times of turning in 10 minutes.③The rest of 60 mice were randomly divided into 6 groups with 10 in each group. The five groups were divided as the same as mentioned above, and the last group was the blank control group. Mice in the 5 former groups were given synestrin tablets CMC suspension with the dose of 2 mg/kg, 0.1 g/L and 0.2 mL/10 g once a day for 12 successive days. Ten days later, mice were administrated as the same ways and dosage mentioned above. Mice in blank control group were perfused with the same volume of saline. Two days after modeling and 40 minutes after administration, mice were injected with oxytocin to observe the latent period and the frequency of twisting reaction in 10 minutes. MAIN OUTCOME MEASURES: Effect of fufang yimucao oral liquid on mice pain model induced by hot board method, twisting body response induced by acetic acid and mice dysmenorrhea model. RESULTS:①Effect of fufang yimucao oral liquid on mice pain model induced by hot board: Thirty minutes after administration, the pain threshold of yimucao oral liquid group and high-, middle- and low-dose fufang yimucao oral liquid groups were respectively (25.42 + 2.10), (22.40 + 3.42), (25.24 + 2.51) and (19.80 + 2.00) s, which were markedly higher than saline group [(17.98 + 1.68) s, P<0.05 - 0.01]. Sixty minutes after administration, the pain threshold of yimucao oral liquid group and high-, middle- and low-dose fufang yimucao oral liquid groups were respectively (27.42±2.17), (23.83+2.66), (27.64+2.64) and (21.51+2.41) s, which were markedly higher than saline group [(17.8+1.75) s, P<0.01]. (r) Effect of fufang yimucao oral liquid on twisting body response induced by celiac injecting acetic acid: The twisting body latent period of yimucao oral liquid group and high-, middle- and low-dose fufang yimucao oral liquid groups were respectively (2.43 + 0.19), (2.09±0.20), (2.60 + 0.14) and (1.85 + 0.35) s, which were markedly higher than saline group [(1.45 + 0.22) s, P<0.01]. The twisting body times in 10 minutes ofyimucao oral liquid group and high-, middle- and low-dose fufang yimucao oral liquid groups were respectively (14.8 + 4.0), (15.8 + 3.5), (12.2 + 3.7) and (18.7 + 3.3) times, which were markedly lower than saline group [(25.0 + 5.0) times, P < 0.01].③Effect of fufang yimucao oral liquid on mice dysmenorrhea model: After injecting estradiol, the twisting body latent period of yimucao oral liquid group and high-,middle-and low-dose fufang yimucao oral liquid groups were respectively (61.8±20.8), (105.8±29.8), (78.9±14.0) and (71.9 + 20.0) s, which were higher than the saline group [(31.6+14.71) s, P<0.01]. The twisting body times in 10 minutes of yimucao oral liquid group and high-, middle- and low-dose fufang yimucao oral liquid groups were respectively (18.1+4.2), (9.5 + 2.8), (16.2 + 3.5) and (19.9+4.6) times, which were lower than the saline group [(28.5±4.7) times, P< 0.01].CONCLUSION: Fufang yimucao oral liquid has a good effect on abirritation, condignly as yimucao oral liquid, besides it does not have obvious dependent effect.

  14. Cytisine derivatives as high affinity nAChR ligands: synthesis and comparative molecular field analysis.

    Nicolotti, O; Canu Boido, C; Sparatore, F; Carotti, A


    A number of new N-substituted cytisine derivatives were prepared and tested, along with similar compounds already described by us and others, as high affinity neuronal acetylcholine receptor ligands. Structure-affinity relationships were discussed in the light of our recently proposed pharmacophore model for nicotinic receptor agonists. The most significant physicochemical interactions modulating the receptor-ligand binding were detected at the three dimensional (3D) level by means of comparative molecular field analysis (CoMFA). The best predictive PLS model was a single-field steric model showing good statistical figures: n = 17, Q2 = 0.717, s(ev) = 0.566, r2 = 0.942, s = 0.275.


    Vivian Roshan D


    Full Text Available BACKGROUND: Sciatica due to lumbar intervertebral disc herniation is one of the most common causes of radicular pain in an adult working population. This study aims at studying the effectiveness of conservative management of lumbar disc herniation as an alternative to surgical measures. METHODS: A prospective study of 100 patients with lumbar disc herniations who were treated conservatively were followed up at intervals of 1 month, 6 months and 1 year. Patients planned for conservative treatment were treated with pharmacological therapy, rest and physiotherapy. Those planned for epidural steroid injections were administered a single dose of steroid one level higher than the lesion in the epidural space. The collected data was analyzed by Chi square. RESULTS: Our results showed that in both genders, epidural steroid infiltration yielded better results than conservative treatment. Occupation had no discernible effect on the magnitude of disc herniation. People with sedentary lifestyle recovered better with epidural steroid infiltration as compared to the heavy physical labor group. Irrespective of disc bulge, protrusion or extrusion, the epidural steroid injection group showed significant improvement in symptoms as compared to conservative treatment. Smokers tended to show delay in the recovery as compared with the non-smoker group. The amount of disc herniation is not directly proportional to the outcome of treatment. CONCLUSIONS: Epidural steroid infiltration showed significant improvement in symptoms of lumbar intervertebral disc herniation thereby avoiding disc surgery. Conservative management for atleast 4 to 6 weeks can be recommended followed by epidural steroid in those patients without improvement. Cessation of smoking should be an integral part of the treatment.

  16. Synapse formation between isolated axons requires presynaptic soma and redistribution of postsynaptic AChRs.

    Meems, Ryanne; Munno, David; van Minnen, Jan; Syed, Naweed I


    The involvement of neuronal protein synthetic machinery and extrinsic trophic factors during synapse formation is poorly understood. Here we determine the roles of these processes by reconstructing synapses between the axons severed from identified Lymnaea neurons in cell culture, either in the presence or absence of trophic factors. We demonstrate that, although synapses are maintained between isolated pre- and postsynaptic axons for several days, the presynaptic, but not the postsynaptic, cell body, however, is required for new synapse formation between soma-axon pairs. The formation of cholinergic synapses between presynaptic soma and postsynaptic axon requires gene transcription and protein synthesis solely in the presynaptic neuron. We show that this synaptogenesis is contingent on extrinsic trophic factors present in brain conditioned medium (CM). The CM-induced excitatory synapse formation is mediated through receptor tyrosine kinases. We further demonstrate that, although the postsynaptic axon does not require new protein synthesis for synapse formation, its contact with the presynaptic cell in CM, but not in defined medium (no trophic factors), differentially alters its responsiveness to exogenously applied acetylcholine at synaptic compared with extrasynaptic sites. Together, these data suggest a synergetic action of cell-cell signaling and trophic factors to bring about specific changes in both pre- and postsynaptic neurons during synapse formation.

  17. Photosynthetic patterns of Cetraria cucullata (Bell. ) Ach. at Anaktuvuk Pass, Alaska

    Moser, T.J.; Nash, T.H. III


    The daily photosynthetic patterns of Cetraria cucullata were followed over the 1976 summer period at Anaktuvuk Pass, Alaska. With the exception of rainy periods, the lichen exhibited a strong diurnal pattern with peak photosynthetic activity occurring between 0300 and 0700 h. This correlated with periods of maximal lichen water retention and the presence of direct solar radiation. When the lichen was moist, a strong gradient in photosynthetic activity was observed with no activity in the lichen bases and maximal activity in the lichen tips.


    Aparajita Mukherjee


    Full Text Available Background:Low back pain is a common problem seen in young female individual.Core strengthening exercises(CSE helps to activate the deep abdominal & back muscles. Combination of core strengthening & stretchingexercise may have positive effects on mechanical low back pain.Objective:The main aim of this clinical studyis to find the combined effect of core strengthening & stretching exercises on reducing pain & disability onfemale subjects with mechanical low back pain (MLBP.Methodology:18 female subjects with MLBP whoparticipated in the experimental study underwent treatment variation for 4 weeks after giving theirinformedconsent. They were evaluated & randomized into CSE group, CSE with iliopsoas stretching group, CSE withhamstring stretching group. Protocol-Pre & post VAS & Oswestry scores were recorded at the start ofthetreatment & at the end of each week for four consecutive weeks.Data Analysis:This was done by usingparametric test one-way analysis of variance (ANOVA followed by Post Hoc Bonferroni Significance level set atp d”0.05.Result:After 4 weeks of exercise therapy there was a significant decrease in pain & disability scoreamong all three groups (pd” 0.01 with more improved results in core strengthening along with hamstringstretching group (pd” 0.01.Discussion & Conclusion:CSE alone & CSE along with ilopsoas stretching exerciseare found to be effective in decreasing pain & disability in subjects with MLBP. Core strengtheningexercisealong with hamstring stretching showed better results in VAS & oswestry scale as compared to othersgroups&found more effective in reducing pain & improving functional activities in MLBP subjects

  19. Physiological response of the epiphytic lichen Evernia prunastri (L.) Ach. to ecologically relevant nitrogen concentrations.

    Munzi, S; Paoli, L; Fiorini, E; Loppi, S


    This study investigated the physiological response of the epiphytic lichen Evernia prunastri to ecologically relevant concentrations of nitrogen compounds. Lichen samples were sprayed for 4 weeks either with water or 50, 150 and 500 μM NH(4)Cl. The integrity of cell membranes and chlorophyll a fluorescence emission (F(V)/F(M) and PI(ABS)) were analyzed. No membrane damage occurred after the exposure period. F(V)/F(M), a classical fluorescence indicator, decreased during the second week of treatment with 500 μM NH(4)Cl and the third week with 50 and 150 μM NH(4)Cl. PI(ABS), an overall index of the photosynthetic performance, was more sensitive and decreased already during the first week with 500 μM NH(4)Cl and the second week with 150 μM NH(4)Cl. Since E. prunastri has been exposed to ammonium loads corresponding to real environmental conditions, these findings open the way to an effective use of this species as early indicators of environmental nitrogen excess. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Geological Mapping of the Ac-H-4 Ezinu Quadrangle of Ceres from NASA's Dawn Misssion

    Scully, Jennifer E. C.; Raymond, Carol A.; Williams, David A.; Buczkowski, Debra L.; Mest, Scott C.; Hughson, Kynan H. G.; Russell, Christopher T.; Kneissl, Thomas; Ruesch, Ottaviano; Frigeri, Alessandro; Combe, Jean-Philippe; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Platz, Thomas; Nathues, Andreas; Hoffmann, Martin; Schaefer, Michael; Park, Ryan


    NASA's Dawn spacecraft is currently orbiting Ceres, a dwarf planet and the largest object in the asteroid belt (diameter of ~940 km). Ceres science data are primarily acquired during three orbits of decreasing altitude: Survey, High Altitude Mapping Orbit (HAMO) and Low Altitude Mapping Orbit (LAMO). The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that undertaken at Vesta [1]. Thus, Ceres' surface is divided into fifteen quadrangles to facilitate systematic HAMO-based and LAMO-based geological mapping. Here we present the LAMO-based geologic map of Ezinu quadrangle (21-66 °N, 180-270 °E). Acquisition of Survey and HAMO data was completed by the submission of this abstract, along with the collection of initial LAMO data. Thus, the current geologic map is based on HAMO (~140 m/pixel) and Survey (~400 m/pixel) mosaics of clear filter Framing Camera images [2]. Framing Camera color images and topography data, derived from the Framing Camera images, are also used to inform the geologic mapping. Updated mapping will be undertaken before the conference, using ~35 m/pixel LAMO Framing Camera mosaics. The key geologic features in Ezinu quadrangle are: linear features, Occator crater, Ezinu crater, Datan and Geshtin craters, and Erntedank Planum. We propose that linear features radial to impact craters (e.g. Occator) are ejecta ray systems, which commonly form as secondary material is ejected during impact crater formation. There is also a prominent set of grooves and chains of pits/craters that are centered near Erntedank Planum (topographically high region) and are cross-cut by ejecta from Occator crater. We interpret these grooves and chains of pits/craters as the surface expression of sub-surface fractures [3, 4]. Occator is a geologically fresh impact crater, and contains the brightest bright spots on Ceres [5], along with bright lobate material, undivided lobate material, hummocky crater floor material, smooth material and smooth crater wall material. Ezinu crater is cross-cut by clusters of craters and contains distinctive sets of linear features, which we provisionally name intra-crater grooves. Datan crater cross cuts Geshtin crater, is almost entirely filled by hummocky crater floor material is the source of a flow, which we map as undivided lobate material. Numerous bright spots are visible in the floor of Geshtin crater. Based on our current geologic mapping, we have developed the following preliminary geologic history: (1) the cratered terrain, grooves and pit chains, and Ezinu and Geshtin craters form early, and (2) more recently, the undivided crater material, Occator ejecta ray system, and Occator and Datan craters, form. Before the conference, we will refine and expand upon this geologic history, and also conduct research into: (i) whether subsurface fractures are conduits for the Occator-bright-spot-forming material, (ii) the formation mechanism of the intra-crater grooves, (iii) types of mass wasting, and (iv) whether the Occator and Geshtin crater bright spots are related. References: [1] Williams et al. (2014) Icarus. [2] Roatsch et al. (2015) Planetary and Space Science. [3] Buczkowski D. L. (2015) AGU, #P44B-05. [4] Scully et al. (2016) LPSC. [5] Nathues et al. (2015) Nature.

  1. Absence of correlation between ACh-induced Ca influx and phosphatidic acid labeling in rat uterus.

    Ichida, S; Moriyama, M; Hirooka, Y; Okazaki, Y; Yoshioka, K


    Rat uterine smooth muscle was preincubated in Ca-depleted modified Locke-Ringer solution to investigate the correlation between the 32Pi incorporation into phosphatidic acid induced by acetylcholine and the contractile response to acetylcholine induced by the addition of CaCl2 (Ca influx). The results showed that in rat uterine smooth muscle under these conditions phosphatidic acid does not act as a Ca ionophore or as a trigger for opening the Ca channel.

  2. Utilisation des grammaires probabilistes dans les t\\^aches de segmentation et d'annotation prosodique

    Nesterenko, Irina


    Nous pr\\'esentons dans cette contribution une approche \\`a la fois symbolique et probabiliste permettant d'extraire l'information sur la segmentation du signal de parole \\`a partir d'information prosodique. Nous utilisons pour ce faire des grammaires probabilistes poss\\'edant une structure hi\\'erarchique minimale. La phase de construction des grammaires ainsi que leur pouvoir de pr\\'ediction sont \\'evalu\\'es qualitativement ainsi que quantitativement. ----- Methodologically oriented, the present work sketches an approach for prosodic information retrieval and speech segmentation, based on both symbolic and probabilistic information. We have recourse to probabilistic grammars, within which we implement a minimal hierarchical structure. Both the stages of probabilistic grammar building and its testing in prediction are explored and quantitatively and qualitatively evaluated.

  3. Desorption of metals from Cetraria islandica (L. Ach. Lichen using solutions simulating acid rain

    Čučulović Ana A.


    Full Text Available Desorption of metals K, Al, Ca, Mg, Fe, Ba, Zn, Mn, Cu and Sr from Cetraria islandica (L. with solutions whose composition was similar to that of acid rain, was investigated. Desorption of metals from the lichen was performed by five successive desorption processes. Solution mixtures containing H2SO4, HNO3 and H2SO4-HNO3 were used for desorption. Each solution had three different pH values: 4.61, 5.15 and 5.75, so that the desorptions were performed with nine different solutions successively five times, always using the same solution volume. The investigated metals can be divided into two groups. One group was comprised of K, Ca and Mg, which were desorbed in each of the five desorption processes at all pH values used. The second group included Al, Fe, Zn, Ba, Mn and Sr; these were not desorbed in each individual desorption and not at all pH values, whereas Cu was not desorbed at all under any circumstances. Using the logarithmic dependence of the metal content as a function of the desorption number, it was found that potassium builds two types of links and is connected with weaker links in lichen. Potassium is completely desorbed, 80% in the first desorption, and then gradually in the following desorptions. Other metals are linked with one weaker link (desorption 1-38% and with one very strong link (desorption below the metal detection limit. [Projekat Ministarstva nauke Republike Srbije, br. III43009 i br. ON 172019

  4. Synthesis, Biological Evaluation, and Molecular Docking of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease.

    Shaik, Jeelan Basha; Palaka, Bhagath Kumar; Penumala, Mohan; Eadlapalli, Siddhartha; Darla Mark, Manidhar; Ampasala, Dinakara Rao; Vadde, Ramakrishna; Amooru Gangaiah, Damu


    Alzheimer's disease onset and progression are associated with the dysregulation of multiple and complex physiological processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene analogs (4a-q) were synthesized and evaluated for their multitarget-directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, and amyloid-β peptide (Aβ) specific targets for Alzheimer's disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nm concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity. Among them, 3-bromobenzylamide derivative 4m exhibited the best acetylcholinesterase inhibitory activity with IC50 value of 13 ± 1.4 nm which is 51-fold superior to galantamine, a reference drug. Kinetic and molecular docking studies indicated 4m as mixed-type inhibitor, binding simultaneously to catalytic active and peripheral anionic sites of acetylcholinesterase. Five compounds 4e, 4f, 4g, 4j, and 4k have shown 1.4- to 2.5-fold of higher antioxidant activities than trolox. Interestingly, the most active compound 4m demonstrated dosage-dependent acceleration of Aβ1-42 aggregation, which may reduce toxicity of oligomers. Overall, these results lead to discovery of fused tricyclic coumarins as promising dual binding site inhibitors of acetylcholinesterase and afford multifunctional compounds with potential impact for further pharmacological development in Alzheimer's therapy. © 2016 John Wiley & Sons A/S.

  5. Geologic Mapping of the Ac-H-6 Quadrangle of Ceres from Nasa's Dawn Mission: Compositional Changes

    Krohn, Katrin; Jaumann, Ralf; Tosi, Federico; Nass, Andrea; Otto, Katharina A.; Schulzeck, Franziska; Stephan, Katrin; Wagner, Roland J.; Williams, David A.; Buczkowski, Debra L.; Mest, Scott C.; Scully, Jennifer E. C.; von der Gathen, Isabel; Kersten, Elke; Matz, Klaus-Dieter; Pieters, Carle M.; Preusker, Frank; Roatsch, Thomas; De Sanctis, Maria Cristina; Zambon, Francesca


    Cereś surface is affected by numerous impact craters and some of them show features such as channels or multiple flow events forming a smooth, less cratered surface, indicating possible post-impact resurfacing [1,2]. Flow features occur on several craters on Ceres such as Haulani, Ikapati, Occator, Jarimba and Kondos in combination with smooth crater floors [3,4], appearing as extended plains, ponded material, lobate flow fronts and in the case of Haulani lobate flows originating from the crest of the central ridge [3] partly overwhelming the mass wasting deposits from the rim. Haulanís crater flanks are also affected by multiple flow events radiating out from the crater and partly forming breakages. Flows occur as fine-grained lobes with well-defined margins and as smooth undifferentiated streaky flows covering the adjacent surface. Thus, adjacent craters are covered by flow material. Occator also exhibits multiple flows but in contrast to Haulani, the flows originating from the center overwhelm the mass wasting deposits from the rim [4]. The flows have a "bluish" signature in the FC color filters ratio. Channels occur at relatively fresh craters. They also show the "bluish" signature like the flows and plains. Only few channels occur at older "reddish" craters. They are relatively fresh incised into flow features or crater ejecta. Most are small, narrow and have lobated lobes with predominant distinctive flow margins. The widths vary between a few tens of meters to about 3 km. The channels are found on crater flanks as well as on the crater floors. The occurrence of flow features indicates viscous material on the surface. Those features could be formed by impact melt. However, impact melt is produced during the impact, assuming similar material properties as the ejecta it is expected to have nearly the same age as the impact itself, but the flows and plains are almost free of craters, thus, they seem to be much younger than the impact itself. In addition, the source of impact melt flows is diffusely distributed but many of the observed flows originate from district sources in the crater interior and the flows, however, are well defined. The compositional differences derived from the color ratio and possible time variable effects related to cryo-processes either volcanic or glacial [1,2]. Furthermore, the suggestion of an occurrence ice within the Cerean crust [5] as well as possible salts incorporated into a regolith layer [4,5,6] indicates similar geological processes as seen on other icy bodies. Some lobate flow-like deposits on Ganymede such as at Sippar Sulcus are suggested to be formed by volcanic eruptions creating a channel and flow, and cutting down into the surface forming a depression. Thus, an endogenic formation process cannot be excluded. References: [1] Jaumann R. et al. (2015) EPSC X, Abstract #2015-83. [2] Jaumann R. et al. (2015) AGU, Abstract #P42A-05. [3] Krohn K. et al. (2016) LPSC XLVII, this issue. [4] Jaumann R. et al. (2016) LPSC XLVII, this issue. [5] McCord T.B. and Sotin C. (2005) J. Geophys. Res., 110, E05009. [6] Castillo-Rogez J.C. and McCord T.B. (2010) Icarus 203, 443-459.

  6. Analiza otoczenia przedsiębiorstwa w szkołach i koncepcjach zarządzania

    Wach, Krzysztof


    In the history of management thought the conceptions of environment have very often changed. In different periods of history and different scientific schools of organization and management scientists has ascribed to the business environment different role and importance. The paper is a kind of synthetic review of opinions on the importance and essence of the business environment. The author chose a couple of selected outlooks and schools, which have had and even still have the crucial impact ...

  7. SAR Aircrew--HH-3F Avionics and HH-3F Flight Preparation. ACH3AV-0442. Second Edition, Revised.

    Coast Guard Inst., Oklahoma City, OK.

    This document contains two U.S. Coast Guard self-study pamphlets that provide training in helicopter flight preparation and avionics duties. Each pamphlet consists of a number of lessons that include objectives, information illustrated with line drawings and/or photographs, and self-quizzes with answers. The avionics course covers the following…

  8. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB


    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incap

  9. Prenatal nicotine alters vigilance states and AchR gene expression in the neonatal rat: implications for SIDS.

    Frank, M G; Srere, H; Ledezma, C; O'Hara, B; Heller, H C


    Maternal smoking is a major risk factor for sudden infant death syndrome (SIDS). The mechanisms by which cigarette smoke predisposes infants to SIDS are not known. We examined the effects of prenatal nicotine exposure on sleep/wake ontogenesis and central cholinergic receptor gene expression in the neonatal rat. Prenatal nicotine exposure transiently increased sleep continuity and accelerated sleep/wake ontogeny in the neonatal rat. Prenatal nicotine also upregulated nicotinic and muscarinic cholinergic receptor mRNAs in brain regions involved in regulating vigilance states. These findings suggest that the nicotine contained in cigarette smoke may predispose human infants to SIDS by interfering with the normal maturation of sleep and wake.

  10. Problem dystansu władzy w szwedzkich materiałach dydaktycznych jako przykład dobrych praktyk

    Marzanna Pogorzelska


    Full Text Available "The idea of power distance in Swedish didactic material as an example of best practice" The text contributes to a discussion on the phenomenon of social construction of inequalities by the system of education. The author, using Swedish textbooks, analyses their contents applying in the examination G. Hofstede’s theory on culture dimensions, focusing on one of these dimensions (power distance. This approach might be an inspiration as far as methodology of didactic materials is concerned, as well as practical ways of introducing equality-oriented contents into school textbooks.

  11. Influenceri na sociálnych sieťach a ich využitie v marketingu

    Petrovčíková, Lucia


    This diploma thesis called "Influencers in Social media and their Use in Marketing" deals with the new current trend in which, instead of well-known celebrities, star just ordinary people. Despite of this, they managed to conquer the masses through social networks thanks to their unique personality and authenticity. The first chapter focuses on online marketing and explains the basic concept of it, its tools and communication mix, along with data on the structure of the Czech Internet populat...

  12. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB


    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incap


    Sadaf Subhi


    Full Text Available Background: Chronic low back pain remains a major health problem. Unfortunately, the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25–50% of patients respond to exercise. At present, however, there are no guidelines regarding the best treatment to help clinicians. As a result, time and money are wasted on treatment which ultimately fail to help the patient. A backache is described as annoying and gripping pain. It can be caused by poor posture, lack of manual handling skills, change in the center of gravity due to expanding abdomen, lack of exercise, or the weight of the baby and the stretching ligaments. Pelvic floor muscle weakness is one of the major cause of chronic backache. Weakness in the pelvic floor muscles is common in females which can lead to debilitating urinary symptoms, affect sexual function and cause chronic backache. Methods: In 3 months, 31 female subjects with mean age of 28 who had taken treatment for their chronic backache, were improvised with pelvic floor strength at our setup, with dramatically good results. 31 subjects with non-responsive chronic back pain who had taken conventional physiotherapy were included in the study. Both married and unmarried were included. Any sign of radiculopathy or inflammation were excluded. After assessing pain using Visual Analogue Scale, the Dr Glazer’s program and Kegel’s contractions were taught. Results: There was significant improvement by 50% on reassessment after 7 days. Then exercises for transverse abdominals were included to get a better response. On completion of the treatment sessions, reduction in pain was 92% on VAS and functional abilities increased by 89%. There was a significant improvement in the quality of life and in pelvic-floor muscle strength. Conclusion: Non-responsive chronic back pain in females when treated with pelvic floor muscle strengthening program showed 40% improvement. This can be implemented in routine practice for the benefit of the patients.

  14. Le professeur Llewellyn Smith achève son mandat de Directeur général

    CERN Press Office. Geneva


    Speakers representing the world community of particle physics praised the outstanding achievements of Prof. Christopher Llewellyn Smith during his five-year mandate as Director General of CERN. The significance of his achievements whilst Director General are difficult to over-estimate. The approval of the construction of the Large Hadron Collider (LHC) in 1994 and the subsequent decision in 1996 to build the accelerator in a single stage, in a period of great economic difficulty, was in large part due to the leadership and tenacity of the Director General.

  15. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase

    Chen, Yun; Zhang, Yiming; Siewers, Verena


    Saccharomyces cerevisiae, acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and nucleus, and cannot be directly transported between these compartments. With the acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the cytoplasm can be transported......Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast...... into the cytoplasm or the mitochondria. However, whether acetyl-CoA generated in the mitochondria can be exported to the cytoplasm is still unclear. Here, we investigated whether the transfer of acetyl-CoA from the mitochondria to the cytoplasm can occur using a pyruvate decarboxylase negative, non...

  16. Ach, mijn martelaartje! : J.B.D. Wibmers postures en de ruimte voor politieke kritiek rond 1820

    Ham, Laurens


    In this article, the oeuvre of J.B.D. Wibmer (1792-1836) is analyzed. This hack writer published several popular magazines and pamphlets between 1818 and 1836, in which sharply satirical opinions were expressed about the protestant church and the Dutch monarchy of William I. A posture analysis of th

  17. Effect of nitrogen supply on the C/N balance in the lichen Evernia prunastri (L.) Ach.

    Munzi, Silvana; Pisani, Tommaso; PAOLI, Luca; RENZI, Monia; Loppi, Stefano


    This study investigated the relationship between nitrogen and carbon in the thalli of the lichen Evernia prunastri, with an emphasis on the role of the C/N balance in the response of this species to N excess. For this purpose, thalli collected at a remote site were sprayed for 5 weeks with NH4NO3 (0.05 and 1 M) and (NH4)2SO4 (0.025 and 0.5 M) solutions, and later analyzed for their C and N content. The results showed that the total N content of thalli increased and the total C content decreas...

  18. Fsiles de novela: paleontologa y literatura en la argentina de fines del siglo XIX y principios del siglo

    Eduardo G. Ottone


    Full Text Available La literatura argentina de la segunda mitad del siglo XIX y comienzos del siglo XX refiri la presencia de mamferos fsiles cenozoicos en las pampas. Gliptodontes y megaterios devinieron en personajes de los textos de Eduardo Ladislao Holmberg, William Henry Hudson, Eduarda y Lucio Victorio Mansilla, Leopoldo Lugones, Geoffroy Franois Daireux, Horacio Quiroga, Hugo Wast, Ezequiel Martnez Estrada, Leopoldo Marechal y Manuel Mujica Lainez. Estos autores contextualizaron a los vertebrados fsiles en escenas humorsticas o realistas, como iconos de la grandeza de la Pampa y la nacin o parodia de estereotipos culturales locales.

  19. 两种电疗仪止痛效应的实验对比研究%Comparing two low frequency electrotherapy's effects on treating aches

    王颖; 吴慧敏; 戴英杰; 卢毓华; 傅叶华; 崔阳


    目的 研究两种电疗仪止痛效应及其作用机制。方法分别应用日本好玛公司原装进口低周波治疗器 (以下简称好玛组 )与台湾产低频调制中频电疗 (以下简称 Likon组 )进行疗前后的皮电、皮温、痛阈及临床疗效的对比研究。结果两组皮电对比差异不显著。两组皮温、痛阈均有非常显著的差异 (P< 0.01,P< 0.05)。两组 5次及 10次疗后对比均有非常显著差异 (P< 0.001)。结论好玛电疗仪具同步加温功能,其加速局部血液循环的作用更加突出,其止痛效应较其他低、中频电疗更显著,且医治软组织损伤的痊愈率高,疗程短。%Objective To discovering the effective mechanics on lab and clinic between using two low frequency impulse electrotherapy.Methods To comparing the resistance of skin,temperature of skin,pain threshold and curative effect by using low frequency current apparatus(Homers,made in Japan)with low frequency modulated medium frequency impulse electrotherapy,(Likon,made in Taiwan) before and after treatment.Result There aren't diference in the resistance of skin,(P=0.15).The temperature of skin in Homers is higher than in Likon(P< 0.01).The pain threshold in Hosmer is more increased than in Likon(P< 0.05).The Curative effect after ten and five times to treat the soft tissue injure in Homer is better than in libon(P< 0.001).Conclusion The homer apparatus has hot effect,so it can promote the blood circulation.Relieved in pain by Hosmer is better than by Likon.the soft tissue injure is recover quicker by Homer than by Likon.

  20. The History of the Data Systems AutoChemist® (ACH) and AutoChemist- PRISMA (PRISMA®): from 1964 to 1986.

    Ohlsén, L; Jungner, I; Peterson, H E


    This paper presents the history of data system development steps (1964 - 1986) for the clinical analyzers AutoChemist®, and its successor AutoChemist PRISMA® (PRogrammable Individually Selective Modular Analyzer). The paper also partly recounts the history of development steps of the minicomputer PDP 8 from Digital Equipment. The first PDP 8 had 4 core memory boards of 1 K each and was large as a typical oven baking sheet and about 10 years later, PDP 8 was a "one chip microcomputer" with a 32 K memory chip. The fast developments of PDP 8 come to have a strong influence on the development of the data system for AutoChemist. Five major releases of the software were made during this period (1-5 MIACH). The most important aims were not only to calculate the results, but also be able to monitor their quality and automatically manage the orders, store the results in digital form for later statistical analysis and distribute the results to the physician in charge of the patient using thesame computer as the analyzer. Another result of the data system was the ability to customize AutoChemist to handle sample identification by using bar codes and the presentation of results to different types of laboratories. Digital Equipment launched the PDP 8 just as a new minicomputer was desperately needed. No other known alternatives were available at the time. This was to become a key success factor for AutoChemist. That the AutoChemist with such a high capacity required a computer for data collection was obvious already in the early 1960s. That computer development would be so rapid and that one would be able to accomplish so much with a data system was even suspicious at the time. In total, 75; AutoChemist (31) and PRISMA (44) were delivered Worldwide. The last PRISMA was delivered in 1987 to the Veteran Hospital Houston, TX USA.

  1. Spontaneous Aching Pain and Peculiar Involuntary Movements: A Case Report of Painful Legs and Moving Toes and Review of the Literature

    Yang-yi Fan


    Full Text Available Painful legs and moving toes (PLMT is a rare syndrome characterized by spontaneous neuropathic pain and peculiar involuntary movements in the lower limbs, especially the toes and feet. As it is a relatively rare disorder worldwide, the exact pathophysiology still remains a mystery. Until recently, numerous methods of clinical treatments have been tried; however, the success rate of the therapies is still very low. Here, we report a case of PLMT and also summarize the recent clinical and research literatures regarding clinical presentation, electrophysiological features, etiology, treatment methods, and prognosis of this disorder. Doctors should be aware of this rare syndrome in a patient with painful and/or restless legs. On the other hand, multiple clinical treatments should be tried, even those which usually produce a poor outcome.

  2. Structural, chemical and nanomechanical investigations of SiC/polymeric a-C:H films deposited by reactive RF unbalanced magnetron sputtering

    Tomastik, C.; Lackner, J. M.; Pauschitz, A.; Roy, M.


    Amorphous carbon (or diamond-like carbon, DLC) films have shown a number of important properties usable for a wide range of applications for very thin coatings with low friction and good wear resistance. DLC films alloyed with (semi-)metals show some improved properties and can be deposited by various methods. Among those, the widely used magnetron sputtering of carbon targets is known to increase the number of defects in the films. Therefore, in this paper an alternative approach of depositing silicon-carbide-containing polymeric hydrogenated DLC films using unbalanced magnetron sputtering was investigated. The influence of the C2H2 precursor concentration in the deposition chamber on the chemical and structural properties of the deposited films was investigated by Raman spectroscopy, X-ray photoelectron spectroscopy and elastic recoil detection analysis. Roughness, mechanical properties and scratch response of the films were evaluated with the help of atomic force microscopy and nanoindentation. The Raman spectra revealed a strong correlation of the film structure with the C2H2 concentration during deposition. A higher C2H2 flow rate results in an increase in SiC content and decrease in hydrogen content in the film. This in turn increases hardness and elastic modulus and decreases the ratio H/E and H3/E2. The highest scratch resistance is exhibited by the film with the highest hardness, and the film having the highest overall sp3 bond content shows the highest elastic recovery during scratching.

  3. Clinical observation of domestic Buprenorphine in treatment of cancer ache%国产丁丙诺啡用于癌痛的临床观察

    潘霞云; 朱明瑶; 潘道波; 马明祥; 陈安基



  4. Association of HLA-DQB1*05:02 and DRB1*16 Alleles with Late-Onset, Nonthymomatous, AChR-Ab-Positive Myasthenia Gravis

    Manuela Testi


    Full Text Available An association of several HLA alleles with myasthenia gravis (MG has been reported. Aim of this work was to analyze the HLA allele profile in a survey of 76 unselected Italian MG patients and in a subgroup characterized by disease onset after the age of 50 years, absence of thymoma, and presence of antiacetylcholine receptor antibodies. We defined this subgroup by the acronym LOAb. Typing was performed at low resolution for HLA-A, -B, and -DRB1 loci with sequence-specific oligonucleotide probe (PCR-SSO; at high resolution for HLA-DQB1 locus by PCR with sequence-specific primers (PCR-SSPS. HLA allele frequencies were compared with 100 healthy controls. No correlation was observed between MG and the studied HLA class I alleles. On the contrary, a strong positive association was found for the HLA class II alleles DQB1*05:02 ( and DRB1*16 ( in the LOAb subgroup ( of MG patients. Association between DQB1*05:02 and some subtypes of MG has been previously reported but not in patients with the LOAb characteristics. Therefore, the HLA allele DQB1*05:02 might be considered as a susceptibility marker for LOAb among Italians.

  5. Methyridine (2-[2-methoxyethyl]-pyridine]) and levamisole activate different ACh receptor subtypes in nematode parasites: a new lead for levamisole-resistance

    Martin, Richard J; Bai, Guangxing; Clark, Cheryl L; Robertson, Alan P


    The development of resistance to all chemotherapeutic agents increases and needs to be addressed. We are interested in resistance in parasitic nematodes to the anthelmintic levamisole. During studies on methyridine, we found that it gave us a new insight into pharmacological changes associated with levamisole resistance. Initially, electrophysiological investigation using a two-micropipette current-clamp recording technique revealed that methyridine acts as a cholinergic agonist on nematode muscle receptors (Ascaris suum). Methyridine (>30 μM) produced reversible concentration-dependent depolarizations and increases in input conductance. Mecamylamine (30 μM) and paraherquamide (0.3 μM) produced reversible antagonism of the depolarization and conductance responses to methyridine. These observations suggest that methyridine, like acetylcholine and levamisole, gates ion channels on the muscle of parasitic nematodes. The antagonistic effects of dihydro-β-erythroidine and paraherquamide on methyridine-induced contractions of A. suum muscle flaps were then examined to determine if methyridine showed subtype selectivity for N-subtype (nicotine-sensitive) or L-subtype (levamisole-sensitive) acetylcholine receptors. Dihydro-β-erythroidine weakly antagonized the effects of methyridine (but had no effect on levamisole responses). The antagonism of methyridine (pA2, 5.9) and nicotine (pA2, 6.1) by paraherquamide was similar, but was less than the antagonism of levamisole (pA2, 7.0). The antagonist profiles suggested that methyridine has a selective action on the N-subtype rather than on the L-subtype. A novel use for a larval inhibition migration assay was made using L3 larvae of Oesophagostomum dentatum. Inhibitory effects of nicotine, levamisole, pyrantel and methyridine on the migration of larvae of levamisole-sensitive (SENS) and levamisole-resistant (LEV-R) isolates were tested at different concentrations. Levamisole and pyrantel (putative L-subtype-selective agonists) concentration–response plots were displaced to the right in LEV-R isolates. Nicotine (an N-subtype-selective agonist) and methyridine produced little shift in concentration–response plots in the LEV-R isolates. Resistance dose ratios were used to calculate the relative selectivity, ρL, for the L-type receptor (levamisole ρL=1.0; pyrantel ρL=0.93; methyridine ρL=0.17; nicotine ρL=0.06). These observations reveal an N-subtype-selective action of methyridine and suggest that levamisole resistance may be associated with a loss of the L-subtype, but not the N-subtype receptors. The pharmacology of methyridine suggests an approach for the treatment of levamisole-resistant parasites. PMID:14581174

  6. [Effect on of pirenzepine on expression of mAChRs in the ocular tissues of guinea pig with form-deprived myopia].

    Liu, Qiong; Yu, Jian; Zeng, Jun-wen


    To study effects of vitreous injecting M(1)-selective muscarinic antagonist, pirenzepine, on expression of M(1) and M(4) receptor in retina, choroid, sclera and iris-ciliary body of guinea pig with form-deprived myopia. Twenty-four 1 - 2 week-old pigmented guinea pigs were randomly divided into four groups. Group1: normal control (N) (n = 6); group 2: simple form-deprived myopia (FDM) (n = 6); group 3: drug control (S) (n = 6); group 4: pirenzepine (P) (n = 6). Expression changes of M(1) and M(4) muscarinic receptors at mRNA level were detected by semi-quantitative RT-PCR in retina, choroid, sclera and iris-ciliary body. 1. After 21 days' treatment, FDM group produced relative myopia of -4.92 D and an axial length of 0.29 mm with significance (P 0.05). Of interest, in the posterior sclera, mRNA expression of group P was significantly greater than that of group S for the M(1) (P pirenzepine, can effectively inhibit form-deprived myopia in guinea pig. M(1) and M(4) subtype in sclera and their cholinergic signaling may participate in muscarinic antagonist inhibition of myopic development.

  7. The lichen Parmelia physodes (L. Ach. as indicator for determination of the degree of atmospheric air pollution in the area contaminated by flourine and sulphur dioxide emission

    M. Świeboda


    Full Text Available On the area involved in the influence of conteminations emitted by the aluminium works and electric power plant, the degree of atmospheric air pollution was evaluated on the basis of the behaviour of healthy thallus of the lichen Parmelia physodes, analysis of fluorine and sulphur content in this thallus and in the bark substrate and the F and SO2 concentrations in the air.

  8. Assessment of air pollution genotoxicity by RAPD in Evernia prunastri L. Ach. from around iron-steel factory in Karabük, Turkey.

    Cansaran-Duman, Demet; Atakol, Orhan; Aras, Sümer


    Lichens are widely used in biomonitoring studies of air pollution, either as bioindicators of air quality or as bioaccumulators of atmospheric deposition. Over the past decade, several molecular techniques have been developed to provide information on diversity, genotoxicology, genetic relationships, etc. The heavy metal contents of Evernia prunastri samples were determined by atomic absorption spectrometry. The Random Amplified Polymorphic DNA Polymerase Chain Reaction (RAPD-PCR) method was used to describe the pattern of DNA band variation in the samples influenced by the environmental pollution. The study was designed to describe the level of pollution in an area contaminated with smoke and waste from an iron-steel factory, and to reveal the level of potential genotoxic agents around this source of pollution. The study also examined the suitability of the lichen samples for the detection of genotoxicity.

  9. a-C(:H) and a-C(:H){sub Z}r coatings deposited on biomedical Ti-based substrates: Tribological properties

    Escudeiro, A., E-mail: [SEG-CEMUC, Department of Mechanical Engineering, University of Coimbra, 3030-788 Coimbra (Portugal); Polcar, T. [National Centre for Advanced Tribology (nCATS), School of Engineering Sciences, University of Southampton, Highfield, Southampton, SO17 1BJ (United Kingdom); Department of Control Engineering, Czech Technical University in Prague, Technicka 2, Prague 6 (Czech Republic); Cavaleiro, A. [SEG-CEMUC, Department of Mechanical Engineering, University of Coimbra, 3030-788 Coimbra (Portugal)


    Amorphous carbon (a-C) based coatings are possible candidates as a surface treatment for various biocompatible materials used in medicine. In this study, the carbon coatings co-sputtered with Zr, deposited by dc unbalanced magnetron sputtering in Ar (non-hydrogenated, i.e. a-C/Zr) and Ar + CH{sub 4} (hydrogenated, i.e. a-C:H/Zr) discharges, were investigated and compared with pure carbon films. Polished pure commercial Ti grade 2 and Ti grade 5 ELI (Ti6Al4V) discs were used as substrates. To improve the coating/substrate adhesion, a gradient Ti-based interlayer was deposited (∼ 450 nm). The coating structure was characterized by X-ray diffraction, X-ray photoelectron spectroscopy and Raman spectroscopy; the chemical composition was measured by electron probe microanalysis. The adhesion was evaluated by scratch-test and the hardness was measured by nanoindentation. Tribological testing of the coatings was carried out using unidirectional pin-on-disc experiments; pure titanium balls were used as counterparts. The wear rate of the coatings was negligible except for the films with the highest Zr content deposited on Ti grade 2 substrates. - Highlights: ► The incorporation of Zr led to formation of nanocrystalline ZrC embedded into C-matrix. ► a-C:(H)-Zr coatings significantly improved the wear resistance of Ti-based alloys. ► Substrate plastic deformation led to lower coating adhesion on Ti grade 2.

  10. Process control by optical emission spectroscopy during growth of a-C:H from a CH4 plasma by plasma-enhanced chemical vapour deposition

    Barholm-Hansen, C; Bentzon, MD; Vigild, Martin Etchells


    of the gas flow. Above a certain flow rate the intensity saturates, since the deposition process is limited by the power input. At low flow rates a large fraction of the feed gas is dissociated and the deposition is limited by the supply of feed gas. A relationship was found for the intensity of the CH 431...... in the process gas. The initial OH intensity was dependent on the ultimate vacuum prior to the plasma cleaning. A correlation was found between the vanishing of the OH line and the appearance of characteristic emission lines From sputtered electrode material....

  11. The optical properties of a-C:H films between 1.5 and 10 eV and the effect of thermal annealing on the film character

    Logothetidis, S.; Petalas, J.; Ves, S.


    The optical properties of amorphous hydrogenated carbon films prepared with various techniques are studied with conventional and synchrotron-radiation spectroscopic ellipsometry (SE) and the pseudodielectric function of diamondlike and graphitelike films is presented in the energy region 1.5-10 eV. Characteristic features of the measured and the calculated electron-energy-loss (EEL) function are found to serve as useful criteria for the classification of such materials. The results and information obtained by SE are compared to those obtained by EEL and Raman spectroscopy techniques, which are the most widely used for this purpose. Thermal annealing experiments up to 675 °C with in situ monitoring of the reveal the undergoing structural changes in the material character from diamondlike into graphitelike during the annealing. The major modifications which turn the material into sp2-like are found to take place around and above 550 °C. The fundamental gap along with other optical parameters of the materials are compared to those of diamond and graphite and their shift with temperature is discussed and used to illustrate further the prevalence of the graphitic character during and after the annealing. Finally, the optimum growth parameters for the production of diamondlike material are discussed in the case of the glow-discharge and ion-beam deposited films.

  12. Tales of the Tail and Sperm Head AchesChanging concepts on the prognostic significance of sperm pathologies affecting the head, neck and tail

    Héctor E Chemes; Cristian Alvarez Sedo


    This article presents an update on the variable prognostic significance of different sperm pathologies in patients with severe male factor infertility due to morphology and motility disorders.Severe asthenozoospermia is one of the leading causes of male infertility as spermatozoa cannot reach the oocyte and/or penetrate normally.Identifying structural causes of sperm immotility was of great concern before the advent of intracytoplasmic sperm injection (ICSI),because immotility was the limiting factor in the treatment of these patients.In these cases,in vitro methods are used to identify live spermatozoa or stimulate sperm motility to avoid selection of non-viable cells.With these advances,fertilization and pregnancy results have improved dramatically.The identification of genetic phenotypes in asthenozoospermia is important to adequately inform patients of treatment outcomes and risks.The one sperm characteristic that seriously affects fertility prognosis is teratozoospermia,primarily sperm head and neck anomalies.Defects of chromatin condensation and acrosomal hypoplasia are the two most common abnormalities in severe teratozoospermia.The introduction of microscopic methods to select spermatozoa and the development of new ones to evaluate sperm quality before ICSI will assure that ultrastructural identification of sperm pathologies will not only be of academic interest,but will also be an essential tool to inform treatment choice.Herein,we review the differential roles played by sperm components in normal fertilization and early embryo development and explore how assisted reproductive technologies have modified our concepts on the prognostic significance of sperm pathologies affecting the head,neck,mid-piece and tail.

  13. Treatment of Female Ache with Compound Gestodene%复方孕二烯酮治疗女性痤疮的临床应用

    黄卓辉; 黄卫宁; 熊春萍; 卢浩锵; 张滨岳


    目的:探讨口服复方孕二烯酮治疗女性痤疮患者的临床疗效. 方法:收集本院2005年3月-2007年11月皮肤科门诊的87例女性痤疮患者,随机分为2组,治疗组46例,采用口服复方孕二烯酮片1片/次,每天1次,每于月经第5天开始,连服21 d,6个周期为l疗程;对照组41例,采用0.025%维甲酸乳膏每晚外涂,同时口服盐酸米诺环素胶囊,50mg/次,每天2次,持续6个月. 结果:治疗组痊愈率(47.83%)、显效率(41.30%)及有效率(10.87%)均分别高于对照组的7.32%、26.83%、19.51%,P<0.001. 结论:复方孕二烯酮治疗女性呈周期性加重或突发的痤疮疗效较好.

  14. Le CERN réagit à l'augmentation du coût du LHC à son achèvement

    CERN Press Office. Geneva


    Director-General, Luciano Maiani, stressed that CERN was now fully engaged in the LHC and outlined the first moves to react to the increased cost to completion of the LHC. The new accelerator is an extremely complex, high-tech project which CERN is building under very severe conditions. However, the technical challenges are solved and industrial production of accelerator elements, and installation are starting.

  15. Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections.

    Sihver, S; Marklund, N; Hillered, L; Långström, B; Watanabe, Y; Bergström, M


    Adult rats were subjected to a moderate lateral fluid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA(A) receptor binding in various brain regions was analysed by quantitative in vitro autoradiography and short-lived positron emission tomography tracers [11C]cyano-dizocilpine, 4-N-[11C]methylpiperidylbenzilate (4-N-[11C]MPB), and [11C]flumazenil, respectively. The binding potential (BP, Bmax/KD) was calculated. The data with [11C]cyano-dizocilpine showed a significant decrease in BP bilaterally for the frontoparietal cortex and hippocampus at both time points, in comparison with that of the sham-operated controls. At 12 h the decrease was significantly more prominent for the ipsilateral cortex and hippocampus than for the contralateral side. The BP of 4-N-[11C]MPB was significantly decreased after 2 h for the trauma-side hippocampus, and after 12 h it had decreased for the trauma-site cortex and the bilateral hippocampus. The [11C]flumazenil exhibited a significant decrease in BP for the trauma-site cortex and the underlying hippocampus by 2 h after the traumatic brain injury. After 12 h a significantly decreased BP was observed only for the trauma-site cortex. The finding of a decreased BP demonstrates the involvement of these receptor systems in the development of cellular dysfunction, which is widespread and not limited to the site of lateral FPI.

  16. 薏苡仁为主治疗脂溢性痤疮%Investigation of Yiyiren as Remedium Cardinale in the Treat of Seborrheic Ache

    候小亮; 崔应珉


    Objective:Investigate the effect of Yiyiren as remedium cardinale in the treat of seborrheic acne. Methods;Use Yiyiren as re-medium cardinal in the treatment of seborrheic acne according to TCM differentiation - treatment. Results: Seborrheic acne is mainly because of splenogastric hygropyrexia and hair follicle blocking by moisture blocking. Yiyiren as remedium cardinal in the treatment of seborrheic acne has evident effect. Conclusion; YiyiRen has satisfied curative effect for seborrheic acne so that the mechanism needs further study.%目的:探讨以薏苡仁为主药治疗脂溢性痤疮的效果.方法:采用中医辨证论治的方法,重用薏苡仁,治疗典型脂溢性痤疮症.结果:脂溢性痤疮主要是由于脾胃湿热上炎,湿气排出不畅堵塞毛囊引起,通过重用薏苡仁能使患者的临床病症得到改善,疗效显著.结论:薏苡仁治疗脂溢性痤疮疗效满意,其机理有待进一步研究.

  17. O tekście i źrόdłach "Punktόw Kazań" Konstantego Szyrwida

    Virginija Vasiliauskienė


    Full Text Available On the text structure and sources of K. Sirvydas’ book of sermons (Punktai sakymų – Punkty Kazań The Jesuit priest Konstantinas Sirvydas (~1580–1631 was one of the most multitalented and creative intellectuals in Lithuania in the 17th century. Using his vast experience as a professor of Vilnius University and a preacher, he compiled two different versions of a trilingual Latin-Polish-Lithuanian dictionary (~1620 and 1631, and wrote the book of sermons Punktai sakymų (‘Points of Gospel’. The importance of this book of sermons for the Lithuanian culture is immeasurable and it is considered the first book of original sermons written in Lithuanian and the first translation from Lithuanian into another language, i.e. into Polish. This book is often deemed the first original book written in Lithuanian. Unfortunately, its textual structure and its sources have not been properly evaluated and described yet. When preparing this scientific edition of his book, it appeared that its text is mostly comprised of: (1 citations from the Holy Scriptures, and paraphrases and allusions to them; (2 citations and paraphrases or allusions to works by the Church Fathers, Saints, Roman authors, etc.; and, finally, (3 Sirvydas’ original text – his commentaries and interpretations on citations, etc. There are citations from most of the books of the Old and New Testament. In his book Sirvydas uses 150 different biblical names. He also quotes from the Church Fathers, French theologians and thinkers, and from the Saints. We mostly find exact word-byword citations from Vulgate in his sermons – not paraphrases or allusions. These citations are the first published fragments from the Holy Scriptures in Lithuanian in the Grand Duchy of Lithuania. With this background information we may to hypothesize that during the first quarter of the 17th century, there might have existed an unknown translation (probably some manuscript of the Holy Scriptures in Lithuanian.   О тексте и источниках сборника проповедей Punktai sakymų (Punkty kazań Константина Ширвида Koнстантин Ширвид (~ 1580–1631 однa из самых универсальных и интеллектуальных личностей, живших и работавших в XVII веке в Литве. K. Ширвид подготовил два издания словаря Dicionarium trium linguarum (~ 1620, 1631 и издал проповеди в виде пунктов Punktai sakymų (PS. Значение PS для литовской культуры огромно. PS считаются первым оригинальным сборником проповедей в Литве и первой литовской книгой, переведенной на польский язык. Однако до сих пор cтoль важный для литовской культуры текст не был изучен и подробно описан. В процессе анализа текста выяснилось, что структура его довольно многогранна. Текст PS состоит из нескольких слоев: (1 цитат и аллюзий Библии; (2 цитат трудов отцов Церкви, цитат или аллюзий других авторов: римских писателей, протестантских авторов, святых; (3 авторского текста самого К. Ширвида, который часто принимает форму комментария к приведенным цитатам. Автор в тексте проповедей цитирует большинство книг Ветхого и Нового Завета. В проповеди упомянуто 150 библейских имен. К. Ширвид цитирует также отцов Церкви и французских богословов и мыслителей, святых. Цитаты из Ветхого и Нового Завета являются одним из первых фрагментов перевода на литовский язык Святого Писания в Великом княжестве Литовском.

  18. Human Disturbance Threats the Red-Listed Macrolichen Seirophora villosa (Ach.) Frödén in Coastal Juniperus Habitats: Evidence From Western Peninsular Italy

    Benesperi, Renato; Lastrucci, Lorenzo; Nascimbene, Juri


    In Europe, coastal dune systems with Juniperus spp. (Natura 2000 habitat code 2250) are a priority habitat for conservation according to the Natura 2000 policies. Currently, anthropogenic pressure is threatening the biodiversity of this habitat. While the impact of human pressure on animals and vascular plants is already documented, information is still scanty for other organisms such as epiphytic lichens. The main aim of this study is to test the effect of human disturbance on the occurrence and abundance of the red-listed macrolichen Seirophora villosa. We also tested the effect of human disturbance on the whole community of epiphytic lichens in terms of species richness and composition. The study was performed along the coast of Tuscany by comparing both disturbed and undisturbed Juniperus stands according to a stratified random sampling design. Our results provided evidence that in coastal systems the long-term conservation of the red-listed macrolichen S. villosa and its characteristic community composed by several Mediterranean species of conservation concern depends on the maintenance of undisturbed Juniperus habitats. Results also support the possibility of using S. villosa as an indicator species of habitat conservation importance and habitat integrity since its occurrence is predicted on nestedness in term of species composition, assemblages of species poor disturbed stands being subsets of those of richer undisturbed stands.

  19. A pharmacodynamic comparison of piperidine and pyridine alkaloid actions at fetal muscle-type nicotinic acetylcholine receptors (nAChR)

    Piperidine and pyridine alkaloids are found in many species of plants including Lobelia spp., Conium spp., Nicotiana spp., and Lupinus spp. Some of these alkaloids cause multiple congenital contracture deformities (MCC) and cleft palates in cattle, pigs, sheep, and goats. The mechanism behind MCC ...

  20. "My Greatest Joy and My Greatest Heart Ache:" Parents' Own Words on How Having a Child in the Autism Spectrum Has Affected Their Lives and Their Families' Lives

    Myers, Barbara J.; Mackintosh, Virginia H.; Goin-Kochel, Robin P.


    Parents of children in the autism spectrum wrote an open-ended answer via an online questionnaire to the question, "How has your child in the autism spectrum affected your life and your family's life?" (N = 493). Using a qualitative content analysis, 15 negative themes and 9 positive themes were identified. Themes are subsumed into five clusters:…

  1. 红蓝光照射治疗痤疮110例%Red Light and Blue Light Therapy in Treating Patients with Ache: 110 Cases

    邵燕磊; 王蕾


    Objective To investigate the clinical efficacy and safety of the red light and blue light therapy on 110 cases of acne patients. Methods Subjects were treated by the red light and blue light therapy alternatively with a total of eight serial biweekly treatment sessions. They were assessed and compared with the reduced rates of acne lesions in patients before and after treatment. Results The total effective rate was 83.09%. The average reduced rates of the non-inflammatory lesions and inflammatory lesions were 52.36% and 69.47% respectively (P<0.05). After three months follow-up, the total effective rate had no significant statistical difference compare to the end of treatment sessions. Conclusion The treatment of acne patients with the red light and blue light is effective in acne. And it has low recurrence rate and fewer side effects.%目的 观察红蓝光照射治疗痤疮的临床疗效和安全性.方法 联合红蓝光治疗110例痤疮患者,每周2次,共8次,计数患者炎性病损及非炎性病损及皮损总数来比较改善率.结果 治疗结束时有效率为83.09%;非炎性皮损及炎性皮损平均改善率分别为52.36%和69.47%,P<0.05;随访3个月,有效率与治疗结束时比较差异无统计学意义.结论 红蓝光治疗痤疮疗效显著、复发率低、不良反应少.

  2. Intermolecular forces between acetylcholine and acetylcholinesterases studied with atomic force microscopy

    张英鸽; 白春礼; 王琛; 赵德禄; 苏明; 林璋; 田芳


    With the aid of atomic force microscopy, the intermolecular forces between acetyleholinesterases (AChE) and its natural substrate acetylcholine (ACh) have been studied. Through force spectrum measurement based on imaging of AChE molecules it was found that the attraction force between individual molecule pairs of ACh and AChE was (10±1) pN just before the quaternary ammonium head of ACh got into contact with the negative end of AChE and the decaying distance of attraction was (4±1) nm from the surface of ACHE. The adhesion force between individual ACh and AChE molecule pairs was (25±2) pN, which had a decaying feature of fast-slow-fast (FSF). The attraction forces between AChE and choline (Ch), the quaternary ammonium moiety and hydrolysate of ACh molecule, were similar to those between AChE and ACh. The adhesion forces between AChE and Ch were (20±2) pN, a little weaker than that between ACh and ACHE. These results indicated that AChE had a steering role for the diffusion of ACh toward it and had r

  3. Fsiles de novela: paleontologa y literatura en la argentina de fines del siglo XIX y principios del siglo Fossils as fictional characters: Argentine paleontology and literature in the late 19th century and the beginnings of the 20th century

    Eduardo G. Ottone


    Full Text Available La literatura argentina de la segunda mitad del siglo XIX y comienzos del siglo XX refiri la presencia de mamferos fsiles cenozoicos en las pampas. Gliptodontes y megaterios devinieron en personajes de los textos de Eduardo Ladislao Holmberg, William Henry Hudson, Eduarda y Lucio Victorio Mansilla, Leopoldo Lugones, Geoffroy Franois Daireux, Horacio Quiroga, Hugo Wast, Ezequiel Martnez Estrada, Leopoldo Marechal y Manuel Mujica Lainez. Estos autores contextualizaron a los vertebrados fsiles en escenas humorsticas o realistas, como iconos de la grandeza de la Pampa y la nacin o parodia de estereotipos culturales locales.Argentine literature from the second half of the 19th century and the early 20th century referred to the presence of Cenozoic fossil mammals in the pampas. Glyptodons and megatheriums became characters in the texts of Eduardo Ladislao Holmberg, William Henry Hudson, Eduarda y Lucio Victorio Mansilla, Leopoldo Lugones, Geoffroy Franois Daireux, Horacio Quiroga, Hugo Wast, Ezequiel Martnez Estrada, Leopoldo Marechal and Manuel Mujica Lainez. These authors contextualize the fossil vertebrates in humoristic or realistic scenes, as icons of the greatness of the nation and the Pampa, or as a parody of local cultural stereotypes.

  4. 围头湾5种海藻提取物 AChE 抑制活性与 DPPH.清除能力的比较%Acetyl Choline Enzyme Inhibitory Activity and DPPH. Radical Scavenging Capacity of the Extracts from Five Seaweeds in Fujian Weitou Bay

    黄晓冬; 李裕红; 黄晓昆; 戴聪杰


    对福建省围头海域5种海藻提取物及萃取部位的乙酰胆碱酶抑制活性与 DPPH.清除能力进行比较研究,并分别测定其总酚与总黄酮含量.结果表明:裙带菜与羊栖菜提取物具有较高含量的总酚与总黄酮;裙带菜的乙酸乙酯部位、二氯甲烷部位和羊栖菜石油醚部位、二氯甲烷部位在10 mg/mL 质量浓度时表现出较强的乙酰胆碱酶抑制活性,并且裙带菜乙酸乙酯部位、二氯甲烷部位以及羊栖菜二氯甲烷部位的DPPH.清除能力均明显高于其他提取物或萃取部位.%The acetyl choline enzyme inhibitory activity and DPPH. radical scavenging capacity of the extracts and its solvent fraction from five kinds of seaweed in Fujian Weitou bay were studied.Results showed that the exracts from Undaria pinnatifida and Sargassum fusiforme had higher concentra-tion of polyphenols and flavonoids.Ethyl acetate fraction and methylene chloride fraction from Un-daria pinnatifida,petroleum ether fraction and dichloromethane fraction from Sargassum fusiforme had strong acetylcholine enzyme inhibitory activity at 10 mg/mL.At the concentration of 1 mg/mL, the DPPH . scavenging abilities of ethyl acetate fraction and methylene chloride fraction from Un-daria pinnatifida ,dichloromethane fraction from Sargassum fusiforme were higher than other ex-tracts or fractions.

  5. Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality.

    Duysen, E G; Li, B; Xie, W; Schopfer, L M; Anderson, R S; Broomfield, C A; Lockridge, O


    The possibility that organophosphate toxicity is due to inhibition of targets other than acetylcholinesterase (AChE, EC was examined in AChE knockout mice. Mice (34-55 days old) were grouped for this study, after it was determined that AChE, butyrylcholinesterase (BChE), and carboxylesterase activities had reached stable values by this age. Mice with 0, 50, or 100% AChE activity were treated subcutaneously with the nerve agent VX. The LD50 for VX was 10 to 12 microg/kg in AChE-/-, 17 microg/kg in AChE+/-, and 24 microg/kg in AChE+/+ mice. The same cholinergic signs of toxicity were present in AChE-/- mice as in wild-type mice, even though AChE-/- mice have no AChE whose inhibition could lead to cholinergic signs. Wild-type mice, but not AChE-/- mice, were protected by pretreatment with atropine. Tissues were extracted from VX-treated and untreated animals and tested for AChE, BChE, and acylpeptide hydrolase activity. VX treatment inhibited 50% of the AChE activity in brain and muscle of AChE+/+ and +/- mice, 50% of the BChE activity in all three AChE genotypes, but did not significantly inhibit acylpeptide hydrolase activity. It was concluded that the toxicity of VX must be attributed to inhibition of nonacetylcholinesterase targets in the AChE-/- mouse. Organophosphorus ester toxicity in wild-type mice is probably due to inhibition or binding to several proteins, only one of which is AChE.

  6. Acetylcholinesterase activity in the cerebrospinal fluid of dogs with seizures.

    Chai, Orit; Sommer, Adi; Zimmerman, Gabriel; Soreq, Hermona; Friedman, Alon; Bdolah-Abram, Tali; Aroch, Itamar; Shamir, Merav H


    Recent studies in animal models have focused on the role of cholinergic elements, mainly acetylcholinesterase (AChE) and the 'readthrough' acetylcholinesterase isoform (AChE-R), in seizures. A prospective double-masked study was conducted to assess the activity of AChE and AChE-R in cerebrospinal fluid (CSF) of 26 dogs post-seizure, 28 dogs with intervertebral disc disease (IVDD) and 16 healthy dogs. AChE was also measured in the serum in the post-seizure and IVDD groups. The results showed no significant differences in CSF AChE among the three groups. AChE-R was not detected in any dog and AChE in the serum was similar between groups. This preliminary study provides new information on AChE and AChE-R in the CSF and sera of dogs following naturally-occurring seizures.

  7. The bispyridinium-dioxime HLö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman

    Jong,; Verhagen, M.A.A.; Langenberg, J.P.; Hagedorn, I.; Löffler, M.


    Purification of (+)-tabun was accomplished by treatment with electric eel acetylcholinesterase (AChE) in order to bind contaminating (-)-tabun, the more potent enantiomer with respect of AChE inhibition. Electric eel AChE inhibited with (-)-tabun and with purified (+)-tabun show similar properties i

  8. Identification and characterization of mutations in housefly (Musca domestica) acetylcholinesterase involved in insecticide resistance

    Walsh, Sinead B.; Dolden, Tracey A.; Moores, Graham D.


    Acetylcholinesterase (AChE) insensitive to organophosphate and carbamate insecticides has been identified as a major resistance mechanism in numerous arthropod species. However, the associated genetic changes have been reported in the AChE genes from only three insect species; their role in confe...... of the AChE protein from Torpedo californica and D. melanogaster....

  9. Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

    Miyazawa, M; Tougo, H; Ishihara, M


    Inhibition of acetylcholinesterase (AChE) activity by essential oils of Citrus paradisi (grapefruit pink in USA) was studied. Inhibition of AChE was measured by the colorimetric method. Nootkatone and auraptene were isolated from C. paradisi oil and showed 17-24% inhibition of AChE activity at the concentration of 1.62 microg/mL.

  10. Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease.

    Kogen, Hiroshi; Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio


    Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text

  11. MMB-4 Inhibition of Aceylcholinesterase Is Similar across Species


    in 50% inhibition of AChE activity ( IC50 ) for RBC ghosts from each species was found to be very similar, differing by roughly two fold; of note...version 5.4). An IC50 value was determined for AChE from each animal species by fitting the percent of AChE activity with respect to MMB 4 concentration...Therefore, AChE activity and inhibition studies were carried out at 435 nm to reduce interference from MMB 4. Comparison of IC50 Values for MMB 4 with AChE

  12. Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX.

    Kuca, Kamil; Musilek, Kamil; Jun, Daniel; Karasova, Jana; Soukup, Ondrej; Pejchal, Jaroslav; Hrabinova, Martina


    Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family.

  13. A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

    Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi


    Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).

  14. Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

    Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi


    We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

  15. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine.

    Darreh-Shori, T; Kadir, A; Almkvist, O; Grut, M; Wall, A; Blomquist, G; Eriksson, B; Långström, B; Nordberg, A


    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  16. Hypo-analytic structures local theory (PMS-40)

    Treves, François


    In Hypo-Analytic Structures Franois Treves provides a systematic approach to the study of the differential structures on manifolds defined by systems of complex vector fields. Serving as his main examples are the elliptic complexes, among which the De Rham and Dolbeault are the best known, and the tangential Cauchy-Riemann operators. Basic geometric entities attached to those structures are isolated, such as maximally real submanifolds and orbits of the system. Treves discusses the existence, uniqueness, and approximation of local solutions to homogeneous and inhomogeneous equations and delimits their supports. The contents of this book consist of many results accumulated in the last decade by the author and his collaborators, but also include classical results, such as the Newlander-Nirenberg theorem. The reader will find an elementary description of the FBI transform, as well as examples of its use. Treves extends the main approximation and uniqueness results to first-order nonlinear equations by means of ...

  17. The doctor practicing western medicine treats the myo- fascia ache syndrome the present situation research%中西医治疗肌筋膜疼痛综合征的现状研究

    谢健周; 查和萍; 范志勇; 何巧宜


    肌筋膜疼痛综合征(myofascial pain syndrome,MPS)是一种复杂的慢性疼痛性疾病,好发于人体多个部位,是颈肩腰背痛的常见病因.本文从现代医学和祖国医学两方面对其治疗现状进行详细论述,并对今后的发展及研究方向提出展望.

  18. An Overiew of Treatment of Chronic Pelvic Ache with Integrated Traditional Chinese and Western Medicine%中西医结合治疗慢性盆腔疼痛概述



    慢性盆腔疼痛是妇科常见症状之一,指持续六个月或以上,且不完全与月经周期及性交有关的盆腔疼痛.在育龄妯女的发病率为3.8%.慢性盆腔疼痛在临床上常见,难处理且易复发,严重影响妇女的工作及性生活质量.目前,越来越多的证据表明中西医结合治疗女性慢性盆腔疼痛有着很好的效果.%Chronic pelvic pain is a common disease in women,manifested by more than six months pain in the lower abdominal area,which is not entirely associated with the menstrual cycle or sexual intercourse.Chronic pelvic pain has a prevalence of 3.8% among women of reproductive age.It is commonly seen in clinic,but difficult to be treated and easily relapses.Chronic pelvic pain may have profound effects on women's work and quality of sexual life.In recent years,more and more evidence suggest that integrated traditional Chinese and western medicine has a great efficancy in treating patients with Chronic pelvic pain.

  19. Clinical Observation on Ache Vulgaris Treated with Cuochuangjing Combined with Facial Mask of Chinese Medicine%痤疮净配合中药面膜治疗寻常痤疮临床观察




  20. Study on the function of chemokine receptor CCR7 in metastasis of stom-ach cancer%趋化因子受体CCR7在胃癌转移中的作用研究

    王欢; 袁武锋; 蒋雷; 费鲜明


    Objective To construct stable expression system of pLVX-Pro-CCR7 and study the function of CCR7 gene in metastasis of stomach cancer. Methods PCR method was used to amplify CCR7 gene and construct pLVX-Puro-CCR7 recombinant plasmid. Lipofection was used to infect SGC7901 cell strain immediately, and puromycin was used to screen the cell strain and establish a cell strain with stable expression. Western blot method was used to test the ex-pression of CCR7 in SGC7901 cells which were stably infected. Transwell method was used to analyze the effect of overly expressed CCR7 gene on in vitro migration of stomach cancer cells of SGC7901. Living imaging was used to ob-serve the metastasis ability of stomach cancer cell strain of SGC7901 which overly expressed CCR7 in nude mice. Re-sults pLVX-Puro-CCR7 recombinant plasmid was successfully constructed and SGC791 cell strain was stably infected. The cell strain was able to correctly translate and express CCR7 protein. Metastasis ability in nude mice and in vitro migration ability of SGC7901 stomach cancer cell strain which overly expressed CCR7 gene significantly improved (P<0.05). Conclusion CCR7 may be involved in the function of promoting metastasis of stomach cancer cells.%目的:构建pLVX-Puro-CCR7稳定表达系统并研究CCR7基因在胃癌转移中的作用。方法采用PCR方法扩增CCR7基因并构建pLVX-Puro-CCR7重组质粒,通过脂质体转染法瞬时转染SGC7901细胞株,嘌呤霉素对该细胞株进行筛选并建立稳定表达细胞株。 Western blot方法检测稳定转染的SGC7901细胞中CCR7表达情况。Transwell方法分析过度表达CCR7基因对SGC7901胃癌细胞体外迁移的影响。活体成像观察过度表达CCR7的SGC7901胃癌细胞株在裸鼠体内转移能力。结果成功构建pLVX-Puro-CCR7重组质粒并稳定转染SGC7901细胞株,该细胞株能够正确翻译及表达CCR7蛋白。过度表达CCR7基因的SGC7901胃癌细胞株体外迁移能力和在裸鼠体内转移能力显著增强(P<0.05)。结论 CCR7可能参与促进胃癌细胞转移的功能。

  1. Effect of Mental Intervention in Alleviating Fear,Ache and Pleural Reaction Induced by Thoracocentesis%心理干预在减轻胸穿患者恐惧疼痛及胸膜反应中的作用

    崔魁丽; 刘卫国; 徐卫华


    目的 探讨心理干预在减轻胸穿恐惧疼痛及术中胸膜反应的作用.方法 将126例患者随机分成两组,对照组(56例)常规胸穿,干预组(70例)加用认知、情绪、行为心理干预.结果 两组患者恐惧发生率间差别有显著性意义(P<0.05),疼痛及术中胸膜反应发生率间差别亦均有显著性意义(P<0.05).结论 心理干预作用显著,临床上应给予高度重视.

  2. Rozmieszczenie i ekologia rozsiewania się chiuastów w zespołach polnych w Gorcach [Distribution and dispersal ecology of weeds in segetal plant communities in the Gorce Mts. (Polish Western Carpathians)

    Jan Kornaś


    Dispersal ecology of 113 taxa of weeds studied. The weight of their diaspores was determined and their morphological adaptations to natural dispersal agents were examined. The role of man in weed dispersal was established by analysing 25 crop seed samples of local origin. Dispersal spectra of cereal crop culture community Geranio-Silenetum vicietosum, root-crop culture community G.-S. veronicetosum, and flax culture community Spergulo-Lolietum remoti were compiled. The reasons of decline of t...

  3. Neuropharmacological modulation of the P3-like event-related potential in a rat two-tone auditory discrimination task with modafinil and NS9283, a positive allosteric modulator of α4β2 nAChRs.

    Grupe, Morten; Grunnet, Morten; Laursen, Bettina; Bastlund, Jesper Frank


    The P300 (P3) event-related potential (ERP) is a neurophysiological signal believed to reflect cognitive processing of salient cues, and is thus used as a measure of attention and working memory. Additionally, P3 amplitude and latency is altered in neurological diseases and can be pharmacologically modulated. As P3-like ERPs can be recorded in rodents, it may serve as a potential translational biomarker of value for drug discovery. Here we investigated whether a positive allosteric modulator of α4β2 nicotinic acetylcholine receptors, NS9283, and the psychostimulant modafinil could modulate P3-like ERPs in healthy adult rats performing an auditory oddball discrimination task. ERPs were recorded with electroencephalography electrodes implanted into mediodorsal (MD) thalamus, medial prefrontal cortex, hippocampus and auditory cortex (AC). P3-like ERPs were detected in all brain regions, displaying larger amplitudes in target trials compared to non-target trials. Administration of modafinil (64 mg/kg) decreased P3-like ERP latency in MD thalamus and AC, whereas NS9283 augmented P3-like ERP amplitude in MD thalamus at 0.3 mg/kg and in AC at 3.0 mg/kg. Additionally, N1 pre-attention peak amplitude in MD thalamus was increased with 0.3 mg/kg NS9283. Neither of the compounds enhanced task performance. Rather, modafinil lowered correct rejections in non-target trials. In summary, our findings reveal pharmacological modulation of the rat P3-like ERP in cortical and subcortical regions by modafinil and NS9283. These findings encourage further exploration of the rat P3-like ERP in order to promote the understanding of its meaning within cognition, as well as its applicability as a translatable biomarker in drug development.

  4. 1844例胃脘痛时间生物节律的临床流行病学研究%Epidemiological investigation of chronobiological rhythm: A report of 1 844 patients with stomach ache

    石建喜; 胡剑北; 程宜福



  5. 抑脂祛痘药膜对兔耳实验性痤疮的作用%Effects of lipid and ache inhibitive cream on acne model of rabbit's ears

    杨柳; 杨文志



  6. 考虑桩土共同作用的连续拱桥计算%The Calculation of Continuous Ached Bridge Considered the Interaction of Soil-Pile

    赵崇臣; 胡达和



  7. The Exploration on the Fowler's Position Applied to Prevent the Psoas Ache Early after the Abdominal Operation%早期半卧位预防腹部术后腰肌酸痛的探讨




  8. Projekt rejestrowania cytowań w artykułach indeksowanych w "Bazie danych o zawartości polskich czasopism technicznych" BazTech : koncepcja ogólna


    The project aims to improve the "Polish Technical Journal Contents" BazTech which now is a database containing bibliographic details and abstracts from the Polish technical journals on engineering, technology, sciences and the environment. The main aim of the project is indexing of references attached to all articles in the BazTech database. The proposed concept assumes organizational methods and technical solutions. The report analysis also another Polish citation databases.

  9. Heat stress and the photosynthetic electron transport chain of the lichen Parmelina tiliacea (Hoffm.) Ach. in the dry and the wet state: differences and similarities with the heat stress response of higher plants.

    Oukarroum, Abdallah; Strasser, Reto J; Schansker, Gert


    Thalli of the foliose lichen species Parmelina tiliacea were studied to determine responses of the photosynthetic apparatus to high temperatures in the dry and wet state. The speed with which dry thalli were activated by water following a 24 h exposure at different temperatures decreased as the temperature was increased. But even following a 24 h exposure to 50 °C the fluorescence induction kinetics OJIP reflecting the reduction kinetics of the photosynthetic electron transport chain had completely recovered within 128 min. Exposure of dry thalli to 50 °C for 24 h did not induce a K-peak in the fluorescence rise suggesting that the oxygen evolving complex had remained intact. This contrasted strongly with wet thalli were submergence for 40 s in water of 45 °C inactivated most of the photosystem II reaction centres. In wet thalli, following the destruction of the Mn-cluster, the donation rate to photosystem II by alternative donors (e.g. ascorbate) was lower than in higher plants. This is associated with the near absence of a secondary rise peak (~1 s) normally observed in higher plants. Analysing the 820 nm and prompt fluorescence transients suggested that the M-peak (occurs around 2-5 s) in heat-treated wet lichen thalli is related to cyclic electron transport around photosystem I. Normally, heat stress in lichen thalli leads to desiccation and as consequence lichens may lack the heat-stress-tolerance-increasing mechanisms observed in higher plants. Wet lichen thalli may, therefore, represent an attractive reference system for the evaluation of processes related with heat stress in higher plants. © Springer Science+Business Media B.V. 2012

  10. Estudio de la Acetilcolinesterasa (ACHE) y la Colinesterasa (CHE) en Animales y Humanos de la Población Andaluza. Su significación clínica.

    Repetto Jiménez, Jesús


    La primera sugerencia sobre la existencia en el suero sanguíneo de un factor capaz de hidrolizar la acetilcolina fue realizada por Dale en 1914; su implicación en la función nerviosa se debe a Loewi y Navratil (1921). Este factor que hidrolizaba los ésteres de colina recibió el nombre de colinesterasa por Stedman y col (1932); posteriormente se distinguieron una pseudocolinesterasa y colinesterasa verdadera (acetil colinesterasa). Se ha investigado mucho ...

  11. Espectrometría de masas de iones secundarios: aportaciones a la técnica y caracterización de capas finas de a-C:H y de a-Si:H

    López Fernández, Francisco


    Entre las técnicas microanalíticas, el SIMS ha experimentado un gran éxito en las dos últimas décadas. Su habilidad para proporcionar datos de composición elemental y estructura, su capacidad para detectar pequeñas concentraciones de elementos y su distribución en profundidad, etc.; ha hecho que el SIMS sea un instrumento muy útil en numerosos campos de la ciencia y la tecnología. Se ha de mencionar también que la limitación más importante que padece la técnica es su falta de carácter cuantit...

  12. The Application of Macro-thinking in College English Te-aching Based on Holism%整体论指导下大学英语宏观教学思维的运用



    整体论指导下的整体教学法有效解决了大学英语教学中教学分离、知识点分散等现象。宏观教学思维在整体论基础上,对整体教学方法进行延伸和扩展,为大学英语教学提供新思路,并用于指导教学实践和学生宏观思维的培养,有助于构建完善的知识网络结构,提高学生自主学习能力。%Based on Holism, Whole Language Teaching Method solves some practical language teaching problems, such as sepa-ration between teaching and learning, scattering of language points.As the extending of Whole Language Teaching, macro-thinking pattern is used to guide modern college English teaching, and it helps to build network language structure,culti-vate macro-thinking ability, and promote students' autonomous learning ability.

  13. 乱流洁净室中换气次数对污染物扩散影响的数值模拟%Effect of ACH on contamination diffusion in turbulent cleanroom

    李云广; 南国良; 马宗虎



  14. Rozmieszczenie i ekologia rozsiewania się chiuastów w zespołach polnych w Gorcach [Distribution and dispersal ecology of weeds in segetal plant communities in the Gorce Mts. (Polish Western Carpathians

    Jan Kornaś


    Full Text Available Dispersal ecology of 113 taxa of weeds studied. The weight of their diaspores was determined and their morphological adaptations to natural dispersal agents were examined. The role of man in weed dispersal was established by analysing 25 crop seed samples of local origin. Dispersal spectra of cereal crop culture community Geranio-Silenetum vicietosum, root-crop culture community G.-S. veronicetosum, and flax culture community Spergulo-Lolietum remoti were compiled. The reasons of decline of the segetal flora with altitude was explained by the limiting action of climatic factors upon weeds.

  15. Performance Technology Program (PTP-S II). Volume VI. A Statistical Model of Nosetip Shape Change for Reentry Vehicles.


    comparison. Specific pre-flight NDE or characterization procedures have been suggested in order to identify billets likely to have a high variance in...Communication fran D. C. Reda 14. D. C. Wilcox , Turbulence Model Transition Predictions: Effects of Surface Roughness and Pressure Gradient. AIAA Paper

  16. Between Speaking and Silence: A Study of Quiet Students

    Reda, Mary M.


    Why are students silent? Using written reflections and interviews, Mary M. Reda examines students' perceptions of speaking and being silent in a first-year composition classroom, and explores how their teachers, classroom relationships, and their own sense of identity shape their decisions to speak or be silent. By challenging many firmly held…

  17. George Orwell e os desdobramentos literários de uma presença no front

    Carlos Gohn


    Full Text Available Esse trabalho apresenta as circunstâncias que rodeiam a ida de George Orwell como combatente voluntário à Espanha e a redação de Homage to Catalonia após seu retorno à Inglaterra.

  18. Pyrgeometer Calibration for DOE-Atmospheric System Research Program Using NREL Method (Presentation)

    Reda, I.; Stoffel, T.


    Presented at the DOE-Atmospheric System Research Program, Science Team Meeting, 15-19 March 2010, Bethesda, Maryland. The presentation: Pyrgeometer Calibration for DOE-Atmospheric System Research program using NREL Method - was presented by Ibrahim Reda and Tom Stoffel on March 15, 2010 at the 2010 ASR Science Team Meeting. March 15-19, 2010, Bethesda, Maryland.

  19. Análise das práticas de ensino da metodologia de investigação na elaboração do trabalho de fim de curso

    Jutema Hebo Quitumba; Juan Antonio López Nuñez; Natalia Campos Soto


    ... e no Brasil.A pesquisa seguiu a perspectiva da metodologia quantitativa e qualitativa e a norma/formato da American Psychological Association (APA) para a redação textual. Usou inquérito por questionário. Recorreu a técnica...

  20. Identification and Biochemical Properties of Two New Acetylcholinesterases in the Pond Wolf Spider (Pardosa pseudoannulata).

    Meng, Xiangkun; Li, Chunrui; Xiu, Chunli; Zhang, Jianhua; Li, Jingjing; Huang, Lixin; Zhang, Yixi; Liu, Zewen


    Acetylcholinesterase (AChE), an important neurotransmitter hydrolase in both invertebrates and vertebrates, is targeted by organophosphorus and carbamate insecticides. In this study, two new AChEs were identified in the pond wolf spider Pardosa pseudoannulata, an important predatory natural enemy of several insect pests. In total, four AChEs were found in P. pseudoannulata (including two AChEs previously identified in our laboratory). The new putative AChEs PpAChE3 and PpAChE4 contain most of the common features of the AChE family, including cysteine residues, choline binding sites, the conserved sequence 'FGESAG' and conserved aromatic residues but with a catalytic triad of 'SDH' rather than 'SEH'. Recombinant enzymes expressed in Sf9 cells showed significant differences in biochemical properties compared to other AChEs, such as the optimal pH, substrate specificity, and catalytic efficiency. Among three test substrates, PpAChE1, PpAChE3 and PpAChE4 showed the highest catalytic efficiency (Vmax/KM) for ATC (acetylthiocholine iodide), with PpAChE3 exhibiting a clear preference for ATC based on the VmaxATC/VmaxBTC ratio. In addition, the four PpAChEs were more sensitive to the AChE-specific inhibitor BW284C51, which acts against ATC hydrolysis, than to the BChE-specific inhibitor ISO-OMPA, which acts against BTC hydrolysis, with at least a 8.5-fold difference in IC50 values for each PpAChE. PpAChE3, PpAChE4, and PpAChE1 were more sensitive than PpAChE2 to the tested Carb insecticides, and PpAChE3 was more sensitive than the other three AChEs to the tested OP insecticides. Based on all the results, two new functional AChEs were identified from P. pseudoannulata. The differences in AChE sequence between this spider and insects enrich our knowledge of invertebrate AChE diversity, and our findings will be helpful for understanding the selectivity of insecticides between insects and natural enemy spiders.

  1. Identification and Biochemical Properties of Two New Acetylcholinesterases in the Pond Wolf Spider (Pardosa pseudoannulata.

    Xiangkun Meng

    Full Text Available Acetylcholinesterase (AChE, an important neurotransmitter hydrolase in both invertebrates and vertebrates, is targeted by organophosphorus and carbamate insecticides. In this study, two new AChEs were identified in the pond wolf spider Pardosa pseudoannulata, an important predatory natural enemy of several insect pests. In total, four AChEs were found in P. pseudoannulata (including two AChEs previously identified in our laboratory. The new putative AChEs PpAChE3 and PpAChE4 contain most of the common features of the AChE family, including cysteine residues, choline binding sites, the conserved sequence 'FGESAG' and conserved aromatic residues but with a catalytic triad of 'SDH' rather than 'SEH'. Recombinant enzymes expressed in Sf9 cells showed significant differences in biochemical properties compared to other AChEs, such as the optimal pH, substrate specificity, and catalytic efficiency. Among three test substrates, PpAChE1, PpAChE3 and PpAChE4 showed the highest catalytic efficiency (Vmax/KM for ATC (acetylthiocholine iodide, with PpAChE3 exhibiting a clear preference for ATC based on the VmaxATC/VmaxBTC ratio. In addition, the four PpAChEs were more sensitive to the AChE-specific inhibitor BW284C51, which acts against ATC hydrolysis, than to the BChE-specific inhibitor ISO-OMPA, which acts against BTC hydrolysis, with at least a 8.5-fold difference in IC50 values for each PpAChE. PpAChE3, PpAChE4, and PpAChE1 were more sensitive than PpAChE2 to the tested Carb insecticides, and PpAChE3 was more sensitive than the other three AChEs to the tested OP insecticides. Based on all the results, two new functional AChEs were identified from P. pseudoannulata. The differences in AChE sequence between this spider and insects enrich our knowledge of invertebrate AChE diversity, and our findings will be helpful for understanding the selectivity of insecticides between insects and natural enemy spiders.

  2. Tissue-specific effects of acetylcholine in the canine heart

    Callø, Kirstine; Goodrow, Robert; Olesen, Søren-Peter;


    INTRODUCTION: Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current (IK,ACh). The effect of ACh in ventricle is still debated. We compare the effect of ACh...

  3. Reliability and validity of the Antioch Child Hygiene Scale: A scale development study

    Ebru Turhan


    Conclusions: Although both ACHS forms (i.e., ACHS-C and ACHS-P were reliable in assessing the hygiene status of children, the reliability was higher for ACHS-P. In addition, validity should be improved in both forms of the ACHS. Nevertheless, both scales can be used to assess the hygiene status in school children.

  4. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima


    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

  5. Kinetic analysis of interactions of different sarin and tabun analogues with human acetylcholinesterase and oximes: is there a structure-activity relationship?

    Aurbek, Nadine; Herkert, Nadja M; Koller, Marianne; Thiermann, Horst; Worek, Franz


    The repeated misuse of highly toxic organophosphorus compound (OP) based chemical warfare agents in military conflicts and terrorist attacks poses a continuous threat to the military and civilian sector. The toxic symptomatology of OP poisoning is mainly caused by inhibition of acetylcholinesterase (AChE, E.C. resulting in generalized cholinergic crisis due to accumulation of the neurotransmitter acetylcholine (ACh) in synaptic clefts. Beside atropine as competitive antagonist of ACh at muscarinic ACh receptors oximes as reactivators of OP-inhibited AChE are a mainstay of standard antidotal treatment. However, human AChE inhibited by certain OP is rather resistant to oxime-induced reactivation. The development of more effective oxime-based reactivators may fill the gaps. To get more insight into a potential structure-activity relationship between human AChE, OPs and oximes in vitro studies were conducted to investigate interactions of different tabun and sarin analogues with human AChE and the oximes obidoxime and HI 6 by determination of various kinetic constants. Rate constants for the inhibition of human AChE by OPs, spontaneous dealkylation and reactivation as well as reactivation by obidoxime and HI 6 of OP-inhibited human AChE were determined. The recorded kinetic data did not allow a general statement concerning a structure-activity relationship between human AChE, OP and oximes.

  6. Toxicological effect of herbicides (diuron and bentazon) on snake venom and electric eel acetylcholinesterase.

    Ahmed, Mushtaq; Latif, Nadia; Khan, Rehmat Ali; Ahmad, Akhlaq


    The toxicological effects of the active ingredients of the herbicides diuron and bentazon on the activity of acetylcholinesterase (AChE) of krait (Bungarus sindanus) venom and electric eel (Electrophorus electricus) were studied. The diuron and entazon caused non-competitive inhibition of AChE from both species. For the venom AChE, the calculated IC50 for diuron and bentazon were found to be 3.25 and 0.14 μM, while for eel AChE, the respective IC50 values were 3.6 and 0.135 μM. In comparison, bentazon was a more potent inhibitor than diuron of AChE from both species. The insecticide lindane did not have any inhibitory effect on AChE activity in either species, even when tested at high concentrations (200-800 μM).

  7. Brain acetylcholinesterase and its molecular forms in a precocial murid, Acomys cahirinus, and rat during post-natal development.

    Michalek, H; Pintor, A; Fortuna, S; Bisso, G M


    Brain acetylcholinesterase (AChE) and its molecular forms of a precocial murid, Acomys cahirinus, characterized by a large hippocampus, were measured during post-natal development and compared with rat. The activity of soluble AChE in Acomys increased slightly up to 4 weeks after birth. The total AChE activity increased somewhat more but, in rats, this increase was still greater. Three main molecular forms of AChE were separated by 7.5% polyacrylamide gel electrophoresis. Their close similarity to the rat AChE forms was assessed by gradient polyacrylamide gel electrophoresis and electrofocusing. Maturation of these forms, i.e., conversion of simple into more complex forms in the soluble fraction of AChE was, however, considerably delayed reaching only after 4 weeks the pattern comparable to that of rat.

  8. Acetylcholinesterase inhibitory properties of some benzoic acid derivatives

    Yildiz, Melike; Kiliç, Deryanur; Ünver, Yaǧmur; Şentürk, Murat; Askin, Hakan; Küfrevioǧlu, Ömer Irfan


    Acetylcholinesterase (AChE) hydrolyses the neurotransmitter acetylcholine to acetic acid and choline. AChE inhibitors are used in treatment of several neurodegeneartive disorder and Alzheimer's disease. In the present study, inhibition of AChE with some benzoic acid derivatives were investigated. 3-Chloro-benzoic acid (1), 2-hydroxy-5-sulfobenzoic acid (2), 2-(sulfooxy) benzoic acid (3), 2-hydroxybenzoic acid (4), 2,3-dimethoxybenzoic (5), and 3,4,5-trimethoxybenzoic (6) were calculated IC50 values AChE enzyme. Kinetic investigations showed that similarly to AChE inhibitors. Benzoic acid derivatives (1-6) investigated are encouraging agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.


    Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits toxicity through inhibition of acetylcholinesterase (AChE). Young animals are markedly more sensitive than adults to the acute toxicity of CPF. We evaluated acetylcholine (ACh) release and its muscarinic recept...

  10. Nucleus-specific translation and assembly of acetylcholinesterase in multinucleated muscle cells


    Multinucleated skeletal muscle fibers synthesize cell surface and secreted oligomeric forms of acetylcholinesterase (AChE) that accumulate at specialized locations on the cell surface, such as sites of nerve-muscle contact. Using allelic variants of the AChE polypeptide chains as genetic markers, we show that nuclei homozygous for either the alpha or beta alleles residing in chimeric myotubes preferentially translate their AChE mRNAs on their respective ERs. These results indicate that the ev...

  11. Acetylcholinesterase is associated with apoptosis in β cells and contributes to insulin-dependent diabetes mellitus pathogenesis

    Bao Zhang; QiOuyang; Bo Zhang; Lu Lu; Xuejun Zhang; Lei Yang; Luyang Yu; Bo Lin; Yanan Hou; Jun Wu; Qin Huang; Yifan Han; Lihe Guo


    Acetylcholinesterase (AChE) expression is pivotal during apoptosis.Indeed,AChE inhibitors partially protect cells from apoptosis.Insulin-dependent diabetes mellitus (IDDM)is characterized in part by pancreatic β-cell apoptosis.Here,we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors.Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model.Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells,primary β cells,and apoptotic pancreatic β cells of MLD-STZ-treated mice.AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days.Blood glucose,plasma insulin,and creatine levels were measured,and glucose tolerance tests were performed.The effects of AChE inhibitors on MIN6 cells were also evaluated.AChE expression was induced in the apoptotic MIN6 cells and primary β cells in vitro and pancreatic islets in vivo when treated with STZ.Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic β cells during IDDM development.The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes,and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice.AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment.Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.

  12. Effects of acetylcholinesterase gene silencing on its activity in cultured human skeletal muscle.

    Mis, Katarina; Mars, Tomaz; Golicnik, Marko; Jevsek, Marko; Grubic, Zoran


    In spite of several reports demonstrating that acetylcholinesterase (AChE [EC]) expression is importantly regulated at the level of its mRNA, we still know little about the relationship between AChE mRNA level and the level of mature, catalytically active enzyme in the cell. Better insight into this relationship is, however, essential for our understanding of the molecular pathways underlying AChE synthesis in living cells. We have approached this problem previously (Grubic et al., 1995; Brank et al., 1998; Mis et al., 2003; Jevsek et al., 2004); however, recently introduced small interfering RNA (siRNA) methodology, which allows blockade of gene expression at the mRNA level, opens new possibilities in approaching the AChE mRNA-AChE activity relationship. With this technique one can eliminate AChE mRNA in the cell, specifically and at selected times, and follow the effects of such treatment at the mature enzyme level. In this study we followed AChE activity in siRNA-treated cultured human myoblasts. Our aim was to find out how the temporal profile of the AChE mRNA decrease is reflected at the level of AChE activity under normal conditions and after inhibition of preexisting AChE by diisopropyl phosphorofluoridate (DFP).AChE activity was determined at selected time intervals after siRNA treatment in both myoblast homogenates and in culture medium to follow the effects of siRNA treatment at the level of intracellular AChE synthesis and at the level of AChE secreted from the cell.

  13. Cholinergic depletion and basal forebrain volume in primary progressive aphasia

    Jolien Schaeverbeke


    In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion.

  14. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    Chen, Aiqiong; Du, Dan; Lin, Yuehe


    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  15. Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase.

    Musilek, Kamil; Holas, Ondrej; Kuca, Kamil; Jun, Daniel; Dohnal, Vlastimil; Opletalova, Veronika; Dolezal, Martin


    Six AChE monooxime-monocarbamoyl reactivators with an (E)-but-2-ene linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and insecticide paraoxon was tested in vitro. The reactivation efficacies of pralidoxime, HI-6, obidoxime, K048, K075 and the newly prepared reactivators were compared. According to the results obtained, one reactivator seems to be promising against tabun-inhibited AChE and two reactivators against paraoxon-inhibited AChE. The best results were obtained for bisquaternary substances with at least one oxime group in position four.

  16. Control levels of acetylcholinesterase expression in the mammalian skeletal muscle.

    Grubic, Z; Zajc-Kreft, K; Brank, M; Mars, T; Komel, R; Miranda, A F


    Protein expression can be controled at different levels. Understanding acetylcholinesterase (EC., AChE) expression in the living organisms therefore necessitates: (1) determination and mapping of control levels of AChE metabolism; (2) identification of the regulatory factors acting at these levels; and (3) detailed insight into the mechanisms of action of these factors. Here we summarize the results of our studies on the regulation of AChE expression in the mammalian skeletal muscle. Three experimental models were employed: in vitro innervated human muscle, mechanically denervated adult fast rat muscle, and the glucocorticoid treated fast rat muscle. In situ hybridization of AChE mRNA, combined with AChE histochemistry, revealed that different distribution patterns of AChE, observed during in vitro ontogenesis and synaptogenesis of human skeletal muscle, reflect alterations in the distribution of AChE mRNA (Z. Grubic, R. Komel, W.F. Walker, A.F. Miranda, Myoblast fusion and innervation with rat motor nerve alter the distribution of acetylcholinesterase and its mRNA in human muscle cultures, Neuron 14 (1995) 317-327). To study the mechanisms of AChE mRNA loss in denervated adult rat skeletal muscle, we exposed deproteinated AChE mRNA to various subcellular fractions in vitro. Fractions were isolated from the normal and denervated rat sternomastoideus muscle. We found significantly increased, but non-specific AChE mRNA degradation capacities in the three fractions studied, suggesting that increased susceptibility of muscle mRNA to degradation might be at least partly responsible for the decreased AChE mRNA observed under such conditions (K. Zajc-Kreft, S. Kreft, Z. Grubic, Degradation of AChE mRNA in the normal and denervated rat skeletal muscle, Book of Abstracts, The Sixth International Meeting on Cholinesterases, La Jolla, CA, March 20-24, 1998, p. A3.). In adult fast rat muscle, treated chronically with glucocorticoids, we found the fraction of early

  17. A New Technique to Rapidly Test Agrochemical Residues In Fruits and Vegetables


    Extraction of AchE, relationship between substrate and enzyme concentration, and inhibition effects of the agrochemicals to AchE are discussed in this paper. Through the re search, the proper AchE concentration for hydrolysis of 1 ml 1mmoL/L substrate and I50 val ues of the agrochemicals to AchE are decided. It is proved that Asch-DTNB method is a rapid test tool for agrochemical residues in fruits and vegetables. A rapid test card has been developed with sensitivity of 0.05mg/L.

  18. [A comparison of the efficacy of the reactivators of acetylcholinesterase inhibited with tabun].

    Cabal, J; Kuca, K; Jun, D; Bajgar, J; Hrabinová, M


    The nerve agent tabun inhibits acetylcholinesterase (AChE; EC by the formation of a covalent bond with the enzyme. Afterwards, AChE is not able to fulfil its role in the organism and subsequently cholinergic crisis occurs. AChE reactivators (pralidoxime, obidoxime and HI-6) as causal antidotes are used for the cleavage of the bond between the enzyme and nerve agent. Unfortunately, their potency for reactivation of tabun-inhibited AChE is poor. The aim of the study was to choose the most potent reactivator of tabun-inhibited AChE. We have tested eight AChE reactivators--pralidoxime, obidoxime, trimedoxime, HI-6, methoxime, Hlö-7 and our newly synthesized oximes K027 and K048. All reactivators were tested using our standard in vitro reactivation test (pH 8, 25 degrees C, time of inhibition by the nerve agent 30 minutes, time of reactivation by AChE reactivator 10 minutes). According to our results, only trimedoxime was able to achieve 50% reactivation potency. However, this relatively high potency was achieved at high oxime concentration (10(-2) M). At a lower concentration of 10(-4) M (the probably attainable concentration in vivo), four AChE reactivators (trimedoxime, obidoxime, K027, and K048) were able to reactivate AChE inhibited by tabun reaching from 10 to 18%.

  19. A comparative study on the relationship between acetylcholinesterase activity and acute toxicity in Daphnia magna exposed to anticholinesterase insecticides.

    Printes, Liane Biehl; Callaghan, Amanda


    Acetylcholinesterase (AChE) activity was measured in Daphnia magna that had been exposed to four organophosphates (OPs; parathion, chlorpyrifos, malathion, and acephate) and one carbamate (propoxur) for 48 h. These results were related to acute toxicity (median effective concentration [EC50] for immobility). For the four OPs, the EC50s were 7.03 pM, 3.17 pM, 10.56 pM, and 309.82 microM, respectively. The EC50 for propoxur was 449.90 pM. Reduction in AChE activity was directly related to an increase in immobility in all chemicals tested. However, the ratio between the EC50 and the AChE median inhibiting concentration ranged from 0.31 to 0.90. A 50% reduction in AChE activity generally was associated with detrimental effects on mobility. However, for acephate, high levels of AChE inhibition (70%) were observed in very low concentrations and were not associated with immobility. In addition, increasing the concentration of acephate further had a slight negative effect on AChE activity but a strong detrimental effect on mobility. Binding sites other than AChE possibly are involved in acephate toxicity to D. magna. Our findings demonstrate different associations between AChE inhibition and toxicity when different chemicals are compared. Therefore, the value of using AChE activity as a biomarker in D. magna will be dependent on the chemical tested.

  20. Evolutionary origin and status of two insect acetylcholinesterases and their structural conservation and differentiation.

    Cha, Deok Jea; Lee, Si Hyeock


    Acetylcholinesterase (AChE) plays a pivotal role in synaptic transmission in the cholinergic nervous system of most animals, including insects. Insects possess duplicated AChE gene loci (ace1 vs. ace2) encoding two distinct AChEs (AChE1 and AChE2). A phylogenetic analysis suggested that the last common ancestor of two aces shared its origin with Platyhelminthes. In addition, the ace duplication event likely occurred after the divergence of Protostomian but before the split of Ecdysozoa. The ace1 lineage exhibited a significantly lower evolutionary rate (d and dN/dS ratio) than the ace2 lineage, suggesting that the ace1 lineage has retained the essential function of synaptic transmission following its duplication. Therefore, the putative functional transition from ace1 to ace2 observed in some Hymenopteran insects appears to be a local and relatively recent event. The amino acid sequence comparison and three-dimensional modeling of insect AChEs identified a few consistent differences in the amino acid residues in functionally crucial domains between two AChEs, which are likely responsible for the functional differentiation between two AChEs. A unique amino acid substitution causing a dramatic reduction in the catalytic activity of AChE1 in some Hymenopteran insects was suggested to be responsible for the aforementioned functional transition of ace. © 2014 Wiley Periodicals, Inc.

  1. Intricate paths of cells and networks becoming "Cholinergic" in the embryonic chicken retina.

    Thangaraj, Gopenath; Greif, Alexander; Bachmann, Gesine; Layer, Paul G


    Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are the decisive enzymatic activities regulating the availability of acetylcholine (ACh) at a given synaptic or nonsynaptic locus. The only cholinergic cells of the mature inner retina are the so-called starburst amacrine cells (SACs). A type-I SAC, found at the outer border of the inner plexiform layer (IPL), forms a synaptic subband "a" within the IPL, while a type-II SAC located at the inner IPL border projects into subband "d." Applying immunohistochemistry for ChAT and AChE on sections of the chicken retina, we here have revealed intricate relationships of how retinal networks became dominated by AChE or by ChAT reactivities. AChE+ cells were first detectable in an embryonic day (E)4 retina, while ChAT appeared 1 day later in the very same cells; at this stage all are Brn3a+, a marker for ganglion cells (GCs). On either side of a faint AChE+ band, indicating the future IPL, pairs of ChAT+ /AChE- /Brn3a- cells appeared between E7/8. Type-I cells had increased ChAT and lost AChE; type-II cells presented less ChAT, but some AChE on their surfaces. Direct neighbors of SACs tended to express much AChE. Along with maturation, subband "a" presented more ChAT but less AChE; in subband "d" this pattern was reversed. In conclusion, the two retinal cholinergic networks segregate out from one cell pool, become locally opposed to each other, and become dominated by either synthesis or degradation of ACh. These "cholinergic developmental divergences" may also have significant physiologic consequences.

  2. Conformationally restrained carbamoylcholine homologues. Synthesis, pharmacology at neuronal nicotinic acetylcholine receptors and biostructural considerations

    de la Fuente Revenga, M; Balle, Thomas; Jensen, Anders A.


    Exploration of small selective ligands for the nicotinic acetylcholine receptors (nAChRs) based on acetylcholine (ACh) has led to the development of potent agonists with clear preference for the α4β2 nAChR, the most prevalent nAChR subtype in the central nervous system. In this work we present th...

  3. Cloning of Acetylcholinesterase Gene in a Microbial Vector.


    regarding the structure and properties of AChE has been obtained from studies with electric eel ( Electrophorus electricus ) and the electric ray (Torpedo...of an active-site-containing peptide from AChE of Electrophorus . This sequence is Trp-Asp-Pro-Asp-Arg-Glu-Met. Snce It Is possible that the region

  4. Effect of the methanol leaves extract of Clinacanthus nutans on the activity of acetylcholinesterase in male mice

    Lau KW


    Conclusion: In conclusion, 14 d oral administration of C. nutans was able to modulate cholinergic neurotransmission by activating AChE activity in mice kidney, liver and heart. Compounds that responsible for the induction of AChE activity in mice liver, heart and kidney and its mechanism needs to be elucidated.


    Ismarulyusda Ishak


    Full Text Available Agriculture is an important component of the Malaysian economy. Pesticides are widely used by farmers to increase crop production. Acetylcholinesterase (AChE is known to play an important role in the degradation of acetylcholine (ACh at the neuromuscular junction of the nervous system. The purpose of this study was to determine the effect of pesticide exposure on serum levels of AChE of farmers. A cross-sectional study was conducted. A total of 95 farmers from Kelantan (n = 49 and Selangor (n = 46 aged between 23 and 71 years were recruited. AChE concentration was measured by spectrophotometry. The results of this study showed that the mean AChE concentrations in farmers from Kelantan and Selangor were 2,715 and 2,660 U/L, respectively, significantly different (p < 0.05 from normal reference value (3500 U/l. Pearson correlation test showed a moderate correlation betweenAChE level and age (r = -0.551 and a strong correlation between AChE level and working period (r = -0.872 in farmers in Kelantan. AChE levels in Selangor were also moderately correlated with age (r = -0.353 and working period (r = -0.515. In conclusion, increasing age and long-term pesticide exposure reduce AChE levels in farmers.

  6. Acetylcholinesterase inhibition and altered locomotor behavior in the carabid beetle pterostichus

    Jensen, Charlotte S.; Krause-Jensen, Lone; Baatrup, Erik


    -dependent difference in behavioral sensitivity to minor AChE depressions. The results demonstrate that automated measurements of locomotor behavior is at least as sensitive an endpoint to organophosphate poisoning as the AChE assay. Further, the correlation between the molecular and behavioral responses in individual...

  7. Different inhibition of acetylcholinesterase in selected parts of the rat brain following intoxication with VX and Russian VX.

    Hajek, Petr; Bajgar, Jiri; Slizova, Dasa; Krs, Otakar; Kuca, Kamil; Capek, Lukas; Fusek, Josef


    Differences between acetylcholinesterase (AChE) inhibition in the brain structures following VX and RVX exposure are not known as well as information on the possible correlation of biochemical and histochemical methods detecting AChE activity. Therefore, inhibition of AChE in different brain parts detected by histochemical and biochemical techniques was compared in rats intoxicated with VX and RVX. AChE activities in defined brain regions 30 min after treating rats with VX and Russian VX intramuscularly (1.0 x LD(50)) were determined by using biochemical and histochemical methods. AChE inhibition was less expressed for RVX, in comparison with VX. Frontal cortex and pontomedullar areas containing ncl. reticularis has been found as the most sensitive areas for the action of VX. For RVX, these structures were determined to be frontal cortex, dorsal septum, and hippocampus, respectively. Histochemical and biochemical results were in good correlation (R(xy) = 0.8337). Determination of AChE activity in defined brain structures was a more sensitive parameter for VX or RVX exposure than the determination of AChE activity in the whole-brain homogenate. This activity represents a "mean" of the activities in different structures. Thus, AChE activity is the main parameter investigated in studies searching for target sites following nerve-agent poisoning contributing to better understanding of toxicodynamics of nerve agents.

  8. Are soluble and membrane-bound rat brain acetylcholinesterase different

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. (Centre de Neurochimie du C.N.R.S., Strasbourg, (France))


    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  9. 0 consenso e a polêmica no texto argumentativo escolar

    Rinaldo Guariglia


    Full Text Available Este estudo apresenta propriedades textuais e discursivas regidas pela argumentação, que respondem pela propagação das idéias do senso comum nas redações argumentativas escolares e, por extensão, das idéias que se confrontam com os enunciados consensuais: a polêmica. Por meio da reflexão bakhtiniana, investigam-se os diálogos com a voz social, com a proposta de redação, e principalmente com o interlocutor-examinador inserem, em meio A dispersão do discurso, uma gama de propriedades que ora são manifestações da categoria consensual, ora da categoria polêmica, sempre de acordo com o exercício argumentativo.

  10. Creación de un recurso educativo digital abierto de acentuación en español: una propuesta para abordar dificultades básicas en el desarrollo de la comunicación escrita a nivel universitario

    Sergio Álvarez Uribe


    Full Text Available La creación de un recurso educativo digital abierto (REDA de acentuación en español responde a una de las dificultades básicas de los estudiantes universitarios frente al dominio de la comunicación escrita. La dinámica del proceso de creación permitió identificar la ausencia de recursos de calidad sobre acentuación y la falta de procedimientos claros y accesibles para profesores no expertos en tecnología, interesados en ofrecer recursos digitales acordes a las expectativas del estudiante de hoy. La experiencia de la creación del REDA de acentuación en español muestra una posible ruta para enfrentar retos similares

  11. Multi-Agent-System till brädspel

    Wahlström, Marco; Karlsson, Jonas


    För att ta reda på hur väl en Multi-Agent-Systems-bot kan stå sig mot andra, icke-MAS-bottar, så har vi implementerat en bot till brädspelet Arimaa. Botten är implementerad i C++ och den kan spela mot andra bottar, eller människor, genom Arimaas officiella hemsida. Syftet har varit att skapa en fullfjädrad bot som både klarar av att spela korrekt, och att spela bra. För att ta reda på om MAS är en bra designfilosofi för Arimaa så har vi utmanat ett antal av de bottar som andra människor skapa...

  12. Marx em tempos de MEGA: os planos e o plano de O Capital

    Leonardo Gomes de Deus


    Full Text Available Resumo Com a publicação de textos inéditos de Marx, tem sido possível avaliar com maior precisão seu itinerário intelectual. O presente artigo investiga os momentos que conduziram o autor a um plano consistente e logicamente articulado para O Capital, em meio à redação de uma série de planos e manuscritos. Utilizam-se para tanto os Grundrisse, o Manuscrito de 1861-1863 e manuscritos redigidos nos anos seguintes, recentemente publicados. Explora-se assim uma perspectiva sobre os planos de redação da obra econômica de Marx, diferente daquela formulada por Roman Rosdolsky.

  13. [A histochemical study of acetylcholinesterase in intact and deafferented cat auditory cortex].

    Genis, E D


    The peculiarities of the AChE distribution were investigated in the intact cat auditory cortex and during early period of its neuronal isolation. It is shown that in the isolated cortex slab the staining of the AChE containing fibre disappeared from the neuropile, while in the intact cortex it was well pronounced. AChE accumulation was observed in the proximal parts of the transsected thalamo-cortical fibres. It is supposed that the AChE-containing fibres in the auditory cortex belong to nonspecific thalamic inputs.

  14. Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme.

    Inestrosa, N C; Alvarez, A; Pérez, C A; Moreno, R D; Vicente, M; Linker, C; Casanueva, O I; Soto, C; Garrido, J


    Acetylcholinesterase (AChE), an important component of cholinergic synapses, colocalizes with amyloid-beta peptide (A beta) deposits of Alzheimer's brain. We report here that bovine brain AChE, as well as the human and mouse recombinant enzyme, accelerates amyloid formation from wild-type A beta and a mutant A beta peptide, which alone produces few amyloid-like fibrils. The action of AChE was independent of the subunit array of the enzyme, was not affected by edrophonium, an active site inhibitor, but it was affected by propidium, a peripheral anionic binding site ligand. Butyrylcholinesterase, an enzyme that lacks the peripheral site, did not affect amyloid formation. Furthermore, AChE is a potent amyloid-promoting factor when compared with other A beta-associated proteins. Thus, in addition to its role in cholinergic synapses, AChE may function by accelerating A beta formation and could play a role during amyloid deposition in Alzheimer's brain.

  15. In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases.

    Kuca, Kamil; Cabal, Jiri; Jun, Daniel; Musilek, Kamil


    In this work, two oximes for the treatment of tabun-inhibited acetylcholinesterase (AChE; EC, K074 (1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide) and K075 ((E)-1,4-bis(4-hydroxyiminomethylpyridinium)but-2-en dibromide), were tested in vitro as reactivators of AChE. Comparison was made with currently used AChE reactivators (pralidoxime, HI-6, methoxime and obidoxime). Human brain homogenate was taken as an appropriate source of the cholinesterases. As resulted, oxime K074 appears to be the most potent reactivator of tabun-inhibited AChE, with reactivation potency comparable to that of obidoxime. A second AChE reactivator, K075, does not attain as great a reactivation potency as K074, although its maximal reactivation (17%) was achieved at relevant concentrations for humans.


    陈莉娜; 吕军; 臧伟进; 于晓江; 孙晓东; 高小利


    Objective To investigate the desensitization of acetylcholine (Ach) on the inhibition effects of blood pressure (BP) in anesthetized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice Ach administration (each was 15μg*kg-1,I.v.), the desensitization on the effect of systemic blood pressure of the first Ach injection towards the subsequent Ach administration was observed. Results When Ach administration intervals were 40, 60, 80, 100 seconds, the percentages of desensitization of Ach on systemic blood pressure were significantly increased (P0.05). Conclusion The results indicated that Ach contents in blood might influence the action of next Ach administration. To some extent, the higher the concentration of Ach in blood, the bigger the ratio of desensitization of exogenous Ach is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.

  17. Copper, aluminum, iron and calcium inhibit human acetylcholinesterase in vitro.

    Pohanka, Miroslav


    Acetylcholinesterase (AChE) is an important part of cholinergic nerves where it participates in termination of neurotransmission. AChE can be inhibited by e.g. some Alzheimer disease drugs, nerve agents, and secondary metabolites. In this work, metal salts aluminum chloride, calcium chloride, cupric chloride, ferric chloride, potassium chloride, magnesium chloride and sodium chloride were tested for their ability to inhibit AChE. Standard Ellman assay based on human recombinant AChE was done and inhibition was measured using Dixon plot. No inhibition was proved for sodium, potassium and magnesium ions. However, aluminum, cupric, ferric and calcium ions were able to inhibit AChE via noncompetitive mechanism of inhibition. Though the inhibition is much weaker when compared to e.g. drugs with noncompetitive mechanism of action, biological relevance of the findings can be anticipated.

  18. Evaluation of potency of known oximes (pralidoxime, trimedoxime, HI-6, methoxime, obidoxime) to in vitro reactivate acetylcholinesterase inhibited by pesticides (chlorpyrifos and methylchlorpyrifos) and nerve agent (Russian VX).

    Musílek, Kamil; Kuca, Kamil; Jun, Daniel


    Nerve agents and pesticides belong to the group of organophosphates. They are able to inhibit irreversibly the enzyme acetylcholinesterase (AChE). Acetylcholinesterase reactivators were designed for the treatment of nerve agent intoxications. Their potency to reactivate pesticide-inhibited AChE was many times evaluated. In this study, five commonly used AChE reactivators (pralidoxime, methoxime, HI-6, obidoxime, trimedoxime) for the reactivation of AChE inhibited by two pesticides (chlorpyrifos and methylchlorpyrifos) were used. Russian VX (nerve agent) as a member of nerve agents' family was taken for comparison. Obtained results show that oximes developed against nerve agent intoxication are less effective for intoxication with organophosphorus pesticides. Especially, methylchlorpyrifos-inhibited AChE was found to be poorly reactivated by the compounds used.

  19. 钢之炼金术士



    @@ The legend tells of a mystical artifact that when it used its possessors power will increase a thousand fold.Anyone possessing this artifact could in theory produce an elixir of extraordinary power that would heal all injuries,and give them evedasUng life.It is rumored to be red;a brilliant,sparkling crimson rivaling the most precious jewel in any museum.The stone's power is equal to the greatest of Nature's fury and beauty alike.

  20. Usefulness of Compile-Time Restructuring of LGDF Programs in Throughput- Critical Applications


    12 2. Processor .................................................................. 16 iv I. m. SCHEDULING...of the hardware and sotare, aloing with die joint h arwaeofwr view. Chapter M is a description of the I(FS and RC scheduling technques Chapter IV is an...with camputationtme. fV e costo fayt ts ste is low. u wil be lii pin otdie mrvolvM in - bclm. e. e. Redae Mewsy Conuewie Once doe cylinder is mapped

  1. Evaluation of cholinergic markers in Alzheimer's disease and in a model of cholinergic deficit


    Cognitive deficits in neuropsychiatric disorders, such as Alzheimer's disease (AD), have been closely related to cholinergic deficits. We have compared different markers of cholinergic function to assess the best biomarker of cognitive deficits associated to cholinergic hypoactivity. In post-mortem frontal cortex from AD patients, acetylcholine (ACh) levels, cholinacetyltransferase (ChAT) and acetylcholinesterase (AChE) activity were all reduced compared to controls. Both ChAT and AChE activi...

  2. NMR determination of Electrophorus electricus acetylcholinesterase inhibition and reactivation by neutral oximes.

    da Cunha Xavier Soares, Sibelle Feitosa; Vieira, Andréia Aguiar; Delfino, Reinaldo Teixeira; Figueroa-Villar, José Daniel


    Neurotoxic organophosphorus compounds (OPs), which are used as pesticides and chemical warfare agents lead to more than 700,000 intoxications worldwide every year. The main target of OPs is the inhibition of acetylcholinesterase (AChE), an enzyme necessary for the control of the neurotransmitter acetylcholine (ACh). The control of ACh function is performed by its hydrolysis with AChE, a process that can be completely interrupted by inhibition of the enzyme by phosphylation with OPs. Compounds used for reactivation of the phosphylated AChE are cationic oximes, which usually possess low membrane and hematoencephalic barrier permeation. Neutral oximes possess a better capacity for hematoencephalic barrier permeation. NMR spectroscopy is a very confident method for monitoring the inhibition and reactivation of enzymes, different from the Ellman test, which is the common method for evaluation of inhibition and reactivation of AChE. In this work (1)H NMR was used to test the effect of neutral oximes on inhibition of AChE and reactivation of AChE inhibited with ethyl-paraoxon. The results confirmed that NMR is a very efficient method for monitoring the action of AChE, showing that neutral oximes, which display a significant AChE inhibition activity, are potential drugs for Alzheimer disease. The NMR method showed that a neutral oxime, previously indicated by the Ellman test as better in vitro reactivator of AChE inhibited with paraoxon than pralidoxime (2-PAM), was much less efficient than 2-PAM, confirming that NMR is a better method than the Ellman test. Copyright © 2013. Published by Elsevier Ltd.

  3. Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.

    Rodríguez-Fuentes, Gabriela; Rubio-Escalante, Fernando J; Noreña-Barroso, Elsa; Escalante-Herrera, Karla S; Schlenk, Daniel


    Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression.

  4. Overexpression of acetylcholinesterase inhibited cell proliferation and promoted apoptosis in NRK cells

    Qi-huang JIN; Heng-yi HE; Yu-fang SHI; He LU; Xue-jun ZHANG


    AIM: To study the potential function of acetylcholinesterase (AChE) in apoptosis through overexpression of AChE in Normal Rat Kidney (NRK) cells. METHODS: AChE activity was detected by the method of Karnovsky and Roots. Activated caspase-3 was analyzed by Western blotting and immunofiurescence with antibody special to activated caspase-3 fragment. The expression plasmids were constructed in pcDNA3.1 containing AChE gene or a fragment of AChE antisense that were got from RT-PCR. Stable expression cell lines were selected by G418 in cells transfected by lipofection. AChE expression was analyzed by RT-PCR and Western blotting. The proliferation rates of transfected cells were examined by the growth curve and cloning efficiency. MTT assay was used to analyze the cell viability. RESULTS: The proliferation rate of the cells transfected with AChE was retarded and the cloning efficiency was lower (28.2 %±3.1% and 48.7 %±2.1%) than cells transfected with vector (56.1%±0.3 %) or AChE-antisense (77.7 %±2.2 %). After 2 d the various clone types were deprived of serum, the residue cell viability were 10.4 %±4.6 % and 12.6 %±6.7 % in the cells transfected with AChE, and 27.4 %±3.5 % in cells with vector, and 50.3 %±7.8 % in cells with AChE-antisense. CONCLUSION: During apoptosis, increase of AChE protein is to inhibit cell proliferation, and then to promote apoptosis in NRK cells.

  5. Mudanças à vista: como Facebook e Twitter participam da rotina dos jornalistas de um meio impresso brasiliense

    Luciana Carla Kwiatkoski


    Full Text Available O jornalismo, desde seu surgimento, passa por adaptações. As mudanças físicas nas redações jornalísticas, ocasionadas pelo avanço tecnológico dos suportes/meios, costumam ser drásticas e aparentes, envolvendo alterações na própria rotina produtiva, na cultura organizacional, nos profissionais e no produto final. Nos últimos anos, Facebook e Twitter - duas das mídias sociais que mais têm adeptos no Brasil - adentraram as redações de meios de comunicação, passando a ser ferramentas de uso comum no jornalismo, e este processo parece estar exigindo mais adaptações. O presente artigo propõe uma discussão sobre o uso dessas mídias pelos jornalistas e sobre as transformações no modo de produção da notícia e sobre algumas das possíveis consequências para o jornalismo. Dados preliminares de pesquisa realizada no jornal Correio Braziliense, envolvendo 25 profissionais em seu trabalho na redação ou fora dela, apontam para a inserção do Facebook e do Twitter no dia a dia dos jornalistas.

  6. A arte de redigir um trabalho científico The art of writing a scientific paper

    Fabio Xerfan Nahas


    Full Text Available A redação científica e suas particularidades são descritas neste artigo. A dificuldade do autor-médico ao escrever, o uso inadequado do jargão médico e as regras básicas de escrita são analisados. O autor é orientado, desde o início da fase de redação do trabalho, a como colocar suas idéias progressivamente no papel de modo a organiza-las em um rascunho inicial e, subseqüentemente, ir melhorando este manuscrito. As idéias de simplificação de escrita, ordem direta e objetividade numérica que são a base da redação científica estão relatadas e discutidas.The special characteristics of the scientific writing are described in this paper. The difficulty of writing of the medical author, the inadequate use of the medical jargon and the writing basic rules are analyzed. The author is oriented since the initial stage of the writing and how to progressively write his ideas, organizing them on a draft and improving the manuscript. Good writing such as the use of simple terms, direct order and objectivity which are reported and discussed.

  7. [Effect of acetylcholine and acetylcholinesterase on the activity of contractile vacuole of Amoeba proteus].

    Bagrov, Ia Iu; Manusova, N B


    Acetylcholine (ACh, 1 microM) stimulates activity of the contractile vacuole of proteus. The effect of ACh is not mimicked by its analogs which are not hydrolyzed by acetylcholinesterase (AChE), i. e., carbacholine and 5-methylfurmethide. The effect of ACh is not sensitive to the blocking action of M-cholinolytics, atropine and mytolone, but is suppressed by N-cholinolytic, tubocurarine. The inhibitors of AChE, eserine (0.01 microM) and armine (0.1 microM), suppress the effect of ACh on amoeba contractile vacuole. ACh does not affect activation of contractile vacuole induced by arginine-vasopressin (1 microM), but it blocks such effect of opiate receptors agonist, dynorphin A1-13 (0.01 microM). This effect of ACh is also suppressed by the inhibitors of AChE. These results suggest that, in the above-described effects of ACh, AChE acts not as an antagonist, but rather as a synergist.

  8. Rapid Detection of Irreversible Acetylcholineasterase Inhibitor by Mass Spectrometry Assay

    蔡婷婷; 张立; 汪蓉; 梁晨; 赵武生; 傅得锋; 张玉荣; 郭寅龙


    Here we developed a rapid method to detect acetylcholinesterase (ACHE) activity by matrix-assisted laser de- sorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) for screening irreversible AChE inhibi- tors. Due to its good salt-tolerance and low sample consumption, MALDI-FTMS could facilitate rapid detection, especially detection in real application. AChE activity was determined through calculating abundance of substrate and product in mass spectrometry. By this approach, we investigated the relation of organophosphorous (OP) con- centrations and AChE inhibition. Shown in different inhibition curves from different OP pesticides, enzyme inhibi- tions still kept good correlation with concentration of OPs. Finally, this AChE-inhibited method was applied to screen whole bloods of four decedents and discuss their death reason. In contrast to healthy persons, three of dece- dents showed low AChE activity, and probably died for irreversible AChE inhibitors. Through the following de- tecting in GC-MS/MS, the possible death reason of these three decedents was confirmed, and another decedent actually died for sumicidin, a non-AChE inhibitor. It demonstrated that screening irreversible AChE inhibitors by detecting enzyme activity in MALDI-FTMS provided fast and accurate analysis results and excluded another toxicants not functioning on ACHE. This method offered alternative choices for indicating the existence of enzyme inhibitors.

  9. Immobilization of acetylcholinesterase via biocompatible interface of silk fibroin for detection of organophosphate and carbamate pesticides

    Xue, Rui; Kang, Tian-Fang; Lu, Li-Ping; Cheng, Shui-Yuan


    An amperometric biosensor for the detection of organophosphate and carbamate pesticides was developed based on the immobilization of acetylcholinesterase (AChE) on regenerated silk fibroin (SF) matrix by non-covalent adsorption. SF and AChE were coated sequentially on the surface of the glassy carbon electrode (GCE) which was modified with multiwall carbon nanotube (MWNTs). The obtained biosensor was denoted as AChE-SF/MWNTs/GCE. The atomic force microscopy images showed that the SF matrix provided a more homogeneous interface for the AChE immobilization. The aggregation of immobilizing AChE was therefore avoided. The cyclic voltammogram of thiocholine at this biosensor exhibited a well defined oxidation peak at 0.667 V (vs. SCE). The inhibition rate of methyl parathion to the immobilized AChE was proportional to the logarithm of the concentration of methyl parathion over the range of the concentration of methyl parathion from 3.5 × 10-6 to 2.0 × 10-3 M with a detection limit of 5.0 × 10-7 M. Similarly, the linearly response range of carbaryl was from 1.0 × 10-7 to 3.0 × 10-5 M with a detection limit of 6.0 × 10-8 M. The experimental results indicate that AChE not only can be immobilized steadily on the SF matrix, but also the bioactivity of immobilizing AChE can be preserved effectively.

  10. 1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies.

    Di Pietro, Ornella; Viayna, Elisabet; Vicente-García, Esther; Bartolini, Manuela; Ramón, Rosario; Juárez-Jiménez, Jordi; Clos, M Victòria; Pérez, Belén; Andrisano, Vincenza; Luque, F Javier; Lavilla, Rodolfo; Muñoz-Torrero, Diego


    A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (>11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Acetylcholine mobilization in a sympathetic ganglion in the presence and absence of 2-(4-phenylpiperidino)cyclohexanol (AH5183)

    Cabeza, R.; Collier, B.


    The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2-(4-phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13-14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recovery from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183-treated ganglia, as determined by the synthesis of (/sup 3/H)ACh from (/sup 3/H)choline, and this (/sup 3/H)ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh, and thus we conclude that ACh synthesized in the presence of AH5183 is a releasable as pre-existing ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with (/sup 3/H)choline) and that synthesized during recovery from the drug's effects (perfusion with (/sup 14/C)choline: the ratio of (/sup 3/H)ACh to (/sup 14/C)ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183-induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183-blocked ganglia, even in the drug's continued presence. Venom-induced release of ACh from AH5183-treated ganglia was not less than the venom-induced release from tissues not exposed to AH5183.

  12. Biochemical and toxicological properties of two acetylcholinesterases from the common bed bug, Cimex lectularius.

    Hwang, Chae Eun; Kim, Young Ho; Kwon, Deok Ho; Seong, Keon Mook; Choi, Jae Young; Je, Yeon Ho; Lee, Si Hyeock


    We examined the molecular and enzymatic properties of two acetylcholinesterases (AChEs; ClAChE1 and ClAChE2) from the common bed bug, Cimex lectularius. Native polyacrylamide gel electrophoresis followed by activity staining and Western blotting revealed that ClAChE1 is the main catalytic enzyme and is abundantly expressed in various tissues. Both ClAChEs existed in dimeric form connected by a disulfide bridge and were attached to the membrane via a glycophosphatidylinositol anchor. To determine their kinetic and inhibitory properties, both ClAChE1 and ClAChE2 were in vitro expressed in Sf9 cells using a baculovirus expression system. ClAChE1 showed higher catalytic efficiency toward acetylcholine, supporting the hypothesis that ClAChE1 plays a major role in postsynaptic transmission. An inhibition assay revealed that ClAChE1 is generally more sensitive to organophosphates and carbamates examined although ClAChE2 was >4000-fold more sensitive to malaoxon than ClAChE1. The relatively higher correlation between the in vitro ClAChE1 inhibition and the in vivo toxicity suggested that ClAChE1 is the more relevant toxicological target for organophosphates and carbamates. Although the physiological function of ClAChE2 remains to be elucidated, ClAChE2 also appears to have neuronal functions, as judged by its tissue distribution and molecular and kinetic properties. Our findings help expand our knowledge on insect AChEs and their toxicological properties.

  13. Inhibition effect of graphene oxide on the catalytic activity of acetylcholinesterase enzyme.

    Wang, Yong; Gu, Yao; Ni, Yongnian; Kokot, Serge


    Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence of the nano-material, graphene oxide (GO), were investigated with the use of molecular spectroscopy UV-visible and fluorescence methods. From these studies, important kinetic parameters of the enzyme were extracted; these were the maximum reaction rate, Vm , and the Michaelis constant, Km . A comparison of these parameters indicated that GO inhibited the catalytic activity of the AChE because of the presence of the AChE-GO complex. The formation of this complex was confirmed with the use of fluorescence data, which was resolved with the use of the MCR-ALS chemometrics method. Furthermore, it was found that the resonance light-scattering (RLS) intensity of AChE changed in the presence of GO. On this basis, it was demonstrated that the relationship between AChE and GO was linear and such models were used for quantitative analyses of GO.

  14. Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

    Misulis, K. E.; Dettbarn, W. D.


    An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.

  15. RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis

    Xiaowen Gong; Weiyuan Ye; Haibo Zhou; Xiaohui Ren; Zhigang Li; Weiyin Zhou; Jun Wu; Yicheng Gong; Qi Ouyang; Xiaolin Zhao; Xuejun Zhang


    Acetylcholinesterase (ACHE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further con-firmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were hetero-geneously expressed in the cisplatin-untreated cyto-plasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the trans-location observed in case of ACHE.

  16. Effect of oxotremorine, physostigmine, and scopolamine on brain acetylcholine synthesis: a study using HPLC

    Bertrand, N.; Beley, A. (Laboratoire de Pharmacodynamie et de Physiologie Pharmaceutique, Faculte de Pharmacie, Dijon, (France))


    The synthesis rate of brain acetylcholine (ACh) was estimated in mice following i.v. administration of ({sup 3}H)choline (Ch). The measurements were performed 1 min after the tracer injection, using the ({sup 3}H)ACh/({sup 3}H)Ch specific radioactivity ratio as an index of ACh synthesis rate. Endogenous and labeled Ch and ACh were quantified using HPLC methodology. Oxotremorine and physostigmine (0.5 mg/kg, i.p.) increased the steady state concentration of brain ACh by + 130% and 84%, respectively and of Ch by + 60% (oxotremorine); they decreased ACh synthesis by 62 and 55%, respectively. By contrast, scopolamine (0.7 mg/kg, i.p.) decreased the cerebral content of Ch by - 26% and of ACh by - 23% without enhancing the synthesis of ACh. The results show the utility of HPLC methodology in the investigation of ACh turnover.

  17. Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

    Herkert, Nadja M; Lallement, Guy; Clarençon, Didier; Thiermann, Horst; Worek, Franz


    Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE.

  18. In vitro Evaluation of New Acetylcholinesterase Reactivators as Casual Antidotes against Tabun and Cyclosarin

    Kuca, Kamil; Jun, Daniel; Jung, Young Sik [Faculty of Military Health Sciences, Trebesska (Cyprus); Kim, Tae Hyuk; Cabal, Jiri [Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)


    Nerve agents (sarin, tabun, soman and VX) are class of military important substances able to cause many severe intoxications during few minutes. Currently, the threat of misuse of these agents is daily discussed. Unfortunately, there is no single antidote able to treat intoxication caused by all of these agents. Owing to this fact, new generation of antidotes, especially acetylcholinesterase (AChE: EC reactivators, is still developed. In this study, we have tested four newly developed AChE reactivators: 1-(4-hydroxyiminomethylpyridinium)- 5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (1), 1-(3-hydroxyiminomethylpyridinium)- 5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (2), 1,5-bis(2-hydroxyiminomethylpyridinium)- 3-oxa-pentane dichloride (3) and 1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxa-pentane dibromide (4) for their potency to reactivate in vitro tabun and cyclosarin-inhibited AChE. Their reactivation efficacy was compared with currently the most promising oxime HI-6 (1-(2-hydroxyiminomethylpyridinium)-3-(4- carbamoylpyridinium)-2-oxa-propane dichloride). According to obtained results, two AChE reactivators 1 and 4 were able to reactivate tabun-inhibited AChE. On the contrary, there was no better AChE reactivator than HI- 6 able to reactivate cyclosarin-inhibited AChE.

  19. Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors

    Susimaire P. Mantoani


    Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization.

  20. Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

    Gotkine Marc


    Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

  1. Linarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo.

    Feng, Xinchi; Wang, Xin; Liu, Youping; Di, Xin


    Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in-vitro and ex-vivo. Ellman's colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In-vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 μM. Ex-vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/Kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/Kg). Molecular docking study revealed that both 4'-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer's disease.

  2. Interactions of butane, but-2-ene or xylene-like linked bispyridinium para-aldoximes with native and tabun-inhibited human cholinesterases.

    Calić, Maja; Bosak, Anita; Kuca, Kamil; Kovarik, Zrinka


    Kinetic parameters were evaluated for inhibition of native and reactivation of tabun-inhibited human erythrocyte acetylcholinesterase (AChE, EC and human plasma butyrylcholinesterase (BChE, EC by three bispyridinium para-aldoximes with butane (K074), but-2-ene (K075) or xylene-like linker (K114). Tested aldoximes reversibly inhibited both cholinesterases with the preference for binding to the native AChE. Both cholinesterases showed the highest affinity for K114 (K(i) was 0.01 mM for AChE and 0.06 mM for BChE). The reactivation of tabun-inhibited AChE was efficient by K074 and K075. Their overall reactivation rate constants were around 2000 min(-1)M(-1), which is seven times higher than for the classical bispyridinium para-aldoxime TMB-4. The reactivation of tabun-inhibited AChE assisted by K114 was slow and reached 90% after 20 h. Since the aldoxime binding affinity of tabun-inhibited AChE was similar for all tested aldoximes (and corresponded to their K(i)), the rate of the nucleophilic displacement of the phosphoryl-moiety from the active site serine was the limiting factor for AChE reactivation. On the other hand, none of the aldoximes displayed a significant reactivation of tabun-inhibited BChE. Even after 20 h, the reactivation maximum was 60% for 1 mM K074 and K075, and only 20% for 1 mM K114. However, lower BChE affinities for K074 and K075 compared to AChE suggest that the fast tabun-inhibited AChE reactivation by these compounds would not be obstructed by their interactions with BChE in vivo.

  3. COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina.

    Arredondo, Juan; Lara, Marian; Ng, Fiona; Gochez, Danielle A; Lee, Diana C; Logia, Stephanie P; Nguyen, Joanna; Maselli, Ricardo A


    Collagen Q (ColQ) is a key multidomain functional protein of the neuromuscular junction (NMJ), crucial for anchoring acetylcholinesterase (AChE) to the basal lamina (BL) and accumulating AChE at the NMJ. The attachment of AChE to the BL is primarily accomplished by the binding of the ColQ collagen domain to the heparan sulfate proteoglycan perlecan and the COOH-terminus to the muscle-specific receptor tyrosine kinase (MuSK), which in turn plays a fundamental role in the development and maintenance of the NMJ. Yet, the precise mechanism by which ColQ anchors AChE at the NMJ remains unknown. We identified five novel mutations at the COOH-terminus of ColQ in seven patients from five families affected with endplate (EP) AChE deficiency. We found that the mutations do not affect the assembly of ColQ with AChE to form asymmetric forms of AChE or impair the interaction of ColQ with perlecan. By contrast, all mutations impair in varied degree the interaction of ColQ with MuSK as well as basement membrane extract (BME) that have no detectable MuSK. Our data confirm that the interaction of ColQ to perlecan and MuSK is crucial for anchoring AChE to the NMJ. In addition, the identified COOH-terminal mutants not only reduce the interaction of ColQ with MuSK, but also diminish the interaction of ColQ with BME. These findings suggest that the impaired attachment of COOH-terminal mutants causing EP AChE deficiency is in part independent of MuSK, and that the COOH-terminus of ColQ may interact with other proteins at the BL.

  4. Effects of Endurance Training on A12 Acetyl Cholinesterase Activity in Fast and Slow-Twitch Skeletal Muscles of Male Wistar Rats

    Ali Gorzi


    Full Text Available Background: Endurance training improves the activity of G4 type acetylcholine esterase (AchE in muscle fibres. The purpose of this study was to investigate the effects of 8 weeks of endurance training (ET on activity of A12 type of AchE in Flexor Hallucis Longus (FHL and Soleus (SOL muscles of rats. Materials and Methods: 16 male wistar rats (age: 10 weeks and weight: 172.17±10.080 gr, were randomly divided in 2 groups (control; N=8 and ET; N=8. Training group carried out 8 weeks (5 session/week of endurance training on animal treadmill with speed of 10 m/min for 30 min at the first week which was gradually increased to 30 m/min for 60 min (70-80% of VO2max at the last week. Forty eight hours after last session of training, FHL and Sol muscles of animals were moved out under sterilized situation by cutting on posterio-lateral side of hind limb. For separating AchE subunits, homogenization and electrophoresis (0.06 non-denaturaing polyacrilamide methods were used. AchE activity was measured by Elisa kit.Results: The activity of this protein significantly (p=0.017 increased in SOL muscle of ET group by 119%, but did not changed in FHL. In both groups (ET and Con, FHL muscle had significantly (ET: p=0.028 and Con p=0.01 higher basic levels of AchE activity compared to SOL muscle. This significant increase in AchE of SOL might be indicative of responsiveness of AchE of this muscle following endurance training for improving acetylcholine (Ach cycle in neuromuscular junction.Conclusion: Endurance training might increase the A12 type AchE activity to improve the Ach cycle as part of the adaptation of neuromuscular junction to increased level of physical activity.

  5. Nanomaterials-Based Optical Techniques for the Detection of Acetylcholinesterase and Pesticides

    Ning Xia


    Full Text Available The large amount of pesticide residues in the environment is a threat to global health by inhibition of acetylcholinesterase (AChE. Biosensors for inhibition of AChE have been thus developed for the detection of pesticides. In line with the rapid development of nanotechnology, nanomaterials have attracted great attention and have been intensively studied in biological analysis due to their unique chemical, physical and size properties. The aim of this review is to provide insight into nanomaterial-based optical techniques for the determination of AChE and pesticides, including colorimetric and fluorescent assays and surface plasmon resonance.

  6. 8-hydroxydihydrochelerythrine and 8-hydroxydihydrosanguinarine with a potent acetylcholinesterase inhibitory activity from Chelidonium majus L.

    Cho, Kyung-Mi; Yoo, Ick-Dong; Kim, Won-Gon


    Ethanol extract of the aerial portion of Chelidonium majus L. inhibited acetylcholinesterase (AChE) activity without a significant inhibition of butyrylcholinesterase (BuChE). Using mass spectrometry and NMR studies, three active constituents were isolated and identified: 8-hydroxydihydrochelerythrine (1), 8-hydroxydihydrosanguinarine (2), and berberine (3). Compounds 1-3 showed potent inhibitory activity against AChE, with IC50 (microM) values of 0.61-1.85. Compound 1 exhibited competitive and selective inhibition for AChE.

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

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


    Background:The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity ofacetylcholinesterase (AChE) in the neuromuscular junction (NMJ).However,till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated.We aimed to investigate the effects of sepsis on the antagonistic actions ofneostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).Methods:A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group,n =12) or CLP (the septic group,n =16).After 24 h,the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured.Meanwhile,the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method.The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.Results:Four of 16 rats in the septic group died within 24 h.The time-response curves of both two concentrations ofneostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L;P =0.009 for 0.5 μmol/L).Meanwhile,the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs.1.047 ± 0.087,P < 0.001).The AChE and AChET mRNA expression levels in the septic group were significantly lower than those in the sham group (P =0.002 for AChE;P =0.00l for AChET).Conclusions:Sepsis strengthened the antagonistic actions ofneostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ.The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

  8. A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors

    Jeon, Jongrye; Nielsen, Ditte Dencker; Wörtwein, Gitta;


    Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpres....... Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance....

  9. Seleção de plantas com atividade anticolinasterase para tratamento da doença de Alzheimer Screening for acetylcholinesterase inhibitors from plants to treat Alzheimer's disease

    Maria Teresa Salles Trevisan


    Full Text Available Alzheimer's disease (AD is a neurodegenerative disease characterized by cognite impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activities. These symptons of AD have been successfully treated with acetylcholinesterase (AchE inhibitors (eg. galanthamine. There still is great interest in finding better AchE inhibitors. We use Ellmann's microplate assay and silica gel thin-layer chromatography (TLC to screen natural products from plants as new sources of AchE inhibitors.

  10. The application of HPLC with on-line coupled UV/MS-biochemical detection for isolation of an acetylcholinesterase inhibitor from narcissus 'Sir Winston Churchill'.

    Ingkaninan, K; Hazekamp, A; de Best, C M; Irth, H; Tjaden, U R; van der Heijden, R; van der Greef, J; Verpoorte, R


    An HPLC with on-line coupled UV/MS-biochemical detection method for acetylcholinesterase (AChE) inhibitors in natural sources has been developed. The potential of this method is shown by the isolation of a new AChE inhibitor from the alcoholic extract of Narcissus 'Sir Winston Churchill'. Combining a prefractionation technique using centrifugal partition chromatography with the on-line HPLC-UV/MS-biochemical detection resulted in the isolation of the active compound that was identified as ungiminorine. This alkaloid shows a mild inhibitory effect on AChE.

  11. Molecular Modeling Studies of Piperidine Derivatives as New Acetylcholinesterase Inhibitors against Neurodegenerative Diseases

    Elaine F. F. da Cunha


    Full Text Available Neurodegenerative disorders are related to the progressive loss of structure or function and, eventually, death of neurons. These processes are responsible for diseases like Parkinson’s, Alzheimer’s, and Huntington’s, and the main molecular target for the drug design against these illnesses today is the enzyme acetylcholinesterase (AChE. Following this line, in the present work, we applied docking techniques to study some piperidine derivative inhibitors of AChE and further propose structures of six new AChE inhibitors as potential new drugs against neurodegenerative disorders. The best inhibitor proposed was submitted to additional molecular dynamics simulations steps.

  12. Acetylcholinesterases of blood-feeding flies and ticks.

    Temeyer, Kevin B; Tuckow, Alexander P; Brake, Danett K; Li, Andrew Y; Pérez de León, Adalberto A


    Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer's disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, including biting flies and ticks. However, resistance to OPs in pests affecting animal and human health has compromised control efficacy. OP resistance often results from mutations producing an OP-insensitive AChE. Our studies have demonstrated production of OP-insensitive AChEs in biting flies and ticks. Complementary DNA (cDNA) sequences encoding AChEs were obtained for the horn fly, stable fly, sand fly, and the southern cattle tick. The availability of cDNA sequences enables the identification of mutations, expression and characterization of recombinant proteins, gene silencing for functional studies, as well as in vitro screening of novel inhibitors. The southern cattle tick expresses at least three different genes encoding AChE in their synganglion, i.e. brain. Gene amplification for each of the three known cattle tick AChE genes and expression of multiple alleles for each gene may reduce fitness cost associated with OP-resistance. AChE hydrolyzes the neurotransmitter, acetylcholine, but may have additional roles in physiology and development. The three cattle tick AChEs possess significantly different biochemical properties, and are expressed in neural and non-neural tissues, which suggest separation of structure and function. The remarkable complexity of AChEs in ticks suggested by combining genomic data from Ixodes scapularis with our genetic and biochemical data from Rhipicephalus microplus is suggestive of previously unknown gene duplication and diversification. Comparative studies between invertebrate and vertebrate AChEs could enhance our understanding of structure-activity relationships. Research with ticks as a model system offers the opportunity to

  13. 信息技术应用对数字化阅读成绩的影响--基于国际学生评估项目的实证研究%Th e Impact of Information Tech noIogy on Stu dents’DigitaI Reading Ach ievement:Evidence from PISA

    陈纯槿; 郅庭瑾


    促进信息技术与教育教学融合发展,依托教育信息化全面推动教育现代化是我国深化教育领域综合改革与发展战略的重要方针,以信息技术应用驱动教育信息化建设则是“十三五”期间加快我国教育信息化进程的“机会窗口”。本文基于国际学生评估项目(PISA)对中国上海、中国香港、韩国、日本及新加坡学生的测试数据,从教育生产函数的研究视角探讨信息技术应用对学生数字化阅读成绩的影响。多层线性模型估计结果表明:1)在控制了学生个体特征及其家庭背景后,学校网络教育资源投入对学生数字化阅读成绩具有正向影响;2)与其他年龄组相比,7-9岁初次接触互联网对学生数字化阅读成绩的正向影响最大;3)使用社交媒介的时间对学生数字化阅读成绩的影响显著为负;4)在校使用平板电脑、笔记本电脑对学生数字化阅读成绩均呈显著负向影响;5)校外上网6小时及以上的学生对学校归属感和幸福感的比例最低,在校孤独感和缺课行为的比例最高。其政策启示是教育管理部门在充分利用先进信息技术扩大优质教育资源覆盖面的同时,要重视信息技术对学生成长和发展产生的不利影响,特别是对儿童接触网络时间和校内外上网时间予以规制,加强中学生使用信息技术学习的正向激励。%Promoting the depth integration ofinformation technology and education is a vital strategy in the process of national comprehensive reform in education. It is also a window ofopportunity to accelerate the course ofeducational informatization. Using the data ofProgramme for International Student Assessment (PISA),this paper examines the effects ofinformation technology on students’digital reading achievement with the framework ofeducational produc-tion function. Estimations ofhierarchical linear modeling show that:1 )Controlling for students’individual charac-teristics and family background,the input ofschool information resources had positive impact on students'digital read-ing achievement. 2)Compared with other age cohort,access to the Internet for students at the first time between 7-9 years old had the biggest positive effect. 3)Using social media had a significantly negative effect on students’digital reading scores. 4)Using tablet and laptop in school had significantly negative effects on students’digital reading a-chievement. 5 )Students who use Internet more than six hours outside the school had lower proportion ofschool belong-ing and happiness,as well as higher school absenteeism ratio and loneliness feeling. These results suggest that educa-tion authorities should pay more attention on the negative effects ofinformation technology on students’growth and development. In particular,parents should control the students’first time access to the Internet. Education authorities should strengthen internal incentives ofinformation technology for students’digital learning.

  14. The Intervention Effect of Pain Education Combined with Progressive Relaxation Training on Puncture Ache of Arteriovenous Fistula in Hemodialysis Patients%疼痛教育联合渐进性放松训练对血透患者动静脉内瘘穿刺疼痛的干预效果

    卓少贤; 谢芳; 汤小玲; 曾蕾; 吴凤金


    目的:探讨疼痛教育联合渐进性放松训练对维持性血液透析患者动静脉内瘘穿刺疼痛的干预效果,为实施疼痛管理提供帮助。方法将86例维持性血液透析患者随机分为观察组和对照组,每组43例。对照组患者在干预期间接受常规动静脉内瘘穿刺护理,观察组患者在穿刺常规护理的基础上进行疼痛教育及渐进性肌肉放松训练为主的护理干预,共干预8w。比较两组患者干预前后状态焦虑、特质焦虑、自我效能感、舒适度及内瘘穿刺疼痛评分,分析此干预方法对缓解动静脉内瘘穿刺疼痛的影响。结果观察组患者干预2、4及8w后的内瘘穿刺疼痛评分比对照组患者同时间点的疼痛评分明显降低( P﹤0.05, P﹤0.01);随着干预时间的延长,观察组患者的疼痛强度逐渐下降,以干预8 w后的疼痛程度下降最显著( P﹤0.001);干预8 w后,观察组患者的状态焦虑评分和特质焦虑评分比干预前及对照组干预后均显著降低(均P﹤0.01),观察组患者的自我效能感评分、心理舒适度、生理舒适度、环境舒适度及整体舒适度水平均比干预前及对照组干预后明显提高( P﹤0.01, P﹤0.05);社会舒适度未见明显改善( P﹥0.05)。结论疼痛教育联合渐进性放松训练有助于减轻动静脉内瘘患者穿刺疼痛引起的焦虑负性情绪、增强其自我效能感、提高舒适度,有效缓解动静脉内瘘穿刺疼痛。%Objective To observe the intervention effect of pain education and progressive relaxation training in hemodialysis pa-tients undergoing puncturing on arteriovenous fistula.Methods 86 hemodialysis patients were randomly divided into the experimental group and the control group, with 43 patients in each group.The control group received routine care, while those in the experimental group accepted pain education and progressive relaxation training intervention based on routine puncture care for 8 weeks.The state anxiety, trait anxiety, self-efficacy and comfort degree of the patients in the two groups were compared before and after intervention, to assess the patients’ piercing pain score.Results The piercing pain scores in the experimental group after intervention 2 weeks, 4 weeks and 8 weeks were lower than those before intervention and in the control group (P﹤0.05, P﹤0.01), The piercing pain scores in the experimental group gradually dropped.After intervention, the piercing pain score of week 8 was the lowest ( P ﹤0.001) .After the 8 weeks intervention, the state anxiety scores and trait anxiety scores in the experimental group were lower than the scores before intervention and those in the control group after intervention ( P﹤0.01) , the self-efficacy, the dimensions of physiol-ogy comfort, psychological comfort , environmental comfort and the overall comfort scores in the experimental group were higher than the scores before intervention and those in the control group after intervention (P﹤0.01), but the dimension of societal comfort did not present statistical difference compared with the scores before intervention and those in control group ( P>0.05 ) .Conclusions The pain education combined with progressive muscle relaxation training could help patients with arteriovenous fistula relieve puncture pain, ease anxiety emotions caused by piercing pain, improve self-efficacy, and promote the patients comfort.

  15. Determining the Optimum Cut-Off Grades in Sulfide Copper Deposits / Określanie Optymalnej Wartości Odcięcia Zawartości Procentowej Pierwiastka Użytecznego W Złożach Siarczku Miedzi

    Rahimi, Esmaeil; Oraee, Kazem; Shafahi, Zia Aldin; Ghasemzadeh, Hasan


    Optimum cut-off grades determination in mining life affects production planning and ultimate pit limit and it is also important from social, economical and environmental aspects. Calculation of optimum cut-off grades has been less considered for mines containing various mineral processing methods. In this paper, an optimization technique is applied to obtain optimum cut-off grades for both concentration and heap leaching processes. In this technique, production costs and different recoveries of heap leaching method directed into modeling different annual cash flows in copper mines. Considering the governing constraints, the Lagrange multiplier method is practiced to optimize the cut-off grades in which the objective function is supposed to maximize Net Present Value. The results indicate the effect of heap leaching process on the optimum cut-off grades of primary and secondary sulfide deposits. Określanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego ma poważny wpływ na planowanie produkcji, określanie ostatecznych limitów zasobów złoża; jest to także ważna kwestia z punktu widzenia kwestii społecznych, ekonomicznych i środowiskowych. Obliczanie optymalnego poziomu odcięcia dla zawartości procentowej pierwiastka użytecznego nie było zwykle szeroko rozważane w przypadku kopalni prowadzących ciągły system przeróbki. W pracy tej przedstawiono technikę optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego z uwzględnieniem zarówno procesów koncentracji jak i ługowania. W metodzie uwzględniono koszty produkcji i różne wskaźniki odzysku rudy, wielkości te wykorzystane zostały do modelowania rocznych przepływów gotówki w kopalniach miedzi. Uwzględniając narzucone ograniczenia, zastosowano metodę mnożników Lagrange'a w celu optymalizacji określania poziomu zawartości procentowej pierwiastka użytecznego, gdzie przyjętą funkcją celu jest maksymalizacja wartości bieżącej netto. Wyniki wskazują wpływ procesów ługowania na zawartość procentową pierwiastka użytecznego w rudzie pochodzącej z pierwotnych lub wtórnych złóż siarczku miedzi.

  16. 小剂量异维A酸联合维生素E治疗中、重度痤疮疗效观察%Observation of Effect of Low Dose of Isotretinoin Combined with Vitamin E on Moderate and Severe Ache Vulgaris



    Objective To observe the curative effect of low dose of isotretinoin combined with Vitamin E on moderate and severe acne vulgaris. Methods Ninety-five cases of moderate and severe acne vulgaris patients were divided into two groups randomly. The treatment group(49 cases)were treated with Isotretinoin Soft Capsules orally, 10mg twice per day and Vitamin E Soft Capsules, 0. 1g twice per day. The control group (46 cases)were treated only with Isotretinoin. Both groups were treated for 8 weeks. Results The efficacy rate of treatment group was 95.92%, while that of control group was 80.43% ( P < 0.05). The incidence of adverse reactions( such as mouth dryness, pruritus, muscle soreness,etc)of treatment group was 57.14% ,while that of control group was 89.13% ( P < 0.01 ). Conclusion The method of low dose of isotretinoin combined with Vitamin E on acne vulgaris is high efficacy and low in incidence of adverse reactions.%目的 了解小剂量异维A酸联合维生素E治疗中、重度痤疮的疗效.方法 将95例中、重度痤疮患者随机分成治疗组(49例)和对照组(46例),治疗组予口服异维A酸10mg和维生素E 0.1g,均2次/d.对照组单纯予异维A酸口服.两组均治疗8周.结果 治疗组有效率为95.92%,明显高于对照组(80.43%),两组不良反应(如口唇干燥、皮肤瘙痒、肌肉酸痛等)发生率分别为57.14%和89.13%,差异均有统计学意义(P<0.05).结论 小剂量异维A酸联合维生素E治疗痤疮疗效高、不良反应少、安全可靠.

  17. Influence of Test Anxiety on Ache Severity of Face Among High Middle School Students of Grade%考试所致焦虑状态对高三学生中痤疮患者面部皮损的影响

    杨志波; 赖火龙; 许斌


    目的 探讨考试所致焦虑是否可加剧痘疮皮损.方法 采用痤疮综合分级系统(GAGS)及考试焦虑量表(sarason TAS)对60名患痤疮的高三学生在平时与考前进行面部皮损计数与心理测评,并分析二者不同时期的变化.结果 考试所致焦虑状态可加重学生皮损(rs=0.486,P=0.026),并以右颊为著(rs=0.625,P=0.002).结论 考试所致焦虑状态可加重学生面部痤疮皮损.

  18. 浅谈英国教学模式课业设计与评估在高职护理专业项目教学中的应用%On the British Design and Evaluation of Academic Te-aching in the Vocational Nursing Program Teaching



    为了突出高职护理专业实用型人才培养的目标和特点,为了更好地把握职业教育工学结合一体化的课程内涵,我们在护理教学中探索推行项目教学法,并使用英国教学模式中的课业设计与评估来提高项目教学法在教学中的效果。%To highlight the vocational nursing practical training objectives and characteristics,in order to better grasp the integration of vocational education courses with engineering content,we explore the implementation of the nursing education project teaching methods and the use of English teaching in the academic to improve project design and evaluation of teaching effectiveness in teaching.

  19. Diseases,formula and Chinese herbal medicines:a study on spleen-stom-ach dampness-heat pattern based on modern literature%基于现代文献的脾胃湿热证疾病分布及处方用药研究

    刘路路; 李婷婷; 吴秀艳; 王天芳; 薛晓琳; 罗清香; 张晓娜; 任红; 侯帅颖; 张佳元


    目的:分析现代文献中脾胃湿热证对应疾病的分布情况及其处方、用药情况,为脾胃湿热证进一步的临床及科研提供一定的参考资料。方法以“脾胃湿热证”为主题词、题名/关键词,系统检索中国知网(CNKI)、万方数据知识服务平台、维普资讯(VIP)3大中文数据库自建库以来到2015年12月31日的所有相关文章,选取其中明确具备脾胃湿热证临床治疗的相关文章,运用Microsoft Excel 2010建立数据库,对相关数据进行统计分析。结果检索到的1681篇文献中,符合纳入标准的共109篇;脾胃湿热证最常见于消化系统疾病(86.41%),还可见于皮肤病(5.83%)等;脾胃湿热证的常用处方是平胃散、藿朴夏苓汤、三仁汤等清热、祛湿类处方,同时还可以合并运用对病(症)治疗的其他功用的处方;脾胃湿热证治疗中使用频率超过1%的中药分别为:黄连、半夏、厚朴、甘草、陈皮、黄芩、茯苓、蒲公英、藿香、苍术、薏苡仁、白豆蔻、白术、枳壳、栀子、延胡索、白芍、吴茱萸、干姜、竹茹、茵陈、石菖蒲、郁金、枳实、柴胡、白及、丹参、杏仁、砂仁、